tbuckley/cabot-search huggingface dataset:
Reliability of diffusing capacity of lung carbon monoxide (DLCO) measurements at 2, 4, and 6 minute time intervals in healthy normals
Authors: Lynnette Reid-Price, Georgette Mchaileh, Ceilito Samson, Lata Jayaram, Anne Marie Southcott
Journal: European Respiratory Journal (2014)

Background: The ATS/ERS lung function testing guidelines (Brusaco, V. et al Eur Respir J 2005; 26: 720-735) recommend a 4 minute interval between diffusion tests to allow adequate gas clearance and prevent contamination of subsequent measures.

Objective: In the absence of supportive evidence, our pilot study of healthy normal subjects aimed to investigate whether there was any significant difference in DLCO measurements when tested at time intervals shorter (2mins) and longer (6 mins) than the recommended 4 minutes.

Methods: We recruited 30 healthy normal volunteers to participate in a prospective cross sectional study. Each underwent 3 visits: Visit 1 spirometry, haemoglobin, and DLCO, as per ATS/ERS reproducibility guidelines. Visits 2 and 3, DLCO only. DLCO time intervals were randomised to 2, 4, or 6 minute intervals per visit. Visits 1, 2, 3 performed within 7 days at ± 2 hours of initial visit.

Results: Baseline characteristics were all non smokers with mean age 38.1 years (10.9), FEV1 3.56L (0.84), FVC 4.34L (1.14). There was no significant difference in DLCO measurements at 2, 4, 6 minutes (NS). The Intraclass Correlation Coefficient was 99%.

Conclusion: These results suggest that DLCO measurements at 2, 4, 6 minutes are equivalent in healthy normals. Our preliminary data raises the possibility that the time taken to measure DLCO may be able to be shortened, however further investigation is required into specific disease states.
Age as prognostic factor in premenopausal breast carcinoma
Authors: A. de la Rochefordière, F. Campana, J. Fenton, J.R. Vilcoq, A. Fourquet, B. Asselain, S.M. Scholl, P. Pouillart, J.-C. Durand, H. Magdelenat
Journal: The Lancet (1993)
Phase II study of sabarubicin (MEN 10755) in newly diagnosed patients with extensive stage small cell lung cancer (ESCLC): Final report
Authors: K. J. O’Byrne, D. Dunlop, W. E. Eberhardt, A. Gillissen, T. O. Wagner, A. Capriati, N. Dickgreber
Journal: Journal of Clinical Oncology (2008)

19043 Background: Despite being sensitive to cytotoxic chemotherapeutic agents and the recent development of effective novel targeted therapies for the management of solid tumours little progress has been made in the management of extensive stage small cell lung cancer (ESCLC). Sabarubicin is a third generation anthracycline with improved preclinical efficacy and tolerability, in particular regarding cardiotoxicity, compared to doxorubicin. The aim of this phase II study was to evaluate the efficacy and safety of sabarubicin (MEN 10755 hydrochloride) in chemotherapy naive patients with ESCLC. Methods: Based on Gehan two-stage design principles 14 patients were enrolled in stage 1, with an additional 12 patients in stage 2 of the study. Patients received 80 mg/m2 on day one of a 21 day cycle. Dose escalation to 90 mg/m2 was allowed if patients did not experience >Grade 1 toxicity on the first course. If, at 90 mg/m2, toxicities ≥Grade 2 occurred (excluding alopecia, anemia, and nausea/vomiting) the dose was reduced to 80 mg/m2. Results: Twenty-six patients were enrolled and eligible for efficacy and safety evaluation. Mean age = 63.5 years (range 37–79). Eight patients (30.8%) were ECOG performance status (PS) 0, 13 (50%), PS 1 and 5 (19.2%), PS 2. The tumor response rate (RR) was 38.5% (10/26) (95% CI 22.43 - 57.46), including one complete and nine partial responses. Ten (38.5%) had stable disease and six, (23.1%) progressive disease. The median duration of response was 4.5 months. The median time to tumour progression was 4.2 months and median overall survival, 10.5 months (95% CI 7.8 - 18.1 months). There were no toxicity related deaths. Severe, predominantly haematological, adverse grade 3 or 4 events were observed in 22 (84.6%) patients including febrile neutropenia in two and cardiotoxicity in one which resolved with treatment. Conclusions: Sabarubicin has significant single agent anti-cancer activity, and is well tolerated, in patients with ESCLC. The observed RR compares with other single agents used in ESCLC whilst the median survival observed is consistent with that seen for standard combination therapies. Further studies with sabarubicin, alone and in combination with other cytotoxic and novel targeted agents, are warranted. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Menarini Ricercue Menarini Ricercue
Anti-IgE antibodies inhibit the expression of amphiregulin in mast cells and suppress remodeling
Authors: Mari Mizuguchi, Masanori Wada, Kiyokazu Kikuchi, Keiichi Akasaka, Kenya Kohyama, Naoto Fueki, Hironori Sagara
Journal: European Respiratory Journal (2012)

