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Biomedical subjects

Mario Plebani

Publications and source records attributed to Mario Plebani.

At least 19 recordsLinked to original sources
PubMed2004

Cord blood cardiac troponin T and troponin I levels in multiple-gestation neonates.

The increased mortality and morbidity rates in multiple-gestation neonates are not completely understood. Troponin measurements have a role in situations where the evaluation of the cardiac damage is difficult, such as in cases of unexplained intrauterine fetal growth restriction or death. These conditions, along with perinatal hypoxic risk and in utero ischemic damage, are frequently found in multiple gestations. In this context, a myocardial damage could be expected more frequently in multiple than in singleton births. We hypothesized that cord blood cardiac troponin T and troponin I, markers of myocardial damage, could be different between singleton and multiple pregnancies and, among twins, between the first- and the second-born twin. Troponins T and I and creatine kinase MB concentrations were not increased in twins at birth and were not different between the first- and the second-born twin. These data suggest that myocardial damage, evaluated by cardiac troponin T, troponin I, and creatine kinase MB measurements, does not seem to be a relevant problem in multiple-gestation neonates.

Birth Order↗
PubMed2004

Non-invasive diagnosis of Helicobacter pylori infection: simplified 13C-urea breath test, stool antigen testing, or DNA PCR in human feces in a clinical laboratory setting?

OBJECTIVES: (1) To compare two stool antigen EIAs (HpSA, FemtoLab) and PCR of ureaseA and cagA in feces, with (13)C-urea breath test (UBT). (2) To ascertain whether a simplified UBT (breath collection time = 10 min) is as reliable as the standard assay (30 min). DESIGN AND METHODS: Helicobacter pylori status was recorded in Group 1 (n = 187) by UBT, H. pylori stool antigen, ureA and cagA PCR in feces. UBT with 10, 20 and 30 min sampling was performed in Group 2 patients (n = 283). RESULTS: The sensitivity and specificity of HpSA, FemtoLab, and ureA were 67% and 99%, 90% and 96%, 35% and 98%, respectively. cagA results were positive in 16/48 H. pylori-positive, and in 5/100 H. pylori-negative patients. The results of UBT with a 10- and 30-min sampling strictly overlapped. CONCLUSION: UBT with 10 min breath collection and FemtoLab stool antigen assay are the most reliable non-invasive tests to diagnose H. pylori infection.

Adult↗
PubMed2004

A large deletion due to a new mutation (intron 13/exon 23) in a sporadic case of severe hemophilia A.

A case of sporadic hemophilia A in a young child was investigated from a molecular biology point of view. The propositus is a 4-year-old severe hemophiliac who was first seen when he was 2 years old. At that time, easy bruising and hematomas were noted because of accidental falls while toddling. The coagulation study showed a prolonged partial thromboplastin time and a factor VIII level of 1.3% of normal. Molecular biologic analysis showed a large deletion involving intron 13 up to exon 23. In the inversion study, the propositus exhibited only a 10 kb band, and this result suggests that intron 22 was deleted while his mother shows a normal pattern. To further examine the length of the deletion, a long polymerase chain reaction by means of primers amplifying the region from exon 13 to 23. In the index patient, an approximate 13-kb product was obtained, whereas no product was obtained from his mother. The mother investigated by means of polymorphism was shown not to be a carrier.

Child, Preschool↗
PubMed2004

Plasma levels of tumor necrosis factor-alpha correlate with the six-minute walk test results in patients with mild to moderate heart failure.

