tbuckley/cabot-search huggingface dataset:
Abstract 19395: Increased Multiple Firing of Single Muscle Vasoconstrictor Neurons during Lower Body Positive Pressure in Human Heart Failure
Authors: Philip J Millar, Hisayoshi Murai, Beverley L Morris, John S Floras
Journal: Circulation (2012)

Introduction: Functionally specific efferent renal sympathetic nerves fire selectively in response to distinct hemodynamic afferent inputs. Using norepinephrine spillover, our group detected a heart failure (HF)-specific cardio-cardiac sympathoexcitatory reflex stimulated by high atrial pressure. Efferent discharge directed at other vascular beds similarly activated by atrial stretch might not be detected by multi-unit sympathetic recordings. Hypothesis: In contrast to healthy controls (CON), in HF some muscle sympathetic fibers respond paradoxically (i.e. increase firing) to increases in filling pressure. Methods: Single-unit muscle sympathetic nerve activity (sMSNA; microneurography) and peripheral venous pressure (PVP; forearm catheter) were recorded from 11 CON and 10 treated HF (LVEF 27±6%) patients at baseline and during non-hypotensive lower body negative pressure (LBNP; -10mmHg) and non-hypertensive lower body positive pressure (LBPP; +10mmHg). sMSNA firing frequency and incidence, and the percentage of multiple within-burst firing was calculated for each condition. Results: PVP was reduced with LBNP (p&lt;0.05) and increased with LBPP (p&lt;0.05) in both groups, with PVP greater in HF across each condition (p&lt;0.05). Blood pressure and heart rate were unchanged by LBNP or LBPP in both groups (p&gt;0.05). We identified 26 and 22 single-units in CON and HF patients, respectively. sMSNA firing frequency was similar (p&gt;0.05) in CON and HF at baseline (30±18 vs. 35±15 spikes/min) and during LBNP (45±24 vs. 42±23 spikes/min) but higher in HF during LBPP (28±17 vs. 40±22 spikes/min, p=0.05). sMSNA firing incidence was similar (p&gt;0.05) in both groups across each condition. The percentage of within-burst multiple spike firing was similar (p&gt;0.05) in CON and HF during baseline (24±9% vs. 24±7%) and LBNP (25±11% vs. 28±14%) but higher in HF during LBPP (17±8% vs. 34±16%, p&lt;0.001). Conclusions: In HF, increases in PVP with non-hypertensive LBPP cause a paradoxical increase in muscle sympathetic single-unit firing frequency and multiple within-burst firing, compared to CON. This provides evidence of a sympathoexcitatory cardiac-skeletal muscle vasoconstrictor reflex in human HF that may be attenuated by normalizing filling pressures.
Evaluation of the role of FDG-PET imaging in malignant pleural mesothelioma (MPM)
Authors: D. G. Power, C. T. Farrelly, R. A. McDermott, K. J. O’Byrne
Journal: Journal of Clinical Oncology (2006)

