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Michael Tamm

Publications and source records attributed to Michael Tamm.

At least 37 records · Page 2Linked to original sources
PubMed2006

ERK1/2 and p38 MAP kinase control MMP-2, MT1-MMP, and TIMP action and affect cell migration: a comparison between mesothelioma and mesothelial cells.

Pleural malignant mesothelioma is a locally aggressive tumor of mesothelial cell origin. In other tumor types high expression of matrix metalloproteinase (MMP)-2, together with membrane-type1-MMP (MT1-MMP), and low levels of the tissue inhibitor of MMP (TIMP)-2 have been correlated with aggressive tumor progression and low survival rates. Therefore, we compared the expression and activation of these three factors and their regulation by two mesothelioma associated growth factors, platelet-derived growth factor (PDGF)-BB, and transforming growth factor (TGF)-beta1 in six human mesothelioma and one mesothelial cell line. Polymerase chain reaction (PCR), immunoblotting, zymography, and small inhibitory RNAs (siRNA) were used to study gene expression, protein activation, and signal transduction. To proof the relevance of our in vitro data immunohistochemistry was performed in tissue sections. PDGF-BB induced, while TGF-beta1 inhibited cell proliferation. PDGF-BB was a chemoattractant for mesothelial cells, and its effect was increased in the presence of TGF-beta1. TGF-beta1 stimulated the de novo synthesis of pro-MMP-2 in both cell types. Pro-MMP-2 synthesis involved p38 MAP kinase. In cell culture and tissue sections only mesothelial cells expressed MT1-MMP. Migration of mesothelioma cells was dependent on the presence of MT1-MMP. Migration, but not proliferation of mesothelioma cells was inhibited by oleoyl-N-hydroxylamide, TIMP-2, and siRNA for MT1-MMP. Our data suggest that in mesothelioma cells the phosphorylation of p38 MAP kinase is deregulated and is involved in pro-MMP-2 expression. Mesothelioma progression depends on an interaction with mesothelial cells that provide MT1-MMP necessary to activate pro-MMP-2 to facilitate migration through an extracellular matrix (ECM) layer.

Becaplermin↗
PubMed2006

Therapeutic bronchoscopy interventions before surgical resection of lung cancer.

BACKGROUND: Therapeutic bronchoscopy is used for endobronchial staging of lung cancer and symptomatic relief of central airway obstruction or postobstructive pneumonia. The aim of this study was to assess the utility of therapeutic bronchoscopy as a complementary tool in the combined bronchoscopic and surgical management of malignant airway lesions before curative lung surgery. METHODS: Seventy-four consecutive patients with nonsmall cell lung carcinoma undergoing a therapeutic bronchoscopy procedure followed by surgery with a curative intent were included. RESULTS: A single interventional bronchoscopic method was used in 27 patients (36%) and a combination of methods in 47 patients (64%). Median forced expiratory volume in 1 second (FEV1) before and after bronchoscopy were 1.7 L and 2.2 L, respectively, and forced vital capacity (FVC) was 2.5 L and 3.3 L, respectively. Sleeve upper lobectomy was performed in 22 patients (30%), sleeve upper bilobectomy in 16 patients (22%), lower bilobectomy in 2 patients (3%), pneumonectomy with sleeve resection in 2 patients (3%), and pneumonectomy in 28 patients (38%). The following surgeries were performed in 1 patient each: sleeve middle lobectomy, sleeve lower lobectomy, carina resection and complex reconstruction, and exploratory thoracotomy. Overall, parenchyma-sparing surgery (lobectomy or bilobectomy) could be performed in 57% patients after therapeutic bronchoscopy. There were no in-hospital deaths or deaths in the first 30 days after surgery. CONCLUSIONS: Therapeutic bronchoscopy can be used as a complementary tool in the combined bronchoscopic and surgical management of malignant airway obstruction before curative lung surgery. Therapeutic bronchoscopy might permit parenchyma-sparing surgery in patients with lung cancer.

