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Biomedical subjects

P Carraro

Publications and source records attributed to P Carraro.

At least 37 records · Page 2Linked to original sources

Urokinase-type plasminogen activator receptor in gastric cancer: tissue expression and prognostic role.

The urokinase-type plasminogen activator (UPA) and its inhibitor PAI-1 are thought to play an important part in gastric cancer (GC) invasion and metastasis. Little is known about the behavior and prognostic impact of the receptor for UPA (UPAR). The aims of the present study were: (1) to measure UPAR, UPA and PAI-1 levels in GC and in non-malignant tissue distant from the tumor (NORM); (2) to evaluate their relationship with histomorphological parameters; and (3) to determine their prognostic value. UPAR, UPA and PAI-1 levels were determined by ELISA in GC and NORM samples from 20 patients with GC undergoing surgery. The GC was also examined in terms of the presence (n = 10) or absence (n = 10) of metastasis, differentiation (five differentiated, 15 undifferentiated) and histotype. Survival was analysed using life table analysis. UPAR, UPA and PAI-1 were significantly higher in GC vs NORM, in the presence of metastasis (UPAR, UPA) and in undifferentiated GC (UPAR, PAI-1). UPAR significantly correlated with UPA and PAI-1. Low levels of UPAR (P = 0.04), UPA (P = 0.007) and PAI-1 (P = 0.02) were associated with a better survival. Our results demonstrate a sharp increase in UPAR in GC and suggest a prognostic role for it. The concomitant activation of UPAR, UPA and PAI-1 in GC confirm the important role of the plasminogen activator system in the process of invasion and metastasis.

Adult↗

The effect of flumazenil on subclinical psychometric or neurophysiological alterations in cirrhotic patients: a double-blind placebo-controlled study.

It is not yet clear if benzodiazepine receptor ligands, implicated in the pathophysiology of hepatic coma, also have a role in subclinical cognitive or neurophysiological alterations in cirrhotic patients. Therefore, we carried out a double-blind, placebo-controlled study to evaluate the effectiveness of flumazenil, a benzodiazepine antagonist, on brainstem auditory evoked responses and on the number connection test in cirrhotic patients with subclinical neurophysiological or cognitive alterations. Thirteen cirrhotic subjects with subclinical neurophysiological or cognitive alterations were studied. A total of 3 mg of flumazenil or saline was infused intravenously. Before and after the infusion, the number connection test was administered and brainstem auditory evoked responses recorded. After 72 h, patients were crossed over. Flumazenil did not influence brainstem auditory evoked responses or the number connection test. A screening test for benzodiazepines was negative in all subjects. We conclude that benzodiazepine receptor ligands have a negligible role, if any, in the pathophysiology of subclinical neurophysiological or cognitive alterations of cirrhotic patients.

Cognition↗

Impaired fibrinolysis and increased protease levels in gastric and duodenal mucosa of patients with active duodenal ulcer.

OBJECTIVES: Cathepsin B and L (cysteine proteases), urokinase- and tissue-type plasminogen activators (serine proteases), and type-1 inhibitor are involved in gastric mucosal injury. We determined tissue protease levels in duodenal ulcer and their relationship to ulcer phase, bleeding tendency, Helicobacter pylori infection, and use of H2-blockers. METHODS: Endoscopic biopsies of antral and duodenal mucosa were obtained from 61 patients with active or healed duodenal ulcer and control subjects. Antigen concentrations were measured by ELISA. RESULTS: Significantly higher levels of cathepsins, urokinase-type plasminogen activator, type-1 inhibitor, and significantly lower levels of tissue-type plasminogen activator were found in active ulcers. Bleeders had the highest cathepsins and urokinase-type plasminogen activator levels. Higher levels of urokinase-type plasminogen activator, cathepsin B, and type-1 inhibitor were observed in Helicobacter pylori-positive patients. CONCLUSIONS: Our results suggest that impaired fibrinolysis (tissue-type plasminogen activator), intramucosal proteases (cathepsins), tissue remodeling, and angiogenesis (urokinase-type plasminogen activator and type-1 inhibitor) are involved in duodenal ulcer formation and healing.

Adult↗

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↗

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↗

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↗

High incidence of anti-FVIII antibodies against non-coagulant epitopes in haemophilia A patients: a possible role for the half-life of transfused FVIII.

