tbuckley/cabot-search huggingface dataset:
Compared with parenteral nutrition, enteral feeding attenuates the acute phase response and improves disease severity in acute pancreatitis
Authors: A C J Windsor, S Kanwar, A G K Li, E Barnes, J A Guthrie, J I Spark, F Welsh, P J Guillou, J V Reynolds
Journal: Gut (1998)

In patients with major trauma and burns, total enteral nutrition (TEN) significantly decreases the acute phase response and incidence of septic complications when compared with total parenteral nutrition (TPN). Poor outcome in acute pancreatitis is associated with a high incidence of systemic inflammatory response syndrome (SIRS) and sepsis.To determine whether TEN can attenuate the acute phase response and improve clinical disease severity in patients with acute pancreatitis.Glasgow score, Apache II, computed tomography (CT) scan score, C reactive protein (CRP), serum IgM antiendotoxin antibodies (EndoCAb), and total antioxidant capacity (TAC) were determined on admission in 34 patients with acute pancreatitis. Patients were stratified according to disease severity and randomised to receive either TPN or TEN for seven days and then re-evaluated.SIRS, sepsis, organ failure, and ITU stay, were globally improved in the enterally fed patients. The acute phase response and disease severity scores were significantly improved following enteral nutrition (CRP: 156 (117-222) to 84 (50-141), p < 0.005; APACHE II scores 8 (6-10) to 6 (4-8), p < 0.0001) without change in the CT scan scores. In parenterally fed patients these parameters did not change but there was an increase in EndoCAb antibody levels and a fall in TAC. Enterally fed patients showed no change in the level of EndoCAb antibodies and an increase in TAC.TEN moderates the acute phase response, and improves disease severity and clinical outcome despite unchanged pancreatic injury on CT scan. Reduced systemic exposure to endotoxin and reduced oxidant stress also occurred in the TEN group. Enteral feeding modulates the inflammatory and sepsis response in acute pancreatitis and is clinically beneficial.
RESTORATION OF CELL-MEDIATED IMMUNITY TO ANIMALS BLOCKED BY A HUMORAL RESPONSE
Authors: George B. MacKaness, Philippe H. Lagrange
Journal: The Journal of Experimental Medicine (1974)

The T cells which mediate delayed-type hypersensitivity (DTH) to sheep red blood cells (SRBC) are blocked by a normal humoral response and cannot be made to function by further immunization. They can be rescued to some extent by treatment with immunopotentiating agents such as cyclophosphamide (CY) which suppresses the antibody response selectively, or by BCG which interferes with the action of serum blocking factors. These two agents together can restore cell-mediated immunity completely, but a further antigenic stimulus is needed to reestablish DTH in mice blocked by a long period of continuous exposure to SRBC.
Effect of surgical lung volume reduction on respiratory muscle function in pulmonary emphysema
Authors: H Teschler, G Stamatis, AA el-Raouf Farhat, FJ Meyer, U Costabel, N Konietzko
Journal: European Respiratory Journal (1996)

Lung volume reduction surgery (LVRS) in patients with severe lung emphysema restores the thoracic configuration to a more normal functional capacity. The aim of this study was to investigate whether reduction in intrathoracic volume by LVRS improves the inspiratory muscle force generation of the respiratory pump. Pulmonary function tests, maximal inspiratory mouth pressure (MIP), sniff nasal inspiratory pressure (SNIP), sniff transdiaphragmatic pressure (Pdi), and inspiratory mouth occlusion pressure (P0.1) were measured in 17 emphysematous patients (mean (+/- SEM) age 53 +/- 2 yrs) before and 1 month after LVRS. The mean value of forced expiratory volume in one second (FEV1) increased (0.82 +/- 0.07 vs 1.12 +/- 0.08 L; p < 0.0001), whilst there was a decrease (p < 0.0001) in residual volume (RV) (337 +/- 31 vs 250 +/- 21 % of predicted), functional residual capacity (FRC) (210 +/- 9 vs 159 +/- 9% pred), and total lung capacity (TLC) (138 +/- 6 vs 110 +/- 5% pred). The mean value of MIP increased by 52% from 4.8 +/- 0.4 to 7.3 +/- 0.6 kPa (p < 0.001), the mean value of SNIP increased by 66% from 3.9 +/- 0.4 to 6.5 +/- 0.5 kPa (p < 0.001), and the mean value of Pdi increased by 28% from 6.0 +/- 0.6 to 7.7 +/- 0.8 kPa (p < 0.05) after LVRS. P0.1 decreased on average by 24% from 0.46 +/- 0.03 to 0.35 +/- 0.02 kPa after LVRS. No significant correlations were found between inspiratory muscle (MIP, SNIP, Pdi) and respiratory drive (P0.1) indices, lung function data, 6 min walk distance, or dyspnoea score. In conclusion, the observed clinical improvement of patients with severe emphysema after lung volume reduction surgery results, in part, from an increased ability of the inspiratory muscles to generate force, which is paralleled by a significant decrease in central respiratory drive.
Galactose elimination capacity as a prognostic index in patients with fulminant liver failure.
Authors: L Ranek, P B Andreasen, N Tygstrup
Journal: Gut (1976)