17113 Background: MPM is a rapidly progressive malignancy with a median survival of 6 to 9 months. Studies in non-small cell lung cancer, gastrointestinal stromal tumours, and breast cancer suggest that Positron Emission Tomography (PET) scanning may predict the clinical outcome of chemotherapy at an early stage of treatment. The role of PET in predicting and monitoring response to treatment in MPM is unclear. In this study we assessed if baseline and early interval PET scanning could be of benefit in MPM, correlating the results with standard Computerised Tomography (CT) assessment using the modified Response Evaluation Criteria In Solid Tumours (RECIST) of Byrne and Nowak. Methods: 10 patients with histologically proven MPM proceeded to baseline PET and CT scanning prior to chemotherapy. In 8 patients a second PET scan was performed within three weeks of commencing treatment. The following PET derived parameters were calculated: Standard Uptake Value (SUV)maximum, SUVaverage, PETvolume, and Total Lesion Glycolysis (TLG). Baseline SUVmaximum and early PET response was compared with CT response and survival. Results: Baseline SUVmaximum predicted subsequent CT response in the 10 patients studied. Four out of 5 patients with baseline SUVmaximum of &lt;15 showed a subsequent partial response on CT, whilst the 5 th patient had resolution of a pleural effusion. All 5 patients with baseline SUVmaximum of &gt;15 had stable or progressive disease on CT. In contrast change in early SUVmaximum from baseline to 3 weeks did not predict subsequent CT response (Kappa value 0.07) in the 8 patients evaluated. Change in PET volume and TLG correlated with subsequent CT response (Kappa value= 0.80 for both). Only 1 patient with a partial response on % PETvolume and %TLG has died 14 months after commencing treatment. The other 3 patients are alive at 17+, 19+ and 20+ months. The 4 patients with stable or progressive disease using these parameters were deceased at 5, 6, 10, and 12 months respectively. Conclusion: PET may be useful in predicting and evaluating response to treatment in MPM. Furthermore, the results suggest that PET response may be a useful prognostic tool in this disease. It is important to use the appropriate PET derived parameters. Further study with a larger patient population is warranted. No significant financial relationships to disclose.
Calcium upregulation by percutaneous administration of gene therapy in patients with cardiac disease (CUPID 2): a randomised, multinational, double-blind, placebo-controlled, phase 2b trial
Authors: Barry Greenberg, Javed Butler, G Michael Felker, Piotr Ponikowski, Adriaan A Voors, Akshay S Desai, Denise Barnard, Alain Bouchard, Brian Jaski, Alexander R Lyon, Janice M Pogoda, Jeffrey J Rudy, Krisztina M Zsebo
Journal: The Lancet (2016)
Breast Cancer and Menopausal Hormone Therapy by Race/Ethnicity and Body Mass Index: Figure 1.
Authors: Rowan T. Chlebowski, Garnet L. Anderson, Aaron K. Aragaki, Ross Prentice
Journal: JNCI Journal of the National Cancer Institute (2015)

In analyses combining estrogen with or without progestin, some observational studies describe minimal breast cancer risk in obese and black women. Therefore, we examined these suggested interactions in the two Women’s Health Initiative (WHI) randomized hormone therapy trials. The estrogen plus progestin trial entered 16 608 postmenopausal women with a uterus, while the estrogen trial entered 10 736 postmenopausal women with prior hysterectomy. Hazard ratios (HRs), 95% confidence intervals (CIs), and P values from log-rank x2 statistics were estimated from Cox proportional hazards models with subgroup analyses based on tests of interaction. All statistical tests were two-sided. Estrogen plus progestin statistically significantly increased breast cancer incidence (HR = 1.28, 95% CI = 1.11 to 1.48, P < .001), with hazard ratios greater than 1 in all body mass index (BMI) subgroups (Pinteraction = .58) and hazard ratios greater than 1 in black and white women (Pinteraction = .96). In contrast, estrogen alone statistically significantly decreased breast cancer incidence (HR = 0.79, 95% CI = 0.65 to 0.90, P = .02), with hazard ratios lower than 1 in all BMI subgroups (Pinteraction = .86) and hazard ratios lower than 1 in black and white women, where analyses with limited numbers suggest somewhat greater reduction in black women (Pinteraction = .09). In summary, estrogen plus progestin and estrogen alone have opposite effects on breast cancer incidence, with no statistically significant interactions by race/ethnicity or BMI. Therefore, observational studies should not combine these two regimens when examining breast cancer risk.
Short-term feeding at the wrong time is sufficient to desynchronize peripheral clocks and induce obesity with hyperphagia, physical inactivity and metabolic disorders in mice
Authors: Yuki Yasumoto, Chiaki Hashimoto, Reiko Nakao, Haruka Yamazaki, Hanako Hiroyama, Tadashi Nemoto, Saori Yamamoto, Mutsumi Sakurai, Hideaki Oike, Naoyuki Wada, Chikako Yoshida-Noro, Katsutaka Oishi
Journal: Metabolism (2016)
Lymphomas in the Wistar Rat After Intrapleural Inoculation of Silica
Authors: Margaret M. F. Wagner, J. C. Wagner
Journal: JNCI Journal of the National Cancer Institute (1972)

