tbuckley/cabot-search huggingface dataset:
Single-agent activity of weekly gemcitabine in advanced non-small-cell lung cancer: a phase II study.
Authors: H Anderson, B Lund, F Bach, N Thatcher, J Walling, H H Hansen
Journal: Journal of Clinical Oncology (1994)

PURPOSE To evaluate the efficacy and safety of gemcitabine, a pyrimidine antimetabolite with activity against solid tumours. PATIENTS AND METHODS Eighty-two patients with unresectable stage IIIa to IV non-small-cell lung cancer (NSCLC) were entered. The first 54 patients received gemcitabine 800 mg/m2, and subsequent patients 1,000 mg/m2, as a 30-minute intravenous infusion on days 0, 7, and 14. Courses of therapy were repeated every 28 days. Twenty percent dosage escalation was permitted after course no.1 if World Health Organization (WHO) toxicity was &lt; or = 1. RESULTS Sixteen (20%; 95% confidence interval [CI], 12% to 31%) of 79 patients assessable for response had independently validated partial responses, with a median duration of 7 months. The overall median survival duration was 7 months. Gemcitabine improved disease-related symptoms (70% patients) and increased WHO performance status (44%). Toxicity was generally mild and reversible. Patients experienced little WHO grade 3 and 4 toxicity, with anemia in four (5%), thrombocytopenia in one (1%), leukopenia in six (7%), and neutropenia in 18 (22%). Infection occurred in nine patients (12%) during the study (four were neutropenic), but there were no episodes of WHO grade 3 or 4 infection. WHO grade 3 and 4 biochemical toxicity occurred with transient elevations of transaminases in 10 patients (12%). Two patients had transient WHO grade 3 elevation of serum creatinine levels, and two developed acute renal failure 4 and 6 weeks after the last dose of gemcitabine. There was no WHO grade 4 symptomatic toxicity. WHO grade 3 vomiting occurred in 31 patients (38%) and grade 3 alopecia in one (1%). Flu-like symptoms were associated with gemcitabine administration in 36 patients (44%). Twenty-six patients (32%) experienced fever (1% WHO grade 3), 33 (40%) ankle edema not associated with cardiac failure, 31 (38%) lethargy, and 11 (13%) dyspnea. CONCLUSION Gemcitabine is an active new agent in the treatment of NSCLC. This schedule was associated with little alopecia or myelosuppression. Gemcitabine warrants further investigation in other malignancies and in combination with other agents.
Bilateral Osteonecrosis of the Tarsus Coincident with Glioblastoma Multiforme
Authors: Manolis Heliotis, Eleftherios Tsiridis, Simon T Donell, Thomas J Marshall, David G Scott
Journal: Journal of the Royal Society of Medicine (2001)

The presence of two rare conditions in a single patient—bilateral osteonecrosis of the tarsal bones and glioblastoma multiforme of the brain—raises the possibility of a causal association.
Surveying the practice of arterialised earlobe capillary blood gas sampling amongst respiratory specialists practitioners
Authors: Jane Young, Karl Sylvester, Jonathan Fuld
Journal: European Respiratory Journal (2013)

Background: Current demand for domically oxygen therapy has resulted in an increased need for blood gas analysis in primary and secondary care settings. Arterialised earlobe blood gas analysis has been deemed an appropriate blood sampling method by which to collect arterial blood for analysis, largely underpinned by data from skin puncture obtained with a scalpel blade and a bung. There is currently no national standardised guideline to inform the best practical approach to the technique.  Method: A questionnaire designed to investigate local sampling practice was distributed to respiratory specialist practitioners at an annual national nurse conference.  Results: 23 organisations were represented: 8 Primary Care, 12 Secondary Care, 1 Community Hospital, 1 Lung Centre, 1 Unknown. All undertook earlobe capillary blood sampling, with none reporting finger tip sampling. 18 used vasodilatation. Skin puncture tool usage: 17 utilised lancets, with 4 using bungs/corks for earlobe support (Mean incision attempts 1.4, range 1-4) 3 utilised needles (mean incision attempts 1.5, range 1-3) 3 utilised scalpel blades all with rubber bungs for earlobe support (mean incision attempts 1.6, range 1-2). Reported sample time across all devices ranged few seconds to five minutes.  Conclusion: There is a variable approach by which arterialised earlobe capillary blood sampling is obtained. More over there is little use of scalpel sampling, on which evidence to support the technique is based. This variability questions the accuracy of the sample obtained and the clinical decisions made upon them, and requires further research.
Effect of Mandatory Centers of Excellence Designation on Demographic Characteristics of Patients Who Undergo Bariatric Surgery
Authors: Junun Bae, Jaime Shade, Amanda Abraham, Brianna Abraham, Leigh Peterson, Eric B. Schneider, Thomas H. Magnuson, Michael A. Schweitzer, Kimberly E. Steele
Journal: JAMA Surgery (2015)

