tbuckley/cabot-search huggingface dataset:
Memory for symptoms in COPD patients: how accurate are their reports?
Authors: P.M. Meek, S.C. Lareau, D. Anderson
Journal: European Respiratory Journal (2001)

The purpose of this study was to examine the accuracy of self-reports of symptom intensity in patients with chronic obstructive pulmonary disease (COPD) and factors that might influence recall of that intensity. Thirty COPD (forced expiratory volume in one second (FEV 1 ) 36±17% predicted) subjects recorded their dyspnoea and fatigue intensity scores on a 0–10 scale for 14 consecutive days. On the fourteenth day, subjects recalled their average, greatest and least symptom intensity for the previous 14 days. General cognitive function, spirometry, and oxygenation were also measured. No significant differences were found between actual and recalled scores for dyspnoea or fatigue. General cognitive function, measured by the Mini Mental State Exam, correlated with the greatest and least dyspnoea and average fatigue difference scores (recall-actual) and contributed to the variance in the average and least dyspnoea recalled scores. The greatest contributor to the variance in the recall scores of both symptoms was the symptom intensity level on the day of recall. These results highlight the importance of current levels of symptom intensity and cognitive function when appraising symptoms in chronic obstructive pulmonary disease patients.
Treatment of Mild to Moderate Obesity with Laparoscopic Adjustable Gastric Banding or an Intensive Medical Program
Authors: Paul E. O'Brien, John B. Dixon, Cheryl Laurie, Stewart Skinner, Joe Proietto, John McNeil, Boyd Strauss, Sharon Marks, Linda Schachter, Leon Chapman, Margaret Anderson
Journal: Annals of Internal Medicine (2006)

Background: Obesity is a major, growing health problem. Observational studies suggest that bariatric surgery is more effective than nonsurgical therapy, but no randomized, controlled trials have confirmed this. Objective: To ascertain whether surgical therapy for obesity achieves better weight loss, health, and quality of life than nonsurgical therapy. Design: Randomized, controlled trial. Setting: University departments of medicine and surgery and an affiliated private hospital. Patients: 80 adults with mild to moderate obesity (body mass index, 30 kg/m2 to 35 kg/m2) from the general community. Interventions: Patients were assigned to a program of very-low-calorie diets, pharmacotherapy, and lifestyle change for 24 months (nonsurgical group) or to placement of a laparoscopic adjustable gastric band (LAP-BAND System, INAMED Health, Santa Barbara, California) (surgical group). Measurements: Outcome measures were weight change, presence of the metabolic syndrome, and change in quality of life at 2 years. Results: At 2 years, the surgical group had greater weight loss, with a mean of 21.6% (95% CI, 19.3% to 23.9%) of initial weight lost and 87.2% (CI, 77.7% to 96.6%) of excess weight lost, while the nonsurgical group had a loss of 5.5% (CI, 3.2% to 7.9%) of initial weight and 21.8% (CI, 11.9% to 31.6%) of excess weight (P < 0.001). The metabolic syndrome was initially present in 15 (38%) patients in each group and was present in 8 (24%) nonsurgical patients and 1 (3%) surgical patient at the completion of the study (P < 0.002). Quality of life improved statistically significantly more in the surgical group (8 of 8 subscores of Short Form-36) than in the nonsurgical group (3 of 8 subscores). Limitations: The study included mildly and moderately obese participants, was not powered for comparison of adverse events, and examined outcomes only for 24 months. Conclusions: Surgical treatment using laparoscopic adjustable gastric banding was statistically significantly more effective than nonsurgical therapy in reducing weight, resolving the metabolic syndrome, and improving quality of life during a 24-month treatment program.
Therapeutic Role of Bisphosphonate and Radiation Combination in the Management of Myeloma Bone Disease
Authors: A. Ugur Ural, Ferit Avcu
Journal: Clinical Cancer Research (2007)

To the Editors: We read the interesting article by Yeh and Berenson ([1][1]) on the therapeutic strategies, such as radiation, surgery, and bisphosphonate therapy, in the management of myeloma bone disease, which is a major cause of morbidity for patients with multiple myeloma. An imidazole-
RETRACTED ARTICLE: Effects of HDM2 antagonism on sunitinib resistance, p53 activation, SDF-1 induction, and tumor infiltration by CD11b+/Gr-1+ myeloid derived suppressor cells
Authors: David J Panka, Qingjun Liu, Andrew K Geissler, James W Mier
Journal: Molecular Cancer (2013)