Crystalline silica was injected into the pleural cavity of standard and specific pathogen-free (SPF) Wistar rats; 39 of 95 SPF rats and 31 of 94 standard rats developed reticuloendothelial tumors, while another third had a “hvperplestic reaction.” The distribution of the silica and of the tumor masses is described together with the histology. Results from an inhalation experiment are briefly compared.
Immediate postoperative instillation of gemcitabine after transurethral resection of bladder tumors
Authors: H. Buettner, C. Stoffregen, J. Heyer, A. Nentwig, A. Boehle
Journal: Journal of Clinical Oncology (2004)

4685 Background: Based on the results of our monocenter phase I study of intravesical administration of gemcitabine (Gemzar) immediately after transurethral resection of superficial bladder cancer (TUR-BT) we performed an extended feasibility study as an amended study procedure at four different sites in Germany. Methods: From July to October 2003, 24 patients (pts.) with cystoscopic diagnosis of superficial bladder cancer (SBC) and the need for TUR-BT were enrolled into the study. 23 pts. were eligible for TUR-BT and drug-instillation (17 male, median age 67.9 years [range 53.7 years –79.8 years]; 6 female, median age 74.6 years [range 64.7 years –75.6 years]); one pt. was finally not operated on due to serious comorbidities. The eligible 23 pts. underwent TUR-BT with complete resection of all visible tumors. Immediately (within the first 1h) after TUR-BT, pts. received 2000 mg gemcitabine in 100 mL unbuffered saline with a dwell time of approx. 30 min (Buettner et al Proc. ASCO (2003) 22:1785). After the instillation, the bladder was evacuated and irrigated with saline until gross haematuria resolved. Pts. were questioned about potential side effects 24 h after the instillation and at 12 weeks at the time of follow-up cystoscopy. Repeated resection without instillation was performed in two pts. with extensive stage pT1 G2 and pT1 G3 tumors, respectively Results: The instillation was well tolerated in all pts. and side effects were transient and did not exceede CTC grade 2 (bleeding grade 1: 1 pt.; haematuria grade 1: 1 pt., grade 2: 3 pts.; dysuria grade 1: 4 pts., incontincence grade 2: 1 pt., sweat grade 1: 1 pt.). Pts. with muscle-invasive tumor (n=1) or no tumor (n=9) were excluded from efficacy analyis, which is not finished. Full efficacy data will be presented at the meeting. Conclusions: The immediate application of gemcitabine after TUR-BT can be safely given into the bladder in a muticenter setting. A double-blind, placebo-controlled randomized phase III study is in progress to evaluate the effect of intravesical gemcitabine on the relapse-free survival rate of SBC. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Lilly Deutschland GmbH Lilly Deutschland GmbH Lilly Deutschland GmbH
Neratinib in combination with trastuzumab for the treatment of advanced breast cancer: A phase I/II study
Authors: R. Swaby, K. Blackwell, Z. Jiang, Y. Sun, V. Dieras, K. Zaman, C. Zacharchuk, C. Powell, R. Abbas, M. Thakuria
Journal: Journal of Clinical Oncology (2009)