Adenocarcinoma↗
PubMed2006

Multitarget fluorescence in situ hybridization elucidates equivocal lung cytology.

The category of equivocal respiratory cytology is a common diagnostic dilemma to both cytopathologists and clinicians. Chromosomal alterations are a hallmark of cancer but are rare or absent in benign conditions. The goal of this study was to test the ability of multitarget fluorescence in situ hybridization (FISH) for dissecting equivocal respiratory cytology into reactive and malignant categories. A consecutive series of 54 Papanicolaou-stained cytologic specimens of the lung was analyzed. The Papanicolaou-stained atypical cell groups were photographed, and the exact locations on the specimens were saved using automated stage and relocation software. The specimens were hybridized with a multitarget FISH probe that contains a mixture of fluorescent probes to the centromeric region of chromosome 6 and to the 5p15, 8q24 (site of the MYC gene) and 7p12 (site of the EGFR gene) loci. The hybridized atypical cells were selectively scored after relocation. A final diagnosis was available in 45 patients, revealing lung carcinoma in 55.5% (n = 25), no evidence of malignancy in 37.8% (n = 17), and pulmonary metastasis of another primary carcinoma in 6.7% (n = 3). FISH results were negative in all 17 patients with benign pulmonary disease and positive in 20 of the 25 patients (80%) with lung carcinoma (p < 0.0001). The sensitivity, specificity, and positive and negative predictive values for detection of malignancy were 79%, 100%, 100%, and 74%, respectively. These data suggest that multitarget FISH in conjunction with automated relocation is a powerful approach for the elucidation of equivocal lung cytology.

Adolescent↗
PubMed2006

Outcome of treated advanced non-small cell lung cancer with and without central airway obstruction.

OBJECTIVE: In patients with advanced non-small cell lung cancer (NSCLC) treated with chemotherapy, we compared survival in patients with treated central airway obstruction to those who did not have central airway obstruction. METHODS: One hundred forty-four patients with advanced and inoperable NSCLC were included. These consisted of 52 consecutive patients treated with therapeutic bronchoscopy plus chemotherapy with or without radiotherapy (group A) and 92 consecutive patients who did not have central airway obstruction treated with chemotherapy alone (group B). Chemotherapy consisted of cisplatin or carboplatin, and one third-generation chemotherapy agent. RESULTS: There was no significant difference in the survival of patients with and without central airway obstruction (p = 0.395). There was no influence of the histologic subtype on survival in both groups combined and also in each group separately. Median survival in patients belonging to group A was 8.4 months and those in group B was 8.2 months; 3-, 6-, and 12-month survival rates in patients in group A were 90%, 71%, and 40%, respectively, and those in group B were 82%, 63%, and 34%. CONCLUSION: Patients having advanced NSCLC with locally treated malignant central airway obstruction in combination with chemotherapy do not have a worse survival compared to those with advanced NSCLC without central airway obstruction. Therapeutic bronchoscopy should be offered to patients with NSCLC and central airway obstruction.

Adenocarcinoma↗
PubMed2006

Progressive pulmonary sarcoidosis--a fibroproliferative process potentially triggered by EGR-1 and IL-6.

BACKGROUND AND AIM OF THE WORK: Sarcoidosis is a chronic granulomatous disorder of unknown etiology. In most patients the disease is self-limited, although for reasons unclear, others progress or die from progressive organ fibrosis. Growth factors have been implicated in the pathogenesis of other fibrotic lung conditions. We have, therefore, examined the relationship between growth factor expression and disease phenotype in sarcoidosis. METHODS: Adopting a target gene approach utilizing gene expression arrays, growth factor gene expression profile was analyzed in the peripheral blood of 12 patients and 12 healthy controls. Expression, functional activity and the effect of oligonucleotide antisense treatment on selected proteins differentially expressed in progressive sarcoidosis were then tested in vitro on primary human lung fibroblasts. RESULTS: Genes regulating angiogenesis were preferentially upregulated in the self-limited form of disease, while early growth response-1 and interleukin-6 were predominantly activated in progressive sarcoidosis. Increased expression of early growth response-1 in sarcoid lung was confirmed by immunohistochemistry. Stimulated human fibroblasts also rapidly expressed interleukin-6 and early growth response-1 and these proteins were found to mediate serum-induced fibroblast proliferation as proliferation could be significantly abrogated with interleukin-6 and early growth response-1 antisense oligonucelotides. CONCLUSION: We conclude that progressive pulmonary sarcoidosis is characterized by a fibroproliferative dysregulation potentially triggered by early growth response-1 and interleukin-6. Our disease model underlines the inability of steroids to prevent ongoing fibroproliferation in the lung.

