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Biomedical subjects

M Plebani

Publications and source records attributed to M Plebani.

At least 163 records · Page 9Linked to original sources

Mistakes in a stat laboratory: types and frequency.

Application of Total Quality Management concepts to laboratory testing requires that the total process, including preanalytical and postanalytical phases, be managed so as to reduce or, ideally, eliminate all defects within the process itself. Indeed a "mistake" can be defined as any defect during the entire testing process, from ordering tests to reporting results. We evaluated the frequency and types of mistakes found in the "stat" section of the Department of Laboratory Medicine of the University-Hospital of Padova by monitoring four different departments (internal medicine, nephrology, surgery, and intensive care unit) for 3 months. Among a total of 40490 analyses, we identified 189 laboratory mistakes, a relative frequency of 0.47%. The distribution of mistakes was: preanalytical 68.2%, analytical 13.3%, and postanalytical 18.5%. Most of the laboratory mistakes (74%) did not affect patients' outcome. However, in 37 patients (19%), laboratory mistakes were associated with further inappropriate investigations, thus resulting in an unjustifiable increase in costs. Moreover, in 12 patients (6.4%) laboratory mistakes were associated with inappropriate care or inappropriate modification of therapy. The promotion of quality control and continuous improvement of the total testing process, including pre- and postanalytical phases, seems to be a prerequisite for an effective laboratory service.

Chemistry, Clinical↗

[Prognostic role of cisteine and serin proteases in gastriC cancer].

Cysteine proteases (cathepsin B and L), the serine protease urokinase-type plasminogen activator and its inhibitor type-1 play an important part in cancer invasion and metastasis. The authors determined the protease concentrations in gastric cancer tissues, using the ELISA method, in patients with gastric cancer. They evaluated the prognostic role of proteases and the relationship that these proteases may have with other histomorphological prognostic parameters such as tumor staging, grading, histotype, Borrmann classification. The Cox survival analysis showed that cathepsin B (p = 0.002), urokinase-type plasminogen activator (p = 0.0001) and the inhibitor type-1 (p = 0.0004) significantly correlated with poor prognosis. The tumor staging, grading, Borrmann classification correlated also significantly with survival time. Urokinase-type plasminogen activator was selected as the single independent variable in the Cox model (p = 0.0001).

Adult↗

Serum tumor markers in colorectal cancer staging, grading, and follow-up.

Early diagnosis of colorectal cancer, a frequent neoplasia in industrialized countries, permits curative surgery. In this study we assessed the clinical role of serum tumor markers determination in diagnosing, staging, and grading colorectal cancer; the role of carcinoembryonic antigen (CEA), CA 19-9, tissue polypeptide antigen (TPA) and CA 72-4 in colorectal cancer follow-up was also assessed. In 114 patients with colorectal cancer, the oncofetal antigen CEA was compared with the membrane-associated glycoproteins CA 19-9, CA 242, and CA 72-4 and with the cytokeratins TPA, tissue polypeptide-specific antigen (TPS) and tissue polypeptide monoclonal antigen (TPM). Overall, the most sensitive indices were TPA and TPS (67% and 70%, respectively). Tumor stage influenced the levels of CEA, CA 19-9, and TPA, but not those of TPS, while tumor grade influenced CEA and TPS, but not CA 72-4, TPA, and TPM. TPA was the most sensitive index in identifying early or well-differentiated colorectal cancers. The sensitivity was enhanced when this marker was determined in combination with CEA, in diagnosing both advanced and early colorectal tumors. Seventy-seven patients were followed up after therapy for at least 18 months. CEA was the most sensitive index of recurrence (58%); however, this sensitivity is too low to consider tumor markers useful in colorectal cancer follow-up.

Adult↗

Serum pepsinogen C: a useful marker of Helicobacter pylori eradication?