<h3>Importance</h3> From February 21, 2006, through September 24, 2013, the Centers for Medicare &amp; Medicaid Services (CMS) required, via the National Coverage Determination manual, that bariatric surgery be performed only in hospitals that had been designated as a Center of Excellence (COE). The effect of this certification requirement on access to bariatric surgery has been reported only anecdotally. <h3>Objective</h3> To investigate whether the COE certification requirement proved to be a barrier to patients' access to bariatric surgical procedures. <h3>Design, Setting, and Participants</h3> Using the National Inpatient Sample, we retrospectively identified patients who underwent bariatric surgery from January 1, 2006, through December 31, 2011. <h3>Exposure</h3> Bariatric surgery. <h3>Main Outcomes and Measures</h3> Logistic regression and<i>χ2</i>tests were used to examine differences in patients' sociodemographic characteristics over time. <h3>Results</h3> A total of 134 227 bariatric surgical patients were identified. The proportion of the population who were older than 64 years increased from 2.9% in 2006 to 7.0% in 2011 (<i>P</i> &lt; .001) and there was a decrease in the proportion of patients who were 49 years and younger (<i>P</i> &lt; .001). The percentage of female patients who underwent bariatric surgery decreased from 80.4% to 78.1% (<i>P</i> &lt; .001) and the percentage of patients who were classified as black, Hispanic, or Asian or Pacific Islander increased from 12.3% to 15.1% (<i>P</i> &lt; .001), 9.7% to 12.5% (<i>P</i> &lt; .001), and 0.3% to 0.4% (<i>P</i> &lt; .001), respectively. The proportion of patients with Medicare increased from 8.5% to 16.3% (<i>P</i> &lt; .001) and those with Medicaid from 6.6% to 11.8% (<i>P</i> &lt; .001). The percentage of patients with private insurance declined from 72.4% to 63.3% (<i>P</i> &lt; .001). The proportion of patients in the lowest income quartile increased from 20.7% to 22.9% (<i>P</i> &lt; .001) while those in the highest income quartile decreased from 25.8% to 23.9% (<i>P</i> &lt; .001). <h3>Conclusions and Relevance</h3> The COE certification requirement by CMS did not appear to limit access to bariatric surgery. Future studies should determine whether CMS's recent (2013) change in policy (ie, removing the mandatory COE certification for bariatric surgical insurance coverage) might sacrifice patient safety without addressing the real cause of limited access to health care.
Phase II trial of docetaxel in patients with advanced or metastatic transitional-cell carcinoma.
Authors: J A McCaffrey, S Hilton, M Mazumdar, S Sadan, W K Kelly, H I Scher, D F Bajorin
Journal: Journal of Clinical Oncology (1997)

PURPOSE A phase II trial of docetaxel was conducted to assess its efficacy and toxicity in patients with advanced transitional-cell carcinoma (TCC) who had failed to respond to prior cisplatin-based therapy. PATIENTS AND METHODS Thirty assessable patients who had failed to respond to or relapsed after one prior cisplatin-containing regimen were treated with docetaxel 100 mg/m2 over 1 hour, every 21 days. All patients were premedicated with dexamethasone and diphenhydramine to reduce allergic reactions. Reductions of subsequent doses were made for severe hematologic toxicity. Prophylactic hematopoietic growth factors were not used. RESULTS Four of 30 patients (13.3%; 95% confidence interval [CI], 3.8% to 30.7%) demonstrated a partial response (PR), with durations of response ranging from 3 to 8 months. The estimated median survival duration for all patients is 9 months (95% CI, 6 to 12 months) with a median follow-up time of 14 months (range, 1 to 27). Hematologic toxicity included anemia, thrombocytopenia, neutropenia, and febrile neutropenia. Nonhematologic toxicity included alopecia and mucositis. Fluid retention was not observed and cutaneous toxicity was mild and infrequent. Dose reductions were necessary for adverse events in 18 patients (60%). CONCLUSION Docetaxel is an active single agent in previously treated patients with TCC of the urothelial tract. Therapy was well tolerated in this patient population but myelosuppression was frequent. Further study in previously untreated patients, both alone and in combination, is warranted.
Outcomes and Prognostic Factors in Recurrent Glioma Patients Enrolled Onto Phase II Clinical Trials
Authors: Eric T. Wong, Kenneth R. Hess, Mary Jo Gleason, Kurt A. Jaeckle, Athanassios P. Kyritsis, Michael D. Prados, Victor A. Levin, W.K. Alfred Yung
Journal: Journal of Clinical Oncology (1999)