Case-Control Studies↗
PubMed2005

Sedative drug requirements during bronchoscopy are higher in cystic fibrosis after lung transplantation.

BACKGROUND: We noted that patients with cystic fibrosis tended to need higher doses of sedatives during bronchoscopy. We undertook this study to assess the sedative drug doses administered during bronchoscopy in lung transplant recipients and to assess if there is a change in the dosage requirements over time following lung transplantation. METHODS: In all, 773 transbronchial biopsy procedures performed via flexible bronchoscopy were analyzed in 140 consecutive lung transplant recipients. Conscious sedation was achieved with intermittent boluses of intravenous midazolam and fentanyl. Intravenous propofol boluses of 10 to 30 mg were administered when optimal sedation was not achieved with midazolam doses of 0.20 to 0.25 mg/kg and fentanyl 2 to 2.5 micrograms/kg. RESULTS: Mean doses of midazolam and fentanyl administered were 0.15+/-0.07 mg/kg (range 0.02 to 0.44 mg/kg) and 1.8+/-0.8 micrograms/kg (range 0.1 to 6.67 micrograms/kg) respectively. Midazolam and fentanyl doses administered to patients with cystic fibrosis were the highest compared to those with other disease types (P<0.0001). Examining the sedative doses administered over time following transplantation, there was a significant linear (P<0.001) and quadratic (P=0.0023) effect of time for midazolam and a significant linear (P=0.003) and a trend (P=0.08) for a quadratic effect for fentanyl. Propofol was effectively used in seven lung transplant recipients in whom adequate sedation could not be achieved with high doses of midazolam and fentanyl. CONCLUSIONS: There is an increase in sedative drug requirement with time for both midazolam and fentanyl after transplantation, which is significantly higher in patients with cystic fibrosis.

Adolescent↗
PubMed2005

Diagnostic value of lung auscultation in an emergency room setting.

BACKGROUND: In daily routine, physicians use history, physical examination and technology-based information such as laboratory tests and imaging studies to diagnose the patients' disease. We determined the diagnostic value of lung auscultation in patients admitted to the Medical emergency room with chest symptoms. METHODS: Two-hundred-and forty-three consecutive patients (137 males), mean age 59.2 years were included. Internal Medicine registrars had to make a presumptive diagnosis, 1) after having taken the history and 2) after having auscultated the lungs. Thereafter, routine diagnostic procedures were performed. The estimated diagnosis was compared with the final diagnosis based on the written report to the Family Practitioner. RESULTS: Two-hundred-eighty-seven diagnoses were made. Eighteen percent of patients suffered from left heart failure, 13% from unexplained chest pain, 10.5% from chest wall pain, and 10.5% from pneumonia. Forty-one percent of the diagnoses were already correct when based only on the patient's history. Lung auscultation improved the diagnostic yield only in 1% and worsened it in another 3%. By multiple logistic regression, normal lung auscultation (OR 0.12 [95CI% 0.053-0.29]) was the independent predictor for not having a lung or heart disease. However, elevation of B-type natiuretic peptide (BNP) (OR 1.16 per 100 pg/ml (95CI% 1.004-1.35), wheezing (OR 0.023 [0.002-0.33]) and pCO2 (OR 0.25 (0.10-0.621) were independent predictors for having a heart disease, whereas wheezing (OR 7.41 [3.26-16.83]) and CRP (OR 1.008 per 10 units [1.003-1.014]) were risk factors for having a lung disease. CONCLUSION: In contrast to history taking, abnormal lung auscultation does not appear to contribute considerably to the final diagnosis in patients presenting with chest symptoms in an emergency room setting. However, normal lung auscultation is a valuable predictor for not having a lung or heart disease, whereas wheezing is a predictor for having a lung disease and not having a heart disease.