Airway remodeling is a characteristic finding of severe, refractory asthma. Recent studies have demonstrated that anti-IgE antibodies have a high response rate in patients with severe asthma. However, the effects of anti-IgE antibodies on established airway remodeling remain to be established. In the present study, we compared the effects of an anti-IgE antibody with those of steroids in a mouse model of airway remodeling. A model of airway remodeling was prepared by continuously sensitizing BALB/c mice with ovalbumin. After preparing the remodeling model, the mice were divided into 4 groups: a group treated with an anti-IgE antibody(A), a group treated with steroids(B), a group that received both treatments(C), and an untreated control group(D). A group, basement membrane thickening, a marker of remodeling, was significantly inhibited, similar to the effect in the B group. In the C group, synergistic effectiveness was obtained. Smooth muscle thickening was significantly inhibited in the A group, and the effect was stronger than that in the B group. Similarly, in the A group significantly suppressed mast cell proliferation and also inhibited the expression of amphiregulin, a steroid-resistance molecule. Smooth muscle thickening positively correlated with amphiregulin expression, and this correlation was weakened by treatment with A group. In the present study, the inhibitory effect of A group on basement membrane thickening was similar to that of B group. However, smooth muscle thickening was more strongly inhibited by A group than by B group, suggesting that the mechanism of action involved the suppression of amphiregulin expression by mast cells.
Common organisms causing community acquired pneumonia
Authors: Safia Shaikh, Zafar Ahmed, Syed Ali Arsalan
Journal: European Respiratory Journal (2013)

INTRODUCTION:  In developing countries like Pakistan pneumonia remains a leading cause of death among the very old, the very young and the chronically ill patients.  We are conducting a study observing the organisms causing community acquired pneumonia. Our secondary outcome is the antibiotic response.  METHODS:  110 patients have been registered from June 2012 to Dec 2012 ages between 20 to 90 years admitted only in Chest Medicine department were included in the study.55 males with a mean age of 55 years, 40 females with a mean age of 65 years. 61% of the patients were hypertensive,40 % of the patients were diabetic, 38% had COPD and 25% were asthmatic. Other co morbidities include IHD,CVA,BPH and OA.  RESULTS:  Among the 110 patients 25 patients had sputum c/s negative, 20 patient had dry cough so sputum samples were not sent,17 patient c/s grew Moraxella Catarrhalis,15 patient c/s grew Klebsiella Pneumoniae, 11 patient c/s grew Haemophilus Influenza, 11 patients c/s grew Pseudomonas Auregenosa, 8 patient c/s grew Staph Aureus and only 3 patient c/s grew Strep Pneumonia  70% of patients responded to amoxicillin with calvalunic acid in combination with clarithromycin ,24% responded to cephalosporin,6% that included pseudomonas auregenosa were required to switch antibiotic to piperacillin+tazobactam  CONCLUSION:  We observed that B-lactams are still the potent drugs for CAP. Co- morbidities and age can affect the common pathogen of CAP. We may observe Klebsiella Pneumonia and Pseudomanas auregenosa in CAP when the patients are immuno compromised and COPD. Different age group may respond differently to same pathogen.
Increased resting energy expenditure and weight loss are related to a systemic inflammatory response in lung cancer patients.
Authors: A J Staal-van den Brekel, M A Dentener, A M Schols, W A Buurman, E F Wouters
Journal: Journal of Clinical Oncology (1995)