Abstract Background The studies reported herein were undertaken to determine if the angiostatic function of p53 could be exploited as an adjunct to VEGF-targeted therapy in the treatment of renal cell carcinoma (RCC). Methods Nude/beige mice bearing human RCC xenografts were treated with various combinations of sunitinib and the HDM2 antagonist MI-319. Tumors were excised at various time points before and during treatment and analyzed by western blot and IHC for evidence of p53 activation and function. Results Sunitinib treatment increased p53 levels in RCC xenografts and transiently induced the expression of p21 waf1 , Noxa, and HDM2, the levels of which subsequently declined to baseline (or undetectable) with the emergence of sunitinib resistance. The development of resistance and the suppression of p53-dependent gene expression temporally correlated with the induction of the p53 antagonist HDMX. The concurrent administration of MI-319 markedly increased the antitumor and anti-angiogenic activities of sunitinib and led to sustained p53-dependent gene expression. It also suppressed the expression of the chemokine SDF-1 (CXCL12) and the influx of CD11b + /Gr-1 + myeloid-derived suppressor cells (MDSC) otherwise induced by sunitinib. Although p53 knockdown markedly reduced the production of the angiostatic peptide endostatin, the production of endostatin was not augmented by MI-319 treatment. Conclusions The evasion of p53 function (possibly through the expression of HDMX) is an essential element in the development of resistance to VEGF-targeted therapy in RCC. The maintenance of p53 function through the concurrent administration of an HDM2 antagonist is an effective means of delaying or preventing the development of resistance.
Systemic inflammation in COPD visualised by gene profiling in peripheral blood neutrophils
Authors: E-J D Oudijk
Journal: Thorax (2005)

The inflammatory process in chronic obstructive pulmonary disease (COPD) is characterised by the presence of neutrophils in the lung that are able to synthesise de novo several inflammatory mediators. The local chronic persistent inflammatory response is accompanied by systemic effects such as cytokine induced priming of peripheral leucocytes and muscle wasting. The preactivation or priming of peripheral blood neutrophils was used to gain more insight into the mechanisms of this systemic inflammatory response.Gene arrays were performed on peripheral blood neutrophils obtained from healthy donors after stimulation in vitro with tumour necrosis factor (TNF)-alpha, granulocyte-macrophage colony stimulating factor (GM-CSF), or both. The expression of many inflammatory genes was regulated in these cells following stimulation. The expression of inflammatory genes in peripheral blood neutrophils in healthy subjects and those with COPD was measured by real time RT-PCR after stimulation with TNFalpha, GM-CSF, interleukin (IL)-8, fMLP, TNFalpha + GM-CSF, and lipopolysaccharide (LPS).The genes regulated in the gene array with TNFalpha/GM-CSF stimulated neutrophils included cytokines (such as IL-1beta), chemokines (such as IL-8), and adhesion molecules (such as ICAM-1). Disease severity as measured by forced expiratory volume in 1 second (FEV(1)) in COPD patients correlated with expression of several of these genes including IL-1beta (r = -0.540; p = 0.008), MIP-1beta (r = -0.583; p = 0.003), CD83 (r = -0.514; p = 0.012), IL-1 receptor 2 (r = -0.546; p = 0.007), and IL-1 receptor antagonist (r = -0.612; p = 0.002).These data are consistent with the hypothesis that progression of COPD is associated with the activation of neutrophils in the systemic compartment. De novo expression of inflammatory mediators by peripheral blood neutrophils suggests a pro-inflammatory role for these cells in the pathogenesis of COPD.
Neurokinin A is the predominant tachykinin in human bronchoalveolar lavage fluid in normal and asthmatic subjects
Authors: L G Heaney, L J M Cross, L P A McGarvey, K D Buchanan, M Ennis, C Shaw
Journal: Thorax (1998)

