Pulmonary (99m)Tc-DTPA aerosol clearance and survival in usual interstitial pneumonia (UIP).

BACKGROUND: Clearance of inhaled technetium 99m-labelled diethylenetriamine penta-acetic acid ((99m)Tc-DTPA) from the lungs is a potential indicator of disease progression in patients with idiopathic pulmonary fibrosis (IPF). METHODS: We prospectively analysed the usefulness of this technique for predicting survival in 106 non-smoking patients with usual interstitial pneumonia (UIP) pattern IPF diagnosed by high resolution CT (HRCT) scanning or histological examination (M/F 65/41, mean (SD) age 61 (11) years). DTPA clearance was analysed according to both mono-exponential and bi-exponential models. Half times for the fast (t(0.5)F) and slow (t(0.5)S) components of clearance, the percentage contribution of the fast component (fF), and half time for mono-exponential approximation to the early part of the clearance curve (t(0.5)) were calculated. RESULTS: The patients had substantially faster t(0.5) (mean 23.9 (9.6) minutes) than normal values (>45 minutes). Thirty seven patients (35%) died during follow up (median 15 months). Univariate Cox regression analysis identified significant predictors of survival as age, forced expiratory volume in 1 second (FEV(1)), forced vital capacity (FVC), total lung capacity (TLC), % predicted TLC, carbon monoxide transfer factor (TLCO), % predicted TLCO, arterial oxygen tension (PaO(2)), oxygen saturation, t(0.5)F, and HRCT fibrosis score. Multiple stepwise Cox regression analysis identified t(0.5)F (p=0.03, hazard ratio 0.747, 95% CI 0.578 to 0.964), % predicted TLC (p=0.02, hazard ratio 0.976, 95% CI 0.956 to 0.995), % predicted TLCO (p=0.003, hazard ratio 0.960, 95% CI 0.935 to 0.986), and age (p=0.003, hazard ratio 1.062, 95% CI 1.021 to 1.104) as independent predictors of survival. CONCLUSION: These data suggest that (99m)Tc-DTPA clearance t(0.5)F measurement may predict survival in patients with UIP pattern IPF.

High dose rate endobronchial brachytherapy in combination with external beam radiotherapy for stage III non-small cell lung cancer.

INTRODUCTION: A phase-II study was planned to test the effect of external beam radiotherapy in combination with endobronchial brachytherapy on the local control and survival of stage-III non-small cell lung cancer patients. MATERIALS AND METHODS: Thirty patients with stage-III non-small cell lung cancer have been treated with 60 Gy external beam radiotherapy and 3 x 5 Gy HDR endobronchial brachytherapy to control tumor and to prolong survival. RESULTS: Therapy regimen was found to be very effective for the palliation of major symptoms, palliation rates were 42.8% for cough, 95.2% for hemoptysis, 88.2% for chest pain and 80.0% for dyspnea. There was a 76.7% tumor response (53.3% complete, 23.3% partial) verified by chest CT scans and bronchoscopy. However, median locoregional disease free survival was 9+/-4 months (95% CI: 1-17) and it was only 9.6% at 5 years. Major side effects were radiation bronchitis (70.0%), esophagitis (6.6%) in the acute period and bronchial fibrosis (25%), esophagial fibrosis (12.5%) and fatal hemoptysis (10.5%) in the late period. Median survival was 11+/-4 months (95% CI: 4-18),and 5-year actuarial survival was 10%. Locoregional disease free survival (P=0.008) and the overall survival was longer (P<0.001) in the patients younger than 60, survival was also improved in the patients with complete response (P=0.019). There were no major complications during catheterisation; early side effects were quite tolerable but severe late complications were around 10%. CONCLUSIONS: It is concluded that endobronchial brachytherapy in combination with external irradiation provides a good rate of response, however does not eradicate locoregional disease and does not prolong survival except for some subgroups such as younger patients.

Evaluation of CMV viral load using TaqMan CMV quantitative PCR and comparison with CMV antigenemia in heart and lung transplant recipients.

