tbuckley/cabot-search huggingface dataset:
Meta-analysis of the REAL-2 and ML17032 trials: evaluating capecitabine-based combination chemotherapy and infused 5-fluorouracil-based combination chemotherapy for the treatment of advanced oesophago-gastric cancer
Authors: A.F.C. Okines, A.R. Norman, P. McCloud, Y.-K. Kang, D. Cunningham
Journal: Annals of Oncology (2009)

The REAL-2 and ML17032 trials demonstrated that the oral fluoropyrimidine, capecitabine, is noninferior to 5-fluorouracil (5-FU) for overall survival (OS) and progression-free survival (PFS), respectively, in advanced oesophago-gastric cancer.Individual patient data were collected on all patients randomised within the trials (n = 1318). Kaplan-Meier survival curves were generated and the log-rank test was used to compare OS and PFS between patients receiving 5-FU combinations and capecitabine combinations. Stepwise multivariate Cox regression analysis was used to calculate corrected hazard ratios (HRs) and 95% confidence intervals (CIs) for OS and PFS. Logistic regression was used for objective response rate. Forest plots with tests of heterogeneity were generated.OS was superior in the 654 patients treated with capecitabine combinations compared with the 664 patients treated with 5-FU combinations; HR 0.87 (95% CI 0.77-0.98, P = 0.02). Poor performance status, age <60 and metastatic disease were independent predictors of poor survival. There was no significant difference in PFS between treatment groups on multivariate analysis. Assessable patients treated with capecitabine combinations were significantly more likely to have an objective response to treatment than those treated with 5-FU combinations; odds ratio 1.38 (95% CI 1.10-1.73, P = 0.006).OS is superior in patients treated with capecitabine combinations compared with 5-FU combinations in advanced oesophago-gastric cancer.
Interactional Issues as Determinants of Alcoholism
Authors: PETER STEINGLASS, SHELDON WEINER, JACK H. MENDELSON
Journal: American Journal of Psychiatry (1971)

The authors describe the patterns of interactional behavior of three familial pairs of chronic alcoholics before, during, and after a 14-day period of experimentally induced intoxication. Their observations have led them to propose that alcoholic behavior can best be understood in the context of how it contributes to the functioning of an ongoing system. Each of the three pairs described split up at the conclusion of the study; the authors speculate that the rigidity of their drinking systems made them particularly susceptible to the "therapeutic" interventions inherent in the study conditions.
Human Cerebrovascular Response to Combined Hypoxia and Hypercapnia
Authors: WILLIAM SHAPIRO, ALBERT J. WASSERMAN, JOHN L. PATTERSON
Journal: Circulation Research (1966)

The N 2 O technique was used in 6 human subjects to measure cerebral blood flow and metabolism during hypoxia and hypercapnia induced by the inhalation of 10% O 2 -5% CO 2 . Ventilation increased from 7.7 to 46.3 liters/min; Pao 2 decreased from 88 to 62 mm Hg; Paco 2 increased from 38 to 45 mm Hg (for each P &lt;.01). Mean cerebral blood flow increased from 56 to 97 ml/100 g/min ( P &lt;.01). Because cerebral O 2 consumption was unchanged, the technique of estimating changes in cerebral flow from arterial-jugular venous O 2 differences was used to follow changes during the first 10 min of inhalation of 10% O 2 -5% CO 2 in 6 additional subjects. The rapidity of cerebral vasodilatation was increased by this combination of stimuli. The enhanced respiratory response produced by breathing 10% O 2 -5% CO 2 appeared responsible for the more rapid cerebrovascular response and may offer some protective benefits. Comparisons of the present data with previous studies lead to the conclusion that simultaneous hypoxia and hypercapnia have additive dilator effects on the cerebral vasculature. Thus, the observed increases in cerebral flow were the sum of their individual effects.
The effects of glucose-insulin-potassium on experimental myocardial infarction in the dog
Authors: M. K. HENG, R. M. NORRIS, T. PETER, H. D. NISBET, B. N. SINGH
Journal: Cardiovascular Research (1978)

