tbuckley/cabot-search huggingface dataset:
Sudden death in patients awaiting coronary artery surgery
Authors: B. S. Lewis, M. S. Gotsman
Journal: Thorax (1974)

<b>Lewis, B. S. and Gotsman, M. S. (1974).</b><i>Thorax</i>, <b>29</b>, 209-214. <b>Sudden death in patients awaiting coronary artery surgery.</b> Six patients with coronary artery disease are described who died suddenly while awaiting an operation to revascularize the myocardium. Each patient had recent onset of severe angina pectoris and this was caused by critical narrowing(s) of 90% or more of a major coronary artery(ies) supplying a large portion of the left ventricular myocardium. The syndrome can be diagnosed only by cardiac catheterization and high quality coronary arteriography. Patients in whom the myocardial blood supply is critically compromised must be recognized. These patients are liable to sudden death and require urgent myocardial revascularization.
Acquisition of echo-Doppler parameters of pulmonary hypertension in COPD
Authors: Andrew Goudie, Pippa Hopkinson, William Anderson, Brian Lipworth, Allan Struthers
Journal: European Respiratory Journal (2012)

Background 

Pulmonary hypertension in COPD is of key prognostic significance. Doppler echo in the presence of TR can estimate RVSP/sPAP. Acquisition rates and TR jet quality are reduced in COPD due to hyperinflation. TR jet quality influences pressure estimation accuracy. An alternative assessment for PH is the time to peak pulmonary flow velocity, pulmonary acceleration time(ACT). An ACT <105 ms suggests PH. We examined the availability/quality of TR jet vs. pulmonary flow waves (PFW) in COPD.

Methods 

COPD patients were invited for echo and PFTs. Availability/quality of TR jet and PFWs were assessed. RVSP was calculated from the max. TR velocity. RAP=10 mmHg. ACT was a 3 measurement avg. using pulse wave Doppler placed in the right ventricular outflow tract.

Results 

A total of 63 patients were screened, 63% male. Mean age 67.8 years(SD8.3); FEV1 1.2 L(0.5);FEV1% 47.3%(16.7);RV/TLC 55%(8.8);SaO2 95.0%(3.6). TR was detected in 43 patients(68%) where TR jet was sufficient for RVSP measurement in 28(44% of total cohort). TR jet quality was poor, fair, good and excellent in 17,10,12, and 4 subjects respectively. Mean RVSP 43 mmHg, 95% CI[39-47]. ACT was measurable in 61 patients(97%) with good or excellent quality PFWs in 58 (95%). Mean ACT 113 ms, 95% CI[108-118]; mean mPAP 25 mmHg, 95% CI[23-28]. Subcostal vs. parasternal acquisition of ACT resulted in superior availability and quality in 80% of patients.

Conclusion 

Contrasting RVSP, ACT is available in almost all COPD patients. TR jet quality is commonly poor whereas that of PFWs is frequently excellent due to the ease of subcostal acquisition. These findings suggest that in addition to RVSP, ACT should be measured routinely when assessing COPD patients for PH.
Bleomycin stimulates lung fibroblast and epithelial cell lines to release eosinophil chemotactic activity
Authors: E Sato, S Koyama, R A Robbins
Journal: European Respiratory Journal (2000)

