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Biomedical subjects

E Pozzi

Publications and source records attributed to E Pozzi.

At least 19 recordsLinked to original sources

Biological prognostic factors in non-small cell lung cancer.

The results of conventional treatments for lung cancer remain poor and long-term survival rates have changed little over the last 10 years. In the same period of time there has been an explosion in the knowledge on the processes of cellular transformation, tumour progression, invasion and metastasis. The major categories of biological events implicated in non-small cell lung cancer include growth factor receptors expression (epidermal growth receptor, p185c-neu), autocrine growth factor production (transforming growth factor alpha), dominant oncogenes activation (ras genes) and deletion of tumour suppressor genes (p53 gene, retinoblastoma gene) and these are some of the abnormalities associated with specific histological types and with poor prognosis. Additional prognostic information can be obtained from the evaluation of the ploidy and proliferative activity of the tumours, carbohydrate antigens expression, presence of neuroendocrine differentiation and the evaluation of markers of the sequential steps involved in the process of tumour dissemination.

Biomarkers, Tumor

Clonal chromosome changes in non-neoplastic ureters.

Cytogenetic analysis was performed on 23 samples from non-neoplastic ureters. Clonal chromosome abnormalities were found in eight. They were: loss of Y chromosome, as a single abnormality (five cases) or associated with trisomy 10 and 20 (one case) or with trisomy 2 (one case); and duplication of Y chromosome (one case). Different numerical and structural sporadic abnormalities were found in nine cases. Immunohistochemical analysis and direct observation using the inverted microscope showed that the cells were mainly of the fibroblastic type. FISH analysis with chromosome 7 alpha-satellite probes failed to detect the presence of trisomy 7 in three epithelial cases tested.

Adult

Activated and memory alveolar T-lymphocytes in idiopathic eosinophilic pneumonia.

To investigate the possible involvement of T-lymphocytes in the immunopathogenesis of idiopathic eosinophilic pneumonia (IEP), we have evaluated the phenotypic characteristics both of peripheral blood and alveolar lymphocytes in six patients with symptomatic IEP, and in 24 healthy nonsmokers as controls, by employing bronchoalveolar lavage (BAL), monoclonal antibodies, and flow-cytometry. In IEP, total and differential cell counts showed a mild alveolitis with an increase of eosinophil percentage and number; the alveolar lymphocyte count was also increased. In BAL, the total number both of CD4+ and CD8+ lymphocytes was significantly raised; CD4+ cells expressed early (CD25) activation antigens. The analysis of CD45R0, CD45RA and CD62L coexpression in IEP patients, when compared to healthy controls, revealed an accumulation of alveolar CD4+ cells showing phenotypic repertoire usually expressed by memory T-cells (CD45R0+, CD45RA-, CD62L-). CD8+ alveolar lymphocytes did not show any significant increase of activation antigen coexpression. Circulating lymphocytes were not significantly increased and showed only a significantly higher CD25 expression. These data suggest that a pivotal role is played by activated and memory CD4+ alveolar lymphocytes in IEP patients.

Adult

In vivo effect of human granulocyte-macrophage colony-stimulating factor (GM-CSF) on neutrophil GM-CSF receptors.

