tbuckley/cabot-search huggingface dataset:
Self-targeting blocks malaria parasite invasion
Authors: Kirk W. Deitsch
Journal: The Journal of Experimental Medicine (2015)

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Insight from Kirk Deitsch



The development of drug resistance is a major problem in combating malaria caused by Plasmodium falciparum , the most deadly human malaria parasite. Resistance to artemisinin, the key component of current treatment regimens, is now being reported in
Interferon-Mediated Oncolysis In Spontaneous Murine Leukemia&lt;xref ref-type="fn" rid="FN1"&gt;1&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Robert L. Kassel, Robert R. Pascal, Adrienne Vas
Journal: JNCI Journal of the National Cancer Institute (1972)

Time and dose studies in AKR mice with leukemia confirmed, on a cellular level, our previous observations on interferon-mediated oncolysis. Tumor-selective cytolytic action was demonstrable by electron microscopy within one-half hour aFter the administration of interferon. Direct in vitro cytotoxicity, by exposure of leukemic lymphocytes to interferon, was not observed. However, passive transFer of cytotoxicity by whole blood or serum From interFeron-treated mice indicated the indirect nature of interferon-mediated oncolysis.
Performance of transbronchial needle aspiration (TBNA) of mediastinal lymphadenopathies in the diagnosis of pulmonary neoplasms
Authors: Rafael Garcia Montesinos, Nuria Maria Reina Marfil, Ezequiel Ortega Sáenz de Tejada, Concepción Mena Escobar, Lidia López López, María Victoria Hidalgo Sanjuán
Journal: European Respiratory Journal (2012)

Objectives:  To know the contribution of TBNA of mediastinal lymphadenopathies in the diagnosis of extension and anatomopathologic diagnosis of lung neoplasms.  Methods:  During 63 months (october 2006-december 2011) we made 184 fiberbronchoscopies (FB) with TBNA to patients with mediastinal lymphadenopathies suspected of neoplastic origin. We performed a “blind” TBNA of the lymphadenopathies larger than 1cm, using a 19 or 21ga neddle, in the presence of the anatomopathologist. We took samples from the ganglionar stations 4R, 7, 10R, 11R and 11L. We take samples until we got a positive result or we did 3-4 perforations, depending on tolerance of the patient. We considered as positive samples which allowed to make a therapeutic decision and negative samples those reported as “carcinoma” without specifying the type, presence of “malignant” or “atypical cells”. The non hospitalized patients were observed 3 hours after the procedure.  Results: The TBNA was (+) for neoplasia in 122(66.3%) patients, giving the diagnosis of extension (N2). The average number of punctures per patient was 1.8; in 58 patients (59.7% of TBNA positives) only one puncture was required. In 41 cases (33.6%) was the only positive sample of FB, and gave the extension and pathological diagnosis. The only complications during FB were small hemorrhages. We did not detect significant clinical or radiological complications following the procedure.  Conclusions:  1.TBNA of mediastinic adenopathies was useful in the extension diagnosis in 122(66.3%) of patients and resulted in diagnosis of lung cancer in 41(33.6%) patients. 2.TBNA was well tolerated and without significant complications.
Comorbidity by smokers - A cumulative effect of exogenic and endogenic factors?
Authors: Zlatka Iankova, Rositsa Ivancheva, Filip Sterev, Vania Youroukova
Journal: European Respiratory Journal (2012)

