Th1 cytokine pattern (IL-12 and IL-18) in bronchoalveolar lavage fluid (BALF) before and after treatment with interferon gamma-1b (IFN-gamma-1b) or colchicine in patients with idiopathic pulmonary fibrosis (IPF/UIP)

BACKGROUND AND AIM: Characterization of the biologic effects of Th1 cytokines will enhance the understanding of idiopathic pulmonary fibrosis (IPF) pathogenesis and treatment selection. Th1 response is characterized by increased expression of IFN-gamma, interleukin (IL)-12 and IL-18. The present study aims to evaluate the role of Th1 cytokines and their possible changes in the bronchoalveolar lavage fluid (BALF), before and after treatment with IFN-gamma-1b or colchicine. PATIENTS AND METHODS: We studied prospectively 10 patients (8 male, 2 female) of median age 67 yr with histologically confirmed IPF/UIP. Patients were randomly assigned to receive either IFN-gamma-1b 200 microg sc (5 patients) or colchicine 1 mg qd (5 patients) plus prednisone 10 mg qd. BALF IL-12 and IL-18 levels were measured before and after treatment. RESULTS: BALF IL-12 levels before and after treatment did not differ significantly between the two treatment groups. However, BALF IL-18 levels were significantly decreased after treatment with IFN-gamma-1b (mean +/- SD, 58.4 +/- 15.6 pg/mL vs 42.8 +/- 4.90 pg/mL, p < 0.05). A significant difference was also found after treatment with colchicine (mean +/- SD, 66.8 +/- 36.9 pg/mL vs 42.6 +/- 1.08 pg/mL, p < 0.01). A significant correlation was found between IL-18 BALF levels and the BALF neutrophils (r = 0.75, p = 0.024). CONCLUSION: Our data suggest the potential role of IL-18 as an inflammatory marker in the pathogenetic pathway of IPF such as its possible downregulation by IFN-gamma-1b treatment. Further studies are needed in a higher number of patients in order to define the precise role of both cytokines during the immunoregulatory response with IFN-gamma-1b.     

Variations in alveolar cell populations, lymphocyte subsets and NK-cells in different stages of active pulmonary sarcoidosis

BACKGROUND: The type and mode of presentation of pulmonary sarcoidosis (radiologic stage, activity) influence alveolar lymphocyte number and subsets as well as other inflammatory cells. AIM: To investigate the variations in alveolar cells, lymphocyte subsets and NK-cells in different radiological stages of active pulmonary sarcoidosis. METHODS: 85 untreated, newly diagnosed patients (32 male, 53 female), median age 47.2+/-14.7 years were investigated. Patients were classified into chest x-ray stages (33 stage I, 27 stage II, 14 stage III and 11 stage IV disease). Bronchoalveolar lavage was performed with 4 portions of 50 mL. Total cells and cell differentials were counted, while CD3+, CD4+, CD8+, CD19+, CD3-CD16/56+ (NK-cells) and CD3+CD16/56+ (NKT-cells) were determined by flow cytometry. Results: Lymphocytosis was high in all stages. Significant differences were found in: a) CD4 between stages I and II and I and IV. b) CD8 between stages I and IV and c) NK and NKT cells between stages I and III. CONCLUSIONS: Variations were observed in alveolar cells and lymphocyte subsets in different stages of pulmonary sarcoidosis. Cells exhibiting cytotoxic activity were increased with stage progression, CD8 from stage I to IV, NK and NKT cells from stage I to III. These cells may be involved in the inflammatory process regulating granuloma formation.     

E-cadherin expression on fine-needle aspiration biopsies in primary lung adenocarcinomas is related to tumor differentiation and invasion

E-cadherin, a cell surface molecule that mediates cell-cell adhesion in normal epithelium, has been shown in recent studies of tissue biopsy to be related to tumor differentiation and invasiveness. The aim of the study was to explore if preoperative E-cadherin expression on fine-needle aspiration biopsy (FNAB) specimens can predict cell differentiation and mediastinal lymph node spread and therefore tailor treatment in patients with primary lung adenocarcinoma. We studied prospectively the relationship between E-cadherin expression on FNABs and the pathological features of 50 cases of primary lung adenocarcinomas, which were diagnosed cytologically and confirmed histologically post-operatively. Expression of E-cadherin was found in 36 (72%) cases. Decreased expression of E-cadherin was correlated with poor grade adenocarcinomas (low grade 33% vs. 100% in high grade, p < 0.005) and lymph node metastasis (positive 43% vs. negative 93%, p < 0.005). No relationship was found between E-cadherin expression and tumor size. CONCLUSION: E-cadherin expression of FNAB specimens can be helpful in predicting tumor cell differentiation, invasiveness and defining a subpopulation of patients with primary lung adenocarcinoma with possible poor outcome, which should be taken into consideration in the proper management of the disease.     

Acute interstitial pneumonia.

