tbuckley/cabot-search huggingface dataset:
Early discharge for patients with exacerbations of chronic obstructive pulmonary disease: a randomised controlled trial
Authors: M M Cotton
Journal: Thorax (2000)

<h3>BACKGROUND</h3> We have previously reported the use of a hospital based respiratory nurse service (Acute Respiratory Assessment Service, ARAS) to support home treatment of patients with exacerbations of chronic obstructive pulmonary disease (COPD). A controlled trial was undertaken to compare early discharge with home treatment supported by respiratory nurses with conventional hospital management of patients admitted with exacerbations of COPD. <h3>METHODS</h3> Patients with COPD admitted as emergencies were identified the next working day. They were eligible for inclusion in the study if the differential diagnosis included an exacerbation of COPD, but were excluded if other medical conditions or acidotic respiratory failure required inpatient investigation or management. Of 360 patients reviewed, 209 were being assessed for other active medical problems and were excluded, 33 potential participants were already involved in research studies and so were ineligible, and 37 did not wish to participate in the study. Eighty one patients were randomised to receive conventional inpatient care (n=40) or to planned early discharge the next working day (n=41). Those discharged early continued treatment at home under the supervision of specialist respiratory nurses. Outcome measures were readmission, additional hospital days, and deaths within 60 days of initial admission. Process measures included number of visits, duration of follow up by the respiratory nurse, and additional treatment provided to support early discharge. <h3>RESULTS</h3> On an intention to treat basis, a policy of early discharge reduced inpatient stay from a mean of 6.1 (range 1–13) days with conventional management to 3.2 (1–16) days with an early discharge policy. Twelve patients (30% conventional management, 29.3% early discharge) were readmitted in each group giving a mean difference in readmission of 0.7% (95% CI of the difference –19.2 to 20.6). In the conventional management group readmitted patients spent a mean of 8.75 additional days in hospital compared with 7.83 days in the early discharge group, giving a mean difference of 0.92 days (95% CI of the difference –6.5 to 8.3). There were two deaths (5%) in the conventional management group and one (2.4%) in the early discharge group, a mean difference of 2.6% (95% CI of the difference –5.7 to 10.8). <h3>CONCLUSIONS</h3> Patients with acute exacerbations of COPD uncomplicated by acidotic respiratory failure or other medical problems can be discharged home earlier than is current practice with support by visiting respiratory nurses. No difference was found in the subsequent need for readmission.
Phase II trial of irinotecan/gemcitabine as second-line therapy for relapsed and refractory small-cell lung cancer: Cancer and Leukemia Group B Study 39902
Authors: C.M. Rocha-Lima, J.E. Herndon, M.E. Lee, J.N. Atkins, A. Mauer, E. Vokes, M.R. Green
Journal: Annals of Oncology (2006)
Ca channels in cardiac myocytes: structure and function in Ca influx and intracellular Ca release
Authors: D Bers
Journal: Cardiovascular Research (1999)

There are Ca channels in the plasma membrane and also the sarcoplasmic reticulum (SR) membrane in cardiac myocytes. The relationship between channel structure, associated proteins and function of these Ca channels is discussed. The sarcolemmal Ca channels are crucial both to the basic cellular electrophysiological properties and control of cardiac contractility (via excitation–contraction coupling). The intracellular Ca release channels (or ryanodine receptors) respond to triggering events mediated by sarcolemmal ion currents and are largely responsible for releasing Ca which activates the myofilaments to produce contraction. Several possible mechanisms of excitation–contraction coupling are discussed. The Ca released from the SR can also feedback on several sarcolemmal ion currents and alter action potential configuration as well as contribute to arrhythmogenesis.
Averting danger from within
Authors: Hema Bashyam
Journal: The Journal of Experimental Medicine (2008)

![Graphic][1] 

Inflammation-related weight loss caused by symbiotic bacteria in A20-deficient mice (middle) is rescued by loss of MyD88 (right). On page 

[451][2], Turer et al. find that loss of a single protein turns symbiotic bacteria into killers.

