tbuckley/cabot-search huggingface dataset:
The Genetics of Allergen-Induced Airway Hyperresponsiveness in Mice
Authors: MARSHA WILLS-KARP, SUSAN L. EWART
Journal: American Journal of Respiratory and Critical Care Medicine (1997)

Airway hyperresponsiveness (AHR) is a fundamental aspect of asthma that has been shown to be influenced by both environmental and genetic factors. Antigen sensitization and challenge of the A/J inbred mouse strain induced AHR, eosinophilic airway inflammation, and lung goblet cell hyperplasia. We discuss the evidence that supports the role of T helper cells and their subsets in determining the airway inflammatory and contractile responses to antigen in a mouse model. Airway hyperresponsiveness and pulmonary eosinophilic inflammation induced by antigen challenge are associated with a Th2 pattern of cytokine expression in the murine lung. CD4 + T cells mediate the airway reaction to antigen, as depletion of CD4 + T cells attenuates the response. The presence of interleukin (IL)-4 induces the Th2 type of immune response, and this cytokine is required for mice to manifest AHR and inflammation to antigen. The Th1 type of immune response is stimulated by IL-12. Antigen-mediated AHR and inflammation are inhibited by IL-12 administration. Airway hyperresponsiveness in the noninflammatory state (without antigen treatment) is inherited in A/J and C3H/HeJ inbred mouse strains. One quantitative trait locus for AHR in progeny derived from these strains is located on murine chromosome 6. We propose that antigen-inducd AHR and inflammation also have heritable components. Based on the available immunological data, genes that influence the balance between Th1 and Th2 cells are logical candidate genes for antigen-induced AHR and inflammation. Knowledge of the genes that determine this phenotype will help us understand the mechanisms of human asthma. Wills-Karp M, Ewart SL. The genetics of allergen-induced airway hyperresponsiveness in mice.
A REVIEW OF GASTRIC ULCER FOLLOW-UP PRACTICES IN A TERTIARY CARE GASTROENTEROLOGY SERVICE
Authors: S McGlacken-Byrne, C Lahiff, P MacMathuna, J Leyden
Journal: Gut (2013)

<h3>Introduction</h3> The Joint Advisory Group (JAG) guidelines1 recommend follow-up gastroscopy within 12 weeks for patients with gastric ulcers at index gastroscopy. <h3>Aims/Background</h3> This study reviews current practice in relation to gastric ulcer follow-up at a tertiary care university hospital. <h3>Method</h3> We conducted a retrospective review of over 700 gastroscopies performed in a four month period from June to September 2012. Patients with newly diagnosed ulcers (n=29) were included in our primary analysis. Those undergoing follow-up endoscopy for previously identified gastric ulcers (n=8) were also included. <h3>Results</h3> Gastric ulcers were found in 29 patients during the study period. Twenty three (79%) patients had biopsies taken. A plan for follow up gastroscopy was stated in 14 (48%) reports. Of these, 12 patients (86%) had follow up procedures booked and 9 (64%) attended for repeat gastroscopies. Median time to follow-up in this group was 61 days (range 3–194) and all patients had either healed (n=3) or healing (n=6) ulcers at follow up. Of patients undergoing gastroscopy for ulcers diagnosed prior to the study period (n=8), persistent mucosal abnormalities were noted in 7 (88%) of patients. Of these, 4 patients (50%) had biopsies taken. Two of these patients (25%) had a third gastroscopy booked for follow-up. <h3>Conclusion</h3> The data suggests that follow-up practices for gastric ulcers are not currently meeting standards set out by JAG guidelines. The performance of follow-up gastroscopy earlier than the recommended interval may result in higher prevalence of persistent mucosal abnormalities, with increased resource use accruing in terms of biopsies taken and further endoscopy.
Common sporting injuries of lower limbs and its management
Authors: Farasat Hussain
Journal: British Journal of Sports Medicine (2010)