The presence of eosinophils in the lungs of patients with pulmonary fibrosis correlates with poor prognosis or resistance to therapy. Furthermore, eosinophils localize to areas undergoing active fibrosis. It was hypothesized that a human lung fibroblast (HFL-1) and a human lung epithelial cell line (BEAS-2B) might release eosinophil chemotactic activity (ECA) in response to bleomycin, a chemotherapeutic agent associated with pulmonary fibrosis. HFL-1 and BEAS-2B cells were cultured in the presence of bleomycin and their supernatant fluids evaluated for ECA by means of a Boyden chamber method. HFL-1 and BEAS-2B cells released ECA in a dose- and time-dependent manner in response to bleomycin, and partial characterization revealed that the ECA was heterogeneous. ECA release from HFL-1 and BEAS-2B cells was significantly reduced by a leukotriene B4 (LTB4) receptor antagonist and an antibody directed against granulocyte-macrophage colony-stimulating factor. HFL-1 cells released LTB4, eotaxin, and GM-CSF constitutively, and BEAS-2B cells released LTB4, eotaxin, regulated on activation, normal T-cell expressed and presumably secreted, and GM-CSF constitutively. In both cases, the release of GM-CSF was significantly increased in response to bleomycin. These data suggest that lung fibroblasts and epithelial cells may modulate eosinophil recruitment into the lung in bleomycin-induced pulmonary fibrosis.
FOXP3 expression in cancer cells and anthracyclines efficacy in patients with primary breast cancer treated with adjuvant chemotherapy in the phase III UNICANCER-PACS 01 trial
Authors: S. Ladoire, G. Mignot, C. Dalban, A. Chevriaux, L. Arnould, C. Rébé, L. Apetoh, R. Boidot, F. Penault-Llorca, P. Fumoleau, H. Roché, M. Spielmann, C. Levy, A. Lortholary, F. Eichler, C. Mesleard, F. Bonnetain, F. Ghiringhelli
Journal: Annals of Oncology (2012)

BackgroundPredictive markers of response to chemotherapy are lacking in breast cancer patients. Forkhead Box Protein 3 (FOXP3) is an anti-oncogene whose absence in cancer cells could confer resistance to DNA damaging agent. So we made the hypothesis that FOXP3 expression predicts the response to anthracyclines in breast cancer patients and that adjuvant chemotherapy adding taxanes to anthracyclines confers an overall survival (OS) benefit over anthracyclines alone, in patients with FOXP3-negative tumors.Patients and methodsExpression of FOXP3 in cancer cells was evaluated by immunohistochemistry in tumor samples from 1097 patients who participated in the PACS01 randomized trial that evaluated in adjuvant setting the adjunction of docetaxel (Taxotere) to anthracyclines in patients with localized breast cancer. Kaplan–Meier analysis and Cox regression model were used to assess OS according to the presence or absence of FOXP3 expression in tumor cells.ResultsFour hundred and five tumors were found to express FOXP3 (37%). FOXP3 expression in breast cancer cells was associated with better OS (P = 0.003). Uni- and multivariate survival analyses according to treatment arm revealed that FOXP3 expression in breast cancer cells is independently associated with improved OS in patients treated with anthracycline-based adjuvant chemotherapy, but not in patients treated with sequential anthracycline–taxane. Moreover, in vitro experiments showed that FOXP3 induction in breast cancer cell lines using histone deacetylase inhibitor enhances anthracyclines efficacy.ConclusionFOXP3 expression in tumor cells may be an accurate predictive biomarker of anthracycline efficacy in breast cancer.
Early efficacy trial of anakinra in corticosteroid-resistant autoimmune inner ear disease
Authors: Andrea Vambutas, Martin Lesser, Virginia Mullooly, Shresh Pathak, Gerald Zahtz, Lisa Rosen, Elliot Goldofsky
Journal: Journal of Clinical Investigation (2014)

Autoimmune inner ear disease (AIED) is a rare disease that results in progressive sensorineural hearing loss. Patients with AIED initially respond to corticosteroids; however, many patients become unresponsive to this treatment over time, and there is no effective alternative therapy for these individuals.We performed a phase I/II open-label, single-arm clinical trial of the IL-1 receptor antagonist anakinra in corticosteroid-resistant AIED patients. Given that the etiology of corticosteroid resistance is likely heterogeneous, we used a Simon 2-stage design to distinguish between an unacceptable (≤10%) and an acceptable (≥30%) response rate to anakinra therapy. Subjects received 100 mg anakinra by subcutaneous injection for 84 days, followed by a 180-day observational period.Based on patient responses, the Simon 2-stage rule permitted premature termination of the trial after 10 subjects completed the 84-day drug period, as the target efficacy for the entire trial had been achieved. Of these 10 patients, 7 demonstrated audiometric improvement, as assessed by pure tone average (PTA) and word recognition score (WRS). In these 7 responders, reduced IL-1β plasma levels correlated with clinical response. Upon discontinuation of treatment, 3 subjects relapsed, which correlated with increased IL-1β plasma levels.We demonstrated that IL-1β inhibition in corticosteroid-resistant AIED patients was effective in a small cohort of patients and that IL-1β plasma levels associated with both clinical hearing response and disease relapse. These results suggest that a larger phase II randomized clinical trial of IL-1β inhibition is warranted.ClinicalTrials.gov NCT01267994.NIH, Merrill & Phoebe Goodman Otology Research Center, and Long Island Hearing & Speech Society.
Vascular Endothelial Growth Factor: A Therapeutic Target for Tumors of the Ewing's Sarcoma Family
Authors: Surita Dalal, Andrea M. Berry, Catherine J. Cullinane, D. Charles Mangham, Robert Grimer, Ian J. Lewis, Colin Johnston, Valerie Laurence, Susan A. Burchill
Journal: Clinical Cancer Research (2005)

