tbuckley/cabot-search huggingface dataset:
PTU-195 Six years of laparoscopic Nissen's fundoplication, was it worth it? An audit of 100 patients: Abstract PTU-195 Table 1
Authors: L Martin, M Stavrou, F El Madani, S Gupta
Journal: Gut (2012)

<h3>Introduction</h3> Nissen9s fundoplication for gastro-oesophageal reflux disease provides good long term control of acid reflux but is often not without unwanted side-effects. We investigated long term outcome of Nissen9s fundoplication at our centre. <h3>Methods</h3> Study group included 100 patients who underwent Nissen9s fundoplication from 2005 to 2011 at our unit. Pre-operative demographics, symptom profile, investigations and operative data were reviewed. Symptoms after surgery (heartburn, dysphagia, bloating and excessive flatus), antacid usage and patient satisfaction were assessed using a follow-up questionnaire. <h3>Results</h3> Average patient age was 47.5 years (19–79 years) with male to female ratio of 57:43. Majority of patients were obese or overweight (79%). Average follow-up was 39 months (3–80 months). Main symptoms included acid reflux (99%), volume reflux (56%) and nocturnal and postural reflux (45%). Gastroscopy revealed hiatus hernia 92%, reflux oesophagitis 71% and Barrett9s oesophagus 11%. pH studies and manometry were undertaken in 90% and 93% of patients respectively. Mean acid exposure time was 16.2% (median 13%, range 1.4%–86%), mean symptom index was 79.25% (median 91%, range 1–100%) and mean Demeester score was 50.51 (median 30, range 4.7–291). Lower oesophageal sphincter pressure was normal in 54%, low in 37% and high in 9% of patients with complete relaxation in 91%. No patient had significant oesophageal dysmotility. No routine follow-up pH studies were undertaken. A primary crural repair with 360° short and floppy fundal wrap was constructed on all the patients. Hiatus was prosthetically reinforced on 17 patients (collagen patch 12, mesh 5). Conversion to open surgery was 2% (splenic bleed, difficult anatomy). Four patients required further surgery during follow-up period (severe dysphagia 2, excessive flatus 1, herniation through the wrap 1). Questionnaire responses from 96/100 patients were analysed (postal 56, telephonic 22, clinic review 18). Most patients (81%) were happy to have undergone surgery and would recommend this procedure to a friend (79%). A total of 58 patients (60%) were not on any anti-acid drugs, however 17 patients (18%) were on regular PPIs. Frequencies of post-operative symptoms are detailed below. Overall outcome was described by patients as excellent 43%, good 38%, fair 11% and poor 8%. <h3>Conclusion</h3> Majority of patients undergoing Laparoscopic Nissen9s fundoplication had good long term control of acid reflux and were happy with their decision to undergo surgery. Wind related side effects are a significant cause for dissatisfaction and must be emphasised during decision making for surgery. <h3>Competing interests</h3> None declared.
Comparative epidemiology of atopic and non-atopic wheeze and diagnosed asthma in a national sample of English adults
Authors: C S Court, D G Cook, D P Strachan
Journal: Thorax (2002)

<b>Background:</b> There is debate as to whether asthma has distinct atopic and non-atopic forms and whether in epidemiological studies asthma cases should be defined by a physician diagnosis or by self-reported asthma symptoms. <b>Methods:</b> A total of 24 952 people aged 11 and over were surveyed as part of the 1995–6 health surveys for England. Participants were asked if they had experienced wheezing in the past year and if they had ever been given a diagnosis of asthma by a doctor. Serum total IgE and house dust mite (HDM) specific IgE were measured. <b>Results:</b> Wheeze in the past year without an asthma diagnosis was more common in men and older age groups, whereas wheeze with an asthma diagnosis was more common in women and younger people. Both types of wheeze were more common in the lower social classes, among ex-smokers and current smokers, and in urban areas. Thirty two percent of people reporting wheezing and 22% of those with diagnosed asthma had neither raised total IgE nor HDM IgE. Among the non-atopic subjects the prevalence of wheeze rose with age and lower social class, largely due to an increase in wheeze without diagnosed asthma. In contrast, among atopic subjects there was no overall trend with age or social class, but wheeze with diagnosed asthma decreased with age. <b>Conclusions:</b> Clear epidemiological differences are evident between adult wheeze with and without an asthma diagnosis and between atopic and non-atopic wheeze. Subjects with diagnosed asthma are more likely to be atopic, but the results challenge the premise that adult asthma is almost always associated with some IgE mediated reaction.
Sources of variability in histological scoring of chronic viral hepatitis
Authors: Marie‐Christine Rousselet, Sophie Michalak, Florence Dupré, Anne Croué, Pierre Bedossa, Jean‐Paul Saint‐André, Paul Calès
Journal: Hepatology (2005)