Adolescent↗
PubMed2005

Patterns of pulmonary complications associated with sirolimus.

Sirolimus inhibits human fibroblast cell proliferation in cell cultures from transbronchial biopsies of lung transplant recipients. However, a few cases of interstitial pneumonitis and bronchiolitis obliterans organizing pneumonia have been recently described in solid organ transplant recipients, including a fatality in a heart transplant recipient. We studied the patterns of pulmonary adverse effects associated with sirolimus in 4 renal transplant recipients who developed pulmonary opacities on chest radiograph, which were proved to be noninfectious in origin. Lung biopsy was performed to obtain histological diagnosis (3 interstitial pneumonitis, 1 necrotizing vasculitis). Symptoms were dyspnea (4), cough (2), hemoptysis (1), fever (1) and eyelid edema (1). Those with interstitial pneumonitis had bilateral basal opacities on chest X-ray, and histopathology showed mild lymphoplasmocytic interstitial inflammation, scattered intraalveolar epitheloid granulomas and a focal pattern of organizing pneumonia. Serum C-reactive protein (CRP) was elevated and bronchoalveolar lavage revealed lymphocytosis (77, 79.5 and 31%). The fourth patient had an opacity localized in the upper lobe, which progressed to both the lower lobes, and histopathology showed multifocal necroses of lung tissue with lymphoplasmocytic vasculitis and scattered granulomas. In this patient, the serum CRP level was not elevated and bronchoalveolar lavage was normal. Pulmonary symptoms and opacities on chest radiograph resolved and the serum CRP level became normal after sirolimus was stopped in all patients. Sirolimus may be a cause of interstitial pneumonitis or pulmonary vasculitis, and withdrawal of sirolimus is therapeutic.

Aged↗
PubMed2005

Human bronchial epithelium controls TH2 responses by TH1-induced, nitric oxide-mediated STAT5 dephosphorylation: implications for the pathogenesis of asthma.

Increased levels of NO in exhaled air in association with increased NO synthetase (NOS)2 expression in bronchial epithelial are hallmark features of asthma. It has been suggested that NO contributes to asthma pathogenesis by selective down-regulation of TH1 responses. We demonstrate, however, that NO can reversibly limit in vitro expansion of both human TH1 and TH2 CD4+ T cells. Mechanistically, NO induces cGMP-mediated reversible STAT5 dephosphorylation and therefore interferes with the IL-2R activation cascade. Human bronchial epithelial cells (HBEC) up-regulate NOS2 after stimulation with IFN-gamma secreted by TH1 CD4+ T cells and release NO, which inhibits both TH1 and TH2 cell proliferation. This reversible T cell growth arrest depends on NO because T cell proliferation is completely restored after in vitro blocking of NOS2 on HBEC. HBEC thus drive the effector end of a TH1-controlled feedback loop, which protects airway mucosal tissues at the potential lesional site in asthma from overwhelming CD4+ TH2 (and potentially TH1) responses following allergen exposure. Variations in the efficiency of this feedback loop provides a plausible mechanism to explain why only a subset of atopics sensitized to ubiquitous aeroallergens progress to expression of clinically relevant levels of airways inflammation.

Asthma↗
PubMed2005

Can airway obstruction be estimated by lung auscultation in an emergency room setting?