<h3>BACKGROUND</h3> Multiple sensory neuropeptides are present in human airways and may contribute to diseases such as asthma. This study quantified and characterised substance P (SP), neurokinin A (NKA), and calcitonin gene related peptide (CGRP) immunoreactivity in bronchoalveolar lavage fluid in asthmatic and normal subjects. <h3>METHODS</h3> Using specific radioimmunoassay (RIA), SP, NKA and CGRP were measured in bronchoalveolar lavage fluid from asthmatic subjects (n = 5), normal subjects (n = 5), atopic non-asthmatic subjects (n = 6), and asthmatic subjects four hours after allergen challenge (n = 12). Peptide immunoreactivity was characterised using high performance liquid chromatography (HPLC) and RIA. <h3>RESULTS</h3> No SP or CGRP immunoreactivity was detected in any of the fractions from samples after extraction, HPLC, and RIA. Non-specific binding resulted in spurious SP immunoreactivity being detected in bronchoalveolar lavage fluid when no extraction process was employed. NKA was detected in significant amounts in asthmatic (median 550, range 425–625 pg/ml) and normal subjects (median 725, range 350–1425 pg/ml). The level of NKA was significantly higher in the asthmatic subjects after allergen challenge (median 750, range 350–1250 pg/ml) than in unchallenged asthmatic subjects (median 600, range 425–600 pg/ml, p&lt;0.01). <h3>CONCLUSIONS</h3> Extraction and characterisation of peptides from bronchoalveolar lavage fluid must be performed to ensure that the measured immunoreactivity represents target peptide. NKA is present in bronchoalveolar lavage fluid in high concentrations and is the predominant tachykinin. The concentrations of NKA are similar in normal subjects and subjects with mild asthma.
Is "boarding" appropriate to help reduce crowding in emergency departments?
Authors: A. Boyle, P. Viccellio, C. Whale
Journal: BMJ (2015)

Moving patients from full emergency departments to corridors outside full wards is safe and necessary when accommodating new emergencies, say <b>Adrian Boyle</b> and <b>Peter Viccellio</b>. But <b>Chris Whale</b> warns of the danger in simply displacing the problem and wants a more comprehensive response to inefficient patient flow
Influence of Year of Diagnosis, Patient Age, and Sociodemographic Status on Recommending Adjuvant Radiation Treatment for Stage I Testicular Seminoma
Authors: Karen E. Hoffman, Ming-Hui Chen, Rinaa S. Punglia, Clair J. Beard, Anthony V. D'Amico
Journal: Journal of Clinical Oncology (2008)

Purpose Adjuvant radiation therapy (ART) for stage I seminoma can cause adverse late effects and alternative postorchiectomy management strategies have been developed. This study evaluated ART trends in the United States and the impact of clinical and sociodemographic factors on ART recommendations. Methods Of men diagnosed with stage I seminoma from 1990 through 2004, 3,125 were identified using the Surveillance, Epidemiology, and End Results cancer registry. A multivariable logistic regression analysis was performed to assess whether there was a significant association between diagnosis year, diagnosis age, race, county education level, region, tumor size, tumor category, and the recommendation for ART. Results There was a significant association (P &lt; .001) between later year of diagnosis and a decrease in ART recommendation. Compared with men diagnosed in 1990 to 1994, men diagnosed in 1995 to 1999, and 2000 to 2004 were less likely to have ART (adjusted odds ratio [OR], 0.63; 95% CI, 0.48 to 0.84; and OR, 0.49; 95% CI, 0.37 to 0.63, respectively). There also was a significant association (P &lt; .001) between county education level and ART recommendation. Men residing in counties with the highest education level were more likely to receive ART than men residing in counties with the lowest education level (OR, 2.12; 95% CI, 1.59 to 2.82). Also, men older than 30 years were more likely to receive ART than men age 30 or younger (OR, 1.26; 95% CI, 1.03 to 1.55). Conclusion ART recommendations for stage I seminoma are declining. Men in less educated regions and the youngest men were less likely to receive a recommendation for ART.
Unrelated Donor Bone Marrow Transplantation for Chronic Myelogenous Leukemia: A Decision Analysis
Authors: Stephanie J. Lee
Journal: Annals of Internal Medicine (1997)

