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Biomedical subjects

Mario Plebani

Publications and source records attributed to Mario Plebani.

At least 55 records · Page 3Linked to original sources
PubMed2005

NT-proBNP in the differential diagnosis of acute dyspnea in the emergency department.

OBJECTIVES: The purpose of this study was to verify the usefulness of NT-proBNP in the differential diagnosis of dyspnea in a population of patients presenting in the ER with breathlessness. DESIGN AND METHODS: In samples from 122 patients presenting in the ER with acute-severe dyspnea and from 25 subjects enrolled as a "comparison group" (NORM), NT-proBNP levels were measured. Patients have been classified on the basis of discharge diagnosis: pulmonary disease (PD, n = 23), pulmonary concomitant to cardiac disease (MIXED, n = 17), pulmonary embolism (EMB, n = 8), cardiac disease (CARD, n = 56), acute myocardial infarction (AMI, n = 11) and other disease (OTHER, n = 7). RESULTS: A significant difference in NT-proBNP values (P <or= 0.05) was found in CARD vs. PD as well as vs. NORM and OTHER groups. 1760 ng/L was the best cut-off value calculated from ROC analysis (AUC +/- SE 0.815 +/- 0.041). Comparing NT-proBNP values and ER diagnosis, a disagreement in 24 patients was observed. Using the discharge diagnosis as the "gold standard," four cases (17%) were found to be FP and 11 cases (46%) were FN according to ER diagnosis, while 2 patients showed false positive and 7 false negative NT-proBNP values. CONCLUSIONS: NT-proBNP measurement represents a useful biochemical tool helping the ER physician in the rapid and reliable recognition of cardiac involvement in patients presenting in the ER with acute-severe dyspnea.

Adult↗
PubMed2005

Urinary ET-1, AVP and sodium in premature infants treated with indomethacin and ibuprofen for patent ductus arteriosus.

The relative potency and interrelationship between vasoactive and natriuretic mediators are thought to be important in the transition from fetal to neonatal life. The relationship between urinary vasoactive factors and sodium excretion has not been adequately addressed in premature infants receiving indomethacin and ibuprofen for therapy of patent ductus arteriosus. Excretion rates of AVP, ET-1 and sodium were measured in premature infants with RDS receiving indomethacin or ibuprofen. Forty-four RDS premature infants (<34-week gestation) with PDA received either ibuprofen (n=22) in an initial dose of 10 mg/kg followed by two doses of 5 mg/kg each after 24 and 48 h or 3 doses at 12-h intervals of indomethacin (n=24), 0.2 mg/kg, infused continuously over a period of 15 min. Urinary ET-1, AVP and sodium excretion were measured before and after treatment. Indomethacin treatment caused a significant decrease in urinary ET-1 and AVP excretion (UET-1/Ucr 0.14+/-0.01 vs. 0.10+/-0.05 fenton/mmol; P<0.05; 24.42+/-6.18 vs. 12.63+/-3.06 pg/mmol; P<0.05, respectively), along with a significant reduction in urinary sodium (92.1+/-36.1 vs. 64.8+/-35.6 mmol/l; P<0.01), fractional excretion of sodium (6.8+/-37.1 vs. 4.5+/-37.1%; P<0.01) and urinary osmolality (276.2+/-103.9 vs. 226.4+/-60.3 mOsmol/kg; P<0.05). Ibuprofen treatment caused a significant decrease in urinary AVP (UAVP/Ucr 24.5+/-3.4 vs. 16.3+/-2.04 pg/mmol; P<0.01), along with a significant decrease in urinary sodium (78.0+/-8.4 vs. 57.0+/-8.0 mmol/l; P<0.05) and in fractional excretion of sodium (7.5+/-1.3 vs. 3.9+/-3.0%; P<0.05), while it did not modify urinary ET-1 excretion. The association of renal ET-1 and AVP activity with sodium excretion in premature infants treated with indomethacin and ibuprofen supports the hypothesis that these factors may play a role in the physiologic changes in sodium excretion.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2005

Intron 2 [IVS2, T-C +4] HFE gene mutation associated with S65C causes alternative RNA splicing and is responsible for iron overload.