Helpful bacteria in the gut
Guided surgery: accuracy and efficacy
Authors: Marjolein Vercruyssen, Margareta Hultin, Nele Van Assche, Krister Svensson, Ignace Naert, Marc Quirynen
Journal: Periodontology 2000 (2014)

Different computer-assisted implant-placement procedures are currently available. These differ in software, template manufacture, guiding device, stabilization and fixation. The literature seems to indicate that one has to accept a certain inaccuracy of ±2.0 mm, which seems large initially but is clearly smaller than for nonguided surgery. A reduction of accuracy to below 0.5 mm seems extremely difficult. A common shortcoming identified in the studies included in this review is inconsistency in how clinical data and outcome variables are reported. Another limitation is the small number of comparative clinical studies. In order to find the best guiding system or the most important parameters for optimal accuracy, more randomized clinical trials are necessary. Information on cost-effectiveness and patient-centered evaluations (i.e. questionnaires and interviews) must also be included.
Atherosclerotic plaques, inflammation, and thoracic aortic dilatation: insights from a population-based transesophageal echocardiographic study with implications for aortic aneurysm formation
Authors: Yoram Agmon, Bijoy K. Khandheria, Irene Meissner, Gary L. Schwartz, JoRean D. Sicks, Angela Fought, W.M. O'Fallon, David O. Wiebers, James B. Seward, A.J. Tajik
Journal: Journal of the American College of Cardiology (2002)
Outcomes for Elderly, Advanced-Stage Non–Small-Cell Lung Cancer Patients Treated With Bevacizumab in Combination With Carboplatin and Paclitaxel: Analysis of Eastern Cooperative Oncology Group Trial 4599
Authors: Suresh S. Ramalingam, Suzanne E. Dahlberg, Corey J. Langer, Robert Gray, Chandra P. Belani, Julie R. Brahmer, Alan B. Sandler, Joan H. Schiller, David H. Johnson
Journal: Journal of Clinical Oncology (2007)

Fit elderly patients with advanced non-small-cell lung cancer (NSCLC) benefit from platinum-based, two-drug chemotherapy. Bevacizumab (B) in combination with carboplatin (C) and paclitaxel (P) improves survival for advanced, nonsquamous NSCLC, as evidenced in Eastern Cooperative Oncology Group (ECOG) 4599. We conducted a subset analysis of ECOG 4599 to determine the outcome for elderly patients.ECOG 4599 randomly assigned patients with advanced nonsquamous NSCLC to PC or to PCB. We analyzed outcome in patients who were at least 70 years of age at the time of study entry. Patient characteristics, efficacy, and toxicity data were compared between PC and PCB for the elderly. Outcomes for elderly and younger patients (< 70 years) treated with PCB were also compared.Among elderly patients (n = 224; 26%), there was a trend towards higher response rate (29% v 17%; P = .067) and progression-free survival (5.9 v 4.9 months; P = .063) with PCB compared with PC, although overall survival (PCB = 11.3 months; PC = 12.1 months; P = .4) was similar. Grade 3 to 5 toxicities occurred in 87% of elderly patients with PCB versus 61% with PC (P < .001), with seven treatment-related deaths in the PCB arm compared with two with PC. Elderly patients had higher incidence of grade 3 to 5 neutropenia, bleeding, and proteinuria with PCB compared with younger patients.In elderly NSCLC patients, PCB was associated with a higher degree of toxicity, but no obvious improvement in survival compared with PC. Data from this unplanned, retrospective analysis justify prospective evaluation of the therapeutic index of PCB regimen in elderly patients.
Stromal mesenteric lymph node cells are essential for the generation of gut-homing T cells in vivo
Authors: Swantje I. Hammerschmidt, Manuela Ahrendt, Ulrike Bode, Benjamin Wahl, Elisabeth Kremmer, Reinhold Förster, Oliver Pabst
Journal: The Journal of Experimental Medicine (2008)

T cells primed in the gut-draining mesenteric lymph nodes (mLN) are imprinted to express α4β7-integrin and chemokine receptor CCR9, thereby enabling lymphocytes to migrate to the small intestine. In vitro activation by intestinal dendritic cells (DC) or addition of retinoic acid (RA) is sufficient to instruct expression of these gut-homing molecules. We report that in vivo stroma cells, but not DC, allow the mLN to induce the generation of gut tropism. Peripheral LN (pLN) transplanted into the gut mesenteries fail to support the generation of gut-homing T cells, even though gut-derived DC enter the transplants and prime T cells. DC that fail to induce α4β7-integrin and CCR9 in vitro readily induce these factors in vivo upon injection into mLN afferent lymphatics. Moreover, uniquely mesenteric but not pLN stroma cells express high levels of RA-producing enzymes and support induction of CCR9 on activated T cells in vitro. These results demonstrate a hitherto unrecognized contribution of stromal cell delivered signals, including RA, on the imprinting of tissue tropism in vivo.
Generation of an HLA-restricted cytotoxic T cell line reactive against cultured tumor cells from a patient infected with human T cell leukemia/lymphoma virus.
Authors: H Mitsuya, L A Matis, M Megson, P A Bunn, C Murray, D L Mann, R C Gallo, S Broder
Journal: The Journal of Experimental Medicine (1983)