BACKGROUND: The plasma levels of brain natriuretic peptide, tumor necrosis factor-alpha, big endothelin-1 and cardiac troponins have been reported to correlate with the severity of heart failure. METHODS: In a single population of 80 outpatients with mild to moderate chronic heart failure the correlation between the patient's functional capacity, as evaluated at a 6-min walk test, the clinical parameters and plasma levels of brain natriuretic peptide, tumor necrosis factor-alpha, big endothelin-1 and cardiac troponins was evaluated. RESULTS: A significant inverse correlation was found with the patient's age (p < 0.0001), NYHA functional class (p < 0.0001), left ventricular dysfunction etiology (ischemic vs dilated cardiomyopathy, p < 0.0005), heart rate (p < 0.05), plasma levels of brain natriuretic peptide (p < 0.05) and of tumor necrosis factor-alpha (p < 0.0005). At multiple regression analysis a correlation was found between the 6-min walk test results and the patient's age (p < 0.05), NYHA functional class (p < 0.01), left ventricular dysfunction etiology (ischemic vs dilated cardiomyopathy, p < 0.05) and tumor necrosis factor-alpha plasma levels (p < 0.05). CONCLUSIONS: In our patients with mild to moderate heart failure, a significant correlation was found between the results of the 6-min walk test and only the plasma concentrations of tumor necrosis factor-alpha among the laboratory parameters analyzed in this study.

Adult↗
PubMed2003

Appropriateness in programs for continuous quality improvement in clinical laboratories.

BACKGROUND: External reviews and the accreditation of medical laboratories involve more than the mere assessment of conformance with standards for organisational processes. The new approaches to quality improvement suggest that, rather than using inspection to correct unusual errors, there should be more emphasis on improving the processes of health care to ensure that desired outcomes are produced. Appropriateness plays a key role in programs for quality improvement. METHODS: Appropriateness in laboratory medicine can be assessed, and improved, through the governance of the entire testing process. This begins with test selection, proceeds through valuable pre-, intra- and post-analytical procedures, and concludes by assuring the correct interpretation and utilization of laboratory information. RESULTS: The International Standard, specifically developed for medical laboratories (ISO 15189) recognizes the value of appropriate interpretation and advisory services, although it does not specify requirements for assessing appropriateness, requesting tests and interpreting results. The effectiveness of clinical laboratories can be assessed by using surrogate markers, which indicate physicians' satisfaction, and clinical audits. Effectiveness is also enhanced by stressing the importance of the technical and professional competence of evaluators. CONCLUSIONS: Inappropriate laboratory utilization unjustifiably increases health care costs, can harm patients and perpetuates the vision of laboratory testing as a commodity. Improvement in laboratory appropriateness can be achieved by seeking a better relationship with physicians and by stressing the role of laboratory specialists in providing clinical advice for the selection of laboratory tests, and the interpretation and utilization of their results, thus leading to more satisfactory clinical outcomes.

Clinical Laboratory Techniques↗
PubMed2003

Interpretative comments and reference ranges in EQA programs as a tool for improving laboratory appropriateness and effectiveness.

INTRODUCTION: Laboratory information is generated when a meaning is given to certain data. This is usually achieved by comparing a laboratory test result with the reference range/decisional limit (RL), and by providing consultation for the interpretation of data, advice, and follow-up testing. AIM: In this paper, we investigate factors affecting the conversion of data into useful information with regard to biochemical markers of myocardial damage (CK-MB mass, myoglobin, and troponins), in view of their importance in detecting myocardial necrosis. Our aim was to report results obtained in order to verify the consensus between laboratories with reference to interpretative comments and the reference ranges/decisional limits added to clinical reports. METHODS: A questionnaire and simulated medical reports on three different patients were distributed to participants (94 laboratories) in the 2001 cycle of the External Quality Assessment (EQA). Moreover, we analysed 113 medical reports sent by laboratories during the most recent EQA cycle 2002, and checked the number of different RLs used, both independent and within the diagnostic system used. We also compared each laboratory result of a control sample, obtained in the 2002 cycle, with declared RL in order to verify the clinical significance of results ("normal" or "pathological") for troponin I and CK-MB. RESULTS: Our findings show that few laboratories regularly add interpretative comments to medical reports. On the contrary, they cooperate with clinicians who require consultation, advice, and information for the appropriate use of biochemical markers. There is a general consensus among participants regarding probable syndromes suggested by the interpretation of the same result and most laboratories also agree on further investigations to be carried out for several diseases. Concerning RL, the data demonstrate that numerous different RLs are used to report the results of the biochemical markers evaluated, both when considered independent of the diagnostic system used and within the diagnostic system used. DISCUSSION AND CONCLUSIONS: The biochemist does not have the opportunity to verify the efficacy of the interpretation that he/she provided. An audit of this activity is therefore required to allow the laboratory to monitor its own performance and to assure good practice. The evaluation of interpretative comments, through specific surveys, should be a prime objective of EQA organisers. Well-designed EQA programs can, moreover, support laboratories in establishing appropriate RL and in verifying the clinical significance of their results with respect to that of other laboratories. Our survey on interpretative comments and the analysis of the RLs further demonstrate how laboratory medicine can contribute to the objective evaluation of the patients' health status.