The effect of glucose-insulin-potassium (GIK) infusions was studied in 45 dogs after left anterior descending coronary artery ligation. GIK caused a modest increase in lactate concentration in small veins draining the infarct but did not affect glucose uptake. No effect on creatine kinase activity in the infarct was seen from GIK, although there was a slight increase in blood flow to the centre of the infarct. We concluded that GIK did not reduce infarct size in this experimental model.
The Central Role of CD4+ T Cells in the Antitumor Immune Response
Authors: Kenneth Hung, Robert Hayashi, Anne Lafond-Walker, Charles Lowenstein, Drew Pardoll, Hyam Levitsky
Journal: The Journal of Experimental Medicine (1998)

The induction of optimal systemic antitumor immunity involves the priming of both CD4+ and CD8+ T cells specific for tumor-associated antigens. The role of CD4+ T helper cells (Th) in this response has been largely attributed to providing regulatory signals required for the priming of major histocompatibility complex class I restricted CD8+ cytolytic T lymphocytes, which are thought to serve as the dominant effector cell mediating tumor killing. However, analysis of the effector phase of tumor rejection induced by vaccination with irradiated tumor cells transduced to secrete granulocyte/macrophage colony-stimulating factor indicates a far broader role for CD4+ T cells in orchestrating the host response to tumor. This form of immunization leads to the simultaneous induction of Th1 and Th2 responses, both of which are required for maximal systemic antitumor immunity. Cytokines produced by these CD4+ T cells activate eosinophils as well as macrophages that produce both superoxide and nitric oxide. Both of these cell types then collaborate within the site of tumor challenge to cause its destruction.
Utilization of Early Invasive Management Strategies for High-Risk Patients With Non–ST-Segment Elevation Acute Coronary Syndromes
Authors: Deepak L. Bhatt, Matthew T. Roe, Eric D. Peterson, Yun Li, Anita Y. Chen, Robert A. Harrington, Adam B. Greenbaum, Peter B. Berger, Christopher P. Cannon, David J. Cohen, C. Michael Gibson, Jorge F. Saucedo, Neal S. Kleiman, Judith S. Hochman, William E. Boden, Ralph G. Brindis, W. Frank Peacock, Sidney C. Smith,, Charles V. Pollack,, W. Brian Gibler, E. Magnus Ohman, for the CRUSADE Investigators
Journal: JAMA (2004)

The American College of Cardiology/American Heart Association (ACC/AHA) guidelines for the management of non-ST-segment elevation acute coronary syndromes (NSTE ACS) recommend early invasive management for high-risk patients, given the benefits with this approach demonstrated in randomized clinical trials.To determine the use and predictors of early invasive management strategies (cardiac catheterization <48 hours following presentation) in high-risk patients with NSTE ACS and to examine the association of early invasive management with mortality.The CRUSADE (Can Rapid Risk Stratification of Unstable Angina Patients Suppress Adverse Outcomes With Early Implementation of the ACC/AHA Guidelines) Quality Improvement Initiative evaluated care patterns and outcomes for 17,926 high-risk NSTE ACS patients (positive cardiac markers and/or ischemic electrocardiographic changes) based on ACC/AHA guidelines recommendations at 248 US hospitals with catheterization and revascularization facilities between March 2000 and September 2002.Use of early invasive management within 48 hours of presentation, predictors of early invasive management, and in-hospital mortality. Results Of the 17,926 patients analyzed, 8037 (44.8%) underwent early cardiac catheterization less than 48 hours following presentation. Predictors of early invasive management included cardiology care, younger age, lack of prior or current congestive heart failure, lack of renal insufficiency, ischemic electrocardiographic changes, positive cardiac markers, white race, and male sex. Patients treated with early invasive management were more likely to be treated with medications and interventions recommended by the ACC/AHA guidelines and had a lower risk of in-hospital mortality after adjusting for differences in clinical characteristics and after comparing propensity-matched pairs (2.5% vs 3.7%, P<.001). Conclusions An early invasive management strategy is not utilized in the majority of high-risk patients with NSTE ACS. This strategy appears to be reserved for patients without significant comorbidities and those cared for by cardiologists and is associated with a lower risk of in-hospital mortality.
Angiotensin II Type 2 Receptor–Mediated Regulation of Rat Neuronal K <sup>+</sup> Channels
Authors: Jeffrey R. Martens, Desuo Wang, Colin Sumners, Philip Posner, Craig H. Gelband
Journal: Circulation Research (1996)