In 25 patients with fulminant hepatic failure the prognostic value of a quantitative liver function test, the galactose elimination capacity, was assessed and comapred with routine liver function tests and clinical features. The galactose elimination capacity was significantly higher (P less than 0-05) in the five patients who survived than in the 20 patients who died. None of the other liver function tests, was significantly different. The values of the galactose elimination capacity overlapped considerably between survivors and non-survivors, but all patients with a galactose elimination capacity below 12-8 mumol galactose/min and kg body weight died. The disease among most patients who died having a galactose elimination capacity greater than 13 mumol ran a subacute course. It is suggested that quantitative liver function tests be included when new treatments of fulminant hepatic failure are investigated.
Cooperative Interactions Between RB and p53 Regulate Cell Proliferation, Cell Senescence, and Apoptosis in Human Vascular Smooth Muscle Cells From Atherosclerotic Plaques
Authors: Martin R. Bennett, Kirsty Macdonald, Shiu-Wan Chan, Joseph J. Boyle, Peter L. Weissberg
Journal: Circulation Research (1998)

Abstract —Compared with vascular smooth muscle cells (VSMCs) from normal vessels, VSMCs from human atherosclerotic plaques proliferate more slowly, undergo earlier senescence, and demonstrate higher levels of apoptosis in culture. The tumor suppressor genes p105 RB (retinoblastoma, acting through the E2F transcription factor family) and p53 regulate cell proliferation, cell senescence, and apoptosis in many cell types. We have therefore determined whether these stable growth properties of plaque VSMCs reflect altered activity of RB and/or p53. VSMCs were derived from coronary atherectomies or from normal coronary arteries from transplant recipients. Compared with normal VSMCs, plaque VSMCs showed a higher ratio of the active (hypophosphorylated) to the inactive (phosphorylated) form of RB and a lower level of E2F transcriptional activity. Cells were stably transfected with retrovirus constructs that inhibited RB or p53 alone or in combination. Suppression of RB alone increased rates of cell proliferation and apoptosis and inhibited cell senescence in normal VSMCs. Suppression of p53 and RB together had similar effects but, additionally, resulted in immortalization of normal VSMC cultures. In contrast, inhibition of RB binding to E2F or ectopic expression of E2F-1 in plaque VSMCs induced massive apoptosis, which required suppression of p53 to rescue cells. Suppression of RB and p53 together increased cell proliferation and delayed senescence but failed to immortalize plaque VSMCs. Inhibition of p53 alone had minimal effects on plaque VSMCs but increased the lifespan of normal VSMCs. We conclude that human plaque VSMCs have slower rates of cell proliferation and earlier senescence than do cells from normal vessels because of a defect in phosphorylation of RB. Furthermore, both disruption of RB/E2F and inhibition of p53 are required for plaque VSMCs to proliferate without apoptosis. This observation may explain the relatively low level of cell proliferation and high level of apoptosis seen in VSMCs in human atherosclerotic plaques.
Wheeze not current asthma affects quality of life in young adults with asthma
Authors: M Matheson
Journal: Thorax (2002)

Background: A study was undertaken to investigate quality of life in asthma, defined by differing criteria, to see which may be most appropriate in epidemiological studies. Methods: The 426 adults were participants in the follow up phase of the European Community Respiratory Health Survey (ECRHS) in Melbourne. As part of the laboratory visit, participants completed the SF-36 quality of life questionnaire, a detailed respiratory questionnaire, and underwent lung function testing. Results: Both the physical component summary and the mental component summary scores were significantly worse in those with wheeze in the previous 12 months than in those without wheeze. Only the mental component summary score was significantly worse in those with current asthma than in those without. In contrast, in those with current asthma or bronchial hyperreactivity only, neither of the summary scales was significantly different between cases and controls. Conclusions: Quality of life is severely impaired in individuals with wheeze in the previous 12 months while individuals with current asthma or bronchial hyperreactivity alone did not appear to have significantly reduced quality of life.
Gene expression analysis predicts insect venom anaphylaxis in indolent systemic mastocytosis
Authors: M. Niedoszytko, M. Bruinenberg, J. J. van Doormaal, J. G. R. de Monchy, B. Nedoszytko, G. H. Koppelman, M. C. Nawijn, C. Wijmenga, E. Jassem, J. N. G. Oude Elberink
Journal: Allergy (2010)