UNLABELLED: A patient with congenital liver fibrosis revealed a high transferrin saturation index and iron overload on liver biopsy. He did not carry the most frequent HFE mutations: C282Y or H63D. Heterozygosity was detected for S65C. Unknown HFE mutations were also sought using a combined denaturing high performance liquid chromatography (DHPLC)/direct sequence approach and another point mutation, a transition T-C (nt 4910), at the fourth base of the donor splice site of intron 2 [HFE, intervening sequence (IVS) 2, T-C +4] was found. Family screening revealed that a daughter carried both S65C and [IVS2, T-C +4]. CONCLUSION: : The existence in our proband of a partly-altered HFE protein in the region encoded by exon 2 might be responsible for the histologically-demonstrated iron overload.

Journal Article↗
PubMed2005

Proteomics: the next revolution in laboratory medicine?

BACKGROUND: The identification of specific genetic alterations and protein profiles associated with disease offers a unique opportunity to develop proteomics-based assays for early diagnosis. By identifying proteins in serum/plasma, a minimally invasive tool is used to assess the presence of disease and to monitor response to treatment and/or disease progression. The potential clinical applications of this tool are broad-based, including the diagnosis not only of cancer but also cardiovascular and neuromuscular diseases, organ transplantation associated conditions, and infertility. METHODS: A number of competing chromatographic techniques have been proposed for overcoming the complexity and labor-intensive manipulations associated with the traditional technique for proteomic analysis, which is based on two-dimensional gel electrophoretic techniques. However, mass spectrometry has now assumed a central role in most proteomic workflows, and several combinations of ionization sources, analyzers and fragmentations devices have been described and developed. RESULTS: Thanks to proteomic applications in the diagnosis of cancer, several research groups have identified proteomic patterns associated with ovarian, prostatic, colorectal and other cancers. While the sensitivity and specificity of these patterns are highly satisfactory, there are still some open questions concerning the standardization, reproducibility, and inter-laboratory agreement of these data. CONCLUSIONS: Proteomics, and, in particular, serum mass spectroscopic proteomic pattern diagnostics, is a rapid expanding field of research. The plasma proteoma has an important position at the intersection between genes and diseases, and clinical laboratories must adapt to a new era of tests based on proteomics and genomics. In the future, mass spectrometry will become an essential tool in the clinical laboratory.

Biomarkers, Tumor↗
PubMed2005

Pancreatic cancer-associated diabetes mellitus: an open field for proteomic applications.

BACKGROUND: Diabetes mellitus is associated with pancreatic cancer in more than 80% of the cases. Clinical, epidemiological, and experimental data indicate that pancreatic cancer causes diabetes mellitus by releasing soluble mediators which interfere with both beta-cell function and liver and muscle glucose metabolism. METHODS: We analysed, by matrix-assisted laser desorption ionization time of flight (MALDI-TOF), a series of pancreatic cancer cell lines conditioned media, pancreatic cancer patients' peripheral and portal sera, comparing them with controls and chronic pancreatitis patients' sera. RESULTS: MALDI-TOF analysis of pancreatic cancer cells conditioned media and patients' sera indicated a low molecular weight peptide to be the putative pancreatic cancer-associated diabetogenic factor. The sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) analysis of tumor samples from diabetic and non-diabetic patients revealed the presence of a 1500 Da peptide only in diabetic patients. The amino acid sequence of this peptide corresponded to the N-terminal of an S-100 calcium binding protein, which was therefore suggested to be the pancreatic cancer-associated diabetogenic factor. CONCLUSIONS: We identified a tumor-derived peptide of 14 amino acids sharing a 100% homology with an S-100 calcium binding protein, which is probably the pancreatic cancer-associated diabetogenic factor.

Animals↗
PubMed2005

Expression analysis and prognostic significance of human kallikrein 11 in prostate cancer.