Medical treatment for Helicobacter pylori (Hp) infection is now recommended in several types of gastroduodenal disease, and its success is usually monitored by hystology. The end-points of our work were to identify the most suitable serum index of Hp eradication among pepsinogen A (PGA), pepsinogen C (PGC), PGA/PGC ratio, gastrin, and IgG anti-Hp (IGG). We studied a total of 289 Hp positive (Giemsa staining) patients, who were treated with 40 mg/day omeprazole (140 cases) or with 480 mg/day bismuth subsalicylate (149 cases) for 4 weeks. All the patients also received 1 g/day metronidazole + 2 g/day amoxycillin for the first 2 weeks of treatment. Two months after the end of therapy, the patient underwent a second endoscopy and Hp histological assessment: the infection was eradicated in 192 and still present in the remaining 97 subjects. Gastrin, PGA, PGC, and IGG were measured before and after therapy. All indices significantly decreased after therapy in eradicated patients, while PGA and gastrin significantly decreased after therapy in both eradicated and noneradicated patients, although in the latter group the variations were less pronounced. We calculated the per cent decrease of the studied indices. PGC, with a decrease of more than 25%, was found to be the most accurate biochemical index. Variation in PGC levels before and after treatment were correlated with corresponding variations in Hp bacterial load. In conclusion, between the different biochemical parameters evaluated, PGC showed the highest clinical efficiency.

Adult↗

Cirrhosis and muscle cramps: evidence of a causal relationship.

The aim of the study was to define the features, prevalence, and pathophysiology of therapy for muscle cramps in cirrhotic patients. The first protocol study included 294 cirrhotic patients and 194 age- and sex-matched controls. Controls were defined as inpatients or outpatients without any clinical and laboratory evidence of liver disease. Features and prevalence of muscle cramps were defined on the basis of a standard questionnaire. As far as the pathophysiological associations of muscle cramps were concerned, the following parameters were evaluated: mean arterial pressure (MAP), nutritional status, liver function tests, plasma volume (PV), plasma renin activity (PRA), and electrolyte, mineral, and acid-base status. The prevalence of cramps was higher in cirrhotic patients than in controls, and it was related to the duration of recognized cirrhosis and to the severity of liver function impairment. At a multiple regression analysis, the presence of ascites, low values of MAP, and high values of PRA were the independent predictive factors for the occurrence of cramps in cirrhosis. In the second protocol study, the effects of a sustained expansion of the effective circulating volume induced by intravenous infusion of human albumin were compared with those of a placebo in 12 cirrhotic patients with more than three cramp crises a week. Compared with the placebo, albumin reduced the cramp frequency (P < .01). In conclusion, an increased prevalence of true muscle cramps occurs in patients with cirrhosis. Our data indicate that the pathophysiological link between cirrhosis and cramps may be represented by the reduction of the effective circulating volume. They also indicate that weekly infusion of human albumin may be an effective treatment for cramps in cirrhosis.

Adult↗

An immunological and genetic study of patients with gestational diabetes mellitus.

The aim of the study was to evaluate the frequency of islet cell (ICA) and insulin (IAA) antibodies and of HLA antigen typing in a group of subjects diagnosed with gestational diabetes mellitus (GDM) in a screening-diagnostic program during pregnancy. ICA, complement-fixing (CF) ICA and other autoantibodies, absolute number and percentage of lymphocyte subpopulations, and HLA antigens were evaluated in 68 women with GDM and compared with those of matched controls. ICA were found in 2 (2.9%) and IAA in 1 (1.5%). Both ICA-positive women had CF-ICA; one of them was receiving insulin therapy. while the other was on a special diet. No correlations were found between ICA and IAA, nor between IAA and insulin treatment. As far as lymphocyte subsets were concerned, we found a significant increase in the absolute number of total and activated (CD3+HLA-DR+) T lymphocytes and a significant increase in the absolute number and percentage of suppressor/cytotoxic T lymphocytes (CD8) and NK lymphocytes (CD57) in GDM patients compared with normal pregnant controls. Concerning frequency for HLA A, B, C, DR antigens in the GDM population, only Cw7 was found to be significantly increased and A10 significantly decreased in comparison with controls. Our study suggests that GDM is a heterogeneous disorder in which few patients present with the immunologic and genetic markers of type 1 diabetes.

