Penetration of pefloxacin and ciprofloxacin into lung tissue.
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4-Quinolones↗
Biomedical subjects
M Mezzetti
Publications and source records attributed to M Mezzetti.
Biologic and clinicopathologic factors as indicators of specific relapse types in node-negative breast cancer.
PURPOSE AND METHODS: We evaluated, in 1,800 patients with node-negative tumors treated with locoregional therapy until relapse, the competitive risks for different types of metastasis by cell proliferation (3H-thymidine labeling index [3H-dT LI]), estrogen receptors (ERs), and progesterone receptors (PgRs), and by the integration of biologic and clinicopathologic information. RESULTS: Hormone receptor status and proliferative activity of the primary tumor were not indicative of contralateral failures. Hormone receptors failed to predict the 8-year incidence of locoregional recurrence, but they were significant indicators of distant metastasis and overall survival. The latter finding was confirmed even in multivariate analysis. Conversely, cell proliferation predicted both locoregional and distant metastases and survival, regardless of patient age, tumor size, and ER and PgR status. Recursive partitioning and amalgamation analysis ascribed to cell proliferation an important prognostic role for locoregional recurrence together with patient age and tumor size. CONCLUSION: Biologic markers, in particular cell proliferation, provide information for the different types of relapse and could complement the predictive role of pathologic staging.
Adult↗
Receptors for cys-leukotrienes in human lung parenchyma: characterization by computer modelling and photoaffinity labelling of binding sites.
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Affinity Labels↗
Furosemide attenuates bronchial responsiveness to antigen challenge "in vitro".
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Acetophenones↗
[Sclerosing hemangioma of the lung: a case report].
The authors present a case of sclerosing hemangioma, a rare benign neoplasm of the lung. The patient presented coughing, blood-tinded spuntum and thoracic pain; chest x-ray showed an irregular shadow close to right hilum. A right superior lobectomy was performed. Immunohistochemical and electronic microscopy studies of the lesion supported its origin from respiratory epithelium.
Histiocytoma, Benign Fibrous↗
The Bcl-2 protein: a prognostic indicator strongly related to p53 protein in lymph node-negative breast cancer patients.
BACKGROUND: The bcl-2 gene (also known as BCL2) encodes for a mitochondrial protein thought to prevent apoptosis of normal cells. The protein has been detected by immunohistochemical procedures in hormonally regulated epithelia. PURPOSE: We analyzed the predictive relevance of Bcl-2 expression on 6-year relapse-free and overall survival in lymph node-negative breast cancers in relation to pathologic (tumor size) and biologic ([3H]thymidine-labeling index, p53 protein expression, and estrogen receptor [ER] status) features. METHODS: The expression of Bcl-2 and p53 was detected by immunohistochemistry on paraffin-embedded sections from 283 node-negative resectable breast cancers treated with local-regional therapy alone until relapse. The [3H]thymidine-labeling index was evaluated on histologic sections after incubation of fresh tumor tissue with [3H]thymidine, and ER content was determined by the dextran-coated charcoal absorption technique. RESULTS: A significantly higher fraction of Bcl-2-positive cells was observed in small, ER-positive, slowly proliferating, and p53-negative tumors than in large, ER-negative, rapidly proliferating, and p53-positive tumors. A stronger association was observed between Bcl-2 and p53 expression than between these variables and [3H]thymidine-labeling index. In univariate analysis, Bcl-2 and p53 expression, [3H]thymidine-labeling index, tumor size, and ER status were indicators for relapse-free and, with the exception of tumor size, overall survival within 6 years of surgery. In multivariate analysis, Bcl-2 failed to maintain its prognostic role for relapse-free and overall survival in the presence of p53 expression, whereas the [3H]thymidine-labeling index was still statistically significant as a predictor for both events. CONCLUSION: The predictive role of Bcl-2 expression on 6-year relapse-free and overall survival was mainly dependent on p53 expression.