This work is an analysis of our studies and literary data about a cumulative effect of tobaco smoke and another risk factors and comorbidity. There is investigated the conection between COPD and COPD and lung cancer (COPD + Ca):  A. Clinicaly.There are follow up 120 smokers with COPD + Ca, 181 smokers with COPD, 50 with lung cancer and 50 health smokers (control group). We proved that: The number of smoked cigarettes (p = 0.009) and air polution at work environment (exogenic factors) are more risky about COPD + Ca than early beginning of tobaco smoke (p = 0.821). Predisposition about Ca is more risky than another diseases in family (14.17 %). Smokers with COPD + Ca and COPD more often have cardiovascular and metabolic diseases than this with lung cancer and control group. Predisposition in family about cardiovascular and metabolic diseases exeed the interval – 2 – 4 %, established with the control group and the group with lung cancer.  B. Experimental. There is investigated lung and bone marrow in rats, treated with tobaco smoke for 30 days. We found a centroacinar emphysema with predominant destruction by massive exposition and bronchiolitis. The micronuclei (erythrocytes with nuclear chromatin) in bone marrow are significant higher compared with the control group (4.35 +/–0.5 / 1.58 +/– 0.33). This results showed that in conjunction with local lung changes occur systemic effects (clastogenesys as a result of cytotoxic effect).  Conclusion: The comorbidity in relationship with tobaco smoke is related with a cumulative effect of exogenic and endogenic factors. There are necessary profound analysis to prove of releated with the cumulative effect of exogenic and endogenic factors comorbidity.
Chronic Myelogenous Leukemia, Version 1.2015
Authors: Susan O’Brien, Jerald P. Radich, Camille N. Abboud, Mojtaba Akhtari, Jessica K. Altman, Ellin Berman, Peter Curtin, Daniel J. DeAngelo, Michael Deininger, Steven Devine, Amir T. Fathi, Jason Gotlib, Madan Jagasia, Patricia Kropf, Joseph O. Moore, Arnel Pallera, Vishnu VB. Reddy, Neil P. Shah, B. Douglas Smith, David S. Snyder, Meir Wetzler, Kristina Gregory, Hema Sundar
Journal: Journal of the National Comprehensive Cancer Network (2014)

Chronic myelogenous leukemia (CML) is usually diagnosed in the chronic phase. Untreated chronic phase CML will eventually progress to advanced phase (accelerated or blast phase) CML. Tyrosine kinase inhibitors (TKIs) have been shown to induce favorable response rates in patients with accelerated and blast phase CML. The addition of TKIs to chemotherapy has also been associated with improved outcomes in patients with blast phase CML. Allogeneic hematopoietic stem cell transplant remains a potentially curative option for patients with advanced phase CML, although treatment with a course of TKIs will be beneficial as a bridge to transplant. This manuscript discusses the recommendations outlined in the NCCN Guidelines for the diagnosis and management of patients with advanced phase CML.
The Renin-Angiotensin and Renal Dopaminergic Systems Interact in Normotensive Humans
Authors: Aruna R. Natarajan, Gilbert M. Eisner, Ines Armando, Shaunagh Browning, John C. Pezzullo, Lauren Rhee, Mustafa Dajani, Robert M. Carey, Pedro A. Jose
Journal: Journal of the American Society of Nephrology (2015)

The renin-angiotensin-aldosterone (RAAS) and renal dopaminergic systems interact to maintain sodium balance. High NaCl intake increases renal synthesis of dopamine and dopaminergic receptor activity, decreasing epithelial sodium transport, whereas sodium deficit activates the RAAS, increasing epithelial sodium transport. We tested the hypothesis that attenuation of the natriuretic effect of dopamine D1-like receptors during salt restriction results in part from increased RAAS activity in seven salt-resistant normotensive adults using a double-blind placebo-controlled balanced crossover design. All subjects attained sodium balance on low (50 mmol Na+/day) and high (300 mmol Na+/day) NaCl diets, administered 4 weeks apart. Sodium, potassium, lithium, para-aminohippurate, and creatinine clearances were measured before, during, and after a 3-hour infusion of fenoldopam, a D1-like receptor agonist, with and without pretreatment with enalapril, an angiotensin converting enzyme inhibitor. On the high NaCl diet, fenoldopam-induced natriuresis was associated with the inhibition of renal proximal and distal tubule sodium transport. On the low NaCl diet, fenoldopam decreased renal distal tubule sodium transport but did not cause natriuresis. The addition of enalapril to fenoldopam restored the natriuretic effect of fenoldopam and its inhibitory effect on proximal tubule sodium transport. Thus, on a high NaCl diet fenoldopam causes natriuresis by inhibiting renal proximal and distal tubule transport, but on a low NaCl diet the increased RAAS activity prevents the D1-like receptor from inhibiting renal proximal tubule sodium transport, neutralizing the natriuretic effect of fenoldopam. These results demonstrate an interaction between the renin-angiotensin and renal dopaminergic systems in humans and highlight the influence of dietary NaCl on these interactions.
Cancer-Related Fatigue
Authors: Ann M. Berger, Amy Pickar Abernethy, Ashley Atkinson, Andrea M. Barsevick, William S. Breitbart, David Cella, Bernadine Cimprich, Charles Cleeland, Mario A. Eisenberger, Carmen P. Escalante, Paul B. Jacobsen, Phyllis Kaldor, Jennifer A. Ligibel, Barbara A. Murphy, Tracey O'Connor, William F. Pirl, Eve Rodler, Hope S. Rugo, Jay Thomas, Lynne I. Wagner
Journal: Journal of the National Comprehensive Cancer Network (2010)