Adult↗

Helicobacter pylori infection enhances mucosal interleukin-1 beta, interleukin-6, and the soluble receptor of interleukin-2.

It is thought that Helicobacter pylori colonization of the gastric mucosa might stimulate the production of several cytokines, which might trigger and maintain the gastric inflammation associated with Helicobacter pylori infection. In the present study we evaluated interleukin-1 beta. interleukin-6, and the soluble receptor of interleukin-2 both in mucosal homogenates and in the sera of Helicobacter pylori-infected (39 cases) and uninfected (40 cases) patients to investigate whether there was any relationship between variations in cytokines and (1) the severity of Helicobacter pylori-associated gastritis or (2) CagA-positive Helicobacter pylori strains. Mucosal, but not serum levels of interleukins-1 and -6 and interleukin-2 receptor were significantly higher in infected than uninfected patients. Serum levels of Helicobacter pylori antibodies were significantly higher in infected than uninfected patients. These levels correlated with mucosal interleukin-1 beta. The degree of antral or body inflammatory grade was higher in infected than in uninfected patients; cytokines levels were higher in patients with high-grade gastritis, most of whom were Helicobacter pylori positive. Patients infected with CagA-positive strains also had higher levels of interleukin-1 beta, but not of interleukin-2 receptor or interleukin-6. In conclusion. Helicobacter pylori infection results in a local increase in interleukins-1 beta and -6 and interleukin-2 receptor associated with high-grade mucosal inflammation. Interleukin-1 beta seems to favor anti-Helicobacter pylori antibody production, and mucosal levels are enhanced mainly in patients infected with cytotoxic Helicobacter pylori strains.

Adult↗

Cytokines may influence tumor growth and spread. An in vitro study in two human cancer cell lines.

Tumor spread may be favored by a reduced production and/or an enhanced degradation of extracellular matrix components (collagen, fibronectin, laminin). Most tumor cell behavior, from growth to spread, may be regulated by cytokines, the exact roles of which, however, are not yet fully understood. We here evaluate the effects of some cytokines (epidermal growth factor, transforming growth factor-beta 1, interleukin-1 alpha, and interleukin-1 beta) on both cell growth and the production of the aminoterminal peptide of type III procollagen, the urokinase plasminogen activator, and the plasminogen activator inhibitor-1 in neoplastic cell lines originating in the pancreas and colon. Cells were stimulated daily with the above cytokines and the aminoterminal peptide of type III procollagen, urokinase plasminogen activator, and plasminogen activator inhibitor-1 were measured in the conditioned media. Epidermal growth factor stimulated cell growth of both cell lines. Transforming growth factor-beta 1 counteracted cell proliferation and stimulated type III procollagen and plasminogen activator inhibitor-1 production only in the colon cancer cell line. Interleukin-1 alpha slightly stimulated cell growth, but inhibited plasminogen activator inhibitor-1 production in both cell lines; interleukin-1 beta did not affect cell growth, but stimulated plasminogen activator inhibitor-1 production by the colon cancer cell line. Our findings suggest that transforming growth factor-beta 1 and interleukin-1 beta may have an antidiffusive effect. These results confirm that cytokine-producing cells have a potential role in stimulating or counteracting tumor growth and spread and also confirm the pivotal role of host-tumor interactions in determining the outcome of a particular neoplasia.

Cell Division↗

Serum procollagen type III peptide in chronic hepatitis B. Relationship to disease activity and response to interferon-alpha therapy.