Lymphocytes from a patient who had an unusually long survival after therapy for a human T cell leukemia/lymphoma virus (HTLV)-associated T cell lymphoma were stimulated in vitro with an autologous tumor cell line, and the generation of cytotoxic T lymphocytes (CTL) was studied. CTL generated were directed against autologous (HTLV-associated tumor cells. These propagated CTL were OKT3+, OKT4-, and OKT8+. The cytotoxic activity required target tumor cells that were infected with HTLV and also expressed histocompatibility antigens in common with the patient, suggesting a major histocompatibility complex-restricted associative recognition of target antigens expressed on the tumor cell membrane.
Epac: Defining a New Mechanism for cAMP Action
Authors: Martijn Gloerich, Johannes L. Bos
Journal: The Annual Review of Pharmacology and Toxicology (2010)

cAMP is a second messenger that is essential for relaying hormonal responses in many biological processes. The discovery of the cAMP target Epac explained various effects of cAMP that could not be attributed to the established targets PKA and cyclic nucleotide-gated ion channels. Epac1 and Epac2 function as guanine nucleotide exchange factors for the small G protein Rap. cAMP analogs that selectively activate Epac have helped to reveal a role for Epac in processes ranging from insulin secretion to cardiac contraction and vascular permeability. Advances in the understanding of the activation mechanism of Epac and its regulation by diverse anchoring mechanisms have helped to elucidate the means by which cAMP fulfills these functions via Epac.
Effect of nitazoxanide in adults and adolescents with acute uncomplicated influenza: a double-blind, randomised, placebo-controlled, phase 2b/3 trial
Authors: Jason Haffizulla, Aaron Hartman, Melanie Hoppers, Harvey Resnick, Steve Samudrala, Christine Ginocchio, Matthew Bardin, Jean-François Rossignol
Journal: The Lancet Infectious Diseases (2014)
Duodenal pH in health and duodenal ulcer disease: effect of a meal, Coca-Cola, smoking, and cimetidine.
Authors: R F McCloy, G R Greenberg, J H Baron
Journal: Gut (1984)

Intraluminal duodenal pH was recorded using a combined miniature electrode and logged digitally every 10 or 20 seconds for five hours (basal/meal/drink) in eight control subjects and 11 patients with duodenal ulcer (five on and off treatment with cimetidine). Over the whole test there were no significant differences in duodenal mean pH or log mean hydrogen ion activity (LMHa) between control subjects and patients with duodenal ulcer, but there were significantly longer periods of duodenal acidification (pH less than 4) and paradoxically more periods of duodenal alkalinisation (pH greater than 6) in the duodenal ulcer group compared with controls. After a meal duodenal mean pH and LMHa fell significantly in both controls and patients with duodenal ulcer, with more periods of duodenal acidification and alkalinisation in the duodenal ulcer group. An exogenous acid load (Coca-Cola) significantly increased the periods of duodenal acidification, and reduced alkalinisation, in both groups. Cimetidine significantly increased mean pH and LMHa and abolished the brief spikes of acidification in four of five patients with duodenal ulcer. Peak acid output (but not basal acid output) was significantly correlated with duodenal mean pH and LMHa but not with the periods of duodenal acidification. Smoking did not affect duodenal pH in either group.
ESGE-ESGENA guideline for quality assurance in reprocessing: Microbiological surveillance testing in endoscopy
Authors: U. Beilenhoff, C. Neumann, J. Rey, H. Biering, R. Blum, V. Schmidt
Journal: Endoscopy (2007)

1. Introduction2. Risk of infections, and potential problem areas during reprocessing3. Responsibilities4. Frequency5. Sampling for routine tests 5.1. Endoscopes 5.2. Final rinse water in washer-disinfectors 5.3. Water supply6. Cultures/culturing 6.1. Liquid samples from endoscope channels 6.2. Swabs 6.3. Water samples 6.4. Additional tests7. Interpretation of results and corrective measures in case of contamination 7.1. Total microbiological count 7.2. Detection of special microorganisms8. Management of outbreak of infectious agent9. References10. Appendix
Phase I Safety, Pharmacokinetic, and Pharmacodynamic Trial of ZD1839, a Selective Oral Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor, in Patients With Five Selected Solid Tumor Types
Authors: J. Baselga, D. Rischin, M. Ranson, H. Calvert, E. Raymond, D.G. Kieback, S.B. Kaye, L. Gianni, A. Harris, T. Bjork, S.D. Averbuch, A. Feyereislova, H. Swaisland, F. Rojo, J. Albanell
Journal: Journal of Clinical Oncology (2002)