NCCN Categories of Evidence and ConsensusCategory 1: The recommendation is based on high-level evidence (e.g., randomized controlled trials) and there is uniform NCCN consensus.Category 2A: The recommendation is based on lowerlevel evidence and there is uniform NCCN consensus.Category 2B: The recommendation is based on lowerlevel evidence and there is nonuniform NCCN consensus (but no major disagreement).Category 3: The recommendation is based on any level of evidence but reflects major disagreement.All recommendations are category 2A unless otherwise noted.Clinical trials: NCCN believes that the best management for any cancer patient is in a clinical trial.Participation in clinical trials is especially encouraged.
Screening for malnutrition in outpatients with pulmonary diseases
Authors: Siebrig Schokker, J. Sebastiaan Vroegop, Luc H. Steenhuis, René Aalbers
Journal: European Respiratory Journal (2011)

Background: Malnutrion has negative effects on patient outcome, in particular in patients with COPD. Recognition of malnutrition in an early phase might be beneficial for patients and screening for malnutrition in an outpatient setting might, therefore, be worthwhile.

Aim: To determine the extent of malnutrition in outpatients with pulmonary diseases using different methods.

Methods: All patients visiting our outpatient department of pulmonary diseases for the first time (period Oct. 2010 - Febr. 2011) were screened for malnutrition. Different methods were used to screen for malnutrition: body mass index (bmi), Short Nutritional Assessment Questionnaire (SNAQ), and a fat free mass measurement (FFM; bio-impedance by Bodystat® 1500).

Results: Data of 121 outpatients (mean age 59, 49% male, 29% COPD) were analysed. Obesity (bmi > 30) was found in 26% of patients and underweight (bmi  65 yrs) was found in 7 patients. The SNAQ score detected 9 and 3 patients being severely or moderately malnourished. FFM revealed 17 patients (14%) with malnutrition. Combining SNAQ and bmi resulted in detection of 17 malnourished patients. However, different patients are detected (Table 1).

View this table:

Table 1. Malnutrition: FFM vs. SNAQ + bmi





A low FFM was found more often in patients with COPD (23%) and in females (21%).

Conclusion: This study revealed malnutrition in 6 to 14% of outpatients with pulmonary diseases. Measurement of bmi only seems to underestimate nutritional problems. The discrepancies in detecting different patients emphasise the need for determining a gold standard for defining and measuring malnutrition.
In vitro evaluation of silver-coated silicone tracheobronchial stents on growth and attachment of clinical isolates
Authors: M. Diez-Ferrer, S. Marti, L. Calatayud, J. Gilabert, C. Ardanuy, S. Borros, R. López-Lisbona, N. Cubero, J. Linares, J. Dorca, A. Rosell
Journal: European Respiratory Journal (2014)

