tbuckley/cabot-search huggingface dataset:
Changes in the Work of Breathing Induced by Tracheotomy in Ventilator-dependent Patients
Authors: JEAN-LUC DIEHL, SOUHEIL EL ATROUS, DOMINIQUE TOUCHARD, FRANÇOIS LEMAIRE, LAURENT BROCHARD
Journal: American Journal of Respiratory and Critical Care Medicine (1999)

Tracheotomy is widely performed on ventilator-dependent patients, but its effects on respiratory mechanics have not been studied. We measured the work of breathing (WOB) in eight patients before and after tracheotomy during breathing at three identical levels of pressure support (PS): baseline level (PS-B), PS + 5 cm H2O (PS + 5), and PS − 5 cm H2O (PS − 5). After the procedure, we also compared the resistive work induced by the patients' endotracheal tubes (ETTs) and by a new tracheotomy cannula in an in vitro bench study. A significant reduction in the WOB was observed after tracheotomy for PS-B (from 0.9 ± 0.4 to 0.4 ± 0.2 J/L, p < 0.05), and for PS − 5 (1.4 ± 0.6 to 0.6 ± 0.3 J/L, p < 0.05), with a near-significant reduction for PS + 5 (0.5 ± 0.5 to 0.2 ± 0.1 J/L, p = 0.05). A significant reduction was also observed in the pressure–time index of the respiratory muscles (181 ± 92 to 80 ± 56 cm H2O · s/min for PS-B, p < 0.05). Resistive and elastic work computed from transpulmonary pressure measurements decreased significantly at PS-B and PS − 5. A significant reduction in occlusion pressure and intrinsic positive end-expiratory pressure (PEEP) was also observed for all conditions, with no significant change in breathing pattern. Three patients had ineffective breathing efforts before tracheotomy, and all had improved synchrony with the ventilator after the procedure. In vitro measurements made with ETTs removed from the patients, with new ETTs, and with the tracheotomy cannula showed that the cannula reduced the resistive work induced by the artificial airway. Part of these results was explained by a slight, subtle reduction of the inner diameter of used ETTs. We conclude that tracheotomy can substantially reduce the mechanical workload of ventilator-dependent patients.
A phase II study of a paclitaxel and oxaliplatin combination in platinum-sensitive recurrent advanced ovarian cancer patients
Authors: P. Viens, T. Petit, A. Yovine, P. Bougnoux, G. Deplanque, P.-H. Cottu, R. Delva, J.-P. Lotz, S.V. Belle, J.-M. Extra, E. Cvitkovic
Journal: Annals of Oncology (2006)
Influence of altitude training on muscle metabolism and performance in man.
Authors: J. Keul, F. Cerny
Journal: British Journal of Sports Medicine (1974)

A good deal of information is available on the influence of hypoxia, or altitude, on physical performance, especially during prolonged exercise (2, 3, 4, 7, 8, 12, 18-22, 29, 33, 34-37, 41, 44, 45, 52).But, more than any other recent event, it was the Olympic Games in Mexico City that aroused so much interest in the problems surrounding altitude and sport performance; Four main questions were, at that time, asked.1. To what extent is performance affected at moderate altitude (about 2,000m -6,600 ft)?2. Can the negative effects be overcome by the processes of adaptation; to what extent can they be overcome; and how long does adaptation take? 3. Can extremely hard training at this altitude lead to any bodily harm? 4. Can the performance at sea level be improved by training at altitude?This last question is still of considerable interest as we are constantly confronted with athletes who want to carry out some portion of their training programme at altitude to improve their performance at sea level. The Delivery of EnergyThe two main energy delivering pathways in the resynthesis of adenosine triphosphate (ATP) should here be recalled to mind:1.The breakdown of energy-yielding substrates without the participation of oxygen; that is, the anaerobic energy delivery.2. The degradation of substrates in which oxygen is the ultimate hydrogen acceptor; that is, the aerobic process.
Formoterol as relief medication in asthma: the jury is still out
Authors: C. Jenkins
Journal: European Respiratory Journal (2003)

Despite concerns that use of long-acting β‐agonists (LABA) could be associated with risk of worsening asthma, to date these drugs have proven safe and highly effective 1,2.Early studies demonstrated no increase in asthma exacerbations when added to inhaled corticosteroids (ICS) aslong-term maintenance medication and subsequent studies have shown significantly reduced risks of exacerbations andimproved, more rapid establishment of asthma control compared to adding more ICS 3–5. Formoterol is a potent LABA with a rapid onset of bronchodilatation 6, 7 and a relatively fast clinical response when added as regular medication for patients whoare symptomatic on ICS alone 5, 8, 9. The question therefore arises, could formoterol with its rapid onset of action, also be used safely and effectively as reliever medication for asthma 10? Are there risks of tolerance associated with regular use of formoterol that could reduce its benefit when used as a reliever for acute symptoms 11?Are there other risks, associated with its adrenergic andmetabolic effects, that could be increased by its use whenadded to regular formoterol, resulting in worse outcomes 12?