To cite this article: Niedoszytko M, Bruinenberg M, van Doormaal JJ, de Monchy JGR, Nedoszytko B, Koppelman GH, Nawijn MC, Wijmenga C, Jassem E, Oude Elberink JNG. Gene expression analysis predicts insect venom anaphylaxis in indolent systemic mastocytosis. Allergy 2011; 66: 648–657. Background: Anaphylaxis to insect venom (Hymenoptera) is most severe in patients with mastocytosis and may even lead to death. However, not all patients with mastocytosis suffer from anaphylaxis. The aim of the study was to analyze differences in gene expression between patients with indolent systemic mastocytosis (ISM) and a history of insect venom anaphylaxis (IVA) compared to those patients without a history of anaphylaxis, and to determine the predictive use of gene expression profiling. Methods: Whole-genome gene expression analysis was performed in peripheral blood cells. Results: Twenty-two adults with ISM were included: 12 with a history of IVA and 10 without a history of anaphylaxis of any kind. Significant differences in single gene expression corrected for multiple testing were found for 104 transcripts (P < 0.05). Gene ontology analysis revealed that the differentially expressed genes were involved in pathways responsible for the development of cancer and focal and cell adhesion suggesting that the expression of genes related to the differentiation state of cells is higher in patients with a history of anaphylaxis. Based on the gene expression profiles, a naïve Bayes prediction model was built identifying patients with IVA. Conclusions: In ISM, gene expression profiles are different between patients with a history of IVA and those without. These findings might reflect a more pronounced mast cells dysfunction in patients without a history of anaphylaxis. Gene expression profiling might be a useful tool to predict the risk of anaphylaxis on insect venom in patients with ISM. Prospective studies are needed to substantiate any conclusions.
Acquired Rifamycin Resistance with Twice-Weekly Treatment of HIV-related Tuberculosis
Authors: William Burman, Debra Benator, Andrew Vernon, Awal Khan, Brenda Jones, Claudia Silva, Chris Lahart, Stephen Weis, Barbara King, Bonita Mangura, Marc Weiner, Wafaa El-Sadr
Journal: American Journal of Respiratory and Critical Care Medicine (2005)

Rifabutin was recommended in place of rifampin during treatment of HIV-related tuberculosis (TB) to facilitate concomitant potent antiretroviral therapy, but this approach has not been evaluated in a prospective study.To evaluate the activity of intermittent rifabutin-based therapy.Patients with culture-confirmed TB were treated under direct supervision with 2 mo of rifabutin, isoniazid, pyrazinamide, and ethambutol (given daily, thrice-weekly, or twice-weekly per the local tuberculosis control program), followed by 4 mo of twice-weekly rifabutin plus isoniazid.Culture-positive treatment failure or relapse.A total of 169 eligible patients were enrolled. Most had advanced HIV disease; the median CD4 cell count and HIV-RNA level were 90 cells/mm3 (interquartile range, 35-175) and 5.3 log10 copies/ml (interquartile range, 4.8-5.7), respectively. Nine (5.3%) patients had culture-positive treatment failure (n = 3) or relapse (n = 6). Eight of these nine (89%) cases had isolates with acquired rifamycin resistance. Treatment failure or relapse was associated with baseline CD4 lymphocyte count, being 12.3% (9/73; 95% confidence interval, 6.5-22.0%) among patients with CD4 < 100 cells/mm3 versus 0% (0/65; 95% confidence interval, 0.0-4.5%) among those with higher CD4 lymphocyte counts (p < 0.01). One hundred thirty-seven (81%) patients received antiretroviral therapy during TB treatment. Adverse events were common, but only two patients (1%) permanently discontinued study drugs.Intermittent rifabutin-based therapy for HIV-related TB was well tolerated, but there was a high risk of treatment failure or relapse with acquired rifamycin resistance among patients with low CD4 lymphocyte counts.
IL-4 abrogates osteoclastogenesis through STAT6-dependent inhibition of NF-κB
Authors: Yousef Abu-Amer
Journal: Journal of Clinical Investigation (2001)