BACKGROUND: Quantitative assessment of cytomegalovirus (CMV) infection using the antigenemia test has been used to monitor CMV infection in heart and lung transplant patients enabling a preemptive treatment strategy. However, the method is labour intensive, samples have to be processed within a few hours and requires skilled interpretation. A comparative prospective evaluation of a real-time TaqMan CMV quantitative PCR (QPCR) with the CMV antigenemia was undertaken. METHODS: A real-time quantitative TaqMan CMV PCR from EDTA bloods was developed. In this study 25 heart transplant and single-lung transplant patients were monitored posttransplantation by antigenemia and TaqMan CMV QPCR. CMV DNA extracted from EDTA blood was amplified by TaqMan QPCR using primers and probe designed from the CMV glycoprotein B (gB) gene. Quantification of the genome copies is extrapolated from a standard curve generated from amplification of quantified standards. RESULTS: Antigenaemia levels and TaqMan CMV QPCR genome copies showed a linear correlation between the two assays (R=0.843, P=0.001). A clinically significant threshold of 50 CMV pp65 antigen positive polymorphonuclear leucocytes (PMNLs) per 200 000 cells previously reported was used to extrapolate an equivalent value of 40 000 (log 4.6) genome copies per ml of blood for the TaqMan CMV QPCR. CONCLUSIONS: The TaqMan system enables a rapid high-throughput of samples. The TaqMan CMV QPCR can be used as an accurate and robust alternative to the antigenemia test to predict CMV disease and to monitor effectiveness of treatment.

Pulmonary function in idiopathic pulmonary fibrosis and referral for lung transplantation.

Of patients awaiting lung transplantation, the death rates are highest in those with idiopathic pulmonary fibrosis (IPF), suggesting that many IPF patients are referred late for transplantation. Therefore this study was undertaken to evaluate baseline pulmonary function test (PFT) and high-resolution computed tomography (HRCT) fibrosis scores, and the relationship to survival in IPF patients younger than 65 yr of age. A total of 115 patients with usual interstitial pneumonia (UIP) were studied. At presentation to a tertiary referral center, PFT and HRCT data were collected and analyzed for prognostic significance: the primary outcome measure was patient death. Based on the length of the waiting list for transplantation, prediction of 2-yr survival was examined. DL(CO) percent predicted and HRCT-fibrosis score were found to be independent predictors of survival and in combination gave the best prognostic prediction. The optimal points on the receiver operating characteristic (ROC) curves for discriminating between survivors and nonsurvivors corresponded to 39% DL(CO) percent predicted, and to a HRCT-fibrosis score of 2.25. The combination of these parameters yielded an optimal point with a specificity and a sensitivity of 84% and 82%, respectively. A model based on a combination of DL(CO) percent predicted and HRCT-fibrosis score may optimize the timing of referral for transplantation.

B-cell isotype control in atopy and asthma assessed with cDNA array technology.

B-cell isotype switching and the production of IgE is regulated by a variety of gene products through different mechanisms. A better understanding of these processes has the potential to identify markers of disease and new therapeutic targets. The aim of the study was to investigate human B-cell isotype control and IgE production in atopy and asthma with cDNA array technology. Eighteen atopic asthmatic, eight atopic nonasthmatic, and fourteen healthy control subjects were included. Peripheral blood mononuclear cells were separated by gradient centrifugation, mRNA was purified, and the reverse-transcribed probes were hybridized to cDNA membranes. Group differences were assessed with the Mann-Whitney U-test. Twenty-three of seventy-eight tested IgE-related genes had significantly altered expression in atopy and asthma compared with that in the healthy subjects. The differentially expressed genes include surface molecules involved in T- and B-cell interaction and activation, cytokines, intracellular signaling products, and transcription factors. In conclusion, both atopic nonasthmatic and atopic asthmatic individuals had activated proinflammatory pathways, a minimal requirement for B-cell isotype switching, and a clear net pro-IgE cytokine climate.

Apoptosis signals in atopy and asthma measured with cDNA arrays.

A variety of studies have stressed the importance of the control of inflammatory cell longevity and the balance of pro-survival and pro-apoptotic signalling. Recently, asthma was found to be associated with reduced apoptosis of inflammatory cells in lung tissue. The aim of the study was to investigate the systemic activation of apoptosis pathways using cDNA array technology in atopy and asthma. Eighteen atopic asthmatics (AA), eight atopic non-asthmatic (AN) and 14 healthy control subjects (C) were included in the study. Peripheral blood mononuclear cells were separated with gradient centrifugation, mRNA purified and the reverse-transcribed probes hybridized to cDNA arrays. The signals were compared by standardizing to the 100 most expressed genes and group differences assessed with the Mann-Whitney U-test. We found a concerted up-regulation of several pro-survival cytokines and growth factors in AN and AA. FAS and FASL were not differentially expressed, but FAST kinase was over-expressed in AN and AA. The tumour necrosis factor pathway was activated in AN and AA with increased cytokine and receptor levels and increased TRAF2, an intracellular signalling product. There were indications of a down-regulated p53 system. In contrast, the Bcl-2 family of genes showed a net pro-apoptotic profile in AN and AA. The group of caspases showed a constant gene expression pattern in all groups. In conclusion, significant differences in the expression of apoptosis-related genes were found in peripheral blood of atopic individuals with and without asthma. cDNA array technology proved to be useful and may be complementary to DNA-based studies in order to analyse interactive and multidimensional pathways as shown here for apoptosis.