PURPOSE: To determine aggregate outcomes and prognostic covariates in patients with recurrent glioma enrolled onto phase II chemotherapy trials. PATIENTS AND METHODS: Patients from eight consecutive phase II trials included 225 with recurrent glioblastoma multiforme (GBM) and 150 with recurrent anaplastic astrocytoma (AA). Their median age was 45 years (range, 15 to 82 years) and their median Karnofsky performance score was 80 (range, 60 to 100). Prognostic covariates were analyzed with respect to tumor response, progression-free survival (PFS), and overall survival (OS) by multivariate logistic and Cox proportional hazards regression analyses. RESULTS: Overall, 34 (9%) had complete or partial response, whereas 80 (21%) were alive and progression-free at 6 months (APF6). The median PFS was 10 weeks and median OS was 30 weeks. Histology was a robust prognostic factor across all outcomes. GBM patients had significantly poorer outcomes than AA patients. The APF6 proportion was 15% for GBM and 31% for AA, whereas the median PFS was 9 weeks for GBM and 13 weeks for AA. Results were also significantly poorer for patients with more than two prior surgeries or chemotherapy regimens. CONCLUSION: Histology is a dominant factor in determining outcome in patients with recurrent glioma enrolled onto phase II trials. Future trials should be designed with separate histology strata.
Respiratory muscle training (REMT) with normocapnic hyperpnoea (NH) improves respiratory muscle strength, exercise performance and ventilatory pattern in COPD patients
Authors: Eva Bernardi, Luca Pomidori, Gaia Mandolesi, Gianluca Grassi, Annalisa Cogo
Journal: European Respiratory Journal (2012)

Few data are available about the effect of RMET in COPD patients even if it has been shown that RMET improves endurance performance and decreases VE during exercise in healthy subjects.  Aim: To evaluate the effect of 4 weeks of RMET with NH (Spirotiger®) on respiratory function and exercise capacity in 23 moderate/severe COPD patients.  Materials and Methods: 20 M, 3 F (aged 42-80). Respiratory function tests (FEV1, FVC, MIP), QoL (St George9s Questionnaire), 6MWT and endurance exercise test (75-80% of peak-work rate measured during an incremental test and performed to the limit of tolerance, tLIM).  9 of 21 patients were instrumented with a portable inductive plethysmografhy (Lifeshirt System) to evaluate breathing pattern during exercise test. After 4 supervised training sessions, the patients trained at home for 4 weeks: 10 min twice a day roughly at 55% of MVV (FEV1x0,375).  Results are reported in Tab.1 and Tab.2.  6 patients dropped out (poor compliance).  Ventilatory pattern after RMT, during tLIM, is characterized by a significantly lower trend of VE and RR with a higher TV (p  Conclusion: After a short RMT, COPD patients show an improvement in MIP, QoL, a higher exercise capacity and an intriguing change in ventilatory pattern during exercise, which improves SpO2.
Tumor Induction in Germfree Rats With Methylazoxymethanol (MAM) and Synthetic MAM Acetate&lt;xref ref-type="fn" rid="FN1"&gt;2&lt;/xref&gt;
Authors: G L Laqueur, E G McDaniel, H Matsumoto
Journal: JNCI Journal of the National Cancer Institute (1967)

The glucoside cycasin, an effective hepatotoxin and carcinogen in conventional rats, fails to produce these effects when administered to germfree rats. The hepatotoxic and carcinogenic effects of cycasin can also be elicited after prior hydrolysis to the aglycone. The aglycone (MAM) and the synthetic aglycone acetate ester produce all the effects in germfree rats of which the intact glucoside is capable only when fed to conventional rats. The aglycone is therefore the proximate carcinogen. Its liberation from the glucoside in conventional rats is mediated in the intestinal tract by a beta-glucosidase of bacterial origin. Intraperitoneal administration of the synthetic aglycone acetate and the free aglycone appears to be the most effective route for tumor induction and, of these resulting tumors, the most frequent are in the intestinal tract.
Molecular and clinical diseasome of comorbidities in exacerbated COPD patients
Authors: Rosa Faner, Alba Gutiérrez-Sacristán, Ady Castro-Acosta, Solène Grosdidier, Wenqi Gan, Milagros Sánchez-Mayor, Jose Luis Lopez-Campos, Francisco Pozo-Rodriguez, Ferran Sanz, David Mannino, Laura I. Furlong, Alvar Agusti
Journal: European Respiratory Journal (2015)

