tbuckley/cabot-search huggingface dataset:
Short and long term repeatability of N2 multiple breath washout indices in children with cystic fibrosis
Authors: Kent Green, Thomas Kongstad, Frederik Buchvald, Marianne Skov, Tania Pressler, Per Gustafsson, Kim G. Nielsen
Journal: European Respiratory Journal (2013)

Rationale:   Multiple breath washout (MBW) is increasingly used as a highly sensitive endpoint in cystic fibrosis (CF) studies. However, repeatability of output variables such as Lung Clearance Index (LCI) and the clinical indices S cond  and S acin  in children with CF (Respiration 2009; 78: 339) are sparsely reported despite being essential prerequisites to implementation in studies of lung disease. We assessed within and between occasion repeatability in CF children during one year.   Methods:   N 2  MBW (Exhalyzer D, EcoMedics AG) in triplets was prospectively performed every month during one year in eight children excluding occasions with clinical pulmonary exacerbations and less than two acceptable trials. Within occasion (Wo) and between occasion (Bo) repeatability of LCI, S cond  and S acin  were expressed as SD and CV%.   Results:   Ninety-eight test occasions were performed and 90% fulfilled inclusion criteria. Mean (SD) LCI, S cond  and S acin  of all tests: 9.01 (1.73), 0.071 (0.031) and 0.090 (0.025), respectively. Estimates (SD) of Bo repeatability of LCI, S cond  and S acin  suggest that changes > 1.55, 0.027 and 0.064 units (mean + 1.96 SD), respectively, could be regarded significant.   Conclusion:   We reported estimates of short- and long-term repeatability of N2 MBW indices in children with CF. These estimates are essential prerequisites to future studies of CF lung disease using N2 MBW variables as primary outcome parameters.
Tamoxifen and bone metabolism in postmenopausal low-risk breast cancer patients: a randomized study.
Authors: B Kristensen, B Ejlertsen, P Dalgaard, L Larsen, S N Holmegaard, I Transbøl, H T Mouridsen
Journal: Journal of Clinical Oncology (1994)

This trial was undertaken to evaluate the effect of adjuvant tamoxifen on bone metabolism in postmenopausal women undergoing surgery for low-risk breast cancer.In an open trial, 25 women were randomized to receive tamoxifen 30 mg/d for 2 years, and 25 women constituted the control group. Twenty women treated with tamoxifen and 23 women in the control group provided data for the analysis. Inclusion criteria were operation for low-risk breast cancer and cessation of menstruations for more than 1 year. Exclusion criteria were presence of metastases, disorders of bone metabolism, contraindications against tamoxifen, use of drugs with influence on bone metabolism, ailments that made bone mineral measurements impossible, and age greater than 65 years. Repeated measurements of bone mineral density and content at the lumbar spine and forearms, serum alkaline phosphatase, phosphate, and ionized calcium were performed in all patients.Lumbar spine bone mineral density increased during the first year in women treated with tamoxifen and then stabilized, compared with decreased bone mineral density in the control group (P = .00074). Bone mineral content at the forearms remained almost stable in tamoxifen-treated women compared with a decrease in the control group (P = .024). Serum alkaline phosphatase, phosphate, and ionized calcium decreased in the tamoxifen group (P < .00001, P = .002, and P = .002, respectively).Tamoxifen has estrogen-like effects on bone metabolism that result in an increase and stabilization of bone mineral density in the axial skeleton and a stabilization of bone mineral content in the appendicular skeleton.
A nasogastric feeding tube placed at the pleural space via bronchial system
Authors: Ahmet Nasir, Aykut Eliçora
Journal: European Respiratory Journal (2012)

Nasogastric feeding tubes (NGFT) used for gastric decompression and feeding at the emergency services and intensive care units. Anatomic malformations, age, worsening of mental conditions due to primary disease or sedation, swallowing difficulties or depression of cough reflexes, intubation are the major risk factors. Tracheobronchial system is the most common reported disposition of NGFT. But intrapleural localization of the NGFTS are very rare. In our case we present a patient with a dispositioned NGFT via bronchial system.  CASE: 93 years old female patient with the diagnosis of ischemic cerebrovascular disease was consulted for acute dyspnea after NGFT insertion. She was unconscious, dyspneic with intercostal retracitions. Breathing sounds were diminished at the right hemithorax. Distal part of the NGFT was seen at the pleural space via tracheabronchial system in chest X-ray. Pleural effusion and pneumothorax were also determined.  NGFT was removed immediately and chest tube thoracostomy was applied. Medical therapy was rearranged due to the patients clinical situation.  NGFT must be applied with care also chest X-ray controls may be helpful for prevention morbidity and mortality of malposition.
Phase I trial of thiotepa in combination with recombinant human granulocyte-macrophage colony-stimulating factor.
Authors: P J O'Dwyer, F P LaCreta, R Schilder, S Nash, C McAleer, L L Miller, G R Hudes, R F Ozols
Journal: Journal of Clinical Oncology (1992)