The occurrence of antibodies (Abs) capable of inhibiting factor VIII (FVIII) coagulant activity is a severe complication in haemophilia A, leading to the inhibition of transfused FVIII activity. It is not known whether, or to what extent, post-transfusion antibodies may also arise against non-coagulant epitopes. Therefore we set up a system capable, in theory, to detect all the FVIII-induced antibodies by use of an enzyme-linked immunoassorbent assay (ELISA) based on coating human recombinant FVIII onto polystyrene microtitre plates. Serum samples from 23 patients affected by haemophilia A of different gravity (22 referred to our Centre and one to the Bari Centre) were analysed. Although only one patient was positive at Bethesda assay, the presence of antibodies in ELISA was detected in 39% of patients in variable degrees; transfusion with FVIII was found to induce a raise in antibody titre, arguing in favour of the specificity of the phenomenon. The clinical relevance of these non-inhibitory antibodies was evaluated in three patients; although half-life did not show any change in the patients without or with low amount of antibodies, FVIII clearance was found enhanced in the patient displaying high titre antibodies. We propose detection of anti-FVIII antibodies by ELISA when routinely assessing haemophilia A patients.

Adolescent↗

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↗

Fluoroenzymometric method to measure cardiac troponin I in sera of patients with myocardial infarction.

The aim of our study was to evaluate the clinical relevance of serum troponin I (TnI) as a marker of ischemic myocardial injury by using an automated fluoroenzymometric assay. The reference range for serum TnI was established by measuring serum TnI concentrations in blood from 75 healthy donors. The concentration was then compared with serum creatine kinase (CK) activity, CK-MB mass, and myoglobin concentrations in 20 patients with myocardial infarction diagnosed according to the WHO criteria, 20 patients with chest pain of nonischemic origin, 9 patients with unstable angina, 11 with stable angina, 11 patients with chronic muscular diseases, 6 patients with muscular trauma without chest contusion, and 13 patients with chronic renal disease. We found that: (a) 99% of the blood donors had TnI concentrations <0.26 microgram/L (detection limit of the assay in our study); (b) TnI values in acute myocardial infarction (AMI) patients 4 h after onset of chest pain showed a sensitivity of 0.769 and a specificity of 1.0 at a decisional concentration for AMI of 1 microgram/L, even in the presence of severe skeletal muscle injuries or renal diseases; (c) the increase in TnI concentrations after infarction (interquartile range 3.25-6 h) and the peak occurred later (interquartile range 11.5-24 h) than the rise found in myoglobin and CK-MB, but the increase persisted much longer (>96 h); (d) receiver-operating characteristic curve analysis showed the high diagnostic accuracy of TnI in diagnosing AMI even in patients in whom traditional biochemical markers are adversely influenced by underlying clinical situations.

Aged↗

Cysteine and serine proteases in gastric cancer.

BACKGROUND: Cysteine proteases (cathepsin B [CATB] and cathepsin L [CATL]), the serine protease urokinase-type plasminogen activator (UPA), and plasminogen activator inhibitor type-1 (PAI-1) are thought to play an important part in cancer invasion and metastasis. The aims of this study were to measure CATB, CATL, UPA, and PAI-1 in gastric cancer (GC) and normal mucosa distant from the tumor (NORM); to evaluate whether tissue levels are related to tumor stage, grade, or histotype; to assess their prognostic relevance; and to examine UPA and PAI-1 expression immunohistochemically. METHODS: Gastric cancer and NORM samples were obtained from 25 patients with gastric cancer patients undergoing surgery (17 males, 8 females; mean age, 62 years; range, 31-84 years). Antigen concentrations were measured using the enzyme-linked immunosorbent assay method. Immunohistochemistry was performed using monoclonal UPA and PAI-1 antibodies. RESULTS: Significantly higher antigen levels were found: (1) in GC vs. NORM (CATB, CATL, UPA, PAI-1) tissues; (2) in GC with versus without metastasis (CATB, CATL, UPA); (3) in poorly or moderately versus well differentiated GC; and (4) in diffuse versus intestinal-type GC (CATB, CATL). Urokinase-type plasminogen activator, PAI-1 and CATB levels had a significant prognostic impact. Cancer and stromal cells, showed immunoreactivity to anti-UPA and anti-PAI-1 antibodies. CONCLUSIONS: These results confirm the important role of CATB, CATL, UPA and PAI-1 in gastric cancer progression. Higher levels are detected in GC with metastases, poorer differentiation, and diffuse histotype, thus identifying patients with a worse prognosis.

Adenocarcinoma↗

[Role and behavior of cathepsin B and cathepsin L in gastric cancer].

Cathepsin B and cathepsin L--cysteine proteinases--may play an important role in cancer invasion and metastasis. The authors determined tissue antigen concentrations of cathepsins, using the ELISA method, in 25 patients with gastric cancer (17 males, 8 females, mean age 62, range 31-84). They evaluated the possible relationship that these proteinases may have with the presence of metastases, differentiation and histotype. Significantly higher cathepsin B and cathepsin L antigen levels were found: 1. in gastric cancer tissues vs. normal tissues distant from tumors (CATB: p < 0.05, CATL: p < 0.005); 2. in diffuse vs. intestinal type cancers (p < 0.05); 3. in patients with poorly vs. well-differentiated cancers (p < 0.05); in gastric cancers with vs. without metastasis (p < 0.05). Their results confirm that cathepsin B and L play an important role in gastric cancer invasion and metastasis. Considering the significantly higher cathepsins detected in cancers with metastasis, a poor differentiation and of diffuse histotype, these proteinases could be useful for identification gastric cancer patients with a poor prognosis.