Lower limb injuries are by far the most common injuries occurring in sports more so in all outdoor games. It is important to have a thorough knowledge of these injuries as also the anatomical structures involved in different types of injuries. Football, hockey, baseball, lawn tennis, badminton, volleyball, kabaddi, kho-kho and all sprinting events including long and high jumps as also all throwing events like discuss and javelin cause a number of lower limb injuries, which need to be attended urgently and dealt in the most advanced scientific manner, so that recovery of the sports person is quick and complete. The availability of advance investigating tools like MRI, CT-SCAN, ultrasonography, nerve conduction mapping and arthroscopy has brought about a complete change in our understanding of the problem of lower limb trauma and has also dramatically changed the treatment protocol. The management of these injuries can be divided into on-field assessment, primary, secondary and tertiary level. This article will primarily deal with the different type of common lower limb injuries and its management protocol.
Mediators of Ischemic Renal Injury
Authors: Joseph V. Bonventre
Journal: Annual Review of Medicine (1988)

Acute renal failure is a serious consequence of renal ischemia. The diagnosis carries an associated high mortality rate. When blood flow to the kidneys is inadequate to supply metabolic demands, a number of pathophysiological changes occur that ultimately result in cell death and tissue dysfunction, characterized by a marked reduction in glomerular filtration rate and associated accumulation of systemic toxins and disorders of fluid and electrolyte metabolism. In this chapter we review the factors that have been implicated as mediators of the renal tissue damage associated with ischemia and reperfusion.
Treatment with epoprostenol of pulmonary arterial hypertension following mitral valve replacement for mitral stenosis
Authors: C G Elliott
Journal: Thorax (2004)

Pulmonary hypertension frequently complicates mitral stenosis. Increased pulmonary artery pressure results from raised left atrial pressure, pulmonary arteriolar constriction, and obliterative changes in the pulmonary vascular bed, and usually responds to surgical relief of mitral stenosis. However, severe pulmonary hypertension may persist after surgical treatment of mitral stenosis. We describe a patient whose severe pulmonary hypertension following mitral valve replacement was treated successfully with continuous intravenous epoprostenol.
Neutrophil CD11b and soluble ICAM‐1 and E‐selectin in community acquired pneumonia
Authors: P. Glynn, R. Coakley, I. Kilgallen, S. O′neill
Journal: European Respiratory Journal (1999)

It was hypothesized that there would be an upregulation of systemic neutrophil CD11b expression in pneumonia. Expression of CD11b and concentrations of soluble intercellular adhesion molecule (ICAM)-1 and E-selectin were evaluated as potential surrogate markers of the severity of pneumonia. Possible age-related immunosenescence in relation to neutrophil CD11b expression in elderly patients with pneumonia was examined for. In patients with community-acquired pneumonia (n = 36) neutrophil CD11b expression was measured by flow cytometry and soluble ICAM-1 and E-selectin concentrations by enzyme-linked immunosorbent assay. An upregulation of neutrophil CD11b expression and increased soluble adhesion molecule concentrations on admission were confirmed, but the concentrations did not correlate with patient Acute Physiology and Chronic Health Evaluation II scores. Neutrophil CD11b expression was similar between elderly (age range 70-100 yrs) and younger (age range 18-70 yrs) patients with pneumonia. In conclusion, there is evidence of neutrophil and endothelial cell activation in pneumonia as indicated by upregulation of CD11b and increased soluble intercellular adhesion molecule and E-selectin, however, they do not appear to be good surrogate markers of severity of infection. Advanced age does not influence adhesion molecule expression in pneumonia.
In vivo effects of IgA and IgG2a anti-CD3 isotype switch variants.
Authors: K J Parlevliet, I J ten Berge, S L Yong, J Surachno, J M Wilmink, P T Schellekens
Journal: Journal of Clinical Investigation (1994)