Breast Neoplasms↗
A multiparametric study on the prognostic value of epidermal growth factor receptor in operable breast carcinoma.
Epidermal growth factor receptor (EGFR) is a potentially useful new biological prognostic and predictive indicator in human breast cancer. Additional research on EGFR is warranted to enhance our information on: i) the method of choice for its detection and quality control issues; ii) its association with novel pathobiological markers of prognosis; iii) its prognostic value in multivariate analysis; and iv) its capability to predict response to hormone therapy and, in the future, to biological treatments using antibodies against the specific receptor or its ligands. In the present study we update previous data on EGFR status, determined immunocytochemically, by prolonging the period of observation up to 5 years and by including, in the multivariate analysis, several new biological indicators. The main results obtained are: i) EGFR is weakly associated with Ki-67 score (p = 0.073) and with p53 expression (p = 0.06); ii) EGFR is a significant indicator for recurrence (p < 0.01 and odds ratio of 2.82) but not for death (p = 0.27 and odds ratio of 1.49); iii) the prognostic power of EGFR is enhanced when combined with the knowledge of S-phase fraction; and iv) in multivariate analysis on relapse-free survival, EGFR and S-phase fraction (likelihood ratio test = 26.40; p < 0.01), c-erB-2 protein and p53 mutant protein expression (likelihood ratio test = 5.94; p = 0.05), cathepsin D (likelihood ratio test = 9.78; p < 0.01), and nodal status (likelihood ratio test = 7.32: p < 0.01) are significant and independent prognostic factors in early-stage breast carcinoma. This new information could be of help for a more rational approach in the use of EGFR as a marker in future clinical research.
Age Factors↗
Efficacy of long-term administration of transdermal nitroglycerin in asymptomatic patients with effort-induced silent myocardial ischemia.
The aim of our study was to investigate the effect of transdermal nitroglycerin (NTG) on effort-induced silent myocardial ischemia in asymptomatic patients treated with beta-blockers or calcium antagonists. The acute effect was compared to two different schedules, continuous (24 h/day) or intermittent (16 h/day), of long-term administration. Ten asymptomatic patients with coronary artery disease and a treadmill test positive for ischemia without angina were enrolled. Both acute (2 days) and long-term (24 days) evaluations were conducted in a randomized, double-blind, crossover fashion. The ergometric parameters were collected on the 1st and the 2nd day of the acute phase (placebo and transdermal NTG, respectively) and at the end of each 12-day period of long-term administration (continuous and intermittent, respectively). Transdermal NTG administration acutely increased (p < 0.05) both time to 1-mm ST segment depression (451 +/- 43.2 vs. 374 +/- 24.1 s) and total exercise time (561.3 +/- 43.2 vs. 419.5 +/- 24.5 s). The acute efficacy was maintained over long-term treatment, regardless of the modality of administration. During continuous and intermittent patch application, time to 1-mm ST segment depression was 437.9 +/- 30.4 and 422 +/- 33.4 s (p = NS vs. acute) and total exercise time was 498.8 +/- 30.4 and 495.1 +/- 33 s (p = NS vs. acute), respectively. Transdermal NTG increases, both acutely and chronically, exercise tolerance in asymptomatic patients with effort-induced silent myocardial ischemia. With the NTG dose we used, tolerance does not seem to be a problem over long-term administration.
Administration, Cutaneous↗
Intratumoral microvessel density and p53 protein: correlation with metastasis in head-and-neck squamous-cell carcinoma.