1004 Background: Neratinib (HKI-272) is an orally administered irreversible pan-ErbB receptor tyrosine kinase inhibitor. In an ongoing phase II study, the preliminary objective response rate was 26% in patients with ErbB2+ advanced breast cancer with prior trastuzumab therapy. This study assessed the safety and preliminary efficacy of the combination of neratinib plus trastuzumab. Methods: Patients with advanced ErbB2+ breast cancer that progressed following trastuzumab therapy were enrolled. The primary endpoint was 16-week progression free survival rate (PFS). In part 1 (dose escalation), patients received neratinib 160 mg or 240 mg daily plus trastuzumab 4 mg/kg IV loading dose then 2 mg/kg weekly. In part 2, patients received weekly trastuzumab with neratinib 240 mg daily. Timed blood samples were collected for PK analyses. PK analysis is ongoing. Results: 45 patients (part 1 n = 8; part 2 n = 37) were enrolled (mean age 52 yr); 9 are active. In part 1, cohorts 1 and 2 were fully enrolled with 4 patients each. No dose limiting toxicities were observed. Most common AEs, any grade, were diarrhea (91%), nausea (51%), anorexia (40%), vomiting (38%), and asthenia (27%). Grade 3/4 AEs were diarrhea (13%), nausea (4%), vomiting (4%). Two patients receiving neratinib 240 mg reported AEs leading to withdrawal. No AEs of congestive heart failure and no significant drops of left ventricular ejection fraction were reported. Among 33 patients evaluable for efficacy, objective response rate was 27% (95% CI, 13% - 46%); 16-week PFS rate (for part 2) 47% (95% CI, 29% - 63%); median PFS was 19 weeks (95% CI 15 - 32 weeks). Conclusions: Neratinib plus trastuzumab was well tolerated with no significant or unexpected toxicities, and demonstrated clinical activity. [Table: see text]
Ondansetron (O) with or without dexamethasone (D) for the prevention of chemotherapy (C)-induced nausea and vomiting (CINV)
Authors: S. Bonicatto, A. Mainella, E. Troncoso, A. Barbero, M. Lavezzaro, G. Zapata
Journal: Journal of Clinical Oncology (2006)

18558 Background: Adition of D to the standard antiemetic treatment for CINV prevention is frequent, despite the lack of benefit evidence in controlled clinical trials. In this study we compare the impact of O treatment with or without D on daily life, in patients (pts) under treatment with high or moderately emetogenic C. Methods: Longitudinal, randomized and prospective study. All pts who received anticancer treatment with high or moderately emetogenic C were included, and randomly assigned to group A (O 8 mg iv and D 8 mg iv) or group B (O 8 mg iv). Evaluable pts did not have to receive any medication which could modify the antiemetic effect of treatment within the 24 hours following the administration of CH and had to be able to answer an autoadministered questionnaire. After 24 hours, the Functional Living Index- Emesis (FLIE), a daily life index which consists of 18 questions divided into two domains: nausea and vomiting, had to be completed. Data were analyzed by independent mean sample t-test, and ANOVA One-Way, with a 0.05 significance level. Results: Between December/04 and November/05 233 patients (age average: 59.24; range 21–87) were randomly assigned to antiemetic treatment with (n = 125) or without D (n = 108). Both groups were well balanced as regards the type of chemotherapy, sex and age, and all patients were evaluable. No significant effects were observed between both groups when the global data were analyzed. However, when the sample was stratified by type of chemotherapy, a significantly lower impairment (55.1 vs 51.3; p &lt; .05) was detected in the nausea domain in those patients who received moderately emetogenic chemotherapy. Conclusion: In our sample of patients we observed benefits in the impact on daily life, by the addition of D to the O as preventive treatment of CINV, in those patients that received moderately emetogenic chemotherapy. No significant financial relationships to disclose.
Oral Contraceptive Use and Prevalence of Self-Reported Glaucoma or Ocular Hypertension in the United States
Authors: Ye Elaine Wang, Caitlin Kakigi, Diego Barbosa, Travis Porco, Rebecca Chen, Sophia Wang, Yingjie Li, Kuldev Singh, Louis R. Pasquale, Shan C. Lin
Journal: Ophthalmology (2016)
No long-term evidence of hyporesponsiveness after use of pneumococcal conjugate vaccine in children previously immunized with pneumococcal polysaccharide vaccine
Authors: Paul V. Licciardi, Zheng Quan Toh, Elizabeth A. Clutterbuck, Anne Balloch, Rachel A. Marimla, Leena Tikkanen, Karen E. Lamb, Kathryn J. Bright, Uraia Rabuatoka, Lisi Tikoduadua, Laura K. Boelsen, Eileen M. Dunne, Catherine Satzke, Yin Bun Cheung, Andrew J. Pollard, Fiona M. Russell, Edward K. Mulholland
Journal: Journal of Allergy and Clinical Immunology (2016)
포스터전시 : 담석을 동반한 간경변증 환자에서 담낭기능평가:간질환이 없는 담석 환자와 비교연구
Authors: 김상균, 감용석, 장재영, 정승원, 박지영, 박정미, 문종호, 김홍수, 이준성, 이문성, 심찬섭, 김부성
Journal: Clinical and Molecular Hepatology (2008)
Radiolabeled anti-prostate specific membrane antigen (PSMA) monoclonal antibody J591 (<sup>177</sup>Lu-J591) for nonmetastatic castration-resistant prostate cancer (CRPC): A randomized phase II trial.
Authors: S. T. Tagawa, N. M. Hahn, D. A. Vaena, D. I. Quinn, W. K. Kelly, P. J. Christos, J. Osborne, S. Vallabhajosula, K. Nadeau, G. Mileo, L. Tyrell, A. Saran, C. Ecker, H. Beltran, S. J. Goldsmith, D. M. Nanus
Journal: Journal of Clinical Oncology (2011)