PURPOSE To determine whether an increased resting energy expenditure (REE) and weight loss in lung cancer patients are related to a systemic inflammatory response. MATERIALS AND METHODS REE was measured by indirect calorimetry using a ventilated hood system. Soluble tumor necrosis factor receptor 55 (sTNF-R55) and sTNF-R75, soluble intercellular adhesion molecule (sICAM)-1, soluble E (sE)-selectin, lipopolysaccharide (LPS)-binding protein (LBP), interleukin (IL)-6, and TNF-alpha were measured using sandwich enzyme-linked immunosorbent assay (ELISA), and C-reactive protein (CRP) was measured by turbidimetry. A cross-sectional study was performed to compare inflammatory mediators between hypermetabolic (REE/Harris Benedict [HB] equation &gt; or = 110%) versus normometabolic (REE/HB &lt; 110%) patients and between patients who lost weight (more than 10% loss of preillness weight) versus those whose weight remained stable. RESULTS Eighty-seven patients with primary non-small-cell lung cancer were consecutively entered onto the study. Mean REE expressed as a percentage of the HB reference values was 118% +/- 12%; 67 patients were considered hypermetabolic. Twenty-six patients had a substantial loss of more than 10% of their preillness weight. Hypermetabolic patients were found to have significantly increased levels of sTNF-R55, sE-selectin, LBP, and CRP compared with normometabolic patients. Weight loss was related with increased levels of the sTNF-Rs, sICAM-1, IL-6, LBP, and CRP. CONCLUSION Hypermetabolism and weight loss are related to the presence of a systemic inflammatory response as reflected by enhanced levels of inflammatory mediators and acute phase proteins in patients with primary non-small-cell lung cancer.
Abstract 240: Interruption of Ivabradine Treatment in Middle-Aged Post-MI Rats May Lead to Heart Failure
Authors: Eduard I Dedkov, Yevgen Bogatyryov, Kunal Oak, Lance P Christensen, Robert J Tomanek
Journal: Circulation Research (2012)

Background: We have previously demonstrated that heart rate reduction (HRR) with the selective cardiac pacemaker I f current inhibitor ivabradine (IVA) improved LV function and coronary perfusion reserve in post-MI middle-aged rats. The beneficial effects of IVA treatment were associated with attenuated collagen accumulation in the surviving LV myocardium and inhibition of the circulatory renin-angiotensin system. However, sustainability of these positive changes after a period of IVA treatment interruption remains to be determined. Methods: MI was induced in 12-month-old male Sprague-Dawley rats by left coronary artery ligation. Twenty four hours later, the rats with a confirmed large transmural MI were randomly assigned in two experimental groups. In a first group, rats were treated with IVA i.p. via osmotic pumps in a dose of 10.5 mg/kg/d for 4 weeks followed by a 4-week period without treatment (MI+IVA). In a second group, rats received placebo for 4 weeks (MI). Sham-operated rats served as a control. Eight weeks after MI, the various LV parameters were examined. Results: During 4 weeks of treatment, heart rate in MI+IVA rats was consistently reduced compared to untreated MI rats (mean of HRR was 27%). After IVA withdrawal, heart rate increased to the levels of the placebo group. Eight weeks after MI, the IVA treated group demonstrated smaller LV free wall infarct size (57.5 ± 2.7% vs. 72.5 ± 2.5%, p&lt;0.01) and greater LV weight/body weight ratio (2.54 ± 0.06 vs. 2.26 ± 0.11 mg/g, p&lt;0.05), indicating greater myocardial compensatory hypertrophy. Furthermore, the interstitial collagen content was significantly lower in the remote LV myocardium of MI+IVA rats compared to MI rats (7.5 ± 0.7% vs. 13.3 ± 1.0% in free wall and 7.3 ± 0.8% vs. 11.2 ± 0.9% in septum, p &lt; 0.01). However, compared to non-infarcted controls, rats of both MI groups had markedly lower LV ejection fraction and coronary perfusion reserve. Conclusions: Our data demonstrate that although beneficial structural changes induced by IVA in post-MI myocardium can be sustainable for a long period of time they cannot prevent deterioration of LV function after withdrawal of treatment. Therefore, we believe that continuous treatment with IVA may be essential for attenuation of heart failure after a large MI.
Methylation of circulating DNA in melanoma patients
Authors: U. R. Hengge, A. Marini, A. Mirmohammadsadegh, S. Nambiar, A. Gustrau, T. Ruzicka
Journal: Journal of Clinical Oncology (2006)