OBJECTIVES Silicone stents are used for treating obstructions of the central airways. Bacterial colonization can result in halitosis, respiratory infections and sepsis. The main objectives were to determine the microorganisms involved in stent colonization and to evaluate silver-coating as a mechanism to reduce bacterial growth and adhesion.  METHODOLOGY Clinical isolates were obtained from bronchial washing (BW) in 32 patients after 1 month of stenting. Silver was deposited on PDMS (polydimethylsiloxane) using plasma treatment. Silicone and silver-coated silicone slides were covered with 10 6  cfu/ml bacterial cultures and incubated 24h at 37°C. Viability of adhered bacteria was assessed by confocal examination of Live/Dead staining on  Pseudomonas aeruginosa  (PA01 strain & clinical isolates) and  Staphylococcus aureus  clinical isolates.  RESULTS The main microorganisms isolated from BW were  P. aeruginosa  (22%),  S. viridans  (22%) and  S. aureus  (15%) .  After 24h of static growth, bacteria adhered to silver-coated slides were dead in contrast to bacteria on uncoated silicone slides. Clinical isolates were more resistant to silver than the  P. aeruginosa  PA01 strain used for these experiments, with the need of concentrations 0.8-0.9 µg/mm 2  for the clinical  P. aeruginosa  isolates, g1 µg/mm 2  for  S. aureus  and 0.4 µg/mm 2  for PA01.  CONCLUSIONS  S. aureus  and  P. aeruginosa  were the main pathogens associated to tracheobronchial silicone stent colonization. Clinical pathogens were more resistant to silver-mediated killing than PA01, with a silver concentration above 1 µg/mm 2  needed to kill clinical pathogens adhered to the silver-coated silicone slides.
Phase I Study of Nivolumab in Combination with Ipilimumab in Metastatic Renal Cell Carcinoma (Mrcc)
Authors: H. Hammers, E.R. Plimack, J.R. Infante, M. Ernstoff, B.I. Rini, D.F. McDermott, A. Razak, S.K. Pal, M. Voss, P. Sharma, C.K. Kollmannsberger, D. Heng, Y. Shen, J. Kurland, J. Spratlin, P. Gagnier, A. Amin
Journal: Annals of Oncology (2014)
A randomised comparison of two tobramycin formulations in cystic fibrosis (CF) patients with chronic pseudomonas aeruginosa (PA) infection for pharmacokinetic and therapeutic equivalence
Authors: Dorota Sands, Ewa Sapiejka, Henryk Mazurek, Grzegorz Gaszczyk
Journal: European Respiratory Journal (2013)

Objective:  Inhalable tobramycin is an accepted therapy to treat chronic PA infection in CF. Efficacious twice daily inhalation is time-consuming for the affected patients. The aim was to evaluate the comparability of TIS I (VANTOBRA) with TIS II (TOBI) regarding drug pharmacokinetics, clinical parameters, inhalation times and safety profile.   Methods:  The drug/device combinations were compared in a randomised, two-period, multi-centre, cross-over 14-week study. 58 patients ≥ 4 years with chronic PA infection were enrolled. Assessments included plasma/sputum AUC and C max , reduction of CFU, FEV 1  % pred, inhalation time and adverse reactions.   Results:  Plasma mean AUC was 4.2 (TIS I) and 4.9 µg*h/ml (TIS II). Plasma mean C max  for both drugs was 1.3 µg/ml. Sputum mean C max  was 1.95 (TIS I) and 1.42 mg/g (TIS II). A log 10  CFU reduction of -1.77 vs. -1.70 was achieved with TIS I and TIS II in treatment phase I and -1.30 vs. 0.12 in treatment phase II. FEV 1  % pred increased by 8.2% (TIS I) and by 4.8% (TIS II), in treatment phase II by 2.40% vs. -0.44%. Mean time per inhalation was 4.4 min (TIS I) and 24.3 min (TIS II). No fatalities occurred. All 4 SAEs were not drug-related. Expected side effects (bronchospasms, tinnitus) were observed in each two TIS I and TIS II patients.   Conclusion:  Lower plasma AUC and higher sputum C max  values of TIS I allowed a better control of PA infection and improved lung function without jeopardizing patient safety. The efficacy/safety profile and reduced inhalation time of TIS I may provide a significant therapeutic benefit for CF patients.
T-cadherin loss induces an invasive phenotype in human keratinocytes and squamous cell carcinoma (SCC) cells<i>in vitro</i>and is associated with malignant transformation of cutaneous SCC<i>in vivo</i>
Authors: D. Pfaff, M. Philippova, S.A. Buechner, K. Maslova, T. Mathys, P. Erne, T.J. Resink
Journal: British Journal of Dermatology (2010)