Inter-observer agreement on activity and fibrosis scores used in chronic viral hepatitis has only been studied under selected conditions. The aim of this study was to identify the sources of variability due to specimen characteristics and observers. This study included 254 liver specimens and 15 pathologists and used the Metavir score. In 44 specimens scored by 4 academic pathologists, agreement of Metavir score was good overall, but better for fibrosis (kappa = 0.59) than for activity (kappa = 0.43) and poor for lobular necrosis (kappa = 0.15). The mean agreement was better for senior (0.60 +/- 0.24) than junior pathologists (0.52 +/- 0.30, P < .05). Mean intrabserver agreement was better than inter-observer agreement (0.77 +/- 0.18 vs. 0.58 +/- 0.26, P < .01). In 157 specimens scored by 2 expert pathologists (one senior, one junior), agreement of Metavir score was only good but greatly improved after consensus reading (fibrosis: kappa = 0.48 and 0.77, activity: kappa = 0.44 and 0.70, respectively, before and after consensus). Several causes of disagreement were identified: specimen length, fibrosis class number, observer bias, and putative causes related to Metavir score or specimen. In an intercenter evaluation involving 59 specimens, 1 expert and 10 nonacademic pathologists, agreement was very poor and did not improve over 5 years for activity (kappa = 0.22-0.25) or fibrosis (kappa = 0.13-0.18). In conclusion, the level of experience (specialization, duration, and location of practice) has more influence on agreement than the characteristics of the specimen (length, fibrosis class number, miscellaneous factors). Agreement can be improved by experienced pathologist or consensus reading.
A Skin-selective Homing Mechanism for Human Immune Surveillance T Cells
Authors: Patrick Schaerli, Lisa Ebert, Katharina Willimann, Andrea Blaser, Regula Stuber Roos, Pius Loetscher, Bernhard Moser
Journal: The Journal of Experimental Medicine (2004)

Effective immune surveillance is essential for maintaining protection and homeostasis of peripheral tissues. However, mechanisms controlling memory T cell migration to peripheral tissues such as the skin are poorly understood. Here, we show that the majority of human T cells in healthy skin express the chemokine receptor CCR8 and respond to its selective ligand I-309/CCL1. These CCR8+ T cells are absent in small intestine and colon tissue, and are extremely rare in peripheral blood, suggesting healthy skin as their physiological target site. Cutaneous CCR8+ T cells are preactivated and secrete proinflammatory cytokines such as tumor necrosis factor–α and interferon-γ, but lack markers of cytolytic T cells. Secretion of interleukin (IL)-4, IL-10, and transforming growth factor–β was low to undetectable, arguing against a strict association of CCR8 expression with either T helper cell 2 or regulatory T cell subsets. Potential precursors of skin surveillance T cells in peripheral blood may correspond to the minor subset of CCR8+CD25− T cells. Importantly, CCL1 is constitutively expressed at strategic cutaneous locations, including dermal microvessels and epidermal antigen-presenting cells. For the first time, these findings define a chemokine system for homeostatic T cell traffic in normal human skin.
Sildenafil Citrate Therapy for Pulmonary Arterial Hypertension
Authors: Nazzareno Galiè, Hossein A. Ghofrani, Adam Torbicki, Robyn J. Barst, Lewis J. Rubin, David Badesch, Thomas Fleming, Tamiza Parpia, Gary Burgess, Angelo Branzi, Friedrich Grimminger, Marcin Kurzyna, Gérald Simonneau
Journal: New England Journal of Medicine (2005)