8027 Background: DNA methylation is a well-known epigenetic phenomenon that occurs in higher order eukaryotes. Changes in the status of DNA methylation of tumor suppressor genes (TSG) is one of the common molecular alterations in many carcinomas. Methods: The purpose of this study was to investigate hypermethylation status of five different genes (TSG and cell cycle genes) involved in tumor suppression and DNA repair. Results: Serum before therapeutic intervention from 32 melanoma patients (stage I = 13; stage II = 9; stage III/IV = 10) was collected, cell-free DNA was isolated and sodium bisulfite conversion of genomic DNA was performed. The methylation status of CpG islands in the promotor region of SOCS1, SOCS2 (suppressors of cytokine signaling 1 and 2); RASSF1a (Ras-association domain family protein 1A); CDKN (D-type p16INK4a cyclin-dependent kinase inhibitor); and MGMT (O6-methylguanine DNA-methyltransferase) were analyzed using methylation specific-PCR (MSP). For comparison, sera from healthy controls (n = 20) and patients with other skin tumors (9 basal cell cancers, 5 Kaposi’s sarcoma) as well as different cancers (5 breast cancers, 5 colon cancers) were also analyzed. In addition, we examined if methylation was involved in silencing of these genes in 20 fresh melanoma specimens and we confirmed the hypermethylation status of SOCS2 using positional methylation analysis (pyrosequencing). Moreover, the expression of these genes was investigated cell lines (BLM, A375, MV3, and M13). Analysis of sera from cutaneous melanoma patients demonstrated circulating hypermethylated SOCS 1 in 59%, SOCS2 in 53%, RASSF1a in 53%, CDKN2a in 50%, while the MGMT did not show clear methylation pattern. Serum of healthy controls showed no methylation of any of the analyzed genes. The mRNA transcript of these genes showed a clear and significant downregulation, except for MGMT, for which an up regulation (7.3 times) was detected being consistent with the lack of promotor methylation. Detailed positional methylation analysis (pyrosequencing) has been performed for these genes and was found to correlate with mRNA expression in the tumor specimens in most cases. Conclusions: Analysis of positional methylation of circulating cell-free DNA seems to be a novel tool for molecular diagnosis in melanoma. No significant financial relationships to disclose.
Abstract 1380: Antioxidants Decrease Neuronal Angiotensin II Type 1 Receptor in Heart Failure: Inhibition of Activator Protein 1 and Jun N-Terminal Kinase
Authors: Dongmei Liu, Lie Gao, Kurtis G Cornish, Irving H Zucker
Journal: Circulation (2007)