Abstract Purpose: We have reported previously that intratumoral microvessel density (MVD) is a significant prognostic indicator of event-free survival in the Ewing's sarcoma family of tumors (ESFT). Here, the angiogenic growth factor expression profile and its relationship with MVD has been investigated in ESFT. Experimental Design and Results: Using ESFT model systems, the potential of these factors as therapeutic targets has been evaluated. A significant correlation (P = 0.02) was observed between vascular endothelial growth factor (VEGF) expression and MVD, consistent with the hypothesis that VEGF regulates the development of microvessels in ESFT. There was no correlation between MVD and any of the other growth factors studied. All six ESFT cell lines studied produced and secreted VEGF; five of six cell lines also secreted placental growth factor, one cell line (A673) at high levels. Tumor conditioned medium induced proliferation of human umbilical vein endothelial cells. Expression of VEGF receptors Flt-1 and Flk-1/KDR was heterogeneous across the cell lines. Both receptor tyrosine kinase inhibitors SU6668 (targets Flk-1/KDR, platelet-derived growth factor receptor-β, and fibroblast growth factor receptor 1) and SU5416 (targets Flk-1/KDR) as well as anti-VEGF agents rhuMAb-VEGF (bevacizumab) and VEGF Trap delayed s.c. growth of ESFT in mice compared with untreated groups: SU6668 (100 mg/kg/d), SU5416 (25 mg/kg/d), rhuMAb-VEGF (10 mg/kg twice weekly), and VEGF Trap (2.5 or 25 mg/kg twice weekly). Conclusions: These data suggest that VEGF is the single most important regulator of angiogenesis in ESFT and may be exploited for therapeutic advantage.
Pulmonary capillary haemangiomatosis coexistence with sinus venosus ASD: morphometric analysis and literature review
Authors: BS Slovis, I Chazova, JE Loyd, BO Meyrick
Journal: European Respiratory Journal (1998)

A 24 yr old white female presented with dyspnoea, orthopnoea, paroxysmal nocturnal dyspnoea, cough and fatigue. Transthoracic echocardiography revealed a sinus venosus atrial septal defect (ASD). Right heart catheterization confirmed severe pulmonary hypertension (80/37 mmHg). A chest radiograph showed enlarged pulmonary arteries with peripheral pruning. Surgical repair of the ASD and lung biopsy were performed. Two days later, she developed right heart failure and was treated with inhaled nitric oxide and then a calcium channel blocker. She failed to improve and was readmitted three months later with severe right heart failure and progressive dyspnoea. While waiting for lung transplantation, she developed haematochezia and died. Light microscopy of lung biopsy and autopsy tissue revealed the structural changes of pulmonary hypertension and focal increases in congested pulmonary capillaries consistent with the diagnosis of pulmonary capillary haemangiomatosis. Quantitative analysis demonstrated that the pathological changes were rapidly progressive.
Cardiometabolic changes after continuous positive airway pressure for obstructive sleep apnoea: a randomised sham-controlled study
Authors: Camilla M Hoyos, Roo Killick, Brendon J Yee, Craig L Phillips, Ronald R Grunstein, Peter Y Liu
Journal: Thorax (2012)