OBJECTIVE: Lung auscultation is a central part of the physical examination at hospital admission. In this study, the physicians' estimation of airway obstruction by auscultation was determined and compared with the degree of airway obstruction as measured by FEV(1)/FVC values. METHODS: Two hundred and thirty-three patients consecutively admitted to the medical emergency room with chest problems were included. After taking their history, patients were auscultated by an Internal Medicine registrar. The degree of airway obstruction had to be estimated (0=no, 1=mild, 2=moderate and 3=severe obstructed) and then spirometry was performed. Airway obstruction was defined as a ratio of FEV(1)/FVC <70%. The degree of airway obstruction was defined on FEV(1)/FVC as mild (FEV(1)/FVC <70% and >50%), moderate (FEV(1)/FVC <50% >30%) and severe (FEV(1)/FVC <30%). RESULTS: One hundred and thirty-five patients (57.9%) had no sign of airway obstruction (FEV(1)/FVC >70%). Spirometry showed a mild obstruction in 51 patients (21.9%), a moderate obstruction in 27 patients (11.6%) and a severe obstruction in 20 patients (8.6%). There was a weak but significant correlation between FEV(1)/FVC and the auscultation-based estimation of airway obstruction in Internal Medicine Registrars (Spearman's rho=0.328; P<0.001). The sensitivity to detect airway obstruction by lung auscultation was 72.6% and the specificity only 46.3%. Thus, the negative predictive value was 68% and the positive predictive value 51%. In 27 patients (9.7%), airway obstruction was missed by lung auscultation. In these 27 cases, the severity of airway obstruction was mild in 20 patients, moderate in 5 patients and severe in 2 patients. In 82 patients (29.4%) with no sign of airway obstruction (FEV(1)/FVC >70%), airway obstruction was wrongly estimated as mild in 42 patients, as moderate in 34 patients and as severe in 6 patients, respectively. By performing multiple logistic regression, normal lung auscultation was a significant and independent predictor for not having an airway obstruction (OR 2.48 (1.43-4.28); P=0.001). CONCLUSION: Under emergency room conditions, physicians can quite accurately exclude airway obstruction by auscultation. Normal lung auscultation is an independent predictor for not having an airway obstruction. However, airway obstruction is often overestimated by auscultation; thus, spirometry should be performed.

Adult↗
PubMed2005

Chlamydia pneumoniae infection after lung transplantation.

BACKGROUND: Chlamydia pneumoniae is established as a common agent of acute respiratory tract infection and has been implicated in the pathogenesis of asthma and chronic obstructive pulmonary disease. Airway disease is a prominent cause of morbidity and mortality after lung transplantation. We investigated the role of C pneumoniae as a pulmonary pathogen after lung transplantation. METHODS: Eighty lung transplant recipients underwent 232 bronchoscopies with bronchoalveolar lavage with or without transbronchial lung biopsy during 1 year for surveillance of rejection and infection, or where clinically indicated. RESULTS: C pneumoniae was detected using nested polymerase chain reaction in 9 of 36 (25%) recipients studied within 30 days of lung transplantation, 3 of whom remained positive on repeat lavage and died from airway disease in the first year post-operatively. By comparison, all 27 recipients with negative lavage survived >1 year. Lavage was positive for C pneumoniae in 18 of 71 (25%) recipients studied >30 days after lung transplantation, 5 of whom had pneumonia and 8 of whom had bronchiolitis obliterans syndrome. Eleven also had acute pulmonary allograft rejection. CONCLUSIONS: Persistent infection with C pneumoniae (whether donor-derived, de novo or re-activated) appears deleterious to pulmonary allograft function and is associated with early mortality, rejection and bronchiolitis obliterans syndrome after lung transplantation. A trial of empiric antibiotic therapy for C pneumoniae may therefore be warranted in the attempt to prevent progressive inflammatory airway disease.

Adult↗
PubMed2005

Urokinase signal transduction and its role in cell migration.