In a previous study, we showed that Ang II type I receptor (AT1R) expression increased in the rostral ventrolateral medulla (RVLM) of chronic heart failure (CHF) rabbits and in normal rabbits infused with intracerebroventricular (ICV) Angiotensin II (AngII). The present study investigated if oxidative stress plays a role in Ang II induced AT1R upregulation and its relationship to the transcription factor activator protein 1 (AP1) in CHF rabbits and in the CATHa neuronal cell line. In neuronal cell cultures, Ang II significantly increased AT1R mRNA by 153 ± 22%, P &lt;0.01; c-Jun mRNA by 90 ± 10%, P &lt; 0.01; NADPH oxidase activity by 126 ± 43%, P &lt; 0.01 versus untreated cells; Tempol, Apocynin and the AP 1 inhibitor Tanshinone II reversed the increased AT1R, c-Jun expression and NADPH oxidase activity induced by AngII. We examined the effect of ICV Tempol on expression of these proteins in the RVLM of CHF rabbits. Compared to untreated CHF rabbits Tempol significantly decreased AT1R protein expression (0.88±0.16 vs. 1.6±0.29, P &lt;0.05), phosphorylated Jnk protein (0.10±0.02 vs. 0.31±0.10, P &lt;0.05), and phosphorylated c-Jun (0.02±0.001 vs. 0.14±0.05, P &lt;0.05). These data suggest that Ang II induces AT1R upregulation at the transcriptional level by activation of oxidative stress and AP1 in both cultured cells and in intact brain. Antioxidant agents may be beneficial in CHF by decreasing AT1R expression through the Jnk and AP1 pathway.
Pilot trial of infusional cyclophosphamide, doxorubicin, and etoposide plus didanosine and filgrastim in patients with human immunodeficiency virus-associated non-Hodgkin's lymphoma.
Authors: J A Sparano, P H Wiernik, X Hu, C Sarta, E L Schwartz, R Soeiro, D H Henry, B Mason, H Ratech, J P Dutcher
Journal: Journal of Clinical Oncology (1996)

PURPOSE To determine the following: (1) the feasibility of combining the antiretroviral didanosine (ddl) with a 96-hour continuous intravenous (IV) infusion of cyclophosphamide (800 mg/m2), doxorubicin (50 mg/m2), and etoposide (240 mg/m2) (CDE) plus filgrastim in patients with non-Hodgkin's lymphoma (NHL) associated with human immunodeficiency virus (HIV) infection; (2) the effect of ddl on CDE-induced myelosuppression and CD4 lymphopenia; and (3) the effect of CDE on serum p24 antigen and quantitative HIV blood cultures. METHODS Twenty-five patients with HIV-related NHL received CDE every 28 or more days. Consecutive patients were assigned in an alternating fashion to group A (ddl given at a standard dose during cycles one, two, five, and six) or group B (ddl given during cycles three, four, five, and six). RESULTS ddl use was associated with less leukopenia (mean nadir, 3.33 v 1.49 x 10(3)/microL; p = .03), neutropenia (2.38 v 1.07 x 10(3)/microL; p = .03), and thrombocytopenia (76 v 48 x 10(3)/microL; p = .059), and fewer RBC (1.6 v 3.1 per cycle; p &lt; .01) and platelet transfusions (0.7 v 1.5 per cycle; p &lt; .01), but had no significant effect on CD4 lymphopenia. Furthermore, lymphomatous bone marrow involvement and low CD4 count were associated with significantly greater myelosuppression. Although there was no substantial change in serum p24 antigen, the HIV blood culture became quantitatively more positive or converted from negative to positive in seven patients (64%). Complete response (CR) occurred in 58% of patients (95% confidence interval, 38% to 78%), median CR duration exceeded 18 months, tumor-related mortality was 20%, and median survival was 18.4 months. CONCLUSION Our results suggest that the CDE and filgrastim regimen is tolerable and effective for patients with HIV-associated NHL, and that combination with ddl is feasible and may result in less myelosuppression.
Prevention, Diagnosis, and Treatment of Invasive Fungal Infections in Patients with Cancer and Neutropenia
Authors: Thomas A. Cumbo, Brahm H. Segal
Journal: Journal of the National Comprehensive Cancer Network (2004)