Sildenafil inhibits phosphodiesterase type 5, an enzyme that metabolizes cyclic guanosine monophosphate, thereby enhancing the cyclic guanosine monophosphate-mediated relaxation and growth inhibition of vascular smooth-muscle cells, including those in the lung.In this double-blind, placebo-controlled study, we randomly assigned 278 patients with symptomatic pulmonary arterial hypertension (either idiopathic or associated with connective-tissue disease or with repaired congenital systemic-to-pulmonary shunts) to placebo or sildenafil (20, 40, or 80 mg) orally three times daily for 12 weeks. The primary end point was the change from baseline to week 12 in the distance walked in six minutes. The change in mean pulmonary-artery pressure and World Health Organization (WHO) functional class and the incidence of clinical worsening were also assessed, but the study was not powered to assess mortality. Patients completing the 12-week randomized study could enter a long-term extension study.The distance walked in six minutes increased from baseline in all sildenafil groups; the mean placebo-corrected treatment effects were 45 m (+13.0 percent), 46 m (+13.3 percent), and 50 m (+14.7 percent) for 20, 40, and 80 mg of sildenafil, respectively (P<0.001 for all comparisons). All sildenafil doses reduced the mean pulmonary-artery pressure (P=0.04, P=0.01, and P<0.001, respectively), improved the WHO functional class (P=0.003, P<0.001, and P<0.001, respectively), and were associated with side effects such as flushing, dyspepsia, and diarrhea. The incidence of clinical worsening did not differ significantly between the patients treated with sildenafil and those treated with placebo. Among the 222 patients completing one year of treatment with sildenafil monotherapy, the improvement from baseline at one year in the distance walked in six minutes was 51 m.Sildenafil improves exercise capacity, WHO functional class, and hemodynamics in patients with symptomatic pulmonary arterial hypertension.
P112 Deeper phenotyping of non CF bronchiectasis through sputum differential counts: Abstract P112 Table 1.
Authors: J Davison, G Johnson, K Jiwa, A Cranson, R Wake, B Hood, T Small, J Birch, A Fisher, A De Soyza
Journal: Thorax (2013)

<h3>Introduction and Objectives</h3> Non CF Bronchiectasis has diverse aetiologies. This includes idiopathic, systemic disease related and as a complication of asthma. Such diversity may be important in determining therapeutic strategies (personalised medicines) and may also be an important consideration in clinical trial design. This is increasingly relevant when neutrophil targeting or eosinophil targeted therapies are being developed. We hypothesised that patients could be phenotyped by sputum cytospins irrespective of suspected aetiology or disease severity. <h3>Methods</h3> Patients underwent a standardised clinical phenotyping protocol including HRCT chest (Anwar <i>et al</i> 2013). Baseline therapy was recorded. Spontaneous sputa were collected in stable state and spirometry was undertaken according to guidelines. Sputum cell counts were calculated using standard methods with data expressed as medians and ranges. <h3>Results</h3> Fifty three patients’ data are reported. The M:F ratio was 1:1.4. The mean FEV1 predicted was 62%, mean FEV1/VC ratio was 64%. Forty three (83%) were on inhaled corticosteroids and 24.5% had a historical diagnosis of asthma and /or ABPA. The predominant cell in sputa was neutrophils, median 94 (range 23–100%), macrophages were the 2nd most prevalent cell type median 2.6 (range 0–75%). Eosinophils showed a skewed distribution with median of 0.2 with a range of 0–24.8%. Four patients had sputum eosinophilia &gt;3%. Of these, only 2 had a history of asthma and / or ABPA being diagnosed. Despite historical diagnoses of asthma and / or ABPA in 13 patients the eosinophil percentage was not statistically different to “non asthmatics”. (P = 0.59 Chi Sq test) This group included features of ABPA in 2 patients and significant atopy in another. <h3>Conclusions</h3> Non CF bronchiectasis patients usually have sputum neutrophil dominance. Sputum eosinophilia is rare (&lt;10% of patients); however such patients may need alternative therapeutic strategies. Excluding bronchiectasis patients with a history of asthma from trials targeting neutrophils seems unnecessary. The neutrophilic predominant profiles in asthmatic bronchiectasis patients suggest either asthma misdiagnosis or that neutrophil predominant asthmatics may be more susceptible to developing bronchiectasis. Longitudinal studies are needed to determine if the sputum cell profiles are static in stable patients. These data may help develop a more personalised medicine approach in bronchiectasis. <h3>References</h3> Anwar GA, <i>et al.</i> 2013 Phenotyping adults with non-cystic fibrosis bronchiectasis: A prospective observational cohort study. <i>Respir Med</i>. Jul;107(7):1001–7. doi: 10.1016/j.rmed.2013.04.013. Epub 2013 May 11.
Generalized pustular and erythrodermic psoriasis associated with bupropion treatment
Authors: N.H. Cox, P.M. Gordon, H. Dodd
Journal: British Journal of Dermatology (2002)