BACKGROUND: Kallikrein 11 (KLK11) is a newly discovered human kallikrein gene that is mainly expressed in the central nervous system and endocrine tissues. KLK11 has two alternative splicing isoforms, known as the brain type and prostate type. Many members of the human kallikrein gene family are differentially expressed in cancer and a few have potential as diagnostic/prognostic markers. METHODS: In the present study, the expression of prostate type variant of KLK11 gene was analyzed by RT-PCR in 66 prostate cancer tissues. Tumors were pulverized, total RNA was extracted, and cDNA was prepared by reverse transcription. KLK11 was amplified by PCR using gene specific primers and its identity was verified by sequencing. Prostate tissues were then classified as KLK5 positive or negative based on eithidium bromide staining in agarose gels and image analysis. RESULTS: KLK11 was found to be highly expressed in 43/66 (65%) of prostate cancer samples. We found a significant negative relationship between KLK11 expression and Gleason score (p = 0.004) and disease stage (p = 0.038). Serum total PSA concentration was found to be lower in patients with overexpression of KLK11 (p = 0.044). CONCLUSIONS: We conclude that down-regulation of the KLK11 gene in advanced and more aggressive tumors may open the possibility of being used as a future biological marker distinguishing the tumor aggressiveness as well as a useful prognostic biomarker for prostate cancer.

Aged↗
PubMed2005

Impact of the elevation of biochemical markers of myocardial damage on long-term mortality after percutaneous coronary intervention: results of the CK-MB and PCI study.

AIMS: Retrospective studies and post hoc analyses have suggested that mild elevations in the creatine kinase-MB (CK-MB) isoenzyme following percutaneous coronary intervention (PCI) may be associated with an increased risk of death in the long term. However, this finding is still controversial, and the prognostic significance of elevations of more sensitive markers of myocardial damage, such as the cardiac troponins, has not been established. In this multicentre prospective cohort study, we evaluated the influence of post-procedural elevations of CK-MB and troponin I (cTnI) on long-term mortality. METHODS AND RESULTS: The CK-MB and PCI study included 3494 consecutive patients undergoing PCI from February 2000 to October 2000 in 16 Italian tertiary centres. Blood samples were collected at baseline, and at 8-12 and 18-24 h after the procedure, and were analysed in a core biochemistry laboratory. CK-MB elevation was detected in 16% of the patients, and was associated with increased 2-year mortality [7.2 vs. 3.8%; odds ratio (OR): 1.9; 95% confidence interval (CI): 1.3-2.8; P<0.001). The degree of CK-MB elevation (peak CK-MB ratio) independently predicted the risk of death (adjusted OR per unit: 1.04; 95% CI: 1.01-1.07; P=0.009). A cTnI elevation was detected in 44.2% of the cases and was not associated with a significant increase in mortality (4.9 vs. 4.0%; OR: 1.2; 95% CI: 0.9-1.7; P=0.2). CONCLUSION: Post-procedural elevations of CK-MB, but not cTnI, influence 2-year mortality.

Aged↗
PubMed2005

Sputum substance P and neurokinin A are reduced during exacerbations of chronic obstructive pulmonary disease.

Involvement of tachykinins in airway inflammation has been demonstrated in animal models, but evidence in humans is sparse. The aim of this study was to quantify the levels of substance P and neurokinin A in induced sputum of patients with chronic obstructive pulmonary disease (COPD) and to compare them with the levels in smokers with normal lung function and healthy nonsmokers. Content of tackykinins was measured in 12 sputum samples collected during stable condition and nine sputum samples collected during exacerbations from 13 COPD patients, in eight sputum samples from smokers with normal lung function and in nine from healthy nonsmokers. Patients with COPD exacerbations had a lower sputum content of substance P compared with the other 3 groups (p<0.05). No differences were found between patients with stable COPD, smokers with normal lung function, and nonsmokers. Sputum levels of neurokinin A were trending in the same direction of substance P, but the significant difference was reached for the paired sputum samples collected from the same COPD patients (n=8) during exacerbation and in stable condition. COPD exacerbations are associated with a reduced sputum content of substance P and neurokinin A. These tackykinins might be involved in COPD exacerbations.

Aged↗
PubMed2005

New biochemical insights into the pathogenesis of osteoarthritis and the role of laboratory investigations in clinical assessment.