We have previously shown that angiotensin II (Ang II), via AT 2 receptors, increases whole-cell K + current in cultured rat hypothalamus and brain stem neurons. We have now investigated the AT 2 receptor–mediated effects of Ang II on the activity of single delayed rectifier K + channels in cell-attached membrane patches. In control recordings (bath, 5.4 mmol/L K + ; pipette, 140 mmol/L K + ), two voltage-dependent channels were recorded with conductances of 34±4 and 56±6 pS, respectively (n=6). When patches were excised, the channels reversed near a membrane potential expected for a K + channel. In cell-attached patches (−40 mV), Ang II (100 nmol/L) increased open probability of the 56-pS K + channel from 0.03±0.01 to 0.21±0.05 (n=3). The selective AT 2 receptor antagonist PD 123319 (1 μmol/L) but not the AT 1 receptor antagonist losartan (1 μmol/L) blocked the actions of Ang II (n=3). The selective AT 2 receptor agonist CGP 42112 (100 nmol/L) produced similar effects to Ang II. Kinetic analysis of the Ang II effect showed that open-time histograms were best fit by two exponential functions. Ang II increased both open-time constants relative to control (control, τ 1 =0.9±0.1 milliseconds, τ 2 =2.3±0.3 milliseconds; Ang II, τ 1 =3.1±0.4 milliseconds, τ 2 =12.1±2.4 milliseconds), and PD 123319 blocked this effect (n=3). The closed-time histogram was not affected by Ang II, PD 123319, or losartan. These results suggest that activation of AT 2 receptors modulates rat hypothalamus and brain stem neuronal whole-cell K + current by increasing the open probability of a 56-pS K + channel.
Neoadjuvant Chemotherapy in Breast Cancer: Significantly Enhanced Response With Docetaxel
Authors: Ian C. Smith, Steven D. Heys, Andrew W. Hutcheon, Iain D. Miller, Simon Payne, Fiona J. Gilbert, Antoinne K. Ah-See, Oleg Eremin, Leslie G. Walker, Tarun K. Sarkar, S. Peter Eggleton, Keith N. Ogston
Journal: Journal of Clinical Oncology (2002)

PURPOSE: To compare the efficacy of neoadjuvant (NA) docetaxel (DOC) with anthracycline-based therapy and determine the efficacy of NA DOC in patients with breast cancer initially failing to respond to anthracycline-based NA chemotherapy (CT). PATIENTS AND METHODS: Patients with large or locally advanced breast cancer received four pulses of cyclophosphamide 1,000 mg/m2, doxorubicin 50 mg/m2, vincristine 1.5 mg/m2, and prednisolone 40 mg (4 × CVAP) for 5 days. Clinical tumor response was assessed. Those who responded (complete response [CR] or partial response [PR]) were randomized to receive further 4 × CVAP or 4 × DOC (100 mg/m2). All nonresponders received 4 × DOC. RESULTS: One hundred sixty-two patients were enrolled; 145 patients completed eight cycles of NA CT. One hundred two patients (66%) achieved a clinical response (PR or CR) after 4 × CVAP. After randomization, 50 patients received 4 × CVAP and 47 patients received 4 × DOC. In patients who received eight cycles of CT, the clinical CR (cCR) and clinical PR (cPR) (94% v 66%) and pathologic CR (pCR) (34% v 16%) response rates were higher (P = .001 and P = .04) in those who received further DOC. Intention-to-treat analysis demonstrated cCR and cPR (85% v 64%; P = .03) and pCR (31% v 15%; P = .06). Axillary lymph node examination revealed residual tumor in 33% of patients who received 8 × CVAP and 38% of patients who received further DOC. In patients who failed to respond to the initial CVAP, 4 × DOC resulted in a cCR and cPR rate of 55% and a pCR rate of 2%. Forty-four percent of these patients had residual tumor within axillary lymph nodes. CONCLUSION: NA DOC resulted in substantial improvement in responses to DOC.
Scoliosis and Trendelenburg sign in a painting by P P Rubens
Authors: S E Hansen
Journal: Annals of the Rheumatic Diseases (2002)