The clinical significance of serum procollagen type III peptide, a marker of active fibrogenesis, was evaluated in 110 hepatitis B surface antigen positive patients with chronic hepatitis (32 chronic persistent hepatitis, 60 chronic active hepatitis, and 18 active cirrhosis), selected on the basis of active viral replication and biochemical activity, including 54 cases treated with interferon-alpha. At presentation the procollagen type III peptide level serum was above normal in 48 (44%) of the 110 patients and the median value was significantly higher than that of healthy carriers with normal transaminases and histology (P < 0.000005). Semiquantitative histological evaluation showed a significant correlation between serum procollagen type III peptide levels and necrosis/inflammation in the subgroup of patients with chronic active hepatitis, but no relationship with the score of fibrosis. Among patients treated with interferon-alpha and with increased fibrogenic activity (indicated by high pretreatment serum levels of procollagen type III peptide), peptide levels were significantly decreased when pretreatment levels were compared with those at 12 months after therapy withdrawal, both in responders to interferon (P = 0.022) and non-responders (P = 0.012). However, serum procollagen type III peptide levels normalized in 75% of responders to interferon with sustained serological and histological remission of liver disease, but in only 21% of non-responders (P = 0.02). These results obtained in a well-defined population suggest that serum procollagen type III peptide is a better marker of active fibrogenesis and inflammation than an indicator of the extent of fibrosis, and that interferon may reduce active liver fibrogenesis in chronic hepatitis B independently of its effect on viral replication. However, a consistent proportion (56%) of our chronic hepatitis B patients had normal serum procollagen type III peptide levels at presentation, thus precluding the clinical use of this marker both for diagnosis of liver injury and for monitoring the therapeutic response to interferon.

Adult↗

Evaluation of antibiotic-induced nephrotoxicity in preterm neonates by determining urinary alpha 1-microglobulin.

alpha 1-Microglobulin (alpha 1-m, protein HC), a relatively low molecular weight protein of about 31,000 daltons, was measured in urine of three groups of 34 preterm neonates: group A consisted of 9 healthy preterm neonates; groups B (n = 13) and C (n = 12) consisted of preterm neonates with suspected or confirmed bacterial infections. Immediately after birth, all group B neonates were treated with ampicillin and aztreonam in combination, and all group C neonates were treated with oxacillin and amikacin in combination. To optimize amikacin administration, computerized individually tailored doses were administered. Urine samples were obtained from a short collection in sterile bags on the 1st, 4th, and 7th day after delivery in all infants. Urinary alpha 1-m concentrations were measured by a turbidimetric method (latex agglutination photometric immunoassay) and results were expressed as a ratio to urinary creatinine. In group A, urinary alpha 1-m concentrations were stable after birth. In group C, alpha 1-m excretion increased immediately within the 1st day of treatment, and over the 1st week of life urinary alpha 1-m levels were significantly higher than in group A (P = 0.033). These data support the conclusion that amikacin administration was the most important factor inducing renal tubular dysfunction in the neonates of group C.

Alpha-Globulins↗

New and traditional serum markers of bone metabolism in the detection of skeletal metastases.

OBJECTIVES: The evaluation of "new" and "traditional" markers of osteoblastic and osteoclastic activity, in patients with bone metastases. DESIGN AND METHODS: Our series consist of 40 patients with clinical, radiological, and scintigraphic evidence of bone metastases, and 40 age-matched healthy subjects. In all samples, traditional markers were evaluated by measuring total alkaline phosphatase (ALP), tartrate-resistant acid phosphatase (TrACP) activity, and osteocalcin (BGP) concentration. To assess new biochemical bone markers, bone isoenzyme of alkaline phosphatase (ALP-B) activity, carboxyterminal propeptide of type I procollagen (PICP), and carboxyterminal telopeptide of type I collagen (ICTP) concentrations were measured. RESULTS: Our findings showed that the best diagnostic efficiency is provided by ICTP (0.94) followed by total ALP (0.90), ALP-B (0.80), and TrACP (0.76). The efficiency of BGP and PICP was, instead, very low (0.64 and 0.60, respectively). CONCLUSION: Our results confirm the utility of the new serum markers such as ALP-B and ICTP assays in detecting bone metastases.

Acid Phosphatase↗

Low molecular mass proteins and urinary enzymes in amniotic fluid of healthy pregnant women at progressive stages of gestation.