Osteoarthritis (OA) is among the most frequent diseases in the population and a common cause of pain and disability in adults. The principal disease hallmarks for assessment of OA are still clinical observation and radiographic aspects. However, the efficacy of therapeutic interventions is complicated by the time required to observe radiographic signs, useful for both diagnosis and assessment. Thus, laboratory markers have received growing attention in recent years, in an attempt to improve diagnosis, assessment of disease activity and severity, and evaluation of therapeutic effects. Many biomarkers have been proposed, in particular those reflecting cartilage and bone turnover and synovitis. Among these, COMP, antigenic keratan sulphate, hyaluronan, YKL-40, type III collagen N-propeptide, and urinary glucosyl-galactosyl pyridinoline appear to be the most promising. However, serum or urinary determinations of these molecules are difficult to interpret adequately due to their complex metabolism. New ultrasensitive methods for C-reactive protein have improved the usefulness of this marker, especially in the assessment of disease activity. Routine examination of synovial fluid is still essential for diagnosis and includes leukocyte count and crystal detection; specialized testing includes the evaluation of the levels of markers of local inflammation such as metalloproteinases and cytokines, which appear to be crucial to the pathogenesis of OA.

Biomarkers↗
PubMed2005

Syngeneic living-donor liver transplantation for hemangioendothelioma: a clinical model for studying liver regeneration.

A 22-year-old Caucasian patient underwent living-donor liver transplantation (LDLT) for hepatic hemangioendothelioma in a healthy liver. The organ donor was his monozygotic twin brother. Surgery was uneventful in both donor and recipient, who received the same postoperative treatment (i.e. no immunosuppression for the recipient). Although both donor and recipient achieved a full liver function recovery, the volume of the recipient's graft increased much more than the donor's residual liver in the first postoperative month (1.6-fold vs. 1.2-fold). This different growth rate correlated with growth hormone (GH)/insulin growth factor (IGF) axis dynamics: the donor had significantly lower insulin-like growth factor 1 (IGF-1), insulin-like growth factor 2 (IGF-2) and insulin-like growth factor binding protein 3 (IGFBP-3) values than the recipient on postoperative days (POD) 3-30, although they had similar GH values. Other potential regenerative factors, e.g. tumor necrosis alpha, interleukin 6 (IL-6), insulin and C peptide did not correlate with liver regeneration rate. The particular endocrine picture of the graft may be explained by a modified GH-hepatocyte interaction due to cold ischemia during preservation resulting in a higher IGF production. Whether this is a potential molecular tool by means of which transplanted partial livers promote their regeneration remains to be seen in a larger number of patients.

Adult↗
PubMed2005

Effect of maternal smoking on breast milk interleukin-1alpha, beta-endorphin, and leptin concentrations and leptin concentrations.

Tobacco smoke is immunotoxic, but the effect of smoking on the immunologic function of the mammary gland of mothers who smoke cigarettes ("smoker mothers") has not been studied. Our objective was to test, in smoker mothers, the colostral and transitional milk concentrations of interleukin-(IL)1alpha. The immunomodulators beta-endorphin and leptin were also tested. Pregnant women who self-identified as smokers (greater than or equal to 5 cigarettes per day through pregnancy) or nonsmokers were recruited for study participation. The study population included 42 smoker and 40 nonsmoker nursing mothers, with otherwise uncomplicated gestation, delivery, and puerperium, who were breast-feeding ad libitum their healthy neonates. Colostrum was obtained on the third postpartum day at 0900 hr and transitional milk on the 10th postpartum day at 0900 hr. IL-1alpha concentrations were significantly reduced in the colostrum of smoker mothers compared with nonsmoker mothers (p < 0.01). Colostral beta-endorphin and leptin concentrations were comparable. No significant differences were found between smoker and nonsmoker lactating mothers in transitional milk concentrations of IL-1alpha, beta-endorphin, and leptin. Moreover, beta-endorphin and leptin concentrations were significantly reduced in transitional milk samples compared with colostrum of both smoker and nonsmoker mothers (p < 0.05); also, IL-1alpha transitional milk concentrations were reduced compared with colostrum, but without any significance. This analysis shows that maternal smoking alters the colostral milk levels of the proinflammatory cytokine IL-1alpha. The altered postnatal provision of alternative source of the proinflammatory cytokine IL-1alpha adds understanding to how breast-feeding could be nonprotective against infections among the neonates nursed by smoker mothers.

Adult↗
PubMed2005

Acute-phase markers of inflammation and glomerular structure in patients with type 2 diabetes.