Some of these questions have already been addressed in two12 week randomised controlled trials. Tattersfield etal. 13 showed in a double-blind study in 362 symptomatic patients taking ICS (mean daily dose 870 µg) that formoterol 4.5 µg as reliever medication was associated with fewer asthma exacerbations and a longer time to first exacerbation compared to terbutaline 500 µg. Serum potassium and electrocardiogram variables were monitored at clinic visits and nodifferences between treatments were shown. The relative risk ratio for an exacerbation requiring oral corticosteroids was 0.55 (95% confidence interval 0.34–0.89). The average daily dose of formoterol was four puffs of 4.5 µg, and this didnot change over the period of the study. In a double-blind randomised controlled …
Natura-Alpha Targets Forkhead Box M1 and Inhibits Androgen-Dependent and -Independent Prostate Cancer Growth and Invasion
Authors: Yirong Li, Martin Ligr, James P. McCarron, Garrett Daniels, David Zhang, Xin Zhao, Fei Ye, Jinhua Wang, Xiaomei Liu, Iman Osman, Simon K. Mencher, Hebert Lepor, Long G. Wang, Peng Lee
Journal: Clinical Cancer Research (2011)

The development of new effective therapeutic agents with minimal side effects for prostate cancer (PC) treatment is much needed. Indirubin, an active molecule identified in the traditional Chinese herbal medicine-Qing Dai (Indigo naturalis), has been used to treat leukemia for decades. However, the anticancer properties of Natura-alpha, an indirubin derivative, are not well studied in solid tumors, particularly in PC.The growth kinetics and invasion ability of on human PC cell lines with or without Natura-alpha treatment were measured by cell proliferation and invasion assays. The antitumor effects of Natura-alpha were examined in nude mice tumor xenograft models, and in a patient with advanced hormone-refractory metastatic PC. Signal network proteins targeted by Natura-alpha were analyzed by using proteomic pathway array analysis (PPAA) on xenografts.Natura-alpha inhibited the growth of both androgen-dependent (LNCaP) and androgen-independent (LNCaP-AI, PC-3, and DU145) PC cells with IC(50) between 4 to 10 mmol/L, and also inhibited invasion of androgen-independent PC cells. Its antitumor effects were further evident in in vivo tumor reduction in androgen-dependent and androgen-independent nude mice tumor xenograft models and reduced tumor volume in the patient with hormone refractory metastatic PC. PPAA revealed that antiproliferative and antiinvasive activities of Natura-alpha on PC might primarily be through its downregulation of Forkhead box M1 (FOXM1) protein. Forced overexpression of FOXM1 largely reversed the inhibition of growth and invasion by Natura-alpha.Natura-alpha could serve as a novel and effective therapeutic agent for treatment of both hormone-sensitive and hormone-refractory PC with minimal side effects.
A Clinical Isolate Strain of Respiratory Syncytial Virus (RSV) Causes Airway Obstruction and Histopathology in Mice Similar to Severe RSV Disease in Infants
Authors: M MOORE, M CHI, J WILLIAMS, P WRIGHT, J CROWEJR, K EDWARDS, V POLOSUKHIN, K GOLENIEWSKA, R PEEBLESJR
Journal: Journal of Allergy and Clinical Immunology (2008)
Acupuncture and Amitriptyline for Pain Due to HIV-Related Peripheral Neuropathy&lt;SUBTITLE&gt;A Randomized Controlled Trial&lt;/SUBTITLE&gt;
Authors: Judith C. Shlay
Journal: JAMA (1998)