To establish the safety and tolerability of ZD1839 (Iressa), a selective epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, and to explore its pharmacokinetic and pharmacodynamic effects in patients with selected solid tumor types.This was a phase I dose-escalating trial of oral ZD1839 150 mg/d to a maximum of 1,000 mg/d given once daily for at least 28 days. Patients with either advanced non-small-cell lung, ovarian, head and neck, prostate, or colorectal cancer were recruited.Eighty-eight patients received ZD1839 (150 to 1,000 mg/d). At 1,000 mg/d, five of 12 patients experienced dose-limiting toxicity (grade 3 diarrhea [four patients] and grade 3 somnolence [one patient]). The most frequent drug-related adverse events (AEs) were acne-like rash (64%) and diarrhea (47%), which were generally mild (grade 1/2) and reversible on cessation of treatment. No change in ZD1839 safety profile was observed with prolonged administration. Pharmacokinetic analysis showed steady-state exposure to ZD1839 in 98% of patients by day 7. Nineteen patients had stable disease and received ZD1839 for >or= 3 months; seven of these patients remained on study drug for >or= 6 months. Serial skin biopsies taken before treatment and at approximately day 28 revealed changes indicative of inhibition of the EGFR signaling pathway.ZD1839 was generally well tolerated, with manageable and reversible AEs at doses up to 600 mg/d and dose-limiting toxicity observed at 1,000 mg/d. ZD1839 treatment resulted in clinically meaningful disease stabilization across a range of tumor types and doses. Pharmacodynamic changes in skin confirmed inhibition of EGFR signaling, which was predicted from the mode of action of ZD1839.
Modern external beam radiation therapy for refractory dissecting cellulitis of the scalp
Authors: P. Chinnaiyan, L.B. Tena, M.J. Brenner, J.S. Welsh
Journal: British Journal of Dermatology (2005)

Dissecting cellulitis of the scalp can be an extremely painful and disfiguring dermatological condition. The associated pain can be severe enough in some cases to require opioid analgesics, and this pain in conjunction with the disfigurement can induce significant emotional distress. Conservative treatments often fail to provide relief. Radiation therapy has been successfully used in the past but with outdated equipment and techniques.To evaluate the efficacy and toxicity of modern external beam radiation therapy techniques for the treatment of dissecting cellulitis of the scalp.Four patients with intractable dissecting cellulitis of the scalp were treated with electrons or a combination of electrons and photons to the entire scalp. Daily fraction sizes were 2.5 or 3 Gy and initially prescribed to 15-21 Gy. Patients were re-evaluated 3-4 weeks after completion of therapy. Any residual hair growth was treated with additional radiation treatments to ensure full epilation, up to a maximum dose of 35 Gy.Rapid resolution of pain was seen in all patients with pain. Regression of nodules and decreased discharge was seen in all patients following treatment and cosmesis was subjectively improved. No long-term toxicity has been observed.Using modern techniques and equipment, radiation therapy appears to be a reasonable option for patients with severe/refractory dissecting cellulitis of the scalp. Acute effects are mild and well tolerated. Aside from alopecia, which was present to some extent in all patients before treatment, no long-term complications have been observed.
Use of lipoteichoic acid-T for pleurodesis in malignant pleural effusion: a phase I toxicity and dose-escalation study
Authors: Najib M Rahman, Helen E Davies, Marc Salzberg, Peter Truog, Rachel Midgely, David Kerr, Colin Clelland, Emma L Hedley, Y C Gary Lee, Robert J O Davies
Journal: The Lancet Oncology (2008)
CHK1 Inhibition Synergizes with Gemcitabine Initially by Destabilizing the DNA Replication Apparatus
Authors: Siang-Boon Koh, Aurélie Courtin, Richard J. Boyce, Robert G. Boyle, Frances M. Richards, Duncan I. Jodrell
Journal: Cancer Research (2015)