Adult↗

Adrenocortical carcinoma. Our experience.

Adrenocortical carcinoma represents only 0.2% of the causes of deaths from cancer and this extremely low incidence rate implies that few medical centers have sufficient experiences to permit logical conclusions to be drawn regarding its treatment. From 1979 to 1993 we operated on 215 patients for adrenal diseases. The male/female ratio was 1:2.5 and the median age was 47 years (range 13-70). Eighty patients presented a clinical picture of hypercortisolism, 66 had a Conn's syndrome and 38 a pheochromocytoma; 30 had a nonfunctioning cortical or medullary tumor and one a metastatic adrenal mass. Of 141 patients with cortical tumors, 19 (13.5%) had malignancy of which 9 (7 males and one female, mean age 62 years) were nonfunctioning and 10 (3 males and 7 females, mean age 43 years, range 15-65) associated with a Cushing's syndrome. Seventeen patients underwent surgery, and two had multiple CT-FNAB-confirmed liver metastases and received o,p'DDD and chemotherapy treatment only. Tumor staging was the following: 3 (16%) stage I patients (tumor size varying from 4 to 5 cm), 7 (37%) stage II patients (tumor size 6-20 cm, mean 12 cm) and 9 (47%) stage III or IV. In 14 of the 17 operated patients the surgical approach was a lateral extraperitoneal incision with 12th rib partial resection. One patient had postoperative hemorrhage and reoperation was necessary. Operative mortality related to adrenalectomy was 0% although in three cases a nephrectomy was necessary because the mass completely surrounded the kidney. Three patients had a second operation 21-48 months after adrenalectomy for local recurrence of the disease. Overall survival time ranged from 2 to 42 months, the one-year survival rate was less than 40% and only six patients are still alive, 2-18 months after surgery. Tumor size and its endocrine functionality did not seem to correlate with prognosis in our experience.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

The role of urokinase-type plasminogen activator and its inhibitor PAI-1 in gastric cancer.

BACKGROUND: It has been proposed that the serine protease urokinase-type plasminogen activator (UPA) and its inhibitor type-1 (PAI-1) may play an important part in cancer spread and metastasis. AIMS OF THE STUDY: 1. To determine the UPA, PAI-1 antigen levels in gastric cancer (GC) and in normal gastric mucosa far from the tumor (NORM). 2. To evaluate changes related to the presence of metastasis, tumor differentiation (grading) and histotype. PATIENTS AND METHODS: Samples of tumor and of normal mucosa were obtained from 25 GC patients undergoing surgery (17 males, 8 females, mean age 62, range 31-84). Antigen concentrations were measured using the ELISA method. RESULTS: Significantly higher UPA and PAI-1 antigen levels were found: 1. in GC vs. NORM tissue; 2. in patients with poorly and moderately differentiated GC vs. well-differentiated GC. UPA was significantly higher in GC with vs. without metastasis. PAI-1 was also higher, though not significantly so, in GC with metastasis than in GC without metastasis. CONCLUSION: Our results confirm that the serine protease UPA and its inhibitor PAI-1 play an important role in GC progression. Considering the higher protease levels detected in GC with metastases and poorer differentiation, UPA and PAI-1 might be useful for identifying gastric cancer patients with a poor prognosis.

Adult↗

A new immunoassay for the measurement of myoglobin in serum.

Because the concentration of serum myoglobin (Mb) increases within 2 to 4 hours after the first sign of acute myocardial infarction, it has been proposed as an early marker of the condition. Our aim was to evaluate a new assay that provides a rapid, quantitative determination of Mb (Baxter Stratus Myoglobin) based on the radial partition technique. We compared the results obtained by this technique with those from nephelometric and radioimmunoassay methods. A significant agreement was observed, the correlation coefficients (r) being 0.999 and 0.996, respectively. The method evaluated provided good reproducibility with CVs between 3.14% and 4.87%, and its linearity and analytical sensitivity were satisfactory. The clinical evaluation of this assay demonstrates that Mb increases in serum of patients with acute myocardial infarction before total creatine kinase and creatine kinase MB isoenzyme. Mb concentration shows an early peak and earlier return to normal values after the necrosis compared to enzymatic activities. Moreover the assay is rapid and fully automated. The method is therefore considered appropriate for contributing to the early diagnosis of AMI in clinical laboratories.

Adolescent↗