Journal Article T‐cadherin loss induces an invasive phenotype in human keratinocytes and squamous cell carcinoma (SCC) cells in vitro and is associated with malignant transformation of cutaneous SCC in vivo Get access D. Pfaff, D. Pfaff Department of Biomedicine, Laboratory for Signal Transduction, Lab. 316, Basel University Hospital, CH 4031 Basel, Switzerland Search for other works by this author on: Oxford Academic Google Scholar M. Philippova, M. Philippova Department of Biomedicine, Laboratory for Signal Transduction, Lab. 316, Basel University Hospital, CH 4031 Basel, Switzerland Search for other works by this author on: Oxford Academic Google Scholar S.A. Buechner, S.A. Buechner Blumenrain 20, CH 4051 Basel, Switzerland Search for other works by this author on: Oxford Academic Google Scholar K. Maslova, K. Maslova Department of Biomedicine, Laboratory for Signal Transduction, Lab. 316, Basel University Hospital, CH 4031 Basel, Switzerland Search for other works by this author on: Oxford Academic Google Scholar T. Mathys, T. Mathys Blumenrain 20, CH 4051 Basel, Switzerland Search for other works by this author on: Oxford Academic Google Scholar P. Erne, P. Erne Division of Cardiology, Kantonsspital Luzern, CH 6000 Lucerne, Switzerland Search for other works by this author on: Oxford Academic Google Scholar T.J. Resink T.J. Resink Department of Biomedicine, Laboratory for Signal Transduction, Lab. 316, Basel University Hospital, CH 4031 Basel, Switzerland Therese J. Resink. E‐mail: Therese‐J.Resink@unibas.ch Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 163, Issue 2, 1 August 2010, Pages 353–363, https://doi.org/10.1111/j.1365-2133.2010.09801.x Published: 01 August 2010
Long-term bosentan therapy improves exercise capacity and hemodynamics in sarcoidosis-associated pulmonary hypertension
Authors: Debbie Qua, Veronica Palmero, Roxana Sulica
Journal: European Respiratory Journal (2012)

Introduction and Rationale

Therapeutic options in sarcoidosis-associated pulmonary hypertension (SPH) are limited. We evaluated the long-term efficacy of Bosentan in SPH.

Methods

Out of 60 consecutive patients with SPH retrospectively reviewed, 45 were eligible for Bosentan therapy and followed for 36 months. We recorded baseline characteristics, hemodynamics and 6-minute walk distance (6MWD) before/after treament, side effects, and vital status. Statistical analysis was perfomed using Student t-test and 1-way ANOVA.

Results

There were 66% Blacks, 64% women, with mean age of 53 years. Most patients (62%) had pulmonary fibrosis, and mean diffusing capacity was 37%. Additional SPH therapy was required in 45% cases; bosentan was discontinued in 5 patients due to liver abnormalities (incidence 11%). One- and 3-year survival rates were 73% and 48%. In 29 patients that remained on bosentan at three years, there were signficant improvements in the 6MWD (p=0.005) and hemodynamics.

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View this table:

Table 1





Conclusions

A subset of SPH patients may benefit from bosentan therapy.