PURPOSE The ability of growth factors to stimulate marrow recovery suggests their potential for use in dose intensification of cytotoxic drugs. We performed a phase I study of the alkylating agent thiotepa in combination with granulocyte-macrophage colony-stimulating factor (GM-CSF), with the goal of dose-escalation of thiotepa. Thiotepa was selected based on its capacity for dose escalation to more than 1 g/m2 in the marrow transplantation setting. PATIENTS AND METHODS The starting dose of thiotepa (75 mg/m2) was the highest dose evaluated in our previous phase I trial. Thirteen patients received 22 courses of thiotepa and GM-CSF. The dose of GM-CSF was 10 micrograms/kg subcutaneously daily in six patients and 5 micrograms/kg in seven patients. RESULTS Three patients (23%) developed grade 3 to 4 neutropenia on the first course, with a recovery to more than 1000/mm3 in 4.7 days (mean). Recovery was as rapid with the 5 micrograms/kg as it was with the 10 micrograms/kg GM-CSF dose. Thrombocytopenia grade 3 to 4 affected seven of 13 (54%) patients in the first course; counts recovered to more than 50,000/mm3 in a median of 15 days. GM-CSF at either dose did not influence markedly the severity or duration of thrombocytopenia, and did not permit dose escalation of thiotepa. Among the seven patients who received a second cycle of treatment, six of seven experienced grade 3 or 4 thrombocytopenia that lasted a median of 15.5 days. Five had thrombocytopenia that lasted more than 35 days after one to three cycles of treatment. Plasma concentrations of thiotepa and tepa were measured by gas chromatography in eight patients. The plasma elimination of thiotepa fit a two-compartment open model with a harmonic mean terminal half-life of 2.44 hours. The mean total body clearance was 217.9 mL/min/m2, and the mean steady-state volume of distribution (Vdss) was 36.8 L/m2. The half-life of tepa was 7.98 hours, and the ratio of the area under the plasma concentration versus time curve (AUC) of tepa to that of thiotepa was 0.79. CONCLUSIONS These data were consistent with our previous observations at this dose, and indicated that the severity of toxicity in these patients was not explained by aberrant pharmacokinetic indices. We conclude that, independent of effects on neutropenia, severe and cumulative platelet toxicity precludes further escalation of thiotepa dose despite the use of GM-CSF.
Reduced expression of TLR3, TLR10 and TREM1 by human macrophages in Chronic cavitary pulmonary aspergillosis, and novel associations of VEGFA, DENND1B and PLAT
Authors: N.L.D. Smith, J. Hankinson, A. Simpson, D.W. Denning, P. Bowyer
Journal: Clinical Microbiology and Infection (2014)
Nintedanib prevents IL-1β-stimulated proliferation of primary human lung fibroblasts from patients with idiopathic pulmonary fibrosis or from control donors
Authors: Franziska Herrmann, Lutz Wollin
Journal: European Respiratory Journal (2014)

Idiopathic pulmonary fibrosis (IPF) is a progressive, severely debilitating disease with a high mortality rate. Nintedanib (BIBF 1120) is a receptor tyrosine kinase inhibitor specific for platelet-derived growth factor receptor, fibroblast growth factor receptor and vascular endothelial growth factor receptor. Its effect on IPF disease progression measured by lung function decline has been investigated in two replicate Phase III clinical trials (INPULSIS-1 and -2) in patients with IPF. Interleukin-1 beta (IL-1β) is a potent pro-fibrotic mediator stimulating fibroblast proliferation a hallmark of IPF.  Aim: To determine the effect of nintedanib on proliferation rate of IL-1β-stimulated primary human lung fibroblasts.  Methods: Primary human lung fibroblasts from patients with IPF (IPF-HPF) and from non-fibrotic control donors (HPF) were incubated with nintedanib (1 nM – 1000 nM) for 30 min. Subsequently the cells were stimulated with IL-1β and cell proliferation was assessed by BrdU assay after 72 h.  Results: IL-1β induced a 4.4-fold and 3.2-fold increase in the proliferation rate of normal human lung fibroblasts and IPF fibroblasts, respectively. Nintedanib prevented the IL-1β-induced increase of fibroblast proliferation in a concentration dependent manner. At human relevant concentrations of 1x10 -7.5  M nintedanib inhibited proliferation of NHLF by 48 % and IPF-HLF by 51 %.  Conclusion: Our data demonstrate that nintedanib inhibits the pro-proliferative fibrotic effect of IL-1β. This may contribute to the clinically documented anti-fibrotic activity of nintedanib in patients with IPF.
Properties of a Chicken Lymphoblastoid Cell Line From Marek's Disease Tumor
Authors: K Nazerian, R L Witter
Journal: JNCI Journal of the National Cancer Institute (1975)