Background: Chronic myelogenous leukemia (CML) is an indolent but ultimately fatal disease. Because the natural history of CML varies and quality of life with CML may be excellent until shortly before death, deciding whether and when to pursue unrelated donor bone marrow transplantation is often difficult. Objective: To compare early transplantation, delayed transplantation, and no transplantation for patients with chronic-phase CML on the basis of discounted, quality-adjusted life expectancy. Design: A Markov model comparing different strategies was constructed. This model considers patient age, quality of life, risk aversion, and the competing risks for CML progression and transplant toxicity. Setting: Therapeutic decision at the time of diagnosis of CML. Patients: The base case is a 35-year-old patient with intermediate-prognosis CML. Younger and older patients with better and worse prognoses are also evaluated. Intervention: Early transplantation, delayed transplantation, and no transplantation. Measurements: Quality-adjusted, discounted life expectancy. Results: For patients with newly diagnosed CML, transplantation within the first year provides the greatest quality-adjusted expected survival, although this benefit decreases with increasing patient age. For a 35-year-old patient with intermediate-prognosis CML, transplantation within the first year results in 5.3 more discounted, quality-adjusted years of life expectancy than does no transplantation. This finding is robust even with varying baseline assumptions. Conclusions: These results support the use of early unrelated donor bone marrow transplantation for most patients with CML.
Mortality and incidence of cancer during 10-year follow-up of the Scandinavian Simvastatin Survival Study (4S)
Authors: Timo E Strandberg, Kalevi Pyörälä, Thomas J Cook, Lars Wilhelmsen, Ole Faergeman, Gudmundur Thorgeirsson, Terje R Pedersen, John Kjekshus
Journal: The Lancet (2004)
Preparation and evaluation of sustained-release diltiazem hydrochloride pellets
Authors: Xiaopeng Han, Linan Wang, Yinghua Sun, Xiaohong Liu, Wanjun Liu, Yuqian Du, Lin Li, Jin Sun
Journal: Asian Journal of Pharmaceutical Sciences (2013)

In this study, diltiazem hydrochloride (DTZ) pellets were prepared successfully by extrusion–spheronization method. Then methacrylic acid and ethylcellulose coating formulations were employed to make the DTZ pellets sustained release. The pellets with different coatings were investigated by in vitro dissolution tests. At last, the pellets with the best coating copolymer were subjected to pharmacokinetic studies in beagle dogs. The dissolution profiles of pellets coated with Eudragit® NE30D were similar to Herbesser®, one of the marketed sustained release capsules. In the bioavailability study, the principal pharmacokinetic parameters of self-made pellets and the marketed ones were comparable; the relative bioavailability of DTZ sustained release capsules compared with Herbesser® was 98.5 ± 36.4%. All the data indicated self-made sustained pellets could prolong the release of DTZ, decrease the fluctuation of drug level in vivo, and increase the compliance of patients.
Phase I Pharmacokinetic and Pharmacodynamic Study of Weekly 1-Hour and 24-Hour Infusion BMS-214662, a Farnesyltransferase Inhibitor, in Patients With Advanced Solid Tumors
Authors: Josep Tabernero, Fredy Rojo, Irene Marimón, Maurizio Voi, Joan Albanell, Marta Guix, Federico Vázquez, Joan Carulla, Michael Cooper, Jordi Andreu, Anne Van Vreckem, Joaquim Bellmunt, Veeraswamy Manne, James A. Manning, Carmen Garrido, Enriqueta Felip, Josep Maria del Campo, Mónica García, Sonia Valverde, José Baselga
Journal: Journal of Clinical Oncology (2005)

Purpose BMS-214662 is a potent, nonpeptide, small molecule inhibitor of human farnesyltransferase (FT). We have conducted a phase I pharmacokinetic (PK) and pharmacodynamic study of BMS-214662 administered intravenously weekly with 1- and 24-hour infusions. The objectives were to determine the dose-limiting toxicities and the recommended dose (RD), to describe PKs, and to evaluate the relationships between BMS-214662 exposure, FT inhibition, downstream signaling, and induction of apoptosis in tumor samples. Patients and Methods Patients with advanced solid tumors and adequate organ function were eligible. The dose was escalated according to a modified Fibonacci schedule. Results BMS-214662 was escalated from 56 to 278 mg/m 2 in 37 patients in the 1-hour schedule, and from 84 to 492 mg/m 2 in 31 patients in the 24-hour schedule. Dose-limiting toxicities included gastrointestinal and renal events. The RDs were 209 mg/m 2 and 275 mg/m 2 in the 1- and 24-hour schedules, respectively. Five patients (three with breast, one with gastric, and one with renal cell cancer) had clinical benefit from treatment. BMS-214662 exhibited linear PKs with area under the concentration-time curves at the RDs of 27 and 32 μM × h in the 1- and 24-hour schedules, respectively. The pattern of FT inhibition in peripheral-blood mononuclear cells at the RDs was different in the two schedules: high (&gt; 80%) but short-lived (≤ 6 hours) in the 1-hour infusion and moderate (&gt; 40%) but long-lived (24 hours) in the 24-hour infusion. BMS-214662 induced apoptosis in tumors but did not inhibit MAPK signaling. Conclusion BMS-214662 can be safely delivered in both the 1-hour and 24-hour infusions at biologically active doses, with the preclinical, PK, and pharmacodynamic profiles favoring the 24-hour schedule.
Thrombocytosis and venous thromboembolism in cancer patients with chemotherapy induced anemia may be related to ESA induced iron restricted erythropoiesis and reversed by administration of IV iron
Authors: David H. Henry, Naomi V. Dahl, Michael A. Auerbach
Journal: American Journal of Hematology (2011)