In an article on Rubens' painting "The Three Graces" Dequeker suggests that hypermobility is a medical explanation of the seeming scoliosis and Trendelenburg sign in the middle figure . 1 But the posture of this middle figure should probably be interpreted as an artistic phenomenon without medical reference.Sculptors in classical Greek and Roman periods often used the contrapposto posture.In this, by putting most weight on one leg, the other leg can be shown in a relaxed and semiflexed position.This undulating between tension and relaxation will animate the figure.A person with normal muscular function and a normal back can perfectly well pose in this way with relaxed hip abductors on the weightbearing side, a descending hip on the opposite side, and a compensating scoliotic posture.This posture is facilitated by support from the arm as in Rubens' painting.If the person tries to take a forward step, relaxation of the muscles of the weightbearing hip can no longer be maintained, and the positive Trendelenburg sign will disappear.In the Renaissance period the use of this contrapposto posture was revived.During his stay in Rome Rubens eagerly studied the then recently excavated Laokoön sculpture with its three distorted figures. 2 He often used such distorted postures in his paintings to give the impression of vigorous muscular characters capable of performing great tasks.The best example is probably "The Debarkation at Marseilles" in the Maria de Medici cycle from 1622 to 1625 for the Luxembourg Palace in Paris. 3 Here, three young women, nereides, with curved muscular backs at the bottom of the picture nearly seem to carry the ship of Maria de Medici.
Effects of Frequency of Contraction and lonic Environment on the Responses of Heart Muscle to Acetylcholine
Authors: WILLIAM F. FRIEDMAN, ROBERT A. BUCCINO, EDMUND H. SONNENBLICK, EUGENE BRAUNWALD
Journal: Circulation Research (1967)

The effects of frequency of contraction and of external calcium and sodium concentration on the inotropic actions of acetylcholine (ACh) on isolated mammalian myocardium were examined. In stimulated left atria of cats, ACh reduced tension development, i.e. exerted a negative inotropic effect, which became more striking as the frequency of contraction was increased and was inhibited by atropine. In cat papillary muscles studied at a low frequency (&lt;42/min), high concentrations of ACh augmented tension development, i.e. produced a positive inotropic effect, which was enhanced by atropine. At high frequencies (&gt;72/min) this positive effect of ACh was abolished. Moreover, at high frequencies, ACh consistently further reduced the normal increment in tension associated with increasing frequency. The magnitude of the positive inotropic action of ACh on papillary muscle was abolished by lowering the extracellular [Na + ] and varied inversely with the extracellular [Ca 2+ ]. These findings were interpreted in terms of a dual action of ACh on the myocardium: (1) an action on the muscarinic receptor that reduces contractility and may be blocked with atropine, and (2) a direct effect on cellular membrane permeability to Ca 2+ that stimulates contractility and may be reduced by prior elevation of intracytoplasmic [Ca 2+ ].
<i>mda-9</i>/Syntenin: A Positive Regulator of Melanoma Metastasis
Authors: Habib Boukerche, Zao-zhong Su, Luni Emdad, Patrick Baril, Brigitte Balme, Luc Thomas, Aaron Randolph, Kristoffer Valerie, Devanand Sarkar, Paul B. Fisher
Journal: Cancer Research (2005)