Clinical Laboratory Techniques↗
PubMed2003

Appropriateness of cholesterol and triglycerides reporting checked by External Quality Assessment programs.

BACKGROUND: The recommendations of the Second Joint Task Force of European and Other Societies on Coronary Prevention and the third Adult Treatment Panel report (ATPIII) released by the National Cholesterol Education Program are based on accumulating evidence concerning the contribution of lipoproteins and other risk factors in the development of coronary heart disease (CHD). The laboratories play an important role in the successful adoption of these guidelines. METHODS: In External Quality Assessment (EQA) programs managed by the Center of Biomedical Research, results and respective reference intervals (RI) are sent as laboratory's medical form. We assessed how well the 200 participants to EQA scheme 2002 for clinical biochemistry reported total cholesterol (TC) and triglycerides (TGs) results according to either European or National Cholesterol Education Program (NCEP) guidelines. RESULTS: Only 18% of laboratories reported total cholesterol concentrations correctly in terms of desirable, borderline-high, and high risk for the CHD development, 12% reported a single desirable value (180, 190, or 200 mg/dl), and 70% reported the RI (85 laboratories in the whole interval, 34 are the only upper reference limit and 15 are the desirable value in addition to RI). The upper reference limit was 200 mg/dl in 65% of cases, but 32% of laboratories presented higher limits, reaching values as high as 250-260 mg/dl. Only the 3.7% of laboratories reported triglyceride concentrations in terms of risk-oriented ranges for the CHD development, 6.8% the single desirable value, and 89.5% the RI. CONCLUSION: Our study demonstrates that the current practice of reporting results for cholesterol and triglycerides does not follow the guidelines, and appropriate changes are required to be made.

Cholesterol↗
PubMed2003

Serum human glandular kallikrein (hK2) and insulin-like growth factor 1 (IGF-1) improve the discrimination between prostate cancer and benign prostatic hyperplasia in combination with total and %free PSA.

BACKGROUND: There is growing evidence describing an association of hK2 and IGFs with cancer. The aim of this study is to investigate the differences in serum levels of hK2 and IGFs in a large group of patients with benign prostatic hyperplasia (BPH) or prostatic carcinoma (CaP) and to examine the value of these variables, as well as their various combinations with PSA, for discriminating between these two clinical entities. METHODS: Human glandular kallikrein 2 (hK2), insulin-like growth factor-1 (IGF-1), free and total PSA concentrations were measured with non-competitive immunological procedures. Receiver operating characteristic (ROC) analysis as well as univariate and multivariate logistic regression analysis were performed to investigate the potential utility of the various markers and their combinations for discriminating between BPH and CaP. RESULTS: hK2 and IGF-1 concentrations were increased in CaP patients, in comparison to BPH patients. hK2/free PSA and free/total PSA ratios (area under the curve, AUC = 0.70) were stronger predictors of prostate cancer than the IGF-1/total PSA ratio (AUC = 0.56) in the group of patients with total PSA <4 microg/L. The hK2/free PSA ratio (AUC = 0.74) was found to have significant discriminatory value in patients with total PSA within the "gray zone" (4-10 microg/L). Multivariate logistic regression models confirmed the observed relationships and identified IGF-1/free PSA and hK2/free PSA as independent predictors of CaP. CONCLUSIONS: hK2/free PSA and IGF-1/free PSA ratios may be useful adjuncts in improving patient selection for prostate biopsy.