IL-4, an anti-inflammatory cytokine, inhibits osteoclast differentiation, but the basis of this effect has been unclear. Osteoclastogenesis requires activation of RANK, which exerts its biologic effect via activation of NF-kappaB. NF-kappaB activation is manifested by nuclear translocation and binding to DNA, events secondary to phosphorylation and dissociation of IkappaBalpha. It is shown here that IL-4 reduces NF-kappaB nuclear translocation by inhibiting IkappaB phosphorylation, thus markedly inhibiting NF-kappaB DNA binding activity and blocking osteoclastogenesis entirely. Residual translocation of NF-kappaB in the presence of IL-4, however, suggests that nuclear mechanisms must primarily account for inhibition of NF-kappaB DNA binding and blockade of osteoclastogenesis. To address this issue, this study examined whether IL-4-induced STAT6 transcription factor blocks NF-kappaB transactivation. The results show that excess unlabeled consensus sequence STAT6, but not its mutated form, inhibits NF-kappaB binding. Furthermore, exogenously added STAT6 protein inhibits NF-kappaB/DNA interaction. Further supporting a role for STAT6 in this process are the findings that IL-4 fails to block osteoclastogenesis in STAT6(-/-) mice but that this blockade can be restored with addition of exogenous STAT6. Thus, IL-4 obliterates osteoclast differentiation by antagonizing NF-kappaB activation in a STAT6-dependent manner.
Worse clinical outcome but similar graft patency in women versus men one year after coronary artery bypass graft surgery owing to an excess of exposed risk factors in women
Authors: Eng-Shiong Tan, Jan van der Meer, Pieter Jan de Kam, Peter H.J.M Dunselman, Barbara J.M Mulder, Carl A.P.L Ascoop, Matthias Pfisterer, Kong I Lie
Journal: Journal of the American College of Cardiology (1999)
A Randomized Trial Comparing Treatments for Varicose Veins
Authors: Julie Brittenden, Seonaidh C Cotton, Andrew Elders, Craig R Ramsay, John Norrie, Jennifer Burr, Bruce Campbell, Paul Bachoo, Ian Chetter, Michael Gough, Jonothan Earnshaw, Tim Lees, Julian Scott, Sara A Baker, Jill Francis, Emma Tassie, Graham Scotland, Samantha Wileman, Marion Kay Campbell
Journal: New England Journal of Medicine (2014)

Ultrasound-guided foam sclerotherapy and endovenous laser ablation are widely used alternatives to surgery for the treatment of varicose veins, but their comparative effectiveness and safety remain uncertain.
Coronary artery spasm.
Authors: M J Butler
Journal: BMJ (1977)

Management of childhood epilepsy SIR,-I hope that Dr H Wykeham Balme (14 May, p 1284) does not imply that all children with epilepsy should live in a home with prdtected staircases, without bathroom locks, and with guards around the fires and radiators; that they should bath in less than three inches of water, go to school accompanied, and not climb trees or go swimming or camping.
Press: Fear of frying: power lines and cancer
Authors: S. Chapman
Journal: BMJ (2001)

Those in the media who believe that high voltage power lines and pylons cause cancer in children are like the plucky, armless black knight in Monty Python's Quest for the Holy Grail : they just won't give up.

Last week they thought their Christmases were all about to come at once when they got wind of a report not yet published that was “expected to show” that the power lines were killers. Even better, among the authors of the report was none other than Sir Richard Doll, whose every mention noted that he was the first to show conclusively the link between smoking and lung cancer. These electricity doomsayers were about to be vindicated over their perennial story by the Mike Tyson of epidemiology: if Doll said there was danger, there was no turning back.

Except for one tiny problem-ette. The then unreleased report was not actually going to say that. The UK National Radiological Protection Board (NRPB) review (http://www.nrpb.org.uk/Absd12-1.htm) published on 6 March …
Hypothyroidism modulates beta adrenergic receptor adenylate cyclase interactions in rat reticulocytes.
Authors: G L Stiles, J M Stadel, A De Lean, R J Lefkowitz
Journal: Journal of Clinical Investigation (1981)

We have investigated alterations in beta adrenergic receptor binding sites of rat reticulocytes occurring in animals rendered hypothyroid by thyroidectomy. Beta adrenergic receptor interactions were assessed by measuring the number of (-)[3H]-dihydroalprenolol binding sites and the ability of an agonist to compete for occupancy of the receptors. The number of receptors was significantly reduced in cells from the hypothyroid animals. In addition, there were significant agonist-specific alterations in binding. Using computer assisted curve fitting techniques, it was found that the ability of (-)isoproterenol to stabilize a high affinity guanine nucleotide sensitive "coupled" form of the receptor was impaired. Reticulocytes from hypothyroid animals have, in addition, a reduction in the concentration of the nucleotide regulatory protein as assessed by the number of 42,000 Mr substrates for cholera toxin catalyzed ADP ribosylation. These alterations are associated with reductions in catecholamine and NaF stimulated adenylate cyclase activity. Diminished coupling of beta adrenergic receptors with other regulatory components of the adenylate cyclase system represents a mechanism by which altered thyroid states modulate beta adrenergic receptor function and beta adrenergic responsiveness of tissues.
Alpha 1-adrenoceptor activity regulates release of adenosine from the ischemic myocardium in dogs.
Authors: M Kitakaze, M Hori, J Tamai, K Iwakura, Y Koretsune, T Kagiya, K Iwai, A Kitabatake, M Inoue, T Kamada
Journal: Circulation Research (1987)