Side effects after the first administration of OKT3, a murine anti-CD3 monoclonal antibody (mAb) of the IgG2a class, are largely attributed to the release of cytokines as a result of T cell activation caused by interaction with Fc receptors (FcR) on human monocytes. As human monocytes possess FcR for murine IgG2a but not for IgA, it is expected that an anti-CD3 mAb of the IgA class causes less side-effects than an IgG2a anti-CD3 mAb of the same idiotype. To test this hypothesis we treated 20 renal transplant patients prophylactically with either IgG2a or IgA anti-CD3 mAb in a prospective randomized double-blind study. The patients received 0.5 mg anti-CD3 mAb, either IgA (T3.A) or IgG2a (T3.G2a), twice daily during 10 d. Rejection incidence after T3.A and T3.G2a was not significantly different. Side effects score after the first administration of mAb was significantly less after T3.A than after T3.G2a (0.7 vs 2.7, P = 0.002). IL-6 and gamma IFN levels increased significantly at 3 h after T3.G2a, but not after T3.A. The TNF peak level occurring at 1 h after T3.A was much lower than after T3.G2a. In plasma, complement and neutrophil activation products only increased after T3.G2a and not after T3.A. Both T3.A and T3.G2a resulted in a complete depletion of CD3+ cells, but after T3.A, CD3 depletion was of shorter duration than after IgG2a. Finally, in contrast to T3.G2a, T3.A did not affect coagulation and fibrinolysis. In conclusion, an anti-CD3 mAb of the IgA class causes hardly any cytokine release and less side-effects as compared with its IgG2a switch variant. Provided T3.A is sufficiently immunosuppressive, it is superior to OKT3.
Endothelium-dependent relaxation and cyclic GMP accumulation in rabbit pulmonary artery are selectively impaired by moderate hypoxia.
Authors: R A Johns, J M Linden, M J Peach
Journal: Circulation Research (1989)

The effect of hypoxia on endothelium-dependent and endothelium-independent vasodilation was studied in phenylephrine-precontracted, isolated rings of rabbit first-branch pulmonary artery. Concentration-dependent relaxation responses to the endothelium-dependent dilators methacholine, ATP, and the calcium ionophore (A23187) as well as to the endothelium-independent dilators sodium nitroprusside and isoproterenol were obtained before, during, and after exposure to hypoxia (PO2 = 42 +/- 1 mm Hg) in the presence of indomethacin (2.8 x 10(-5) M). This moderate degree of hypoxia inhibited (p less than 0.05) endothelium-dependent but not endothelium-independent relaxation responses without producing irreversible vascular damage. In parallel experiments, cyclic GMP accumulation in pulmonary vascular rings in response to maximal doses of the above vasodilators was measured in the presence and absence of hypoxia. Cyclic GMP accumulation in response to endothelium-dependent dilators (methacholine, ATP, and A23187) was inhibited (p less than 0.05) by hypoxia while cyclic GMP accumulation in response to the endothelium-independent dilator sodium nitroprusside was not. When phenylephrine precontracted vessels were exposed to hypoxia in the absence of vasodilators, a small, transient increase in tension occurred, which was greater in endothelium-intact than in endothelium-denuded vessels (0.70 +/- 0.12 vs. 0.09 +/- 0.03 g, respectively; p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
Standards in the NHS
Authors: C. Shaw
Journal: Journal of the Royal Society of Medicine (2005)

Sixty years ago, the new National Health Service promised that a doctor would be assured ‘freedom... to pursue his professional methods in his own individual way, and not to be subject to outside clinical interference’.1 But after thirty years, the Chief Medical Officer, Sir George Godber, set out to define a ‘Cogwheel’ structure for the accountability and self-regulation of hospital doctors,2 and soon a non-governmental inquiry reported ‘It is a necessary part of a doctor's professional responsibility to assess his work regularly in association with his colleagues.’3 In evidence to the Royal Commission on the NHS in 1977, the British Medical Association was ‘not convinced of the need for further supervision of a qualified doctor's standard of care’. In its final report, the Commission responded, ‘We are not convinced that the professions regard the introduction of medical audit and peer review with a proper sense of urgency.’4

Thus, thirty years ago, standards in the NHS referred not to clinical practice or services but to buildings, equipment, capacity and allocation of resources.5 Any defects in the system were blamed on shortage of staff, money or facilities—after all, the NHS was then one of the cheapest comprehensive health systems in the world. There was little effort to examine how those resources were used or whether they could yield better clinical results. There had been several public scandals about the treatment of patients, the behaviour of doctors and the management of institutions, particularly in long-term care. But few people were keen for improvement, or even recognized a need for it. Tradition and the stout defence of clinical freedom made the management of doctors as easy as herding cats.
Protective effect of liver ischemic preconditioning on liver and lung injury induced by hepatic ischemia-reperfusion in the rat
Authors: Carmen Peralta, Neus Prats, Carme Xaus, Emilio Gelpí, Joan Roselló-Catafau
Journal: Hepatology (1999)