The frequent occurrence of comorbidities in patients with chronic obstructive pulmonary disease (COPD) suggests that they may share pathobiological processes and/or risk factors. To explore these possibilities we compared the clinical diseasome and the molecular diseasome of 5447 COPD patients hospitalised because of an exacerbation of the disease . The clinical diseasome is a network representation of the relationships between diseases, in which diseases are connected if they co-occur more than expected at random; in the molecular diseasome, diseases are linked if they share associated genes or interaction between proteins. The results showed that about half of the disease pairs identified in the clinical diseasome had a biological counterpart in the molecular diseasome, particularly those related to inflammation and vascular tone regulation. Interestingly, the clinical diseasome of these patients appears independent of age, cumulative smoking exposure or severity of airflow limitation. These results support the existence of shared molecular mechanisms among comorbidities in COPD.
Essentials of sports nutrition, second edition
Authors: K Inge
Journal: British Journal of Sports Medicine (2004)

Fred Brouns. John Wiley and Sons, 2002, £24.95, pp 227, softcover. ISBN 0471497657

The author summarises the aim of this book in his preface as “to give a scientific but easily understandable overview of aspects related to nutrition and physical activity”, and it does just that.

Having published numerous scientific studies himself, this well respected author, Brouns, is certainly qualified to write such a text. …
Risk-based recommendations for mammographic screening for women in their forties.
Authors: M Gail, B Rimer
Journal: Journal of Clinical Oncology (1998)

PURPOSE To develop risk-based recommendations for mammographic screening for women in their 40s that take into account the woman's age, race, and specific risk factors. METHODS We assumed that regular mammographic screening is justified for a 50-year-old woman, even one with no risk factors, and that a younger woman with an expected 1-year breast cancer incidence rate as great or greater than that of a 50-year-old woman with no risk factors would benefit sufficiently to justify regular screening. Recommendations under this criterion were based on age- and race-specific breast cancer incidence rates from the National Cancer Institute's (NCI's) Surveillance, Epidemiology, and End Results (SEER) Program; assessments of risk factors from the Breast Cancer Detection and Demonstration Project (BCDDP); and reports in the literature. RESULTS Two methods, the exact-age procedure (EAP) and the grouped-age procedure (GAP), were developed. The less precise GAP only requires following a flow diagram. The proportion of white women recommended for screening by the EAP ranges from 10% for 40-year-old women to 95% for 49-year-old women, and the corresponding percentages for black women are 16% and 95%. The assumptions that underlie the guidelines are discussed critically. CONCLUSION For women or physicians who prefer an individualized approach in deciding whether to initiate regular mammographic screening in the age range of 40 to 49 years, the present report offers recommendations based on individualized risk-factor data and clearly stated assumptions that have an empiric basis. These recommendations can be used to facilitate the counseling process.
Abstract 79: Mitochondrial Mechanisms of Structural and Electrical Remodeling in Atrial Fibrillation
Authors: Cevher Ozcan, Emily Battaglia, Rebeccah Young, Gen Suzuki, John M Canty
Journal: Circulation Research (2014)