<h3>Rationale and objectives</h3> Impaired insulin sensitivity (ISx), increased visceral abdominal fat (VAF) and liver fat are all central components of the metabolic syndrome and characteristics of men with obstructive sleep apnoea (OSA). The reversibility of these observed changes with continuous positive airway pressure (CPAP) treatment in men with OSA has not been systematically studied in a randomised sham-controlled fashion. <h3>Methods</h3> 65 men without diabetes who were CPAP naïve and had moderate to severe OSA (age=49±12 years, apnoea hypopnoea index (AHI)=39.9±17.7 events/h, body mass index=31.3±5.2 kg/m<sup>2</sup>) were randomised to receive either real (n=34) or sham (n=31) CPAP for 12 weeks. At 12 weeks, all subjects received real CPAP for an additional 12 weeks. <h3>Measurements and main results</h3> Main outcomes were the change at week 12 from baseline in VAF, ISx and liver fat. Other metabolic outcomes were changes in the disposition index, total fat, and blood leptin and adiponectin concentrations. The AHI was lower on CPAP compared with sham by 33 events/h (95% CI−43.9 to −22.2, p&lt;0.0001) after 12 weeks. There were no between-group differences at 12 weeks in VAF (−13.0 cm<sup>3</sup>, −42.4 to 16.2, p=0.37), ISx (−0.13 (min<sup>−1</sup>)(μU/ml))<sup>−1</sup>, −0.40 to 0.14, p=0.33), liver fat (−0.5 cm<sup>3</sup>, −3.8 to 2.7, p=0.74) or any other cardiometabolic parameter. At 24 weeks, ISx (3.2×10<sup>4</sup> (min<sup>−1</sup>)(μU/ml))<sup>−1</sup>, 0.9×10<sup>4</sup> to 6.0×10<sup>4</sup>, p=0.009), but not VAF (−1.4 cm<sup>3</sup>, −19.2 to 16.4, p=0.87) or liver fat (−0.2 Hounsfield units, −2.4 to 2.0, p=0.83) were improved compared with baseline in the whole study group. <h3>Conclusion</h3> Reducing visceral adiposity in men with OSA cannot be achieved with CPAP alone and is likely to require weight-loss interventions. Longer-term effects of CPAP on other cardiometabolic markers such as ISx require further investigation to fully examine time dependencies. <h3>Trial Registration Number</h3> ACTRN12608000301369.
Computed Tomography Screening for Lung Cancer: Principles and Results
Authors: Claudia I. Henschke
Journal: Clinical Cancer Research (2005)

In modern healthcare, one of the most public, most important, and at the same time complicated and scientifically demanding topics is screening for a cancer. Mammographic screening for breast cancer has been, in the last few years, a particularly hotly disputed topic in scientific and public policy circles, with similar confusion and frustration widely reported and thus disseminated by the mass media. Most remarkably, this debacle has taken place against the backdrop of, and despite,a truly enormous amount of completed research designed to address the usefulness of such screening. To avoid a "mammography" debacle for lung cancer, the fundamental principles of screening need to be presented as we have come to think of them. Although it is generally accepted that low-dose computed tomography (CT) screening leads to early diagnosis of lung cancer in a high percentage of the cases, the logical consequence of the current knowledge is that annual CT screening prevents death from lung cancer. Thus, it is not whether CT screening is effective, rather the magnitude of its benefit which needs to be determined. We will illustrate our approach by discussing the Early Lung Cancer Action Project and its New York and International sequels.
Preclinical Evaluation of Novel Glutamate-Urea-Lysine Analogues That Target Prostate-Specific Membrane Antigen as Molecular Imaging Pharmaceuticals for Prostate Cancer
Authors: Shawn M. Hillier, Kevin P. Maresca, Frank J. Femia, John C. Marquis, Catherine A. Foss, Nghi Nguyen, Craig N. Zimmerman, John A. Barrett, William C. Eckelman, Martin G. Pomper, John L. Joyal, John W. Babich
Journal: Cancer Research (2009)