This study evaluates whether preconditioning could modulate the injurious effects of tumor necrosis factor (TNF) on liver and lung following hepatic ischemia-reperfusion (I/R) by inhibiting hepatic postischemic TNF release. The inhibition of hepatic TNF release from Kupffer cells with gadolinium chloride (GdCl 3 ) previous to ischemia maintained TNF at control levels, attenuating the increases in transaminases, vascular permeability, and edema associated with hepatic I/R injury. TNF addition reverted this beneficial effect, indicating the implication of the TNF released mainly from Kupffer cells in hepatic I/R injury. Preconditioning prevented hepatic TNF increases, thus attenuating the liver injury, while TNF addition abolished the benefits of preconditioning. Inhibition of nitric oxide (NO) synthesis abolished the effect of preconditioning, whereas GdCl 3 addition avoided the injurious effect of NO inhibition. In addition, NO administration before I/R offered similar results to those found in preconditioning, while TNF addition abolished the benefits of NO. Thus, the effect of preconditioning on TNF release after hepatic I/R is mediated by NO. Inhibition of hepatic TNF release from Kupffer cells with GdCl 3 prevented both the increase in plasma TNF and the injurious effect in lung seen after hepatic I/R, and these effects were reverted with TNF addition. Preconditioning resulting in reduced hepatic TNF levels prevented the systemic TNF release, thus reducing the lung damage following hepatic I/R. However, TNF addition abolished the protective effect of preconditioning on lung injury. These findings indicate that preconditioning attenuates hepatic postischemic TNF release from Kupffer cells, thus probably reducing the liver and lung injury following hepatic I/R, and that this effect of preconditioning is mediated by NO.
Abstract 14097: Cardiovascular Event Prediction and Risk Reclassification by Coronary, Aortic, and Valvular Calcification in the Framingham Heart Study
Authors: Udo Hoffmann, Joseph M Massaro, Ralph D'Agostino, Sekar Kathiresan, Caroline S Fox, Christopher J O'Donnell
Journal: Circulation (2013)

Background: We determined whether vascular and valvular calcification predict incident major coronary heart disease (CHD), cardiovascular disease (CVD), and all cause mortality independent of Framingham Risk Factors (FRF) in the community-based Framingham Heart Study. Methods: Coronary artery calcium (CAC), thoracic aortic calcium (TAC), abdominal aortic calcium (AAC), and mitral or aortic valve calcium (MVC and AVC, respectively) were measured by cardiac computed tomography in 3454 participants free of known CVD in the Offspring and 3rd Generation cohorts of the Framingham Heart Study. All participants were of white ethnicity and were followed for incident major CHD, major CVD, and all cause mortality through a median of 5 years. We tested association of CAC, TAC, AAC, MVC and AVC with endpoints using multivariate Cox proportional hazards models, and analyzed improvement in discriminatory value beyond FRF via the c-statistic and net reclassification index (NRI). Results: Event rates during follow up were...
The epidemiology of groin injury in senior football: a systematic review of prospective studies
Authors: Markus Waldén, Martin Hägglund, Jan Ekstrand
Journal: British Journal of Sports Medicine (2015)

Groin injuries are troublesome in men's and women's football.To review the literature on the epidemiology of groin injury in senior football and compare injury occurrence between sexes.Studies were identified through a search of PubMed, EMBASE, CINAHL and Web of Science, in the reference lists of the selected articles and the authors' bibliographies. The number of injuries, percentage of groin injury from all injuries and rate of groin injury per 1000 h were extracted. Exposure and injury data were aggregated across included studies and the absolute differences in groin injury proportion and rate of groin injury were compared between sexes. Risk of bias was assessed using a 5-item checklist.34 articles met the study criteria and were included. The proportion of groin injury in club-seasonal football was 4-19% in men and 2-14% in women. Aggregated data analysis (29 studies) showed a higher relative proportion of groin injury in men than in women (12.8% vs 6.9%, absolute difference 5.9%, 95% CI 4.6% to 7.1%). The rate of groin injury varied from 0.2 to 2.1/1000 h in men and 0.1 to 0.6/1000 h in women's club football, and aggregated analysis (23 studies) showed a more than two-fold higher rate in men (0.83/1000 h vs 0.35/1000 h, rate ratio 2.4, 95% CI 2.0 to 2.9). High risk of bias was identified for participant selection (18 studies), exposure (17 studies) and precision estimate (16 studies).Groin injuries are frequent in senior football and are more common in men than women. Future research needs to be of higher quality.
Anti-signal recognition particle autoantibodies: marker of a necrotising myopathy
Authors: G J D Hengstman, H J ter Laak, W T M Vree Egberts, I E Lundberg, H M Moutsopoulos, J Vencovsky, A Doria, M Mosca, W J van Venrooij, B G M van Engelen
Journal: Annals of the Rheumatic Diseases (2006)