Abstract Metastasis is a significant event in cancer progression and continues to pose the greatest challenge for a cancer cure. Defining genes that control metastasis in vivo may provide new targets for intervening in this process with profound therapeutic implications. Melanoma differentiation associated gene-9 (mda-9) was initially identified by subtraction hybridization as a novel gene displaying biphasic expression during terminal differentiation in human melanoma cells. Mda-9, also known as syntenin, is a PDZ-domain protein overexpressed in many types of human cancers, where it is believed to function in tumor progression. However, a functional role of mda-9/syntenin in tumor growth and metastasis and the signaling pathways involved in mediating these biological activities remain to be defined. Evidence is now provided, using weakly and highly metastatic isogenic melanoma variants, that mda-9/syntenin regulates metastasis. Expression of mda-9/syntenin correlates with advanced stages of melanoma progression. Regulating mda-9/syntenin expression using a replication-incompetent adenovirus expressing either sense or antisense mda-9/syntenin modifies the transformed phenotype and alters metastatic ability in immortal human melanocytes and metastatic melanoma cells in vitro and in vivo in newborn rats. A direct relationship is observed between mda-9/syntenin expression and increased phosphorylation of focal adhesion kinase, c-Jun-NH2-kinase, and p38. This study provides the first direct link between mda-9/syntenin expression and tumor cell dissemination in vivo and indicates that mda-9/syntenin expression activates specific signal transduction pathways, which may regulate melanoma tumor progression. Based on its ability to directly alter metastasis, mda-9/syntenin provides a promising new focus for melanoma cancer research with potential therapeutic applications for metastatic diseases.
Phase II Evaluation of Sorafenib in Advanced and Metastatic Squamous Cell Carcinoma of the Head and Neck: Southwest Oncology Group Study S0420
Authors: Stephen K. Williamson, James Moon, Chao H. Huang, Perry P. Guaglianone, Michael LeBlanc, Gregory T. Wolf, Susan G. Urba
Journal: Journal of Clinical Oncology (2010)

We conducted a phase II trial to evaluate the efficacy and safety of single-agent sorafenib in chemotherapy-naïve patients with metastatic or recurrent squamous cell carcinoma of the head and neck (SCCHN). The primary end point was response probability (ie, confirmed complete and partial response [PR]).Chemotherapy-naïve patients with metastatic, persistent, or recurrent SCCHN who received one induction or fewer or received an adjuvant chemotherapy regimen, who had adequate organ function, and who had a performance status <or= 1 were eligible. Sorafenib was administered orally at 400 mg twice daily on a continuous basis in 28-day cycles. Responses were evaluated according to RECIST (Response Evaluation Criteria in Solid Tumors).Sorafenib was generally well tolerated. Of the 41 eligible patients assessed for adverse events, one experienced a grade 4 adverse event as a result of an asymptomatic pulmonary embolus. The most common grades 2 to 3 adverse events were fatigue, anorexia, stomatitis/oral pain, abdominal pain, hand-foot syndrome, weight loss, and hypertension. There was one confirmed PR and two unconfirmed PRs. The estimated confirmed response probability was 2% (95% CI, 0% to 13%). The estimated median progression-free survival was 4 months (95% CI, 2 to 4 months), and the estimated median overall survival was 9 months (95% CI, 7 to 14 months).Sorafenib was well tolerated. Although response was poor, progression-free and overall survival times compare favorably with previous Southwest Oncology Group, phase II, single-agent trials.
Irrigated Radiofrequency Catheter Ablation Guided by Electroanatomic Mapping for Recurrent Ventricular Tachycardia After Myocardial Infarction
Authors: William G. Stevenson, David J. Wilber, Andrea Natale, Warren M. Jackman, Francis E. Marchlinski, Timothy Talbert, Mario D. Gonzalez, Seth J. Worley, Emile G. Daoud, Chun Hwang, Claudio Schuger, Thomas E. Bump, Mohammad Jazayeri, Gery F. Tomassoni, Harry A. Kopelman, Kyoko Soejima, Hiroshi Nakagawa
Journal: Circulation (2008)