Context.—Peripheral neuropathy is common in persons infected with the human immunodeficiency virus (HIV) but few data on symptomatic treatment are available.Objective.—To evaluate the efficacy of a standardized acupuncture regimen (SAR) and amitriptyline hydrochloride for the relief of pain due to HIV-related peripheral neuropathy in HIV-infected patients.Design.—Randomized, placebo-controlled, multicenter clinical trial. Each site enrolled patients into 1 of the following 3 options: (1) a modified double-blind 2 × 2 factorial design of SAR, amitriptyline, or the combination compared with placebo, (2) a modified double-blind design of an SAR vs control points, or (3) a double-blind design of amitriptyline vs placebo.Setting.—Terry Beirn Community Programs for Clinical Research on AIDS (HIV primary care providers) in 10 US cities.Patients.—Patients with HIV-associated, symptomatic, lower-extremity peripheral neuropathy. Of 250 patients enrolled, 239 were in the acupuncture comparison (125 in the factorial option and 114 in the SAR option vs control points option), and 136 patients were in the amitriptyline comparison (125 in the factorial option and 11 in amitriptyline option vs placebo option).Interventions.—Standarized acupuncture regimen vs control points, amitriptyline (75 mg/d) vs placebo, or both for 14 weeks.Main Outcome Measure.—Changes in mean pain scores at 6 and 14 weeks, using a pain scale ranging from 0.0 (no pain) to 1.75 (extremely intense), recorded daily.Results.—Patients in all 4 groups showed reduction in mean pain scores at 6 and 14 weeks compared with baseline values. For both the acupuncture and amitriptyline comparisons, changes in pain score were not significantly different between the 2 groups. At 6 weeks, the estimated difference in pain reduction for patients in the SAR group compared with those in the control points group (a negative value indicates a greater reduction for the "active" treatment) was 0.01 (95% confidence interval [CI], −0.11 to 0.12; P =.88) and for patients in the amitriptyline group vs those in the placebo group was −0.07 (95% CI, −0.22 to 0.08; P=.38). At 14 weeks, the difference for those in the SAR group compared with those in the control points group was −0.08 (95% CI, −0.21 to 0.06; P=.26) and for amitriptyline compared with placebo was 0.00 (95% CI, −0.18 to 0.19; P=.99).Conclusions.—In this study, neither acupuncture nor amitriptyline was more effective than placebo in relieving pain caused by HIV-related peripheral neuropathy.
A Psychiatric Dialogue on the Mind-Body Problem
Authors: K S Kendler
Journal: American Journal of Psychiatry (2001)

Of all the human professions, psychiatry is most centrally concerned with the relationship of mind and brain. In many clinical interactions, psychiatrists need to consider both subjective mental experiences and objective aspects of brain function. This article attempts to summarize, in the form of a dialogue between a philosophically informed attending psychiatrist and three residents, the major philosophical positions on the mind-body problem. The positions reviewed include the following: substance dualism, property dualism, type identity, token identity, functionalism, eliminative materialism, and explanatory dualism. This essay seeks to provide a brief user-friendly introduction, from a psychiatric perspective, to current thinking about the mind-body problem.
Presence of diabetes mellitus and steatosis is associated with liver stiffness in a general population: The Rotterdam study
Authors: Edith M. Koehler, Elisabeth P.C. Plompen, Jeoffrey N.L. Schouten, Bettina E. Hansen, Sarwa Darwish Murad, Pavel Taimr, Frank W.G. Leebeek, Albert Hofman, Bruno H. Stricker, Laurent Castera, Harry L.A. Janssen
Journal: Hepatology (2015)