 [1]: pending:yes
BCG vaccination in childhood is not related to pulmonary immunity against M. tuberculosis in adults
Authors: Christian Herzman, Giovanni Sotgiu, Tom Schaberg, Martin Ernst, Steffen Stenger, Christoph Lange
Journal: European Respiratory Journal (2014)

Background:  Neonatal vaccination with Mycobacterium bovis Bacille Calmette-Guerin (BCG) reduces the risk of infection with M. tuberculosis and the risk for severe forms of tuberculosis in children.   Objectives:  Evaluation of the effect of neonatal M. bovis BCG vaccination on sensitization with M. tuberculosis antigens in adults.   Methods:  Adult healthy M. tuberculosis exposed healthcare workers and household tuberculosis contacts and cured tuberculosis patients were recruited. Interferon-g release assays (IGRAs) were performed on blood and mononuclear cells from bronchoalveolar-lavage (BALMC). BALMC were co-cultured with M. tuberculosis in growth inhibition assays.   Results:  512 individuals with known M. bovis BCG vaccination status were recruited. Of 505 HIV-uninfected, 322 (64%) were vaccinated, while 183 (36%) were not. In 170 of 483 contacts with known blood IGRA status, the IGRA result was positive. Of the 88 subjects from which a BALMC IGRA was performed, 26 had a positive result. M. tuberculosis-specific IGRA responses were not associated with M. bovis BCG vaccination status (ORs were 1.09, P= 0.66, and 0.81, P= 0.68, for blood and BAL respectively). The frequency of PPD responsive BAL mononuclear cells was higher in vaccinated versus non-vaccinated persons with a median (IQR) of 22 (6-101) versus 8 (1-44) spot forming cells per 200.000 BALMC, respectively (P=0.0468). In BALMC based growth inhibition assays, M. tuberculosis growth rates did not differ between M. bovis BCG-vaccinated and non-vaccinated subjects.   Conclusions:  Early childhood vaccination with M. bovis BCG does not protect from infection with M. tuberculosis in adulthood as defined by IGRA testing.
Double-blind, randomized study of primary hormonal treatment of stage D2 prostate carcinoma: flutamide versus diethylstilbestrol.
Authors: A Chang, B Yeap, T Davis, R Blum, R Hahn, O Khanna, H Fisher, J Rosenthal, R Witte, R Schinella, D Trump
Journal: Journal of Clinical Oncology (1996)

Patients with stage D2 prostate carcinoma are often treated initially with hormones to decrease endogenous testosterone. Therapy with diethylstilbestrol (DES), leuprolide, or bilateral orchiectomy has been reported to be equivalent. DES is the cheapest preparation, but has the potential for serious cardiovascular or thromboembolic complications. Flutamide is a novel antiandrogen with fewer side effects.The Eastern Cooperative Oncology Group (ECOG) conducted a double-blind, randomized study to compare the efficacy of flutamide (250 mg three times daily) to DES (1 mg three times daily) as the primary hormonal therapy for patients with stage D2 prostate cancer. Patients were stratified by performance status, disease sites, and history of cardiovascular disease at randomization.Forty-eight patients received DES and 44 flutamide. Patient characteristics were evenly distributed between the two treatments. The overall response rate was similar (DES, 62%; flutamide, 50%). Grade III or worse cardiovascular or thromboembolic toxicity developed in 33.3% of patients on DES and in 17.6% on flutamide (P = .051). Other toxicities were similar between the two treatment arms. However, DES produced significantly longer time to treatment failure (26.4 v 9.7 months, P = .016) and longer survival than flutamide (43.2 v 28.5 months, P = .040).As the primary hormonal therapy for stage D2 prostate cancer, DES caused more serious cardiovascular or thromboembolic complications than flutamide. Despite this, flutamide was not as active an initial agent as DES. However, the effectiveness of flutamide in conjunction with other agents compared with DES remains undetermined, and the optimal initial hormone therapy of stage D2 prostate cancer requires further studies.