Invasive fungal infections are a major cause of morbidity and mortality in patients with prolonged neutropenia and in allogeneic hematopoietic stem cell transplant recipients. The degree and duration of neutropenia influence the risk of opportunistic fungal infections. Because Candida and Aspergillus species are the major causes of invasive fungal infections in neutropenic patients, the fungal section of the NCCN guidelines focus on these two pathogens. Effective prevention and therapy of invasive fungal pathogens is a priority in highly immunocompromised patients with cancer. Three strategies in preventing and treating patients at high risk for fungal infection will be considered: (1) prophylaxis; (2) empirical therapy; and (3) treatment for probable or proven fungal infection. In addition to more effective antifungal agents, growing interest has been noted in novel non-culture detection methods to facilitate early diagnosis of invasive fungal infections.
The increased incidence of Mycoplasma pneumoniae in France in 2011 was polyclonal, mainly involving M. pneumoniae type 1 strains.
Authors: S. Pereyre, A. Touati, J. Petitjean-Lecherbonnier, A. Charron, A. Vabret, C. Bébéar
Journal: Clinical Microbiology and Infection (2012)
TAS3681: New class of androgen receptor antagonist with androgen receptor downregulating activity.
Authors: Kazuhisa Minamiguchi, Masanao Seki, Hiroki Aoyagi, Daisuke Kajiwara, Tomoko Mori, Norio Masuko, Ryouto Fujita, Shigeo Okajima, Yukio Hayashi, Eiji Sasaki, Teruhiro Utsugi
Journal: Journal of Clinical Oncology (2015)

266 Background: The persistent activation of the androgen receptor (AR) signaling axis plays a major role in castration-resistant prostate cancer (CRPC). This knowledge has driven the clinical development of new inhibitors of androgen production (e.g., abiraterone) and AR signaling (e.g., enzalutamide). However, in many patients, the efficacy is short-lived and eventually resistance appears. Reactivation of AR signaling occurs by several mechanisms in CRPC. In this study, we report the biological properties of TAS3681, a new AR antagonist with AR downregulating activity, and propose this concept as a potential new approach for the treatment of CRPC. Methods: For assay of AR transactivation, COS-7 cells were transiently transfected with androgen-responsive reporter gene construct and expression vectors encoding wt or mu ARs. The transfected cells were treated with TAS3681 and androgen in steroid depleted media for 24 h, and luciferase activity was measured. For an in vivo pharmacodynamic assay to confirm AR downregulation in tumor, TAS3681 was orally dosed in CRPC tumor xenograft model. Tumor was isolated and AR level in tumor was determined by Western blot. Results: TAS3681 suppressed the growth of AR positive prostate cancer (PCa) cells but did not affect that of AR-negative DU145 PCa cells, indicating a dependency on AR for efficacy. TAS3681 did not stimulate AR nuclear translocation and suppressed wt and mu ARs (including F876L) transactivation in cells, indicative of its pure AR antagonist profile. In contrast to enzalutamide, TAS3681 effectively suppressed androgen-independent AR transactivation by growth factors and cytokines via AR downregulating activity. Interestingly, in PCa cells which express full-length and splice variant AR, TAS3681 reduced the expression of both ARs. Moreover, TAS3681 treatment effectively decreased AR level in CRPC tumors in vivo. Conclusions: TAS3681 exerts an anti-androgenic effect via two mechanisms of action: pure AR antagonism and AR decreasing activity. It is expected that TAS3681 has a potential to overcome the resistance to current and 2nd-generation therapies targeting AR signaling.
Impact of vaccination on invasive pneumococcal disease in adults with focus on the immunosuppressed
Authors: Anna Sangil, Mariona Xercavins, Mònica Rodríguez-Carballeira, Marta Andrés, Montse Riera, Elena Espejo, Josefa Pérez, Javier Garau, Esther Calbo
Journal: Journal of Infection (2015)
Towards nanomedicines of the future: Remote magneto-mechanical actuation of nanomedicines by alternating magnetic fields
Authors: Yuri I Golovin, Sergey L Gribanovsky, Dmitry Y Golovin, Natalia L Klyachko, Alexander G Majouga, Аlyssa M Master, Marina Sokolsky, Alexander V Kabanov
Journal: Journal of Controlled Release (2015)