Urokinase and its receptor uPAR play a role in cell migration that is being actively characterized. We previously reported that urokinase potentiates cell migration in human airway smooth muscle cells only where there is some primary migratory stimulus such as PDGF or recent exposure to growth medium. In this study, we examined the signaling of urokinase through its receptor, which lacks an intracellular domain and is presumed to act through associations with other membrane proteins. Whereas PDGF (30 min) and PDGF with urokinase increased the amount of the tyrosine dephosphorylase SHP2 in the membrane fraction, urokinase alone (30 min) decreased membrane SHP2. Analysis of the time course of urokinase stimulation showed that SHP2 was brought into association with the urokinase receptor uPAR between 2.5 and 20 min of urokinase, and later dissociated from it. Focal adhesion kinase was steadily lost from association with uPAR during urokinase stimulation, but its phosphorylation state increased and it became cleaved to smaller molecules. Association of uPAR with caveolin also decreased during urokinase stimulation. In contrast, the tyrosine kinase Src increased in the membrane fraction in response to urokinase stimulation. Disruption of raft structures by cyclodextrin treatment led to potentiation of PDGF chemotaxis, similar to urokinase action. Blocking of dephosphorylase activity with vanadate reduced basal cell migration and blocked the action of urokinase on PDGF chemotaxis. These observations support a role for urokinase in altering the phosphorylation state of focal adhesions, leading to breakdown of their structure and facilitation of cell motility.-Carlin, S. M., Resink, T. J., Tamm, M., Roth, M. Urokinase signal transduction and its role in cell migration.

Cell Line↗
PubMed2005

Multitarget FISH analysis in the diagnosis of lung cancer.

The aim of the present study was to explore the diagnostic usefulness of the multitarget fluorescence in situ hybridization (FISH) test, LAVysion (Vysis, Downers Grove, IL), for the detection of lung cancer cells in cytologic specimens. Specimens from bronchial washings, bronchial brushings, and transbronchial fine-needle aspirates (TBNAs) from 100 patients with suspected lung cancer and from a control group of 71 patients with nonneoplastic lung disorders were analyzed. FISH positivity was defined as more than 5 cells with gains of at least 2 chromosomes or gene loci. FISH significantly improved the sensitivity of bronchial brushings from 49% to 73%. The specificities of FISH and cytologic examination were 87% and 100%, respectively. In contrast, FISH provided no additional diagnostic information in TBNAs and bronchial washings. There was no increased prevalence of genetic changes in contralateral bronchial washings from patients with lung cancer compared with the control group. The quantity of previous smoking had no effect on the prevalence of chromosomal changes.

Adult↗
PubMed2005

Detection of hypoventilation during thoracoscopy: combined cutaneous carbon dioxide tension and oximetry monitoring with a new digital sensor.

BACKGROUND: Changes in Paco(2) have not been described during thoracoscopy under sedation-assisted local anesthesia. We hypothesized that hypoventilation might occur secondary to administration of sedatives and decreased ventilation in one lung. AIM: Prospectively measure cutaneous carbon dioxide tension (Pcco(2)) in addition to pulse oximetric saturation (Spo(2)) using a new combined digital sensor to examine the occurrence of hypoventilation during thoracoscopy under sedation-assisted local anesthesia. SETTING: University hospital. METHODS: Following validation studies, Pcco(2) was prospectively measured in 16 consecutive patients undergoing thoracoscopy under sedation-assisted local anesthesia using a combined digital earlobe sensor measuring Spo(2) (percentage) and Pcco(2) (millimeters of mercury). All patients received supplemental oxygen. Routine BP monitoring and Spo(2) was continued. Patients received IV hydrocodone, 5 mg, and intermittent boluses or IV midazolam and pethidine. RESULTS: Mean baseline Pcco(2) measurement was 39.1 +/- 7.2 mm Hg (+/- SD) [range, 27.5 to 50.5 mm Hg], and peak measurement during the procedure was 52.3 +/- 10.3 mm Hg (range, 37.2 to 77 mm Hg) [p < 0.001]. Median and mean changes in Pcco(2) measurement from baseline were 13.0 mm Hg and 13.2 +/- 5.3 mm Hg (range, 5.5 to 27.8 mm Hg), respectively. Mean fall in Spo(2) during the procedure was 4.6 +/- 3.2% (range, 1 to 14%). CONCLUSIONS: Thoracoscopy performed under sedation-assisted local anesthesia is associated with significant hypoventilation. Combined measurement of Spo(2) and Pcco(2) during thoracoscopy is a novel approach in the monitoring of ventilation, enhancing patient safety, and might allow to guide the administration of sedation in a better way.