Aged↗
PubMed2003

Endothelin receptor blockade lowers plasma aldosterone levels via different mechanisms in primary aldosteronism and high-to-normal renin hypertension.

BACKGROUND: Endothelin (ET)-1 contributes to raising blood pressure (BP) and inducing cardiovascular disease by vasoconstriction and potent stimulation of aldosterone secretion. In the rat this latter effect occurs via ET(B) receptors; in humans in vitro studies implicated both ET(A) and ET(B) receptors, but there is no conclusive evidence in vivo. METHODS: We recruited 13 consenting hypertensive patients: six with primary aldosteronism (PA) and seven with high-to-normal renin hypertension (HNRH). They were infused with a low dose (200 nmol/min for 5 min followed by 100 nmol/min for 10 min) of the ET(A)-selective antagonist BQ-123 either alone or, on a different day, together with an identical dose of the ET(B)-selective antagonist BQ-788. Plasma aldosterone, cortisol and ACTH concentration and plasma renin activity (PRA) were measured with radioimmunoassay at -15, 0, 30, 60, 120, 240, 360 min, while BP was recorded non-invasively. RESULTS: BQ-123 alone and combined with BQ-788 significantly lowered mean BP in both PA and HNRH patients (by 6-10 mmHg at nadir; P<0.01). In PA patients, a short-lived decrease of aldosterone was elicited by combined BQ-123 and BQ-788 (-14%; P<0.05), but not by BQ-123 alone; cortisol, ACTH, and PRA were unaffected by either treatment. In HNRH patients, BQ-123 both alone and combined with BQ-788 lowered aldosterone (-39 and -28%, respectively) and PRA (-43 and -16%, respectively), while cortisol and ACTH were unaffected. CONCLUSIONS: Endogenous ET-1 contributes to maintaining the high BP values and the aldosterone secretion in both PA and HNRH patients. In the former patients, the aldosterone secretagogue effect of ET-1 is mediated via ET(B) receptors, while in the latter it occurs mainly via ET(A)-mediated stimulation of renin production.

Adrenocorticotropic Hormone↗
PubMed2003

Clinical value and measurement of specific IgE.

The diagnosis of human allergic diseases involves the combined use of a careful clinical history, physical examination, and in vitro and in vivo assay methods for the detection of IgE antibodies of defined allergen specificities. In vivo (skin testing) and in vitro (measurement of specific IgE in serum) techniques cannot be considered interchangeable, the former reflecting not only the presence of IgE but also mast cell integrity, vascular and neural responsiveness. Both techniques have similarities and differences, advantages and disadvantages. Recently introduced "second generation" immunoassays have continued to improve the analytical sensitivity and reproducibility thanks to automation and improved reagent quality. Quantitative assays may allow the use of specific clinical thresholds able to differentiate symptomatic from asymptomatic patients. False-negative and false-positive results should derive from lability of some major extracts, and from possible cross-reactivities, respectively. Characterization of allergens at a molecular and submolecular level and, where necessary, the use of recombinant allergens can reduce cross-reactions and further improve the quality of immunoassays.

Allergens↗
PubMed2003

Methotrexate for immunosuppression in life-supporting pig-to-cynomolgus monkey renal xenotransplantation.