TPS193 Background: Biochemical recurrence without evidence of PC on standard CT/MRI and bone scans after local therapy is common. Salvage radiotherapy affords a cure to select patients (pts) with PSA relapse, but most progress because of micrometastatic PC outside of the radiation field. J591 is a monoclonal antibody that targets the extracellular domain of PSMA. A phase II trial of single-dose 177Lu-J591 radioimmunotherapy (RIT) in pts with progressive, metastatic (met) CRPC demonstrated excellent targeting of met sites, efficacy, and acceptable toxicity [Tagawa et al, ASCO 2008]. RIT appears to have its greatest impact in the setting of minimal disease [Kaminski, NEJM 2005; Leonard, JCO2005; Press, JCO 2006] and the beta emission of 177Lu is best suited for lesions 1-3 mm in diameter [O’Donoghue, J Nuc Med 1995] (i.e. micrometastatic disease). Methods: In this multicenter DOD-sponsored study, men with high-risk CRPC (PSA doubling time < 8 months and/or PSA > 20 [Smith, JCO 2005]) and no evidence of disease on CT/MRI and bone scans are randomized 2:1 to receive double-blinded 177Lu-J951 vs 111In-J591 (control) and undergo planar gamma camera imaging with SPECT following infusion. All pts receive ketoconazole plus hydrocortisone. The primary endpoint of the study is 18-month met-free survival. 140 pts will be treated to allow 80% power with a 2-sided alpha of 5% to detect a 25% absolute difference (50% vs 75% met-free) in radiographically apparent mets at 18 months (with interim analysis after 50% of pts have at least 12 months follow up). Secondary/exploratory endpoints include evaluation of radiolabeled J591 imaging to detect sites of mets not apparent on standard CT/MRI and bone scan, validation of adrenal androgen levels as biomarkers for ketoconazole [Ryan Clin Cancer Res 2007], analysis of circulating tumor cells captured via CellSearch methodology as well as PSMA-GEDI capture [Gleghorn, Lab Chip 2010] for PSMA expression and counts to predict the appearance of radiographic metastases, and exploration of hemostatic/fibrinolytic/angiogenic plasma biomarkers.
srRNA evolution and phylogenetic relationships of the genus Naegleria (Protista: Rhizopoda).
Authors: P R Baverstock, S Illana, P E Christy, B S Robinson, A M Johnson
Journal: Molecular Biology and Evolution (1989)

A rapid RNA sequencing technique was used to partially sequence the small-subunit ribosomal RNA (srRNA) of four species of the amoeboid genus Naegleria. The extent of nucleotide sequence divergence between the two most divergent species was roughly similar to that found between mammals and frogs. However, the pattern of variation among the Naegleria species was quite different from that found for those species of tetrapods characterized to date. A phylogenetic analysis of the consensus Naegleria sequence showed that Naegleria was not monophyletic with either Acanthamoeba castellanii or Dictyostelium discoideum, two other amoebas for which sequences were available. It was shown that the semiconserved regions of the srRNA molecule evolve in a clocklike fashion and that the clock is time dependent rather than generation dependent.
Neoplastic meningitis—Is MRI as sensitive as CSF cytology?
Authors: H. M. Strik, P. Proemmel, S. Pilgram-Pastor, J. H. Buhk
Journal: Journal of Clinical Oncology (2009)