Properties of a chicken lymphoblastoid cell line (MSB-1) from a Marek's disease tumor were studied. The cell line grew well at 41° C in medium RPMI-1640 supplemented with 10% bovine fetal serum and had a doubling time of 8–12 hours. Cells grown in stationary suspension culture did not attach to the vessel and had the morphology of typical Iymphoblasts. At 37° C, the cell line grew initially but ceased to divide after several subcultures. In subcultures maintained for 48–72 hours 1–2% of the cells produced Marek's disease virus (MDV)-specific intracellular and membrane antigens and contained herpesvirus particles when examined by the electron microscope. Cocultivation of these cells with duck or chicken embryo fibroblast cultures resulted in transfer of infection and production of microplaques typical of MDV. Peripheral nerve lesions and lymphoid tumors characteristic of Marek's disease were caused by inoculation of susceptible chicks with MSB-1 cells or duck cells infected with strain BC-1 of MDV recovered from the MSB-1 cell line. No specific tumors were produced at the site of inoculation and infection was readily transmitted to cagemates. Tumors were also produced in the skeletal muscles and seemed to be largely virus induced. MSB-1 cell line was free of C-type virus particles.
GIST-RISK study: Risk of recurrence in primary resectable GIST
Authors: A. Lopez-Pousa, V. Artigas Raventos, J. Lucena de la Poza, Á. Díaz de Liaño Arguelles, J. Fernández Hernández, J. Bernal Jaulín, P. Talavera Eguizabal, R. Martí Obiol, S. Delgado Rivilla, E. Martínez Molina
Journal: Journal of Clinical Oncology (2009)

e21514 Background: Several risk classification scales have been proposed to estimate the risk of recurrence after surgery for primary GIST, identifying different factors: location, tumor biology, the patients (pts), and type of surgery. Methods: Between June 2007 and December 2008 we performed a retrospective study on primary GIST pts, to analyze potential prognostic factors for recurrence, according to the risk classifications proposed by Fletcher and Miettinen, and the impact of clinical and treatment variables. Results: As of October 2008 a total of 79 pts were enrolled. Pts characteristics: male 59.5%; median age 69 years (27–90). Symptoms: abdominal pain 33%; hematemesis 32%; abdominal mass 11%; anemia 10%; non-symptoms 20.3%. Two pts received preoperative imatinib. Laparotomy was performed in 69.7%, laparoscopic resection in 27.8% and both in 2.5% of pts (2 pts intraoperative tumor rupture). A R0 resection was performed in 74 pts (93.7%), R1 in 3 pts (3.8%) and R2 resection in 2 (2.5%) pts. Tumor location: 54 gastric, 25 non gastric. Median size 5.4 cm (range 0.5–35). Tumor size: &lt;5cm 46%, 5–10cm 39% and &gt;10cm 15% of pts. Mitotic index (per 50 HPF): ≤5 mitosis 69%, 6–10 mitosis 15% and &gt;10 mitosis 16%. Histology: spindle-shaped 63%, epithelioid 6%, mixed cells 11%, not available 19%. Inmunohistochemistry: CD117 + 95%. Mutational analysis was obtained in 5 pts (four exon 11; one exon 18 mutation). Adjuvant imatinib was administered to 13 pts (16.5%). According to Fletcher: high-risk 31,1%, intermediate-risk 29,7%, low-risk 28,4%, very low-risk 10.8% of pts. According to Miettinen: high-risk 19.4%, moderate-risk 9.7%, low-risk 27.9%, very low-risk 20.8%, none risk 11.1%, insufficient data 11.1% of pts. Conclusions: Preliminary results shows a different risk of recurrence according to NIH consensus or Miettinen scales, with more than 60% versus 30% of pts with intermediate-high risk of recurrence. This study is still ongoing, additional data and follow-up will be provided. No significant financial relationships to disclose.
Ambrisentan and Tadalafil Up-front Combination Therapy in Scleroderma-associated Pulmonary Arterial Hypertension
Authors: Paul M. Hassoun, Roham T. Zamanian, Rachel Damico, Noah Lechtzin, Rubina Khair, Todd M. Kolb, Ryan J. Tedford, Olivia L. Hulme, Traci Housten, Chiara Pisanello, Takahiro Sato, Erica H. Pullins, Celia P. Corona-Villalobos, Stefan L. Zimmerman, Mohamed A. Gashouta, Omar A. Minai, Fernando Torres, Reda E. Girgis, Kelly Chin, Stephen C. Mathai
Journal: American Journal of Respiratory and Critical Care Medicine (2015)