Given that little is known about the prevalence of, and factors associated with, liver fibrosis in the general population, we aimed to investigate this in a large, well‐characterized cohort by means of transient elastography (TE). This study was part of the Rotterdam Study, a population‐based study among individuals ≥45 years. All participants underwent abdominal ultrasound and TE. Liver stiffness measurement (LSM) ≥8.0 kilopascals (kPa) was used as a cutoff suggesting clinically relevant fibrosis. Of 3,041 participants (age, 66.0 ± 7.6 years) with reliable LSM, 169 (5.6%) participants had LSM ≥8.0 kPa. Age (odds ratio [OR]: 2.40; 95% confidence interval [CI]: 1.72‐3.36; P &lt; 0.001), alanine aminotransferase (ALT; OR, 1.24; 95% CI: 1.12‐1.38; P &lt; 0.001), smoking (OR, 1.77; 95% CI: 1.16‐2.70; P = 0.008), spleen size (OR, 1.23; 95% CI: 1.09‐1.40; P = 0.001), hepatitis B surface antigen, or anti–hepatitis C virus positivity (OR, 5.38; 95% CI: 1.60‐18.0; P = 0.006), and combined presence of diabetes mellitus (DM) and steatosis (OR, 5.20; 95% CI: 3.01‐8.98; P &lt; 0.001 for combined presence) were associated with LSM ≥8.0 kPa in multivariable analyses. The adjusted predicted probability of LSM ≥8.0 kPa increased per age decade, with probabilities ranging from 1.4% (0.9‐3.6) in participants ages 50‐60 years to 9.9% (6.8‐14.5) in participants &gt;80 years. Participants with both DM and steatosis had the highest probabilities of LSM ≥8.0 kPa (overall probability: 17.2% [12.5‐23.4]; this probability did not increase with age [ P = 0.8]). Conclusion : In this large population‐based study of older adults, LSM ≥8.0 kPa, suggestive of clinically relevant fibrosis, was present in 5.6% and was strongly associated with steatosis and DM. In the context of an aging population and an increased prevalence of DM and obesity, this study illustrates that liver fibrosis may become a more prominent public health issue in the near future. (H epatology 2016;63:138–147)
Clinical Characterization Might Help in Preventing Osteonecrosis of the Jaw
Authors: Athanassios Kyrgidis, Charalambos Andreadis
Journal: Clinical Cancer Research (2008)

To the Editors: We read with considerable interest the article by Raje et al. (1) shedding light on clinical, radiographic, and biochemical markers concerning biphosphonate osteonecrosis of the jaw (ONJ). The investigators highlight that most information regarding ONJ has been from case series and case reports (1). This was correct until recently as we reported the first pair-matched case-control study addressing potential risk factors for ONJ development in breast cancer patients under zolendronic acid medication (2).Raje et al. (1) report that 7 of 11 patients did undergo tooth extraction. They do not, however, comment on tooth extractions as a potential risk factor. In our study, we report tooth extraction as the most potent ONJ predictor. Moreover, a recent article provides evidence that mucosal wound healing following tooth extractions could be actually defective, also showing that apoptosis is unlikely to be the key mechanism for keratinonocyte damage caused by biphosphonates (3).Another issue pointed out by Raje et al. (1) concerns ONJ incidence differences in the Greek and US populations. This could hardly be attributable to more tooth extractions in the Greek population probably because of poor hygiene (4); thus, it could be an issue of differential susceptibility to ONJ in the Greek population. Susceptibility differences could exist, given that we reported decreased susceptibility to adenocarcinoma among Greek patients with Barrett's esophagus and inflammatory bowel disease, perhaps attributable to Bax-protein overexpression (5).Raje et al. (1) point out that two studies from Greece suggest zolendronic acid medication might be an independent risk factor for ONJ development. Zolendronic acid is considered the most potent osteoclast inhibitor (2), and in our institution, we have witnessed more ONJ in patients receiving zolendronic acid rather than other bisphosphonate treatment. Hitherto, we are monitoring this variable in a cohort study (2). Pharmacogenomics is a promising field in cancer treatment and the investigators conclude (3) that clinical and laboratory end points will be validated in future prospective clinical trials (1). This is very true, but to our point of view, more attention should be paid in prevention of ONJ, if possible via simple risk predictors. In this regard, we have shown that ONJ is associated with tooth extraction and use of overdentures, currently updating the American Society of Clinical Oncology's level of evidence from V to III (2). We therefore concluded, based on evidence, that oncologists should refer their patients for baseline dental evaluation and potential pretreatment before engaging bisphosphonate therapy (2). Evidence provided by Raje et al. (1) shedding light on the pathophysiologic basis of the above association strengthens our point.No potential conflicts of interest were disclosed.
Synthetic lethal analysis of Caenorhabditis elegans posterior embryonic patterning genes identifies conserved genetic interactions.
Authors: L Ryan Baugh, Joanne C Wen, Andrew A Hill, Donna K Slonim, Eugene L Brown, Craig P Hunter
Journal: Genome biology (2005)