The term "acute interstitial pneumonia" (AIP) describes an idiopathic clinicopathological condition, characterized clinically by an interstitial lung disease causing rapid onset of respiratory failure, which is distinguishable from the other more chronic forms of interstitial pneumonia. It is synonymous with Hamman-Rich syndrome, occurring in patients without pre-existing lung disease. The histopathological findings are those of diffuse alveolar damage. AIP radiologically and physiologically resembles acute respiratory distress syndrome (ARDS) and is considered to represent the small subset of patients with idiopathic ARDS. It is frequently confused with other clinical entities characterized by rapidly progressive interstitial pneumonia, especially secondary acute interstitial pneumonia, acute exacerbations and accelerated forms of cryptogenic fibrosing alveolitis . Furthermore, many authors use the above terms, both erroneously and interchangeably. It has a grave prognosis with >70% mortality in 3 months, despite mechanical ventilation. This review aims to clarify the relative clinical and pathological issues and terminology.     

Availability of antidotes in hospital pharmacies in Greece

We determined the availability of poisoning antidotes in the pharmacies of state hospitals in Greece and in Health Centers of the island of Crete. A questionnaire survey was sent to all pharmacy directors of hospitals with emergency departments, asking them to report anonymously the amount currently in stock of each of 12 common antidotes. Questionnaires were sent to 100 pharmacy directors and 68 (68%) of them replied. Only 2 (3%) of the 68 hospitals stocked all 12 antidotes. The percentage of sufficient stocking for individual antidotes ranged from 6% (for digoxin immune fab) to 91% (for methylene blue). Recent circulation of government guidelines for antidote stocking and hospital type had no significant effect on antidote stocking. In a multiple regression analysis, hospital type (prefectural, regional, university hospital) and smaller hospital size were not predictors of the number of antidotes sufficiently stocked. Storing of key poisoning antidotes is inadequate in regional as well as in prefectural hospitals in Greece. Antidotes, including those which should be used without delay to be effective, are often not available, even for the commoner poisons in Greece such as pesticides.     

Bcl-2 expression as an apoptotic index in non small cell lung carcinomas

To evaluate the bcl-2 protein expression in non small cell lung carcinomas (NSCLC) as an index of apoptosis of these tumors, in fine needle aspiration biopsies (FNABs) of the lung, we studied thirty-eight cases of NSCLC (25 bronchogenic adenocarcinomas and 13 squamous. carcinomas. Bcl-2 protein was used as the primary antibody (monoclonal, DAKO) by Alkaline-phosphatase method. Very light haematoxylin was performed as the counterstain. The results were compared and confirmed histologically. A cytoplasmatic expression of the bcl-2 protein was found in 72% (18 out of 15) of the bronchogenic adenocarcinomas while 61.54% (8 out of 13) of squamous carcinomas showed bcl-2 expression. For the quantitative analysis of our results, we used the t-test and the difference between those two histologic types was regarded as statistically significant with p < 0.001.     

Interleukin-6 and its relationships to acute phase proteins in serous effusion differentiation

The aim of the study was to assess the discriminative power of cytokine interleukin 6 (IL-6) between transudative and exudative pleural and peritoneal effusions, and to compare IL-6 with common acute phase proteins in serous effusion differentiation. One hundred and forty-five consecutive patients with pleural or peritoneal effusion underwent diagnostic parecentesis. Patients were categorized in three groups. Malignant effusion (group A) 56 patients, non-malignant effusion (group B) 46 patients and transudate (group C) 43 patients. Serum and effusion levels of IL-6, C-reactive protein (CRP), alpha2-macroglobuline (alpha2-MG), alpha1-antitrypsin (alpha1-AT) and alpha1-acid glycoprotein (alpha1-AG) were determined. Serum IL-6 levels were significantly higher in groups A and B in comparison to group C (p<0.001 and 0.001, respectively). In addition, serum IL-6 levels were higher in group A compared to group B (p<0.001), while the studied acute phase proteins were not significantly different. All the studied parameters were higher in the effusions of groups A and B compared to group C. At a cut-off value of 72.1 fmol/ml IL-6 had a sensitivity of 82.6-89.3%, specificity of 88.4-90.7% and positive predictive value of 90.7-94.6% among the three groups. Our results suggest that IL-6 at levels > or =72.1 fmol/ml, alpha1-AT at > or =170 mg/dl and alpha1-AG at > or =52.3 mg/ml give strong evidences for malignancy in exudates.     

Phase 1 trial of lipoplatin and gemcitabine as a second-line chemotherapy in patients with nonsmall cell lung carcinoma

BACKGROUND.: Lipoplatin is a new liposomal cisplatin that already has been tested in solid tumors, with encouraging results. The purpose of the current study was to determine the maximum tolerated dose (MTD) and the dose-limiting toxicity (DLT) of a 21-day regimen of lipoplatin plus a fixed dose of gemcitabine in patients with refractory or resistant nonsmall cell lung carcinoma (NSCLC) with an Eastern Cooperative Oncology Group (ECOG) performance status of 相似文献