The effect of in vivo administration of recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) on neutrophils GM-CSF receptor, was investigated in patients with neoplastic diseases and normal hematopoiesis. Patients were divided into two groups. Group A received a single dose of rhGM-CSF (5 micrograms/kg/day) and receptor studies were performed 90 min and 48 h after treatment. Group B received three doses, administered subcutaneously every 24 h and receptor studies were performed 90 min after first injection and 24 h after the last. Before treatment neutrophils only displayed high-affinity receptors (KD 85 +/- 53 pM; number of receptors/cell 1318 +/- 567). The first injection of rhGM-CSF produced a transient leucopenia and the internalization of GM-CSF receptor on neutrophils in both groups of patients: 90 min after s.c. administration receptors could not be detected with conventional binding studies. In group A patients, 48 h after a single dose of rhGM-CSF, receptors, albeit with a decreased affinity (KD = 240 +/- 131 pM; number of receptors/cell 783 +/- 494) were again expressed. In group B patients, 24 h after the last rhGM-CSF injection, low intermediate affinity receptors not present before treatment appeared (KD 720 +/- 175 pM; number of receptor/cell 1222 +/- 179). They were associated with a low number of high affinity receptors (KD = 9 +/- 4 pM; number of receptors/cell 106 +/- 44). These observations indicate that more than one type of GM-CSF receptor may exist on neutrophils. It may be suggested that in vivo the regulation of the GM-CSF receptor is different from that in vitro and is related to the presence of the cytokine in patient blood.

Dose-Response Relationship, Drug

Intercellular adhesion molecule-1 is upregulated on peripheral blood T lymphocyte subsets in dual asthmatic responders.

To examine the role of adhesion molecules in T cell recruitment and activation during allergen-induced late asthmatic response (LAR), we evaluated the expression of lymphocyte function-associated antigen-1 alpha (LFA-1 alpha) and intercellular adhesion molecule-1 (ICAM-1) on peripheral blood T lymphocyte subsets from atopic asthmatic patients and their changes following allergen inhalation challenge. 12 atopic asthmatic patients were studied. Six patients showed only a single early response after allergen challenge, and six developed a dual response. At baseline, dual responders (DR) had a significantly higher expression of ICAM-1 on CD4+ and CD8+ T lymphocytes as compared with both single early responders (P < 0.005 and P < 0.02, respectively) and controls (P < 0.001, both comparisons). Allergen challenge was followed by a decrease of CD8+ ICAM-1+ T lymphocytes in all DR (P < 0.05) and of CD4+ ICAM-1+ T lymphocytes in four out of six DR, at the time of the LAR. At the same time, a significant rise in serum levels of the soluble form of ICAM-1 was observed in DR. These results suggest that peripheral blood immunoregulatory T lymphocytes are in a higher state of activation in DR as compared with early responders. The upregulation of ICAM-1 on these cells may be important in enhancing airway inflammation in patients with LAR.

Adolescent

Pidotimod in the treatment of patients affected by bacterial exacerbations of chronic bronchitis.

A multicentre double-blind placebo-controlled study was conducted in order to assess the effects of pidotimod ((R)-3-[(S)-(5-oxo-2-pyrrolidinyl) carbonyl]-thiazolidine-4-carboxylic acid, PGT/1A, CAS 121808-62-6), a new synthetic biological response modifier, on the clinical picture of bacterial exacerbations of chronic bronchitis. Seven centres of respiratory diseases participated in the trial. A total of 137 patients, 103 males and 34 females (mean age: 65.0 years) were admitted to the study. The trial was subdivided into 3 phases. During the first 8-day phase (D0-D8), 68 patients received 800 mg pidotimod orally (one sachet) twice daily and an antibiotic treatment (amoxycillin plus clavulanic acid: 1 g twice daily), while 69 patients received placebo (one sachet) and antibiotic according to the same dosage schedule. In the second 7-day phase (D8-D15), while the double-blind therapy proceeded, the antibiotic treatment was stopped. The third phase (D15-D45) consisted of a 30-day follow-up period. Five clinical observations, at D0, D4, D8, D15 and D45, were scheduled. The Skin test, to evaluate immunocompetence, was carried out at D0, D15 and D45. The faster improvement of symptomatology (dyspnoea, cough, sputum, hyperpyrexia) in the patients in the pidotimod group compared with the placebo group was reflected in recovery time: mean 8.9 days in the pidotimod group versus 10.7 days in the placebo group (p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Chromosome changes in benign prostatic hyperplasia and their significance in the origin of prostatic carcinoma.