Background: The mechanisms responsible for atrial electro-anatomic remodeling during the development of atrial fibrillation (AF) are not known. Mitochondria determine atrial myocyte cell survival and function by regulating cellular oxidative and metabolic stress. We therefore postulated that mitochondria play a central role in the remodeling of atrial myocardium and the pathogenesis of AF. Methods: Our hypothesis was tested in a novel murine model (cardiac specific LKB1 knockout (KO)) where there is a high rate of sinus rhythm progressing to AF (95% of mice). Structural and electrophysiological properties of atria were studied in sinus rhythm and AF. Multiple parameters including the ECG, cardiac MRI, echocardiography, histopathology and immunoblotting in KO mice were compared with age- and gender-matched wild type controls. Results: LKB1 KO mice developed biatrial enlargement while in sinus rhythm that progressively increased as persistent AF developed. Apoptotic and necrotic myocyte death produced a substantial reduction in atrial cardiomyocytes (44%) that was replaced by fibrosis (34% vs 4.9%, p&lt;0.05) and non-myocyte cells. In KO atria, there was a 6 fold increase in TUNEL positive nuclei and significant elevations of caspase 3 (10.4±1 vs 3.6±0.5 AU, p&lt;0.05) and caspase 9 (1.4±0.1 vs 0.7±0.06 AU, p&lt;0.05) activity. Mitochondrial reactive oxygen species were increased in KO atria (13.6±0.7 vs. 4.2±1 AU, p&lt;0.05). In addition to extracellular matrix remodeling, cell-to-cell coupling was disrupted in KO atria with reduced gap junction proteins such as connexin 40 (0.24±0.03 vs 0.82±0.01 AU, p&lt;0.05) and connexin 43 (1.4±0.1 vs 14.4±1 AU) (p&lt;0.05). Electron microscopy showed impaired ultrastructure of mitochondrion and myofibrils in atrial myocytes. Conclusions: We conclude that mitochondria play a pivotal role in the genesis of AF. Mitochondrial ROS generation and caspase activation lead to progressive cardiomyocyte loss and the transition of sinus rhythm to paroxysmal and persistent AF. These findings raise the possibility that therapies directed at maintaining atrial mitochondrial function may prevent the development of chronic AF.
The positive relationship between alcohol and heart disease in eastern Europe: potential physiological mechanisms
Authors: Martin Mckee, Annie Britton
Journal: Journal of the Royal Society of Medicine (1998)

Research into the effect of alcohol on cardiovascular disease has indicated protective effects from moderate consumption. These observations, made in industrialized countries, have influenced policies on alcohol in countries where the situation may be quite different—specifically, where consumption is substantially higher or patterns of drinking are different. In central and eastern Europe and the former Soviet Union, a growing body of epidemiological research indicates a positive rather than negative association between alcohol consumption and cardiovascular deaths, especially sudden cardiac deaths. By means of a systematic review of published work, we examine whether there is a physiological basis for the observed association between alcohol and heart disease seen in eastern Europe, focusing on the effects of high levels of consumption and of irregular or binge drinking. In binge drinkers, cardioprotective changes in high-density lipoproteins are not seen, and adverse changes in low-density lipoproteins are acquired. Irregular drinking is associated with an increased risk of thrombosis, occurring after cessation of drinking. It predisposes both to histological changes in the myocardium and conducting system and to a reduction in the threshold for ventricular fibrillation. Measures of frequency as well as quantity of consumption should be included in epidemiological studies. Taken with the epidemiological evidence emerging from eastern Europe, these observations have important implications for estimates of the burden of disease attributable to alcohol.
Autophagy induction by low dose cisplatin; the role of p53 in autophagy
Authors: Sei Hoon Yang, Kang Kyoo Lee, Sun Rock Moon
Journal: European Respiratory Journal (2012)

Cisplatin has been mainly used for lung-cancer,. However, cisplatin has many side effects, so the usage of cisplatin has a limitation. Recently, autophagy has become an important mechanism of cell death. The purpose of this study was to determine whether low dose cisplatin treated lung cancer cell induce autophagy and the autophagy inhibition resulted in apoptosis or necrosis. H460 cells were treated with 5 μM or 20 μM cisplatin for 12, 24, or 48 h. To detect the cisplatin-induced autophagy, we examined the autophagic vacuoles, and LC3 localization. To confirm the low-dose of cisplatin could induce autophagy, we detectd acidic vesicle using autophagy specific inhibitors(3-MA). To confirm the result of autophagy inhibition, we had done Annexin-V/PI and cell cycle assay. To find out the cisplatin mediated autophagic mechanisms, we examined the apoptotic regulator, p53. We used p53-/- null cancer cell line, H1299, to prove the role of p53 during autophagy. Low dose of cisplatin(5 μM) induced the autophagy after 24 h treatment in H460. Also low dose of cisplatin showed autophagic vacuoles and cytoplasmic LC3 formation in H460. The induction of autophagy by low dose cisplatin was inhibited by 3-MA, which was proven by reduced acidic vesicles. When the autohpagy inhibited, Annexin-V+/PI- and subG1 was an increased. The inhibition of autophagy resulted in decrease of LC3B-II band. Also cleaved caspase-3 and PARP were increased. Taken together, low dose cisplatin induced autophagy and the inhibition of autophagy resulted in the apoptosis.