Intracardiac thrombus in Behçet's disease: a systematic review.

BACKGROUND: Intracardiac thrombus formation is a rare but serious complication of Behçet's disease. We aimed to review the clinical and pathologic correlates of cardiac thrombus formation in the context of Behçet's disease. METHODS AND RESULTS: A comprehensive search of the medical literature was conducted using MEDLINE including bibliographies of all selected articles. Although the disease has a unique geographic distribution, being most common in the population of the ancient Silk Route, cases complicated by intracardiac thrombus have mostly originated from the Mediterranean basin and the Middle East. Young men appear to be most at risk, with the right heart the most frequent site of involvement. The first symptoms and signs of the disease frequently precede systemic organ manifestations. In those cases in which intracardiac thrombus occurs, it is apparent in more than half of cases on first recognition of the disease. CONCLUSION: A diagnosis of Behçet's disease should be considered if a patient presents with a mass in the right-sided cardiac chambers, even in the absence of the characteristic clinical features of the condition. This is particularly applicable if the patient is a young man from the Mediterranean basin or the Middle East.

Endobronchial metastasis from osteosarcoma of bone: treatment with intraluminal radiotherapy.

Lung parenchymal metastases are common manifestations in patients with osteosarcoma; however, spread to the major airway itself is extremely rare. We present a young man who had been previously treated with surgical resection following preoperative chemotherapy and immediate postsurgical adjuvant chemotherapy for proximal tibial osteosarcoma. He developed metastasis to the major airways. The patient was treated with intraluminal radiotherapy (ILT) for the endobronchial metastasis. This is the first report of an endobronchial osteosarcoma that was treated with ILT with a complete endoscopic response. ILT provided excellent palliation in this particular case.

Chylothorax, chylopericardium and lymphoedema--the presenting features of signet-ring cell carcinoma.

This report describes a patient with chylous pleural and pericardial effusions in conjunction with severe lymphoedema resembling elephantiasis. The chylous effusions and generalized lymphoedema were associated with a signet-ring cell carcinoma.

Acute purulent exacerbation of chronic obstructive pulmonary disease and Chlamydia pneumoniae infection.

In order to investigate the role of bacteria, including Mycoplasma pneumoniae and especially Chlamydia pneumoniae in acute purulent exacerbations of chronic obstructive pulmonary disease (COPD), we examined sputum specimens and acute and convalescent sera taken 26 d apart from 49 outpatients experiencing an acute purulent exacerbation of COPD. The sera were tested for antibodies to C. pneumoniae with the microimmunofluorescence test, and for antibodies to M. pneumoniae with the indirect fluorescence antibody test. Routine microbiologic culture of sputum yielded potentially pathogenic microorganisms in 12 of the 49 patients (24%). Three patients (6%) showed serologic evidence of recent M. pneumoniae infection. Seven patients showed high IgG titers of >/= 1:1,024 to C. pneumoniae, and an additional four had a fourfold increase in IgG titer, suggesting reinfection with C. pneumoniae. Sputum from two of these 11 patients also grew Streptococcus pneumoniae, and one grew Moraxella catarrhalis. Patients with and without serologic evidence of current C. pneumoniae infection showed no significant differences in clinical features or pulmonary function. The high incidence of infection with C. pneumoniae (the sole causal agent in 16% of cases, and the causal agent with other agents in 6%) provides insight into the importance of this organism among agents leading to exacerbations of COPD in Turkey.

Pulmonary Langerhans' cell histiocytosis: radiologic resolution following smoking cessation.

We describe two patients with histologically proven pulmonary Langerhans' cell histiocytosis in whom radiologic improvement occurred following smoking cessation. The patients had 23- and 25-pack-year smoking histories, respectively. High-resolution CT revealed multiple small nodules, located predominantly in the upper and middle lung fields. There was a close temporal relationship between smoking cessation and radiologic improvement.