Objective: To elucidate the clinical importance of the anti-signal recognition particle (SRP) autoantibody in patients with myositis. Methods: Retrospective systematic assessment of the clinical, laboratory and histological characteristics of 23 anti-SRP-positive patients from six European centres. Data were compared with a large group of anti-SRP-negative patients with myositis published previously. Results: Clinically, patients with anti-SRP autoantibodies often had a severe symmetric proximal muscle weakness resulting in marked disability, dysphagia and highly elevated levels of serum creatine kinase. Three patients had typical dermatomyositis rashes. The disease was associated with the occurrence of extramuscular signs and symptoms including interstitial lung disease. No association was found with an increased risk of cardiac involvement, and the disease carried a reasonably favourable prognosis with most patients responding to treatment. None of the patients had the typical histological features of myositis. Most muscle biopsy specimens showed the presence of necrotic muscle fibres and no inflammatory infiltrates. Conclusions: Anti-SRP autoantibodies are associated with a syndrome of a necrotising myopathy in the spectrum of immune-mediated myopathies that differs from typical polymyositis. Further studies are needed to elucidate the pathogenesis and to clarify the role of the anti-SRP autoantibodies in this unique disease.
Caspase-Independent Cell Death Is Involved in the Negative Effect of EGF Receptor Inhibitors on Cisplatin in Non–Small Cell Lung Cancer Cells
Authors: Hirohito Yamaguchi, Jennifer L. Hsu, Chun-Te Chen, Ying-Nai Wang, Ming-Chuan Hsu, Shih-Shin Chang, Yi Du, How-Wen Ko, Roy Herbst, Mien-Chie Hung
Journal: Clinical Cancer Research (2013)

Abstract Purpose: Results of multiple clinical trials suggest that EGF receptor (EGFR) tyrosine kinase inhibitors (TKI) exhibit negative effects on platinum-based chemotherapy in patients with lung cancer with wild-type (WT) EGFR, but the underlying molecular mechanisms are still uncertain. Studies that identify the mechanism of how TKIs negatively affect patients with WT EGFR are important for future development of effective strategies to target lung cancer. Thus, we returned to in vitro study to investigate and determine a possible explanation for this phenomenon. Experimental Design: We investigated the effects of TKIs and cisplatin on caspase-independent cell death (CID) and the role of CID in the efficacy of each drug and the combination. Furthermore, we studied the mechanism by which EGFR signaling pathway is involved in CID. Finally, on the basis of the identified mechanism, we tested the combinational effects of cisplatin plus suberoylanilide hydroxamic acid (SAHA) or erastin on CID. Results: We found that gefitinib inhibited cisplatin-induced CID but not caspase-dependent apoptotic cell death. In WT EGFR cells, gefitinib not only inhibited CID but also failed to induce apoptosis, therefore compromising the efficacy of cisplatin. Inhibition of EGFR-ERK/AKT by gefitinib activates FOXO3a, which in turn reduces reactive oxygen species (ROS) and ROS-mediated CID. To overcome this, we showed that SAHA and erastin, the inducers of ROS-mediated CID, strongly enhanced the effect of cisplatin in WT EGFR cells. Conclusion: TKI-mediated inhibition of CID plays an important role in the efficacy of chemotherapy. Moreover, FOXO3a is a key factor in the negative effects of TKI by eliminating cisplatin-induced ROS. Clin Cancer Res; 19(4); 845–54. ©2012 AACR.