Prostate-specific membrane antigen (PSMA) is expressed in normal human prostate epithelium and is highly up-regulated in prostate cancer. We previously reported a series of novel small molecule inhibitors targeting PSMA. Two compounds, MIP-1072, (S)-2-(3-((S)-1-carboxy-5-(4-iodobenzylamino)pentyl)ureido)pentanedioic acid, and MIP-1095, (S)-2-(3-((S)-1carboxy-5-(3-(4-iodophenyl)ureido)pentyl)ureido)pentanedioic acid, were selected for further evaluation. MIP-1072 and MIP-1095 potently inhibited the glutamate carboxypeptidase activity of PSMA (K(i) = 4.6 +/- 1.6 nmol/L and 0.24 +/- 0.14 nmol/L, respectively) and, when radiolabeled with (123)I, exhibited high affinity for PSMA on human prostate cancer LNCaP cells (K(d) = 3.8 +/- 1.3 nmol/L and 0.81 +/- 0.39 nmol/L, respectively). The association of [(123)I]MIP-1072 and [(123)I]MIP-1095 with PSMA was specific; there was no binding to human prostate cancer PC3 cells, which lack PSMA, and binding was abolished by coincubation with a structurally unrelated NAALADase inhibitor, 2-(phosphonomethyl)pentanedioic acid (PMPA). [(123)I]MIP-1072 and [(123)I]MIP-1095 internalized into LNCaP cells at 37 degrees C. Tissue distribution studies in mice showed 17.3 +/- 6.3% (at 1 hour) and 34.3 +/- 12.7% (at 4 hours) injected dose per gram of LNCaP xenograft tissue, for [(123)I]MIP-1072 and [(123)I]MIP-1095, respectively. [(123)I]MIP-1095 exhibited greater tumor uptake but slower washout from blood and nontarget tissues compared with [(123)I]MIP-1072. Specific binding to PSMA in vivo was shown by competition with PMPA in LNCaP xenografts, and the absence of uptake in PC3 xenografts. The uptake of [(123)I]MIP-1072 and [(123)I]MIP-1095 in tumor-bearing mice was corroborated by single-photon emission computed tomography/computed tomography (SPECT/CT) imaging. PSMA-specific radiopharmaceuticals should provide a novel molecular targeting option for the detection and staging of prostate cancer.
Use of Stress Echocardiography to Predict Mortality in Patients With Diabetes and Known or Suspected Coronary Artery Disease
Authors: Thomas H. Marwick, Colin Case, Stephen Sawada, Charles Vasey, Leanne Short, Michael Lauer
Journal: Diabetes Care (2002)

OBJECTIVE—This study sought to determine whether stress echocardiography using exercise (when feasible) or dobutamine echo could be used to predict mortality in patients with diabetes. RESEARCH DESIGN AND METHODS—Stress echo was performed in 937 patients with diabetes (aged 59 ± 13 years, 529 men) for symptom evaluation (42%) and follow-up of known coronary artery disease (CAD) (58%). Stress echocardiography using exercise was performed in 333 patients able to exercise maximally, and dobutamine echo using a standard dobutamine stress was used in 604 patients. Patients were followed for ≤9 years (mean 3.9 ± 2.3) for all-cause mortality. RESULTS—Normal studies were obtained in 567 (60%) patients; 29% had resting left ventricular (LV) dysfunction, and 25% had ischemia. Abnormalities were confined to one territory in 183 (20%) patients and to multiple territories in 187 (20%) patients. Death (in 275 [29%] patients) was predicted by referral for pharmacologic stress (hazard ratio [HR] 3.94, P &amp;lt; 0.0001), ischemia (1.77, P &amp;lt; 0.0001), age (1.02, P = 0.002), and heart failure (1.54, P = 0.01). The risk of death in patients with a normal scan was 4% per year, and this was associated with age and selection for pharmacologic stress testing. In stepwise models replicating the sequence of clinical evaluation, the predictive power of independent clinical predictors (age, selection for pharmacologic stress, previous infarction, and heart failure; model χ2 = 104.8) was significantly enhanced by addition of stress echo data (model χ2 = 122.9). CONCLUSIONS—The results of stress echo are independent predictors of death in diabetic patients with known or suspected CAD. Ischemia adds risk that is incremental to clinical risks and LV dysfunction.
5-Lipoxygenase, a Marker for Early Pancreatic Intraepithelial Neoplastic Lesions
Authors: Rene Hennig, Paul Grippo, Xian-Zhong Ding, Sambasiva M. Rao, Markus W. Buchler, Helmut Friess, Mark S. Talamonti, Richard H. Bell, Thomas E. Adrian
Journal: Cancer Research (2005)