OBJECTIVES: Amniotic fluid alpha1-microglobulin (alpha1-m) and beta2-microglobulin (beta2-m) levels, as well as N-acetyl-beta-D-glucosaminidase (NAG) and alanine aminopeptidase (AAP) activities, were measured in the course of uncomplicated pregnancies to assess their variations as gestation progresses. DESIGN AND METHODS: Samples were obtained from 141 healthy pregnant women divided into three groups on the basis of gestational stage. Quantitative estimation of proteins was performed immunometrically and enzyme activities were determined spectrophotometrically. RESULTS: It was found that, during pregnancy, alpha1-m and beta2-m concentrations as well as AAP activity significantly decrease, although their reduction patterns vary. Controversial results were found for NAG activity: the normalization of values for amniotic fluid creatinine significantly changed the reduction pattern of this enzyme. No statistically significant differences were found between male and female fetuses for amniotic fluid values of the biochemical substances studied. CONCLUSIONS: The behavior observed for alpha1-m, beta2-m, and AAP might be linked to the progressive development and maturation of fetal renal tubular function. Amniotic fluid total NAG activity seems not to depend only on fetal urinary excretion.

Acetylglucosaminidase↗

Fibronectin and antithrombin as markers of pre-eclampsia in pregnancy.

INTRODUCTION: The differential diagnosis between pre-eclampsia and chronic hypertension is not easy, but is essential to proper management of a pregnancy. Patients presenting pre-pregnancy hypertension can be treated conservatively, if not a superimposed pre-eclampsia occurs, controlling pressure pharmacologically and completing the pregnancy with a natural delivery. In pre-eclampsia, hypertension is merely the visible sign of a process of endothelial damage and coagulation cascade activation which is often destined to emerge clinically on a dramatic scale. MATERIALS AND METHODS: The study involved 18 women with physiological pregnancies, 19 with pre-eclampsia and 13 with chronic hypertension since superimposed pre-eclampsia. The following laboratory tests were performed: PT, PTT, AT-III, proteins C and S, platelet count, D-dimer, fibrinogen and plasma fibronectin. The three groups were compared using the Kruskall Wallis test, the median test and, for multiple comparisons, the Mann-Whitney test. A 'P' value of < 0.01 was considered as statistically significant. RESULTS: The values for plasma fibronectin were higher in the pre-eclampsia group (410 mg/l (253-727)) than in controls (262 mg/l (183-385)) (P < 0.01) and values for AT-III were lower in the pre-eclampsia group (73% (40-100)) than in controls (93% (80-126) (P < 0.01) (Table 2). The groups with chronic hypertension revealed no such significant differences, however, in relation to the control group (fibronectin = 296 mg/l (198-530), AT-III = 86% (75-103)). CONCLUSIONS: Measuring antithrombin and fibronectin to monitor any onset of pre-eclampsia can help the obstetrician to avoid important diagnostic and therapeutic errors.

Adult↗

beta-endorphin in plasma and monocytes in juvenile headache.

Interictal serum levels of serotonin and plasma and mononuclear cell concentrations of beta-endorphin were measured in 20 juvenile patients (13 suffering from migraine without aura and 7 from episodic tension-type headache) before and after 3 months of L-5-hydroxytryptophan treatment (5 mg/kg/day) and compared with a control group of 17 headache-free healthy subjects. While no significant differences in serum serotonin levels emerged between the three groups (migraine 104.6 +/- 26 micrograms/L, tension-type headache 90.7 +/- 26.2 micrograms/L, controls 96 +/- 32.9 micrograms/L), significantly lower plasma and mononuclear cell concentrations of beta-endorphin were found in both patient groups by comparison with the healthy controls (beta-endorphin in plasma: migraine sufferers 16.2 +/- 4.2 pmol/L [P < 0.05], tension-type headache subjects 14.5 +/- 1.7 pmol/L [P < 0.001] vs controls 21.3 +/- 4.6 pmol/L and respectively, beta-endorphin in mononuclear cells: migraine sufferers 110.5 +/- 16.4 pmol/10(6) GB/L [P < 0.001], tension-type headache subjects 142.3 +/- 22.7 pmol/10(6) GB/L [P < 0.001] vs controls 359.3 +/- 31.6 pmol/10(6) GB/L). No differences emerged between the two clinical forms of headache for the plasma and mononuclear cell concentrations of beta-endorphin. After L-5-hydroxytryptophan treatment, serum serotonin and both plasma and mononuclear cell beta-endorphin levels tended to be higher, though not significantly so, than prior to treatment, and the clinical score (frequency x intensity of headache attacks) was significantly lower in both headache groups than at the baseline. This study supports the theory that opiate analgesic system function is abnormally low in juvenile primary headache as in adults, and confirms that administering serotoninergic precursor drugs increases beta-endorphin, even in the peripheral blood, and may favorably affect clinical symptoms.