Summary Severe drug eruptions may cause diagnostic and therapeutic difficulty when they mimic or provoke endogenous patterns of dermatosis. We report three patients with known psoriasis in whom use of bupropion (Zyban®), prescribed to assist with cessation of smoking, led to severe pustular or erythrodermic exacerbation of psoriasis within 3–5 weeks. All patients were systemically unwell and required hospitalization to control the disease flare.
Proximate delivery of a large experimental dose from salbutamol MDI induces epithelial airway lesions in intubated rabbits.
Authors: I A Spahr-Schopfer, J Lerman, E Cutz, M T Newhouse, M Dolovich
Journal: American Journal of Respiratory and Critical Care Medicine (1994)

The delivery of aerosolized drugs by metered dose inhaler (MDI) to intubated patients can be substantially improved by actuating the MDI through a narrow catheter placed inside the tracheal tube. However, the deposition of increased quantities of drug, surfactant, in particular oleic acid, and chlorofluorocarbon propellants on the lung surface could result in adverse effects not observed after oral MDI administration. To investigate this hypothesis, 42 adult intubated rabbits (six groups, n = 6 to 9/group) received Ventolin MDI, Ventolin placebo, a placebo MDI containing lecithin as surfactant, instilled salbutamol sulfate, instilled oleic acid solution, or no treatment (control). Heart rate, invasive blood pressure, and hemoglobin oxygen saturation, recorded continuously for the 3-h experiment, were unchanged from baseline (awake) values. Sections of trachea and lungs were reviewed blindly and graded using a four-point, nine-variable Ophoven scale. Blood was obtained after either 1 puff or 20 puffs MDI salbutamol to determine the pharmacokinetic profile of salbutamol. Multiple doses of both Ventolin and Ventolin placebo aerosols produced significant lesions to the epithelium of the trachea and main bronchi (p < 0.05). The histologic injury after lecithin placebo or salbutamol solution did not differ significantly from control, and all were significantly less than that observed after Ventolin MDI administration. Instilled oleic acid caused gross airway lesions. Maximum serum concentrations of salbutamol were 4.4 +/- 1.8 ng/ml after 1 puff and 419 +/- 168 ng/ml after 20 puffs. After 20 puffs, the total body clearance of salbutamol was 108 +/- 27 ml/min/kg, volume of distribution was 3.6 +/- 1.8 L/kg, and the elimination half-life was 22 +/- 7 min.(ABSTRACT TRUNCATED AT 250 WORDS)
In Vivo Nitrate Tolerance Is Not Associated With Reduced Bioconversion of Nitroglycerin to Nitric Oxide
Authors: Jørn Bech Laursen, Alexander Mu¨lsch, Søren Boesgaard, Petr Mordvintcev, Simon Trautner, Nicolai Gruhn, Jens Erik Nielsen-Kudsk, Rudi Busse, Jan Aldershvile
Journal: Circulation (1996)

Background In vitro data suggest that reduced bioconversion of nitroglycerin (NTG) to nitric oxide (NO) contributes to the development of vascular and hemodynamic tolerance to NTG. We examined the in vivo validity of this hypothesis by measuring NTG-derived NO formation by in vivo spin-trapping of NO in vascular tissues from nitrate-tolerant and -nontolerant rats. Methods and Results Five groups (n=6 to 8 each) of conscious chronically catheterized rats received NTG (0.2 or 1 mg/h IV) for 72 hours (nitrate-tolerant groups). Four other groups received either NTG vehicle (placebo, for 72 hours) or were left untreated (control). Nitrate tolerance was substantiated by a reduced (55% to 85%) hypotensive response to NTG in vivo and a reduced relaxation to NTG in isolated aortic rings. NTG-derived NO formation in aorta, vena cava, heart, and liver was measured as NOFe(DETC) 2 and NO-heme complexes formed in vivo during 35 minutes combined with ex vivo cryogenic electron spin resonance spectroscopy. NO formation was significantly ( P &lt;.05) increased in all tissues in nitrate-tolerant rats in an NTG dose–dependent manner. Furthermore, the amount of NO formed from a bolus dose of NTG (6.5 mg/kg over 20 minutes) was similar in nitrate-tolerant and -nontolerant rats. Conclusions The results suggest that vascular and hemodynamic NTG tolerance occurs despite high and similar rates of NO formation by NTG in tolerant and nontolerant target tissues. This finding is compatible with the assumption that reduced biological activity of NO, rather than reduced bioconversion of NTG to NO, contributes to in vivo development of nitrate tolerance.
Reactive oxygen metabolites and arterial thrombosis
Authors: G Ambrosio
Journal: Cardiovascular Research (1997)