Type 2 diabetes is frequently associated with an inflammatory status; the relationships between low-grade inflammation and diabetic nephropathy are still unclear. The aim of this study was to evaluate the relationships between acute-phase markers of inflammation, glomerular structure, and albumin excretion rate (AER) in type 2 diabetes. In 74 patients with type 2 diabetes (23 normoalbuminuric, 30 microalbuminuric, and 21 proteinuric) fibrinogen, serum amyloid A protein (SAA), C-reactive protein (CRP), and IL-6 were determined. AER was measured on three 24-h urine collections; GFR was measured by 51Cr EDTA plasma clearance. A kidney biopsy was performed, and mesangial fractional volume [Vv(mes/glom)] and glomerular basement membrane (GBM) width were estimated by electron microscopic morphometric analysis. CRP, fibrinogen, SAA, and IL-6 differed among groups, with proteinuric patients having the highest levels. SAA and fibrinogen correlated with AER (P < 0.03 and P < 0.001, respectively). GBM width and Vv(mes/glom) increased from normoalbuminuric to proteinuric patients [P < 0.005 normoalbuminuric and microalbuminuric versus proteinuric for GBM, P < 0.01 normoalbuminuric versus proteinuric for Vv(mes/glom)]. In patients with increased GBM width (> 396 nm), CRP, SAA, and IL-6 were higher than in patients with normal GBM width (P < 0.003, P < 0.004, and P < 0.0004, respectively). GBM width was directly correlated with fibrinogen (r = 0.33, P < 0.002) and IL-6 (r = 0.25 P < 0.05). In conclusion, this study demonstrates that acute-phase markers of inflammation are associated with nephropathy status and GBM thickening, suggesting a role for inflammation in the pathogenesis of diabetic glomerulopathy.

Acute Disease↗
PubMed2005

Correlations between clinical presentation, brain natriuretic peptide, big endothelin-1, tumor necrosis factor-alpha and cardiac troponins in heart failure patients.

BACKGROUND: The term "biochemical marker" of heart failure is used to define a biochemical substance whose plasma levels correlate with the clinical and hemodynamic status and predict the prognosis of patients with heart failure. The aim of this study was to prospectively evaluate, in a single population of patients with heart failure, the correlations between the plasma levels of brain natriuretic peptide (BNP), big endothelin-1 (BET-1), tumor necrosis factor-alpha (TNF-alpha), cardiac troponin I (cTnI) and T (cTnT), the clinical presentation, and the left ventricular function. METHODS: The study population included a series of 120 patients (97 males, 81%, mean age 56+/-12 years) in NYHA functional class I (49%), II (20%), III (26%), IV (5%) who were admitted to our institution or followed up as outpatients. All patients underwent cardiologic evaluation, standard electrocardiography, two-dimensional echocardiography, and venous blood sampling on the same day. RESULTS: At univariate analysis the following correlations were found to be significant: all the laboratory parameters correlated with the NYHA class (BNP r = 0.63, BET-1 r = 0.56, cTnI r = 0.25, cTnT r = 0.24, TNF-alpha r = 0.23); BNP (r = -0.39) and BET-1 (r = -0.27) with left ventricular ejection fraction; BNP (r = 0.37) and BET-1 (r = 0.21) with the degree of mitral insufficiency; BNP (r = -0.39), BET-1 (r = 0.25) and TNF-alpha (r = -0.19) with systolic blood pressure; cTnT (r = 0.34), cTnI (r = 0.33), BNP (r = 0.22) and BET-1 (r = 0.19) with heart rate; BNP with age (r = 0.33) and body mass index (r = -0.28). The plasma levels of BNP, BET-1, cTnT and cTnI were significantly higher in case of systemic or pulmonary congestion. At multiple regression analysis the following correlations were still present: BNP with the NYHA functional class (p < 0.005) and with pulmonary venous congestion (p < 0.05); BET-1 with the presence of pulmonary venous congestion (p < 0.005); TNF-alpha with the NYHA class (p < 0.05) and systolic blood pressure (p < 0.001); cardiac troponins with heart rate (p < 0.05). CONCLUSIONS: The plasma concentrations of BNP and BET-1 showed the best and comparable correlations with parameters describing the clinical status of patients with heart failure, in particular with the presence of pulmonary venous congestion. The value of the plasma concentration of TNF-alpha and those of cardiac troponins were found to be limited in patients with relatively stable heart failure.

Biomarkers↗