5-Hydroxytryptophan↗

Increased levels of cathepsin B and L, urokinase-type plasminogen activator and its inhibitor type-1 as an early event in gastric carcinogenesis.

BACKGROUND: Cysteine proteases [cathepsin B (CATB), cathepsin L (CATL)], the serine protease urokinase-type plasminogen activator (UPA) and its inhibitor type-1 (PAI-1) play an important part in cancer invasion. No data are available on the relationship between these proteases and gastric precancerous changes. AIMS: To determine CATB, CATL, UPA, PAI-1 in chronic atrophic gastritis, intestinal metaplasia and gastric epithelial dysplasia, as precancerous changes, and to compare these data with those obtained in gastric cancer. PATIENTS: Endoscopic biopsies were obtained from 12 patients with gastric cancer (cancerous tissue), 33 patients with chronic atrophic gastritis (all with intestinal metaplasia and 12 with dysplasia) and from 47 control subjects, for a total of 92 patients. METHODS: Antigen concentrations were measured using ELISA methods. Immunohistochemistry was performed using monoclonal anti-CATB and anti-PAI-1 antibodies. RESULTS: CATB, CATL, UPA and PAI-1 were significantly higher in chronic atrophic gastritis than in controls (CATB: P < 0.001; CATL: P < 0.005; UPA: P < 0.000001; PAI-1: P < 0.005). The same was observed for cancer. CATB and UPA were significantly higher in chronic atrophic gastritis, with versus without dysplasia (P < 0.05). Dysplastic epithelia showed strong immunoreactivity to PAI-1 and CATB. CONCLUSIONS: Our study demonstrates that cathepsins, UPA and PAI-1 may have a role not only in the process of cancer invasion, but also in the progression of precancerous changes into cancer.

Adult↗

Gastric antioxidant, nitrites, and mucosal lipoperoxidation in chronic gastritis and Helicobacter pylori infection.

We have evaluated gastric juice pH, nitrites and vitamin C levels, mucosal glutathione, and malondialdehyde, a marker of lipid peroxidation, in patients with chronic gastritis undergoing endoscopy. Patients had chronic gastritis with (n = 28) or without (n = 60) atrophy and/or concomitant Helicobacter pylori infection. Nineteen healthy subjects, without major macroscopic or histologic changes, were included as controls. Ten subjects were studied before and after H. pylori eradication. Vitamin C levels were low in atrophic gastritis (p < 0.006) and H. pylori infection (p < 0.02). Nitrite concentrations and pH were significantly higher in atrophy (p < 0.005 and 0.0001). Glutathione turnover was higher than normal in gastritis, with higher levels of oxidized glutathione (p < 0.02). Gastric malondialdehyde levels were significantly increased by gastritis (p < 0.05) and H. pylori infection (p < 0.05). Overall, more active gastritis coincided with lower vitamin C levels and higher malondialdehyde levels. After H. pylori eradication a drop in mucosal MDA levels was observed (p = 0.04). In summary, chronic gastritis and H. pylori infection correlate with increased free-radical production, reduced gastric vitamin C levels, and increased glutathione turnover. The possible implications of these changes in the pathogenesis of gastric damage and in carcinogenesis are intriguing.

Adult↗