The goal of this study was to test the hypothesis that alpha 1-adrenoceptor activity plays a key role in the release of adenosine from the ischemic myocardium. In 51 open-chest dogs, the left anterior descending coronary artery was perfused through an extracorporeal bypass tube from the carotid artery, and adenosine release into the local coronary vein was measured by the radioimmunoassay technique following the reduction of perfusion pressure for 20 minutes under alpha 1-, alpha 2-, and beta-adrenoceptor attenuations. Adenosine and lactate concentrations in the coronary arterial and venous blood sampled from the perfused area were determined, as well as fractional shortening. In the untreated condition, adenosine release was significantly (p less than 0.01) increased from 1.7 +/- 0.8 (SEM) to 8.8 +/- 1.3 nmol/100 g/min, 20 minutes after the onset of hypoperfusion (coronary blood flow: 28 +/- 2 ml/100 g/min) following the initial overshoot release. Neither beta- nor alpha 2-adrenoceptor attenuation affected the increase in adenosine release during hypoperfusion except for the slight attenuation of the overshoot release by beta-attenuation. In contrast, intracoronary infusions of prazosin and phentolamine during coronary hypoperfusion markedly attenuated (p less than 0.01) release of adenosine (1.8 +/- 0.7 nmol/100 g/min at 20 minutes). The extents of decreases in fractional shortening and lactate production were comparable between the untreated and alpha 1-adrenoceptor attenuation.(ABSTRACT TRUNCATED AT 250 WORDS)
A novel adult human ventricle slice preparation for cardiac drug discovery and safety pharmacology
Authors: M. J. Curtis
Journal: Cardiovascular Research (2011)

The editorial refers to ‘Organotypic slice culture from human adult ventricular myocardium’ by M. Brandenburger et al ., doi:10.1093/cvr/cvr259. 

Cardiac drug discovery and cardiac safety pharmacology assessment both require new models/methods to advance strategy.1–6 Ventricular arrhythmias are no longer a major focus for therapeutic drug discovery, and to become so again, a range of new preclinical models and a novel experimental strategy will be required for detecting desirable effects on cardiac electrophysiology and rhythm.2,3 In the field of cardiac safety pharmacology, new chemical entities that possess the desired target specificity are entered into high throughput screens (HTS) for safety pharmacology frontloading, including assessment of torsades de pointes liability.4–6 An integrated safety assessment strategy has appeared during the past 10 years, and optimization of the deployment of the numerous available constituent methods continues to evolve.4 Part of this involves the search for more inexpensive, more predictive medium-throughput screens that fit somewhere between the crude HTS methods, and the expensive and technically demanding late-stage safety screens.4–6

In cardiac safety and discovery, the headline goals are the same: to determine what a drug does to cardiac ion channels and how this manifests as an integrated outcome (i.e. effect on action potential configuration, conduction and refractoriness, rhythm and function).1–6 The human ventricular slice preparation described by Brandenburger et al .7 may have a role both in antiarrhythmic drug discovery and in safety assessment going forward. Its potential value arises from several of its aspects.

First, it is a human tissue preparation. In research, we justify the use of animals on the basis of the utility of the readout vs. ethical considerations. Readout utility, in drug discovery and safety assessment, …
Optimizing Chemotherapy-Free Survival for the ER/HER2-Positive Metastatic Breast Cancer Patient
Authors: Stefan Glück, Carlos L. Arteaga, C. Kent Osborne
Journal: Clinical Cancer Research (2011)

The recent incremental advances made in the treatment of metastatic breast cancer have elicited potential for survival extension in this treatable, yet incurable, population of breast cancer patients. Clinicians have focused on targeted therapies, which aim at signaling receptors such as the human epidermal receptor superfamily, the estrogen receptor, VEGF, the insulin-like growth factor receptor, the hepatocyte growth factor receptor (cMET), phosphoinositide 3-kinase, mTOR, and many others.