Methotrexate (MTX) has been used successfully as an immunosuppressant in rodent xenotransplantation models, but the data generated so far with MTX in pig-to-baboon cardiac transplantation studies have been disappointing. The potential of this agent was consequently explored in a life-supporting pig-to-primate renal model using the cynomolgus monkey as the recipient species. Introductory in vitro and in vivo pharmacokinetic and pharmacodynamic studies with MTX were conducted in three cynomolgus monkeys. Subsequently, 10 cynomolgus monkey recipients of a life-supporting kidney from human decay-accelerating factor transgenic pigs were administered MTX intravenously according to three different regimens. All the animals also received cyclosporine A and steroids. In addition, mycophenolate sodium (MPS) was administered post-operatively in two of the three groups of transplanted animals. At clinically relevant concentrations, MTX is able in vitro to inhibit the mixed lymphocyte reactions (MLR) in cynomolgus monkeys. After intravenous administration, moreover, exposure of cynomolgus monkeys to MTX appeared to be higher than had been previously reported in baboons. Graft function was observed in the transplanted animals, which survived from 0 to 41 days. All but two animals revealed acute humoral rejection in the explanted graft and developed diarrhea. Diarrhea was the cause of euthanasia in five cases. It was unrelated to the administration of MPS and associated with severe histopathological signs of enteritis. This study demonstrates that the pharmacokinetic and pharmacodynamic profiles if MTX vary substantially between non-human primate species. In vitro, MTX has immunosuppressive properties in the cynomolgus monkey at clinically relevant concentrations. In vivo, MTX has a very narrow therapeutic window in cynomolgus monkeys, however, as it does in baboons. We conclude that MTX is scarcely effective as an immunosuppressant, be it for induction or maintenance, in pig-to-cynomolgus monkey renal xenotransplantation.

Animals↗
PubMed2003

Helicobacter pylori infection in children and adults: a single pathogen but a different pathology.

BACKGROUND: The aims of this retrospective study were to ascertain in large series of children and adults: the relationship of the infecting strain to gastric mucosal lesions; and the relationship of the infecting strain to its duodenal localization. MATERIALS AND METHODS: We studied 307 and 604 consecutive children and adults. In gastric mucosal samples H. pylori was cultured, genotyped and histologically assessed, while inflammation, activity and intestinal metaplasia were graded. In a subset of 171 patients H. pylori ureaseA (ureA) and cagA genes were amplified (PCR) using mucosal biopsies from the duodenum. RESULTS: H. pylori infection was diagnosed in 40 children and 308 adults. cagA was identified in 50% and 65.5% of infected children and adults. Antral activity was associated with the density of infecting bacteria (p <.001) and with cagA (p <.01). Intestinal metaplasia was correlated with cagA (p <.001). The ureA gene was found in 56 duodenal samples from 82 H. pylori positive patients. Duodenal H. pylori ureA was significantly more frequent in patients with duodenal diseases than in those without (p <.01), cagA positive strains being mainly involved in the infection of this anatomical area (p <.01). CONCLUSIONS: A severe H. pylori-associated gastritis is more prevalent when the density of infecting bacteria is high and when cagA positive strains cause the infection. The most virulent cagA positive H. pylori colonizes not only the gastric, but also the duodenal mucosa, which can be directly damaged by the bacteria itself or by its products.

Adolescent↗
PubMed2003

Helicobacter pylori infection and gastric autoimmune diseases: is there a link?

BACKGROUND: Helicobacter pylori is thought to be involved in atrophic body gastritis. We explored the prevalence of H. pylori infection in asymptomatic subjects with gastric parietal cell antibodies, as well as in patients with pernicious anemia, to evaluate a possible role of H. pylori gastric infection in gastric autoimmunity. PATIENTS AND METHODS: We studied 79 consecutive asymptomatic subjects with parietal cell antibodies, 24 patients with pernicious anemia, and 66 parietal cell antibody-negative controls. All patients underwent gastric biopsies for histology and detection of H. pylori. Red blood cell count and volume, serum levels of gastrin, pepsinogen I, iron, folic acid, vitamin B12, and circulating antibodies to H. pylori and to intrinsic factor were also determined. RESULTS: We found an atrophic body gastritis in 14 of the 79 asymptomatic subjects with parietal cell antibodies (18%) and in 2 of the 66 controls (3%) (p =.01). Mean levels of gastrin were increased (p <.0001), while those of pepsinogen were reduced (p <.001) compared with controls. H. pylori was identified at the gastric level and/or circulating anti-H. pylori antibodies were detected in 46 parietal cell antibody-positive subjects (58%) compared with 26 controls (39%) (p =.03). In patients with pernicious anemia we found an atrophic body gastritis in 18 of 24 cases (75%) (p <.001 vs. controls). Mean levels of gastrin were markedly increased (p <.0001) and those of pepsinogen I decreased (p <.0001) relative to controls. Only five of these patients (21%) had evidence of H. pylori infection compared with 46 of the parietal cell antibody-positive subjects (58%) (p =.003) and 26 of the controls (39%). Considering all patients with gastric autoimmunity (i.e. with parietal cell antibodies and/or with pernicious anemia), H. pylori was found in 44 of 72 of those without atrophy (61%) but in 6 of 31 with gastric body atrophy (19%) (p <.001), indicating that H. pylori infection is greatly reduced when gastric acid secretion decreases. CONCLUSIONS: The frequent detection of H. pylori infection in subjects with early gastric autoimmunity, indicated by the presence of parietal cell antibodies, suggests that H. pylori could have a crucial role in the induction and/or the maintenance of autoimmunity at the gastric level.