Squamous-cell carcinoma of the head and neck includes a heterogeneous group of tumours of the upper air and food passages for which prognosis is difficult to assess. In fact, patients in comparable stages may have diverse clinical courses and responses to similar treatments. In order to better define the prognosis of each patient there is therefore a need to identify novel biological markers which reflect more accurately growth rate, progression and metastatic potential of each tumour. We assessed whether metastases correlate with microvessel counts (i.e. intratumoral vascularity) using the CD-31 monoclonal antibody (MAb) and p53 mutant protein expression, determined in the primary by immunocytochemical methods in 70 patients with locally advanced head and neck cancer. Patients were treated with concurrent chemo-radiotherapy; 50 of these presented loco-regional node metastasis at diagnosis whereas 3 cases, initially node-negative, developed distant metastasis during the period of observation. No feature was predictive for objective response to treatment. The overall mean and median blood vessel density at "hot spots" was 37.42 and 36, respectively, and 57% of the tumours expressed p53 mutant proteins. These 2 biological markers were significantly associated. Patients with metastases (loco-regional and distant) had a significantly higher mean blood-vessel density than those without tumour spread. Also, patients with p53-positive (+/++) tumours had a significantly higher incidence of metastasis than those with negative ones. Multivariate analysis showed that both vascularity and stage, but not p53 expression, are significant and independent predictors of metastasis in this series.
Adult↗
Concurrent carboplatin (CBDCA), vindesine (VDS) and radiotherapy in stage III non small cell lung cancer (NSCLC).
AIMS: Aim of the study was to test, in a cooperative and prospective trial, the effectiveness and feasibility of a chemoradio-therapy program in stage III non small cell lung cancer (NSCLC). METHODS: The schedule consisted in carboplatin (CBDCA) 150 mg/m2/iv on days 1, 3, 5 and vindesine VDS 2.5 mg/m2/iv on days 1, 8, 15, 22 every 4 weeks for 2 cycles followed by radiotherapy 60 Gy with CBDCA 50 mg/m2 weekly as radioenhancer. The same schedule was proposed as neoadjuvant treatment in 10/47 patients (stage III A) and as exclusive treatment in 37/47 (stage III B) admitted patients. RESULTS: In the neoadjuvant subgroup partial remission was obtained in 5/10 patients, and 3 of them underwent surgery with consequent CR. In the stage III B subgroup, 2 complete remissions were obtained (survival 14 and 9+ months). Toxicity was mild. CONCLUSIONS: Our results confirm the feasibility of the schedule in stage III NSCLC.
Antineoplastic Combined Chemotherapy Protocols↗
Heterogeneity of binding sites for ICI 198,615 in human lung parenchyma.
We have identified and characterized two different subclasses of binding site for the novel peptido-leukotriene (LT) antagonist, [3H]ICI 198,615, in membranes from human lung parenchyma using a receptor-ligand assay. This novel compound is representative of a new class of LT receptor antagonists and it has been demonstrated to be several orders of magnitude more potent and selective than most other LT antagonists described to date. The binding of [3H]ICI 198,615 is rapid, specific and saturable. Equilibrium was reached within 5-10 min. Non linear fitting of dissociation time courses has revealed the presence of two different components (K(off)1 = 8.3 +/- 6.8 x 10(-4) sec-1 and K(off)2 = 0.79 +/- 1.66 x 10(-3) sec-1) of the kinetic curves, suggesting heterogeneity of the binding sites. Computer analysis of equilibrium binding data obtained at 25 degrees results in a model with two classes of binding sites, a high affinity-low capacity class with Kd1 = 0.024 +/- 0.014 nM and Bmax1 = 0.015 +/- 0.004 pmol/mg protein and a low affinity-high capacity class with Kd2 = 6326 +/- 3859 nM and Bmax2 = 473 +/- 383 pmol/mg protein. In competition studies, LTD4 was also found to interact with two classes of binding site (Kd1 = 0.016 +/- 0.008 nM and Kd2 = 15195 +/- 8965 nM). On the contrary, LTE4 and LTC4 were found to interact with a homogeneous class of sites only with Kd = 7466 +/- 4629 nM and Kd = 428 +/- 73 nM, respectively. Furthermore, we have evaluated the effect of a number of LT antagonists on the binding of [3H]ICI 198,615. Ro 24-5913 (Kd = 3.0 +/- 2.1 nM), FPL55712 (Kd = 4945 +/- 2868 nM), LY171883 (Kd = 19628 +/- 12365 nM), SKF 104353 (Kd = 74.2 +/- 46 nM) and its enantiomer SKF 104373 (Kd = 13627 +/- 6813 nM) were found to interact with a single class of binding sites. The present studies indicate a heterogeneity of binding sites for ICI 198,615 in membranes from human lung parenchyma and that ICI 198,615 is a very potent and selective antagonist of LTD4 receptors in this tissue.