Scleroderma-associated pulmonary arterial hypertension (SSc-PAH) is a rare disease characterized by a very dismal response to therapy and poor survival. We assessed the effects of up-front combination PAH therapy in patients with SSc-PAH.In this prospective, multicenter, open-label trial, 24 treatment-naive patients with SSc-PAH received ambrisentan 10 mg and tadalafil 40 mg daily for 36 weeks. Functional, hemodynamic, and imaging (cardiac magnetic resonance imaging and echocardiography) assessments at baseline and 36 weeks included changes in right ventricular (RV) mass and pulmonary vascular resistance as co-primary endpoints and stroke volume/pulmonary pulse pressure ratio, tricuspid annular plane systolic excursion, 6-minute walk distance, and N-terminal pro-brain natriuretic peptide as secondary endpoints.At 36 weeks, we found that treatment had resulted in significant reductions in median (interquartile range [IQR]) RV mass (28.0 g [IQR, 20.6-32.9] vs. 32.5 g [IQR, 23.2-41.4]; P < 0.05) and median pulmonary vascular resistance (3.1 Wood units [IQR, 2.0-5.7] vs. 6.9 Wood units [IQR, 4.0-12.9]; P < 0.0001) and in improvements in median stroke volume/pulmonary pulse pressure ratio (2.6 ml/mm Hg [IQR, 1.8-3.5] vs. 1.4 ml/mm Hg [IQR 8.9-2.4]; P < 0.0001) and mean ( ± SD) tricuspid annular plane systolic excursion (2.2 ± 0.12 cm vs. 1.65 ± 0.11 cm; P < 0.0001), 6-minute walk distance (395 ± 99 m vs. 343 ± 131 m; P = 0.001), and serum N-terminal pro-brain natriuretic peptide (647 ± 1,127 pg/ml vs. 1,578 ± 2,647 pg/ml; P < 0.05).Up-front combination therapy with ambrisentan and tadalafil significantly improved hemodynamics, RV structure and function, and functional status in treatment-naive patients with SSc-PAH and may represent a very effective therapy for this patient population. In addition, we identified novel hemodynamic and imaging biomarkers that could have potential value in future clinical trials. Clinical trial registered with www.clinicaltrials.gov (NCT01042158).
Phase II trial of docetaxel/irinotecan therapy in metastatic esophageal cancer: evidence for activity in previously untreated patients
Authors: B. Burtness, M. K. Gibson, J. Lacy, E. Rowen, L. Thomas, R. E. Sipples, M. L. McGurk, J. Murren, A. Forastiere
Journal: Journal of Clinical Oncology (2005)