Adult↗
PubMed2003

Effects of Th2 cytokines on expression of collagen, MMP-1, and TIMP-1 in conjunctival fibroblasts.

PURPOSE: To determine whether cytokines involved in chronic allergic conjunctival disorders may affect formation of giant papillae and tissue remodeling. METHODS: Conjunctival fibroblast cultures were challenged with different concentrations of human recombinant interleukin (IL)-4, IL-13, interferon (IFN)-gamma and tumor necrosis factor (TNF)-alpha. Procollagens I (PIP) and III (PIIIP), matrix metalloproteinase (MMP)-1 and -9, and tissue inhibitor of metalloproteinase (TIMP)-1 were measured in supernatants, and their respective mRNAs were evaluated by RT-PCR. RESULTS: IL-4 and -13 (10 ng/mL) significantly increased production and expression of PIP compared with nonstimulated cells, whereas IFN-gamma elicited the opposite effect, at both the protein and mRNA levels. Both IL-4 and -13 significantly decreased production of MMP-1 and increased that of TIMP-1, whereas TNF-alpha increased production of MMP-1 and -9. Expression of MMP-1 was reduced by IL-4 and increased by the other tested cytokines, whereas expression of TIMP-1 was increased by all tested cytokines. CONCLUSIONS: IL-4 and -13 increased production of collagen and modified the equilibrium between MMP-1 and its inhibitor, TIMP-1. These effects were partially opposed by IFN-gamma and TNF-alpha.

Cell Division↗
PubMed2003

Tear levels and activity of matrix metalloproteinase (MMP)-1 and MMP-9 in vernal keratoconjunctivitis.

PURPOSE: To study levels and activity of matrix metalloproteinase (MMP)-1 and -9 and their tissue inhibitor (TIMP-1) in tears of patients with vernal keratoconjunctivitis (VKC), with and without severe corneal damage. METHODS: Tear samples were obtained from 16 patients with active VKC and 10 normal control subjects, after clinical evaluation and tear cytology. Tear levels of pro-MMP-1, pro-MMP-9, and TIMP-1 were measured by enzyme-linked immunosorbent assay (ELISA). Collagenase and gelatinase activity were measured in tears by MMP activity assays. Immunohistochemistry was performed on a fragment of superficial keratectomy from two vernal corneal ulcers. RESULTS: Tear levels of pro-MMP-1 and pro-MMP-9 were significantly increased in patients with VKC compared with control subjects (P < 0.001). MMP-1/TIMP-1 and MMP-9/TIMP-1 molar ratios were significantly increased (P < 0.001) in VKC. MMP-1 and MMP-9 activities were significantly increased in VKC tears compared with control samples (P < 0.005). MMP-9 activity correlated significantly with corneal involvement and giant papillae formation. Immunohistochemistry showed positive staining for MMP-9, fibronectin, and eosinophil cationic protein (ECP) on the superficial corneal stroma of the ulcer bed, but no inflammatory cells. CONCLUSIONS: Increased levels and activity of MMP-1 and -9 and an imbalance between MMPs and TIMP may be involved in the pathogenesis of VKC.

Adolescent↗