Adult↗
PubMed2005

Significant progress in palliative treatment of non-small cell lung cancer in the past decade.

STUDY OBJECTIVES: Prospective randomized trials (PRTs) have suggested that third-generation agents (eg, gemcitabine, the taxanes, and vinorelbine) improve the survival time of patients with non-small cell lung cancer (NSCLC). However, < 30% of unselected NSCLC patients fulfill the eligibility criteria of such trials. We analyzed the outcomes of all consecutive and unselected patients with inoperable NSCLC in a single institution to determine whether there was an improvement in survival over time, and if so, to identify the factors that were associated with improved survival. METHODS: A total of 230 documented patients with NSCLC at the Basel University Hospital treated after 1990 were analyzed retrospectively. Break points by year of treatment were determined using sequential Cox proportional hazards regression models and the Kaplan-Meier estimator. Multivariate analysis was used to determine which factors were associated with improved survival over time. RESULTS: A marked improvement of survival was found since the introduction of the third-generation agents in 1997. The 1-year (40% vs 19%, respectively) and 2-year survival rates (23% vs 5%, respectively, p < 0.0001) of patients in whom NSCLC had been diagnosed since 1997 were significantly better than those prior to 1997. The two cohorts did not differ significantly in sex, stage, performance status, weight loss, and lactate dehydrogenase levels. The improvement since 1997 was due to better best supportive care (p < 0.025), better first-line chemotherapy (median overall survival [OS] time (9.2 vs 6.9 months, respectively; p < 0.0016), and better second-line chemotherapy (p < 0.0001). Finally, patients who received therapy with platinum plus a third-generation drug had significantly better outcomes than those who received an older therapy regimen (median OS time, 9.3 vs 6.7 months, respectively; p < 0.027). CONCLUSIONS: A significant improvement of survival in patients with NSCLC was observed in the last decade. The results of PRTs for palliative treatment of NSCLC seem to be applicable to an unselected group of patients with NSCLC, and therapeutic nihilism in the palliative setting seems not to be justified.

Adult↗
PubMed2005

Nebulized lidocaine for flexible bronchoscopy: a randomized, double-blind, placebo-controlled trial.

OBJECTIVE: Topical anesthesia for flexible bronchoscopy can be administered via transcricoid injection, nebulizer, or directly through the bronchoscope in a "spray as you go" fashion. We performed a prospective, randomized, double-blind, placebo-controlled trial to evaluate whether nebulized lidocaine provides additional benefit and reduces the total anesthetic dose required during bronchoscopy. SETTING: Tertiary care university hospital. METHODS: One hundred fifty patients (93 men; age, 20 to 89 years) undergoing diagnostic flexible bronchoscopy were randomized to receive either 4 mL of 4% lidocaine (160 mg) or 4 mL of saline solution as placebo via nebulization. Combined sedation was achieved using 5 mg of IV hydrocodone and midazolam boluses. Supplemental lidocaine doses and total midazolam required as judged by the bronchoscopist were recorded for each patient. After the procedure, both bronchoscopists and patients charted their perception of cough on a 10-cm visual analog scale (VAS). Similarly, patients recorded their discomfort related to the procedure on a 10-cm VAS. RESULTS: The most common procedures were BAL in 77 cases (51%), transbronchial biopsy in 40 cases (27%), and transbronchial needle aspiration in 34 cases (23%). Outcome parameters, including hemodynamic findings, duration of the procedure, cough scores for physicians and patients, discomfort score for patients, midazolam doses, and supplemental lidocaine doses, were similar in both groups. Mean total lidocaine dose required in the lidocaine group was 318 +/- 41 mg and was significantly higher than the total dose required in the placebo group (157 +/- 44 mg [+/- SD]) [p < 0.001]. CONCLUSION: Additional nebulized lidocaine cannot be recommended for flexible bronchoscopy performed under combined sedation.

Administration, Inhalation↗