Arterial thrombus formation is the result of complex events which require the interaction of damaged vessel walls with blood cellular elements and coagulation factors, and in which several mediators may play a role.In this context, the role of 'classical' chemical mediators such as thrombin, thromboxane or serotonin in initiating andror amplifying intravascular thrombus formation is well established.However, it is now being recognized that certain chemical species formed in the metabolism of oxygen may also be involved in the process of arterial thrombosis.This review will focus on recent evidence in this field.
Myocardial Conditioning
Authors: Michel Ovize, Hélène Thibault, Karin Przyklenk
Journal: Circulation Research (2013)

Myocardial conditioning is an endogenous cardioprotective phenomenon that profoundly limits infarct size in experimental models. The current challenge is to translate this paradigm from the laboratory to the clinic. Accordingly, our goal in this review is to provide a critical summary of the progress toward, opportunities for, and caveats to, the successful clinical translation of postconditioning and remote conditioning, the 2 conditioning strategies considered to have the broadest applicability for real-world patient care. In the majority of phase II studies published to date, postconditioning evoked a ≈35% reduction of infarct size in ST-segment–elevation myocardial infarction patients. Essential criteria for the successful implementation of postconditioning include the appropriate choice of patients (ie, those with large risk regions and negligible collateral flow), timely application of the postconditioning stimulus (immediately on reperfusion), together with proper choice of end points (infarct size, with concomitant assessment of risk region). Remote conditioning has been applied in planned ischemic events (including cardiac surgery and elective percutaneous coronary intervention) and in ST-segment–elevation myocardial infarction patients during hospital transport. Controversies with regard to efficacy have emerged, particularly among surgical trials. These disparate outcomes in all likelihood reflect the remarkable heterogeneity within and among studies, together with a deficit in our understanding of the impact of these variations on the infarct-sparing effect of remote conditioning. Ongoing phase III trials will provide critical insight into the future role of postconditioning and remote conditioning as clinically relevant cardioprotective strategies.
Cellular uncoupling can unmask dispersion of action potential duration in ventricular myocardium. A computer modeling study.
Authors: M D Lesh, M Pring, J F Spear
Journal: Circulation Research (1989)

Although slow conduction is a requirement for the preparation of sustained reentry, it alone is not sufficient for the initiation of reentry. Additionally, unidirectional block and recovery of excitability distal to the site of block must occur. Thus, a comprehensive description of the electrophysiological determinants of reentry must explain both slow conduction and unidirectional block. Although there is a growing body of research exploring the influence of axial resistivity and anisotropy on slow conduction, somewhat less is known about the relation of axial resistivity to spatial dispersion of action potential duration, a condition favorable to the development of unidirectional block. We hypothesized that when cells are well coupled, local differences in intrinsic action potential duration are not evident and that, as axial resistivity increases, local variation in action potential duration becomes manifest. We tested this hypothesis in a numerical model of electrical propagation in a grid of resistively coupled ionic current sources simulating a sheet of ventricular myocardium. Spatial dispersion of intrinsic action potential duration was simulated by varying the magnitude of the fully activated slow inward conductance in Beeler-Reuter membrane ionic kinetics. By then altering coupling resistance, we showed that dispersion of manifest action potential duration is masked in the setting of normal low-resistance cellular coupling and unmasked by increased axial resistance. When nonuniform anisotropy was simulated, dramatic pacing-site-dependent changes in both the pattern of activation and dispersion of action potential duration were noted. These findings may be important in understanding the mechanism of reentrant tachycardia initiation in the border zone of chronic, healed myocardial infarctions where evidence suggests that abnormal cellular coupling is the predominant electrophysiological derangement. In this study, we have shown, using a detailed ionic current-based model of cardiac electrical propagation, that changes in axial resistivity can modulate how spatial dispersion of intrinsic action potential duration is manifest.
The Resident Staff and Patient Care
Authors: John G. Freymann
Journal: JAMA (1966)

<h3>To the Editor:—</h3> In the recent paper by Stapleton and Zwerneman on the influence of a resident staff on the quality of patient care (<b>194</b>:877, 1965), I believe the authors failed to consider one conclusion. There were differences between the teaching and nonteaching services, but they were relatively minor and the quality of care on both was obviously good. I do not think this justifies the conclusion in the accompanying editorial that "the studies referred to above seem to indicate clearly that improvement in the quality of care is not dependent upon the presence of an approved program in graduate medical education." Quite the contrary! If the educational program is as successful as Dr. Stapleton's, the effect would be manifested through the work of the staff even when no interns or residents were present. If the stimulus of graduate students failed to carry beyond their physical presence, the quality