Cytogenetic studies of benign prostatic hyperplasia (BHP) are scarce. We analyzed primary cell cultures obtained from biopsies of prostatic tissues from 10 patients (mean age: 60.7 years) with histologic diagnosis of BHP to compare the eventual chromosome changes with those reported in prostatic adenocarcinoma. Clonal chromosome abnormalities were noted in five of the 10 cases, with loss of Y chromosome in all. In one case, a clonal t(1;20) was observed with a -Y clone. Different numerical and structural sporadic abnormalities were evident in eight. Chromosome 1 was the chromosome most frequently involved in sporadic rearrangements. We concluded that -Y is a frequent nonrandom chromosome abnormality in BHP in this sample of patients. Immunohistochemical studies showed that loss of Y occurs in fibroblasts and not in epithelial cells; therefore, this anomaly is not related to cancer development.

Adenocarcinoma

Adenosine deaminase activity and fibronectin levels in bronchoalveolar lavage fluid in sarcoidosis and tuberculosis.

We have studied Adenosine Deaminase (ADA) activity and Fibronectin (FN) levels in Bronchoalveolar Lavage Fluid (BALF) from 50 patients with Sarcoidosis (15 active, 35 non active) and from 24 patients with Pulmonary Tuberculosis in order to evaluate relationships between both ADA and FN in BALF and alveolitis data. BALF ADA activity increases in active sarcoidosis as well as in tuberculosis, as a result of activation, differentiation and proliferation of blood-derived mononuclear alveolar cells. In sarcoidosis this hypothesis is supported by the significant positive correlation observed between ADA activity and both the number of alveolar CD4+ lymphocytes and the number of alveolar lymphocytes bearing activation antigens (CD25 and VLA-1). BALF FN levels increase, showing highest values in active sarcoidosis. ADA and FN elevation in BALF from active sarcoidosis patients could be suggested as additional markers of disease activity. Highest BALF ADA/Albumin ratio observed in pulmonary tuberculosis patients suggests an increased local production and differentiates pulmonary tuberculosis from active sarcoidosis. Increased FN/Albumin ratio observed in non active sarcoidosis appears to be related to a similar mechanism during the reparative process following granulomatous inflammation.

Adenosine Deaminase

Rapid identification of mycobacteria from culture using acridinium-ester-labelled DNA probes.

OBJECTIVES: Our study used newly developed acridinium-ester-labelled DNA (AE-DNA) probes on 183 mycobacterial isolates, performing the tests on 12B Bactec vials and Loewenstein-Jensen (LJ) slants. METHODS: The probe results were verified using the conventional method as a reference. RESULTS: The probe for M. tuberculosis complex correctly identified 131 of 133 M. tuberculosis isolates, with two false negatives and no false positives, for a sensitivity of 98.5% and a specificity of 100%. The M. gordonae probe correctly identified 27 out of 27 M. gordonae isolates, with no false negatives and one false positive, for a sensitivity of 100% and a specificity of 90.9%. One hundred sixty-eight of the 183 isolates were screened in accordance with an algorithm, designed primarily for the rapid detection and identification of M. tuberculosis. CONCLUSION: The use of the algorithm considerably reduced detection time: M. tuberculosis strains were identified within 16.2 +/- 2.3 days, while identification by conventional method required 35.7 +/- 5.5 days. Probe testing resulted in a cost increase of 67.8%.

Algorithms

Lomefloxacin versus amoxicillin in the treatment of acute exacerbations of chronic bronchitis: an Italian multicenter study.