ESA therapy can increase hemoglobin, decrease blood transfusions, and improve quality of life in patients with chemotherapy induced anemia (CIA). Despite its benefits, ESA therapy increases the risk of venous thromboembolism (VTE) in cancer patients by 50% and can also cause iron restricted erythropoiesis in CIA patients, which may augment the tendency to develop VTE. We postulated that thrombocytosis, a risk factor for VTE in cancer patients, in CIA patients on ESA therapy might be a result of ESA induced iron restricted erythropoiesis. We performed a retrospective analysis of 187 CIA patients who were randomized to receive weekly Epoetin and IV ferric gluconate, oral ferrous sulfate, or no iron for 8 weeks. Nineteen patients experienced 29 VTEs, and patients, whose platelets increased to ≥350,000 cells/uL were three times more likely to experience a VTE (OR 2.9, P = 0.036, logistic regression) with a four times greater incidence of VTE (IRR 4.4, P = 0.001, Poisson regression). Patients treated with IV iron were significantly less likely to develop platelets of ≥350,000 cells/uL (IRR 0.7, P = 0.013, Poisson regression) and had a decreased incidence of VTE. Our study suggests that ESA associated VTE in CIA patients may be, in part, related to the thrombocytosis of ESA induced iron restricted erythropoiesis and may be countered by IV iron.
Generation of definitive hematopoietic stem cells from murine early yolk sac and paraaortic splanchnopleures by aorta-gonad-mesonephros region–derived stromal cells
Authors: Sahoko Matsuoka, Kohichiro Tsuji, Hiroaki Hisakawa, Ming-jiang Xu, Yasuhiro Ebihara, Takefumi Ishii, Daisuke Sugiyama, Atsushi Manabe, Ryuhei Tanaka, Yasuo Ikeda, Shigetaka Asano, Tatsutoshi Nakahata
Journal: Blood (2001)
Peripheral Arterial Disease Detection, Awareness, and Treatment in Primary Care
Authors: Alan T. Hirsch
Journal: JAMA (2001)

ERIPHERAL ARTERIAL DISEASE2][3][4][5] A regional pilot study of community screening for PAD demonstrated that patient awareness of the PAD diagnosis was low and associated with low atherosclerosis risk factor, antiplatelet, and claudication treatment intensity. 5There have been no national efforts in the United States to detect PAD in communitybased office practice, to assess both physician and patient awareness of the diagnosis, or to assess the intensity of medical treatments.PAD has not emerged as a focus of public health ef-
Role of surgery in pulmonary multidrug-resistant tuberculosis
Authors: L P. Ormerod
Journal: Thorax (2007)

Feasible in the context of a good national programme in resource-limited settings, but doubts remain over how widely this may be able to be implemented

Multidrug-resistant tuberculosis (MDR-TB) is a form of TB with high level resistance to both isoniazid and rifampicin, with or without associated resistance to other antituberculosis drugs. The spectrum of this form of TB now ranges from “basic” MDR-TB, with resistance only to rifampicin and isoniazid, to XDR-TB where there is additional extensive drug resistance to at least three of the six main classes of second-line antituberculosis drugs.1 The extent of the problem of MDR-TB has been examined by cross-sectional surveys of drug resistance either in clinical series or whole country cohorts by the World Health Organisation (WHO).2 Such cross-sectional surveys, however, underestimate the burden and number of such cases because they do not take into account the amount of TB in high-burden countries. If the exercise is repeated …
A case of primary cutaneous natural killer/T-cell lymphoma, nasal type, with indolent clinical course: monoclonal expansion of Epstein-Barr virus genome correlating with the terminal aggressive behaviour
Authors: D. Watabe, H. Kanno, T. Inoue-Narita, H. Onodera, W. Izumida, S. Kowata, T. Sawai, T. Akasaka
Journal: British Journal of Dermatology (2008)