Background— Recurrent ventricular tachycardia (VT) is an important cause of mortality and morbidity late after myocardial infarction. With frequent use of implantable cardioverter-defibrillators, these VTs are often poorly defined and not tolerated for mapping, factors previously viewed as relative contraindications to ablation. This observational multicenter study assessed the outcome of VT ablation with a saline-irrigated catheter combined with an electroanatomic mapping system. Methods and Results— Two hundred thirty-one patients (median LV ejection fraction, 0.25; heart failure in 62%) with recurrent episodes of monomorphic VT (median, 11 in the preceding 6 months) caused by prior myocardial infarction were enrolled. All inducible monomorphic VTs with a rate approximating or slower than any spontaneous VTs were targeted for ablation guided by electroanatomic mapping during sinus rhythm and/or VT. Patients were not excluded for multiple VTs (median, 3 per patient) or unmappable VT (present in 69% of patients). Ablation abolished all inducible VTs in 49% of patients. The primary end point of freedom from recurrent incessant VT or intermittent VT after 6 months of follow-up was achieved for 123 patients (53%). In 142 patients with implantable cardioverter-defibrillators before and after ablation for intermittent VT who survived 6 months, VT episodes were reduced from a median of 11.5 to 0 ( P &lt;0.0001). The 1-year mortality rate was 18%, with 72.5% of deaths attributed to ventricular arrhythmias or heart failure. The procedure mortality rate was 3%, with no strokes. Conclusions— Catheter ablation is a reasonable option to reduce episodes of recurrent VT in patients with prior myocardial infarction, even when multiple and/or unmappable VTs are present. This population remains at high risk for death, warranting surveillance and further study.
Wheezing childhood phenotypes from birth to 7 years using latent class analysis
Authors: Caroline Lodge, Sophie Zaloumis, Adrian Lowe, Lyle Gurrin, Melanie Matheson, David Hill, Clifford Hosking, Christine Axelrad, Cecilie Svanes, Michael Abramson, Katrina Allen, Shyamali Dharmage
Journal: European Respiratory Journal (2012)

Introduction:  Childhood asthma prevention is hampered by the heterogeneity of childhood wheeze.  Aim:  To refine childhood wheeze phenotypes (0 to 7 years) using latent class analysis (LCA).  Methods:  A high risk birth cohort (n=620) recorded: current wheeze 18 times to age 2 years; yearly (ages 3 to 7), and at 12; eczema by age 6 months; food allergen sensitization aged 1 year; aeroallergens at 2 years; lower respiratory tract infection (LRT) by 1 year, and parental asthma. LCA of wheeze at 23 times defined the optimal number of wheezing classes from model fit parameters.  Results:  Five latent classes were identified. (Non-wheezers, n= 264 (42.7%)). All wheezing classes except early transient had greater risk of wheeze aged 12. Also: early transient wheeze (27.5%) was associated with LRT (OR 3.0; 95%CI 1.6, 5.7); early persistent wheeze (5.7%) with LRT (OR 6.8; 2.8, 16.7) and aeroallergen sensitization (OR 5.0; 1.8, 13.9); intermediate onset wheeze (20.7%) was associated with both these factors and eczema (OR 2.6; 1.7, 4.7), food sensitization (OR 2.7; 1.5, 4.7) and parental asthma (OR 2.2; 1.0, 4.5); late onset wheeze (3.5%) had no associations.  Conclusion:  LCA on wheeze in a high risk cohort yielded 5 classes up to age 7. In contrast to previous studies, food sensitization and early eczema were only related to the intermediate class suggesting this may be the group where atopic march is most relevant.  Figure 1: LCA of wheeze