9566 Background: Although CSF cytology and MRI are standard methods for the diagnosis of neoplastic meningitis (NM), this complication of neoplastic disease still remains to be difficult to detect in some cases. We therefore re-evaluated the sensitivity of gadolinium(GD)-enhanced MRI and cerebrospinal-fluid (CSF)-cytology for the diagnosis of LM differentially for solid and haematological malignancies and for normal or elevated cell counts. Methods: We identified retrospectively 101 cases of NM diagnosed in our CSF laboratory since 1990 with complete data of both MRI and CSF-cytology. 34 had haematological, 67 solid neoplasms. CSF-cell counts were increased in 63 and normal in 35 patients. Results: For haematological neoplasms, MRI was positive in 53%. CSF cytology was positive in 97%. In solid tumours, we found MRI-sensitivity of 0.81 and cytological sensitivity of 0.76. With normal CSF-cell-counts, MRI was positive in 63%, (0.57 haematological, 0.75 solid malignancies), CSF-cytology in 78%, (0.9 in haematological, 0,64 in solid neoplasms). In cases of increased cell-counts, MRI-sensitivity was 0.75 (0.52 for haematological, 0.87 for solid malignancies), and sensitivity of CSF-cytology was 0.89 (1.0 for haematological and 0.82 for solid neoplasms). 23 patients were treated with intrathecal MTX or Ara-C, 16 patients with liposomal Ara-C. 62 patients were not treated intrathecally. Conclusions: We confirmed here the high overall sensitivity of MRI for the diagnosis of neoplastic meningitis. The best sensitivity, however, was seen in solid tumours and elevated cell counts. In haematological malignancies, a markedly lower sensitivity of MRI was seen. Of note, we consider the very high sensitivity of cytology in haematological malignancies to be artificial due to methodological reasons of this retrospective study. We conclude that MRI is a very sensitive method to detect NM especially in solid tumours and elevated cell counts. With normal cell counts and haematological neoplasms, CSF-cytology remains to be superior to radiological methods. [Table: see text]
<i>Lancet</i>retracts paper by disgraced Canadian researcher
Authors: Caroline White
Journal: BMJ (2016)

The Lancet has retracted a 1992 study by the Canadian self proclaimed “father of nutritional immunology,” Ranjit Kumar Chandra, on the grounds that its reliability “can no longer be assured.”1

The study—a major trial that reported an improvement in older people’s immunity and infection risk after taking nutritional supplements2—was the second of Chandra’s studies to be retracted within the past six months.

In October The BMJ retracted his 1989 study into the immune benefits of baby formula after receiving a suppressed report of an inquiry of his research, completed in 1995 by his former employer, Memorial University of Newfoundland, after allegations of data fabrication.3

Doubts about the plausibility of the Lancet study first …
Response to pulmonary rehabilitation: toward personalised programmes?
Authors: Nicolino Ambrosino, Enrico M. Clini
Journal: European Respiratory Journal (2015)

Personalised pulmonary rehabilitation with multidimensional response profiling could aid efficiency and effectiveness <http://ow.ly/TouTt> Clinical practice should be based on the best scientific evidence, which does not always correspond to evidence-based medicine, involving guidelines, meta-analyses and protocols as a basis for clinical approach [1, 2]. There is no need of further randomised controlled trials (RCTs) for evidence that pulmonary rehabilitation (PR) improves daily symptoms, exercise performance and health status in patients with chronic obstructive pulmonary disease (COPD), independently of disease stage and complexity [3]. Although the direct demonstration of a clear benefit in survival is lacking (as is also true for most therapies used in COPD), PR is well recognised as a fundamental part of the integrated care of these patients and it has been incorporated in most guidelines for their management [4].