Abstract Combining cell-cycle checkpoint kinase inhibitors with the DNA-damaging chemotherapeutic agent gemcitabine offers clinical appeal, with a mechanistic rationale based chiefly on abrogation of gemcitabine-induced G2–M checkpoint activation. However, evidence supporting this mechanistic rationale from chemosensitization studies has not been consistent. Here we report a systematic definition of how pancreatic cancer cells harboring mutant p53 respond to this combination therapy, by combining mathematical models with large-scale quantitative biologic analyses of single cells and cell populations. Notably, we uncovered a dynamic range of mechanistic effects at different ratios of gemcitabine and CHK1 inhibitors. Remarkably, effective synergy was attained even where cells exhibited an apparently functional G2–M surveillance mechanism, as exemplified by a lack of both overt premature CDK1 activation and S-phase mitotic entry. Consistent with these findings, S–G2 duration was extended in treated cells, leading to a definable set of lineage-dependent catastrophic fates. At synergistic drug concentrations, global replication stress was a distinct indicator of chemosensitization as characterized molecularly by an accumulation of S-phase cells with high levels of hyperphosphorylated RPA-loaded single-stranded DNA. In a fraction of these cells, persistent genomic damage was observed, including chromosomal fragmentation with a loss of centromeric regions that prevented proper kinetochore-microtubule attachment. Together, our results suggested a “foot-in-the-door” mechanism for drug synergy where cells were destroyed not by frank G2–M phase abrogation but rather by initiating a cumulative genotoxicity that deregulated DNA synthesis. Cancer Res; 75(17); 3583–95. ©2015 AACR.
Activation and inactivation of a non-selective cation conductance by local mechanical deformation of acutely isolated cardiac fibroblasts
Authors: A Kamkin
Journal: Cardiovascular Research (2003)

Objective: We describe mechanically induced non-selective cation currents in isolated rat atrial fibroblasts, which might play a role as a substrate for mechano-electrical feedback in the heart. Methods: Isolated fibroblasts were used for voltage-clamp analysis of ionic currents generating mechanically-induced potentials. Fibroblasts were mechanically deformed (compressed or stretched) by two patch-pipettes. Results: These cells had a resting potential (E0) of −37±3 mV and an input resistance of 514±11 MΩ. At intracellular pCa 7 (patch-pipette solution), compression of 2 or 3 μm shifted E0 from −36±7 to −17±3 mV, and to −10±2 mV. Compression by 2 or 3 μm induced a negative difference current (at −45 mV −0.06±0.02 and −0.20±0.04 nA, respectively) with a reversal potential (Erev) of approx. 0 mV. The currents were carried by Na+, K+ and Cs+ ions, and were blocked by application of 8 μM Gd3+. Stretch of 2 or 3 μm hyperpolarized E0 from −34±4 to −45±5, and to −61±7 mV and induced a positive difference current (at −45 mV: 0.04±0.02 and 0.18±0.03 nA) with an Erev close to 0 mV. Application of Gd3+ shifted E0 to potentials as negative as EK (−90±4 mV). Cell dialysis with 5 mM BAPTA (pCa 8) or 5 mM Ca2+/EGTA (pCa 6) had no influence on non-selective cation currents suggesting that Ca2+ dependent conductances are unlikely to contribute. Conclusion: Compression of the isolated cardiac fibroblast caused depolarization of the membrane by activating inward currents through a non-selective cation conductance (Gns). Stretch hyperpolarizes the fibroblast, however, not by Ca2+ activation of K+-conductance. Ion selectivity, Erev, and Gd3+-sensitivity of stretch suppressed currents suggest that stretch reduces Gns that is activated by compression.
T Cell Receptor (TCR) Engagement in Apoptosis-defective, but Interleukin 2 (IL-2)–producing, T Cells Results in Impaired ZAP70/CD3-ζ Association
Authors: Almudena G. Sahuquillo, Anne Roumier, Emma Teixeiro, Rafael Bragado, Balbino Alarcón
Journal: The Journal of Experimental Medicine (1998)

We have previously shown that a tyrosine to leucine replacement in the transmembrane region of T cell receptor (TCR)-β results in a deficient induction of CD95-L and apoptosis upon TCR triggering in a transfected T cell line. By contrast, interleukin (IL)-2 production and the expression of CD25 and CD69 were normally induced. Since the mutation in TCR-β also resulted in impaired association of CD3-ζ, it was proposed that this chain is specifically required for the induction of apoptosis. We now show that the deficient induction of CD95-L and apoptosis does not derive from a general lower production of second messengers, since intracellular Ca2+ fluxes and tyrosine phosphorylation of total proteins were elicited at wild-type levels. Unlike in T cell clones stimulated with partial agonists, both p21 and p18 forms of tyrosine-phosphorylated CD3-ζ were detected, although the overall level of tyrosine-phosphorylated CD3-ζ was low. More strikingly, inducible association of ZAP70 to CD3-ζ was strongly inhibited, despite a normal induction of ZAP70 tyrosine phosphorylation. Finally, ZAP70 was not concentrated near the plasma membrane in the apoptosis-deficient cells. These results suggest that CD3-ζ is necessary for engagement of a specific signaling pathway leading to CD95-L expression that also needs the recruitment of ZAP70.