4070 Background: Docetaxel/irinotecan combination demonstrates synergy in preclinical models and has activity in a range of solid tumors. Irinotecan and taxanes have recognized activity in esophageal cancer. We wished to determine the activity of weekly docetaxel/irinotecan combination in advanced esophageal cancer. Methods: Patients (pts) were eligible who had metastatic squamous cell or adenocarcinoma of the esophagus, had measurable disease, and had not received prior chemotherapy for metastatic disease. Performance status (PS) 0 or 1 and adequate end organ function were required, including normal bilirubin, transaminases less than 1.5 x upper limit of normal (ULN) and alkaline phosphatase less than 2.5 x ULN. Pts received oral dexamethasone premedication, docetaxel 35 mg/m2 over 30 minutes and irinotecan 50 mg/m2 on days 1 and 8 of a 21 day cycle. Tumor assessments were performed by CT after 9 weeks of therapy. Results: 29 previously untreated pts have enrolled and accrual to this cohort has been completed. 27 (93%) were male, median age was 60 (range 32 - 74), 23 (79%) had PS 1 and 23 (79%) had adenocarcinoma. 1 pt had prior esophagectomy. All other pts in this cohort had distant metastatic disease at presentation. 13/28 (46%) had 1 or 2 dose reductions. 7/29 (24%) had grade (gd) 3/4 neutropenia. 2/29 (7%) had gd 3 anemia. 9/29 (31%) had gd 3/4 diarrhea. 24 pts are evaluable for response (pts inevaluable due to docetaxel hypersensitity, withdrew from study, too early). 7/24 (29%) attained a partial response (PR), 1/24 attained a CR (4%), and 9/29 (31%) had stable disease. Responses were seen for each histology. The median time on treatment for this cohort was 3 m (range 0 - 9). The median number of cycles delivered was 5 (range <1 - 9). Median survival is 6.7 months (range 0.4–21+). 8 pts are alive at 1.4–21 m. A second cohort has accrued 15 previously treated patients. Accrual to this cohort is ongoing. Conclusions: Weekly docetaxel/irinotecan combination is active in pts with adenocarcinoma or squamous cell carcinoma of the esophagus. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Aventis Aventis, Pfizer, Sanofi
Predictors of success for pulmonary rehabilitation in patients awaiting lung transplantation
Authors: Rainer Gloeckl, Klaus Kenn, Andreas Soennichsen, Bernd Sczepanski, Sandra Winterkamp, Martina Boensch, Tobias Welte
Journal: European Respiratory Journal (2014)

Background  Aim of this study was to investigate whether pulmonary rehabilitation (PR) is also effective in the management of patients awaiting lung transplantation (LTx) and whether there are any predictors of success.  Methods  In an observational clinical pre-post-trial we investigated the effects of an inpatient PR (mean: 34 ±15 days) in 811 LTx candidates. We compared baseline and follow up data of patients with COPD, Alpha-1-Antitrypsin deficiency (AATD), interstitial lung disease (ILD) or cystic fibrosis (CF) with regard to exercise capacity (6MWD) and health related quality of life (HRQL; SF36). Multivariate stepwise regression analysis was performed to detect predictors of PR outcome.  Results  811 data sets from consecutive patients who were referred to our rehabilitation center prior to LTx could be analyzed (COPD: 360; AATD: 127; ILD: 195; CF: 69; other: 60). Overall, 6MWD increased by 56±58m (p  Conclusions  We could show that specialized PR in patients with end-stage lung disease awaiting LTx may lead to significant and clinically relevant improvements in exercise capacity and HRQL regardless of the underlying disease or any of the above mentioned parameters. Further studies should evaluate the relevance of such PR effects on the clinical course of patients with end stage lung disease and their outcome after LTx.
Understanding the Utility of Adjuvant Systemic Therapy for Primary Breast Cancer
Authors: Charles L. Loprinzi, Stephan D. Thomé
Journal: Journal of Clinical Oncology (2001)

PURPOSE: Physicians and patients require quantitative information on the expected benefits of adjuvant therapy for primary breast cancer to make appropriate treatment decisions. To date, there has not been any widely available method for estimating the benefits from adjuvant systemic therapy, in terms of long-term disease-free survival probabilities, in patients with primary breast cancer. METHODS: Baseline prognostic information for primary breast cancer patients was estimated by asking 11 breast cancer specialists to complete a questionnaire on baseline prognosis and then using mean values. Data on the relative benefits of adjuvant therapy were culled from systematic reviews and randomized controlled trials. A computer algorithm was developed to calculate 10-year absolute outcome data. Results from this evaluation were compared with a previously described actuarial algorithm. RESULTS: Individual prognostic estimates varied within a group of breast cancer specialists, but mean values of their estimates closely followed published data. Translation of expected benefits of adjuvant therapy from relative to absolute terms was performed with a simple computer algorithm. The data were translated into tabular forms to facilitate user-friendly clinical use. CONCLUSION: The provided data should facilitate a better understanding of the absolute magnitude of benefit for available systemic adjuvant therapies in individual women with primary breast cancer. This should allow patients to make more informed decisions about their options.
Robot-Assisted Vitreoretinal Surgery
Authors: Takashi Ueta, Yoshiharu Yamaguchi, Yoshihiro Shirakawa, Taiga Nakano, Ryuichi Ideta, Yasuo Noda, Akio Morita, Ryo Mochizuki, Naohiko Sugita, Mamoru Mitsuishi, Yasuhiro Tamaki
Journal: Ophthalmology (2009)