Asthma↗
[Mechanical suturing devices in bronchopulmonary surgery].
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Bronchi↗
Protective effect of nedocromil sodium on the IL1-induced release of GM-CSF from cultured human bronchial epithelial cells.
Cultured human bronchial epithelial cells constitutively produce granulocyte-macrophage colony-stimulating factor (GM-CSF). The synthesis and release of GM-CSF is upregulated in bronchial epithelium of patients with symptomatic asthma and this may contribute to the local activation of inflammatory cells in their bronchial mucosa. The cause of this upregulation of GM-CSF expression is unknown, but an increased release of interleukin-1 (IL1) from other airway resident cells might be involved, as an increase in GM-CSF production can be induced in vitro in normal bronchial epithelial cells by IL1 and the airway secretions of asthmatics contain high amounts of this cytokine. In the present study, we have evaluated the effect of the anti-inflammatory and antiasthmatic drug, nedocromil sodium, on the spontaneous and IL1-induced expression of GM-CSF in cultured bronchial epithelial cells. This compound, at the concentration of 10(-5) M, reduced the IL1-induced increase in GM-CSF release from epithelial cells by more than 40%, but it did not affect the constitutive production of GM-CSF.
Anti-Inflammatory Agents, Non-Steroidal↗
[The clinical and prognostic significance of symptomatic and silent ischemia on the exercise test in patients with a prior myocardial infarct].
The aim of the study was to assess clinical/prognostic significance of exercise-induced ischemia in patients with healed myocardial infarction. From May 1988 to January 1991, 777 consecutive patients underwent a symptom-limited (Bruce protocol) treadmill test at least 1 year after myocardial infarction. Clinical and ergometric data were entered in a prospective way in our data base. The exercise-test was positive in 231 out of 777 patients and 2 different subgroups were retrospectively identified depending on criteria of interruption: 156 patients with painless exercise-ST depression; 75 patients with painful exercise-ST depression. The main results (mean +/- SD) were analyzed with Student t test and chi 2 test. Patients with silent ischemia had longer exercise duration (547 +/- 153 s versus 395 +/- 173 s; p < 0.001) and higher double product (22.98 +/- 0.5 versus 19.71 +/- 0.4; p < 0.001) than symptomatic patients. Ischemic threshold was lower (double product: 17.98 +/- 0.4 versus 21.22 +/- 0.4; p < 0.001 with onset of ST depression at 297 +/- 148 s versus 448 +/- 147 s; p < 0.001) and time to ST normalization was longer (368 +/- 155 s versus 234 +/- 212 s; p < 0.001) in patients with painful ischemia. Patients with angina and ST depression had significantly higher prevalence of downsloping ST depression in the recovery phase (68% versus 37%; p < 0.001) and a higher prevalence of treadmill exercise score indicating high risk (49% versus 3.2%; p < 0.001). The 2 groups when compared with 99 patients with negative test post-AMI were significantly different.(ABSTRACT TRUNCATED AT 250 WORDS)
Aged↗
[Personal observations on surgical therapy of pulmonary metastases of renal carcinoma].
Renal cancer has an high incidence of metastasizing and its metastases are just a little responsive to chemo and radiotherapy. Because of this, thoracic surgeons began to have experiences on surgical resections of lung metastases from renal cancer. Pulmonary metastases can be isolated or multiple and may appear at the same time of renal cancer discovery or after it, and they generally have a very slow evolution. Authors report their own 15 years old experience on lung metastases from renal cancer resections.