Nine centers in Italy participated in a worldwide, multicenter study comparing the effectiveness and safety of lomefloxacin and amoxicillin in patients with acute exacerbations of chronic bronchitis caused mainly by gram-negative pathogens. The 157 enrolled patients received either 400 mg lomefloxacin once daily (n = 78) or 500 mg amoxicillin every 8 hours (n = 79) for 7-10 days. A total of 131 patients were evaluable for bacteriologic efficacy and 154 for clinical efficacy. At 2-4 days after the conclusion of treatment, the bacterial eradication rate was 84.8% for lomefloxacin-treated patients and 64.6% for amoxicillin-treated patients (p = 0.0065); the clinical success rate (cure plus improvement) for lomefloxacin was 94.7% and for amoxicillin was 83.3% (p = 0.0212). The reinfection rate was lower in the lomefloxacin group than in the amoxicillin group (3.0% vs 13.8%, p = 0.0382). Both drug regimens were well tolerated. Once-a-day treatment with 400 mg lomefloxacin was more effective than 500 mg amoxicillin three times daily for the treatment of acute exacerbations of chronic bronchitis caused by gram-negative pathogens.

Acute Disease

Clonal chromosome changes in renal carcinoma do not correlate with clinical stages and histopathologic grades.

We analyzed the correlations between chromosome abnormalities and clinical and histopathologic characteristics in 77 cases of renal cell carcinoma (RCC). Chromosome changes such as +5,+7,+8,+10,+18,+X,+Y, and -Y have been excluded from the analysis because they also occur in nonneoplastic kidney tissue and cytogenetic analysis indicates that these anomalies are not involved in tumor progression. The most frequent specific chromosome abnormalities in this sample were 3p rearrangements, trisomy 17, and hyperdiploidy and were not related to tumor stage or grade or to development of distant metastases.

Adult

[Clinical study for the evaluation of the tolerability of O-(beta-hydroxy-ethyl)-rutoside in the treatment of hemorrhoids during the 3d trimester of pregnancy and in the postpartum period].

Hemorrhoidal disease is particularly frequent in the last trimester of pregnancy and immediately after birth. The aim of the present study was to evaluate the efficacy and tolerability of high doses of O-(beta-hydroxyethyl)-rutoside in patients affected by this pathology. Forty-two women with hemorrhoid varices of varying severity which had appeared during the last trimester of pregnancy or immediately post-partum were treated by administering 3 g/day of the substance in question for 14 consecutive days. At the start and end of treatment a series of clinical and objective parameters were measured and at the end of treatment efficacy and tolerability were assessed. The latter was found to be excellent; in fact, it was not necessary to suspend treatment in any of the subjects treated. Clinical efficacy, assessed by the researcher, was judged to be positive in 95% of cases treated. Clinical improvements in the parameters examined were statistically significant (p < 0.01). The results obtained confirm the value of oral therapy using O-(beta-hydroxyethyl)-rutoside in pregnant or puerperal patients since the preparation was found to be efficacious and easily managed, above all significantly reducing pain, subjectively the most urgent symptom to be treated.

Adult

Lymphocyte subpopulations analysis in pleural fluid and peripheral blood in patients with lymphocytic pleural effusions.

Lymphocyte subpopulations analysis by an 11-monoclonal antibody (MoAb) panel was carried out in pleural fluid and in peripheral blood in 30 patients affected by newly diagnosed, untreated pleural effusion of different etiology determinated with bacteriological, cytological or histological criteria. Lymphocytes were the predominant cell type, in pleural fluid, in neoplastic pleural effusions as well as in congestive heart failure pleural effusions and, especially, in tuberculous pleural effusions. Lymphocyte analysis in pleural fluid and in peripheral blood suggests the involvement of different mechanisms for the lymphocyte accumulation in the pleural space according to different etiologies. Tuberculous pleural effusions showed an evident CD4+ and TEC T5.9+ lymphocyte accumulation from peripheral blood. In these patients, cutaneous skin test response to purified protein derivative was strongly related to this situation. In neoplastic pleural effusions there was a lower percentage of CD4+ lymphocytes, reflecting circulating lymphocyte pool; however, in neoplastic pleural effusions, various lymphocyte patterns may be sometimes observed depending on different histologies. Passive lymphocyte accumulation seems to be the most important mechanism in congestive-heart-failure pleural effusions.

Adult