Abstract Phenotypic robustness is evidenced when single-gene mutations do not result in an obvious phenotype. It has been suggested that such phenotypic stability results from 'buffering' activities of homologous genes as well as non-homologous genes acting in parallel pathways. One approach to characterizing mechanisms of phenotypic robustness is to identify genetic interactions, specifically, double mutants where buffering is compromised. To identify interactions among genes implicated in posterior patterning of the Caenorhabditis elegans embryo, we measured synthetic lethality following RNA interference of 22 genes in 15 mutant strains. A pair of homologous T-box transcription factors ( tbx-8 and tbx-9 ) is found to interact in both C. elegans and C. briggsae , indicating that their compensatory function is conserved. Furthermore, a muscle module is defined by transitive interactions between the MyoD homolog hlh-1 , another basic helix-loop-helix transcription factor, hnd-1 , and the MADS-box transcription factor unc-120 . Genetic interactions within a homologous set of genes involved in vertebrate myogenesis indicate broad conservation of the muscle module and suggest that other genetic modules identified in C. elegans will be conserved.
Stage-related proliferative activity determines c-myb functional requirements during normal human hematopoiesis.
Authors: D Caracciolo, D Venturelli, M Valtieri, C Peschle, A M Gewirtz, B Calabretta
Journal: Journal of Clinical Investigation (1990)

To determine if MYB protein is preferentially required during specific stages of normal human hematopoiesis we incubated normal marrow mononuclear cells (MNC) with c-myb antisense oligodeoxynucleotides. Treated cells were cultured in semisolid medium under conditions designed to favor the growth of specific progenitor cell types. Compared with untreated controls, granulocyte-macrophage (GM) CFU-derived colonies decreased 77% when driven by recombinant human (rH) IL-3, and 85% when stimulated by rH GM colony-stimulating factor (CSF); erythroid burst-forming unit (BFU-E)- and CFU-E-derived colonies decreased 48 and 78%, respectively. In contrast, numbers of G-CSF-stimulated granulocyte colonies derived from antisense treated MNC were unchanged from controls, though the numbers of cells composing these colonies decreased approximately 90%. Similar results were obtained when MY10+ cells were exposed to c-myb antisense oligomers. When compared with untreated controls, numbers of CFU-GM and BFU-E colonies derived from MY10+ cells were unchanged, but the numbers of cells composing these colonies were reduced approximately 75 and greater than 90%, respectively, in comparison with controls. c-myc sense and antisense oligomers were without significant effect in these assays. Using the reverse transcription-polymerase chain reaction, c-myb mRNA was detected in developing hematopoietic cells on days 0-8. At day 14 c-myb expression was no longer detectable using this technique. These results suggest that c-myb is required for proliferation of intermediate-late myeloid and erythroid progenitors, but is less important for lineage commitment and early progenitor cell amplification.
HLA-B∗27 subtype specificity determines targeting and viral evolution of a hepatitis C virus-specific CD8+ T cell epitope
Authors: Katja Nitschke, Alejandro Barriga, Julia Schmidt, Jörg Timm, Sergei Viazov, Thomas Kuntzen, Arthur Y. Kim, Georg M. Lauer, Todd M. Allen, Silvana Gaudieri, Andri Rauch, Christian M. Lange, Christoph Sarrazin, Thomas Eiermann, John Sidney, Alessandro Sette, Robert Thimme, Daniel López, Christoph Neumann-Haefelin
Journal: Journal of Hepatology (2013)
Localized Gene-Specific Induction of Accessibility to V(D)j Recombination Induced by E2a and Early B Cell Factor in Nonlymphoid Cells
Authors: Peter Goebel, Noel Janney, Joaquín R. Valenzuela, William J. Romanow, Cornelis Murre, Ann J. Feeney
Journal: The Journal of Experimental Medicine (2001)

Accessibility of immunoglobulin (Ig) gene segments to V(D)J recombination is highly regulated and is normally only achieved in B cell precursors. We previously showed that ectopic expression of E2A or early B cell factor (EBF) with recombination activating gene (RAG) induces rearrangement of IgH and IgL genes in nonlymphoid cells. VκI genes throughout the locus were induced to rearrange after transfection with E2A, suggesting that the entire Vκ locus was accessible. However, here we show that Ig loci are not opened globally but that recombination is localized. Gene families are interspersed in the DH, Vκ, and Vλ loci, and we show that certain families and individual genes undergo high levels of recombination after ectopic expression of E2A or EBF, while other families within the same locus are not induced to rearrange. Furthermore, in some families, induction of germline transcription correlates with the level of induced recombination, while in others there is no correlation, suggesting that recombination is not simply initiated by induction of germline transcription. The induced repertoire seen at 24 hours does not change significantly over time indicating the absence of many secondary rearrangements and also suggesting a direct targeting mechanism. We propose that accessibility occurs in a local manner, and that binding sites for factors facilitating accessibility are therefore likely to be associated with individual gene segments.