Pancreatic cancer has an abysmal prognosis because of late diagnosis. Therefore, it is important to identify risk factors if we are to be able to prevent and detect this cancer in an early, noninvasive stage. Pancreatic intraepithelial neoplasias (PanIN) are the precursor lesions which could be an ideal target for chemoprevention. This study shows up-regulation of 5-lipoxygenase (5-LOX) in all grades of human PanINs and early lesions of pancreatic cancer in two different animal models (EL-Kras mice and N-nitrosobis(2-oxopropyl)amine-treated hamsters) by immunohistochemistry. The results were consistent in all tissues examined, including seven chronic pancreatitis patients, four pancreatic cancer patients, one multiorgan donor, nine EL-Kras mice, and three N-nitrosobis(2-oxopropyl)amine-treated hamsters, all with PanINs. Overexpression of 5-LOX in NIH3T3 cells resulted in greater sensitivity of these cells to the growth inhibitory effects of the 5-LOX inhibitor Rev5901. These findings provide evidence that 5-LOX plays a key role in the development of pancreatic cancer. Furthermore, the lipoxygenase pathway may be a target for the prevention of this devastating disease.
Automatic regulation of the cuff pressure in endotracheally-intubated patients
Authors: R. Farré, M. Rotger, M. Ferrer, A. Torres, D. Navajas
Journal: European Respiratory Journal (2002)

To avoid tracheal wall damage or inadvertent falls of the endotracheal tube cuff pressure ( P cuff ) in intubated and mechanically-ventilated patients, the authors devised a simple procedure for automatic and continuous regulation of P cuff . The procedure, only requiring a simple aquarium air pump and conventional tubing, was first tested at the bench when applied to an intubated and ventilated lung model, including an artificial trachea with an externally-variable section. The clinical performance of the procedure was tested in eight intubated patients, in whom the endotracheal tube cuff was connected to the designed P cuff regulator during 24 h. The bench test showed that the procedure was able to maintain P cuff constant, regardless of the changes imposed in the tracheal section. It was also effective in maintaining P cuff during routine mechanical ventilation. Actual P cuff recorded over the 24-h period always coincided with the target value within ±2 cmH 2 O in all the patients. The procedure devised to maintain endotracheal tube cuff pressure is readily implemented, cheap, easy to operate and can be used regardless of the specific ventilator or tube used. Routine implementation of this procedure may be useful for protecting the trachea from tissue damage and for reducing the risk of ventilator-associated pneumonia.
The extent of the collateral circulation influences the postprandial increase in portal pressure in patients with cirrhosis
Authors: A. Albillos, R. Banares, M. Gonzalez, M.-V. Catalina, O. Pastor, R. Gonzalez, C. Ripoll, J. Bosch
Journal: Gut (2006)

In cirrhosis, repeated flares of portal pressure and collateral blood flow provoked by postprandial hyperaemia may contribute to variceal dilation and rupture.
Correlation between sputum cytology and lung physiology in asthma and COPD subjects in Indian population
Authors: Neha Iyer, Rahul Kodgule, Moinodin Shaikh, Sonali Harangule, Sapna Madas, Sundeep Salvi, Bill Brashier
Journal: European Respiratory Journal (2012)

Airway cellular inflammation is known to contribute to the pathophysiological consequences of asthma and COPD; however, the differences in their profile and association with lung function parameters have not been investigated in Indian population. We aimed to investigate the relationship between inflammatory cellular profile and lung functions in asthma and COPD. Methods: 25 asthma & 29 COPD patients underwent pre/post spirometry in accordance to ATS/ERS criteria & sputum induction with 3% hypertonic saline, processed with 0.1%DTT to investigate cellular inflammatory profile in their airways. Results: A significant difference was observed between COPD & asthma in total median neutrophil counts [113.6 (IQR:65.4, 161.8) x106/g vs 5.9 (IQR:0.1, 30.2) x106/g, p=