Carcinoma, Renal Cell↗
Eicosanoid release and mepyramine, LTC4 and LTD4 binding in passively sensitized human lung parenchyma in vitro.
In vitro passive sensitization of human lung parenchyma with hyper-immune serum did not affect the release of prostaglandin D2 (PGD2) or leukotriene (LT)-like activity upon challenge with anti-IgE antibody with respect to control lung, despite a marked difference in IgE levels between control (C) and sensitized (S) tissue. Binding studies with [3H]LTC4, [3H]LTD4 and [3H]mepyramine (a histamine H1 antagonist) showed a statistically significant increase in the amount bound in sensitized vs control lung for [3H]mepyramine only. Contractile response to 5 x 10(-5) M histamine (H) in C and S lung parenchymal strips did not correlate with binding data. It is concluded that in vitro elevated IgE levels do not affect the interaction of sulfidopeptide leukotrienes with their putative receptors. As for the observed increase in [3H]mepyramine binding, this might not represent a true increase in histamine receptors on lung smooth muscle cells.
Animals↗
Time course of IL1 and IL6 synthesis and release in human bronchial epithelial cell cultures exposed to toluene diisocyanate.
We have previously demonstrated that human bronchial epithelial cells release appreciable amounts of interleukin 1 (IL1) and interleukin 6 (IL6) when exposed to toluene diisocyanate (TDI) in vitro. TDI is an inflammatory and asthmogenic stimulus presumed to act at least in part through immunological mechanisms. The epithelial cell-derived IL1 and IL6 can promote T cell activation and proliferation in culture, and if this also happens in vivo they may contribute to the persistence of the inflammatory response of the bronchial mucosa observed in TDI-sensitive asthmatics. In this study, we confirmed the release of biologically active IL1 beta and IL6-like substances from bronchial epithelial cells exposed to isocyanates in vitro, and related the rate and the magnitude of the cytokine secretion with the pattern of IL1 beta and IL6 gene expression and the extent of epithelial cell injury. In the epithelial cell cultures exposed to TDI, there was a parallel, progressive increase in the expression of IL6 mRNA and in the secretion of IL6 protein between 48 hours and 6 days after exposure. By contrast, although increasing amounts of biologically active IL1 beta were detected in the supernatants of TDI-exposed epithelial cells throughout the 6-day period following exposure, augmented levels of IL1 beta mRNA were only evident 6 days after exposure, suggesting that TDI exposure might have initially affected the enzymatic cleavage of the intracellular IL1 beta precursor and the mechanisms which regulate the secretion of mature IL1 beta.
Blotting, Northern↗
Human bronchial epithelial cells modulate CD3 and mitogen-induced DNA synthesis in T cells but function poorly as antigen-presenting cells compared to pulmonary macrophages.
This study was undertaken to investigate the ability of bronchial epithelial cells (ECs) to function as accessory cells. Pulmonary monocytes were our reference cells. ECs and pulmonary monocytes were isolated from the bronchial mucosa and pulmonary parenchyma of subjects undergoing lobectomy for standard clinical reasons. Circulating autologous T cells were rigorously depleted of accessory cells to the extent that they lost the capacity to respond to mitogenic lectins alone. ECs restored mitogen-induced DNA synthesis and DNA synthesis triggered by CD3 cross-linking in T cells, as did pulmonary macrophages, and this was unrelated to HLA-DR expression. The ability of promoting T cell proliferation after CD3 cross-linking was, in part, due to the secretory products of ECs, since their supernatants were also effective. Interferon-gamma-treated ECs were capable of presenting antigens to autologous T cells. This was an HLA-DR-restricted phenomenon, but EC efficiency in this system was less than 40% of efficiency demonstrated by pulmonary monocytes. However, ECs greatly upregulated antigen-specific responses supported by pulmonary monocytes.
Antigen-Presenting Cells↗