tbuckley/cabot-search huggingface dataset:
S28 Increased Incidence of COPD Exacerbations Following Influenza Vaccination
Authors: GC Donaldson, BS Kowlessar, ARC Patel, AJ Mackay, R Singh, S Brill, JA Wedzicha
Journal: Thorax (2012)

<h3>Introduction</h3> Influenza vaccination prevents substantial morbidity, and mortality, and the spread of infection, but patients still sometimes refuse vaccinations due to concerns over adverse reactions. Our aim was to determine the relative risk of COPD exacerbations post-vaccination. <h3>Methods</h3> We analysed data before and after 162 vaccinations given to 112 patients in the London COPD cohort between 2009 and 2011. Patients recorded on daily diary cards increase in respiratory symptoms. Exacerbations were defined as ≥2 days of 2 major symptoms (new or increased breathlessness, sputum volume or purulence) or 1 major and 1 minor symptom (cold, increased cough, increased wheeze, sore throat). Patients were telephoned in Oct 2011 and asked about recent or forthcoming vaccinations; other dates were known from previous years when recorded diary cards or reported at clinic visits. The risk of COPD exacerbation in the two post-vaccination periods, days 1–2 and 3–14 were calculated relative to the patient’s baseline risk assessed over the year before and after vaccination using a self-controlled case series approach. The data was also simply analysed with a Chi-squared test of the proportion of exacerbations in the two weeks before and after vaccination. <h3>Results</h3> There was a 3.31 fold (95% CI 1.5–7.4; P=0.004) increased risk of COPD exacerbation 1–2 days post influenza vaccination, and a 1.8 fold risk (1.2–2.9; p=0.007) 3–14 days afterwards. In the two weeks prior to vaccination there were 5/162 exacerbations and 26/162 in the two weeks post vaccination (p&lt;0.001). All 5 of the exacerbations before and 17/26 exacerbations after vaccination were treated with antibiotics and/or oral steroids. Using thie healthcare utilisation definition of COPD exacerbations, there were still significantly more events post vaccination (p=0.008). Figure 1 shows the average number of new or increased respiratory symptoms recorded by the patients during the 3 weeks before and after vaccination. <h3>Conclusion</h3> The incidence of COPD exacerbation increases immediately after influenza vaccination. COPD patients should be warned about increased respiratory symptoms after their influenza vaccination. Future studies should investigate the mechanisms underlying these increased symptoms in order to intervene and prevent them effectively.
Antioxidative Properties of Acetylsalicylic Acid on Vascular Tissues From Normotensive and Spontaneously Hypertensive Rats
Authors: Rong Wu, Daniel Lamontagne, Jacques de Champlain
Journal: Circulation (2002)

Background — The mechanisms of the beneficial cardiovascular effects of acetylsalicylic acid (ASA, aspirin) therapy are not completely understood. Oxidative stress and inflammation play important roles in the development of cardiovascular diseases. Methods and Results — In this study, we tested the hypothesis that ASA treatment could reduce superoxide anion (O 2 − ) generation in aortic ring and in cultured aortic smooth muscle cells (SMCs) from normotensive (WKY) and hypertensive (SHRs) rats by means of the Lucigenin-enhanced chemiluminescence method. Although ASA did not show any short-term effect in vitro and in vivo, long-term oral treatment (100 mg/kg/day, 12 days) significantly reduced the basal O 2 − production by 27% and 45% in aorta of normotensive and hypertensive rats, respectively, in association with a reduction of the NAD(P)H oxidase activity in both groups. These effects were dose-dependent from 10 to 100 mg/kg/day. Similar effects were observed in SMCs following long-term incubation (48 hours) with ASA. ASA treatment also completely inhibited the angiotensin II–induced hypertension and O 2 − production. Moreover, ASA treatment significantly improved the impaired aortic relaxation response to acetylcholine and markedly attenuated the age-dependent development of hypertension in SHRs. Conclusion — Long-term ASA treatment in vivo markedly reduced vascular O 2 − production through lowering the NAD(P)H oxidase activity in both normotensive and hypertensive rats. These antioxidative properties of ASA are likely involved in the restoration of aortic vasorelaxation, in the attenuation of the development of hypertension in young SHRs, and in the prevention of hypertension following long-term angiotensin II infusion.
Impact of pegylated interferon and ribavirin on morbidity and mortality in patients with chronic hepatitis C and normal aminotransferases in France
Authors: Sylvie Deuffic-Burban, Gérard Babany, Isabelle Lonjon-Domanec, Pierre Deltenre, Valérie Canva-Delcambre, Sébastien Dharancy, Alexandre Louvet, Françoise Roudot-Thoraval, Philippe Mathurin
Journal: Hepatology (2009)

Clinicians continue to raise questions concerning the necessity of treating chronic hepatitis C virus (HCV)-infected patients with normal alanine aminotransferase (N-ALT), in light of their slower progression to cirrhosis than patients with elevated alanine aminotraferase (E-ALT). This study was undertaken to predict the impact of pegylated interferon (IFN) and ribavirin on HCV-related morbidity and mortality in patients with N-ALT. A previous Markov model was adapted to separately simulate patients with N-ALT (30%) and those with E-ALT (70%). The model estimates fibrosis progression rates according to age, sex, and whether ALT levels are normal or elevated, assuming that patients with E-ALT have a 2.6 times higher progression than those with N-ALT. It takes into account improvement in HCV screening and treatment and competitive mortality. We assumed that N-ALT patients were treated 80% less frequently between 2002 and 2004 and 70% less frequently from 2005 on, as obtained in real life from three multicentric cohorts (Hepatys, Adequation, Persee). Antiviral treatment of HCV-infected populations might reduce 2008-2025 HCV-related morbidity and mortality by 34,200 cases of cirrhosis (36%, 33,000-35,000), 22,400 complications (28%, 21,000-23,000) and 17,500 deaths (25%, 17,000-18,000), including 3000 cases of cirrhosis (22%, 2000-5000), 1200 complications (15%, 1000-1700), and 1000 deaths (14%, 900-1300) in the N-ALT population, despite a probability of receiving treatment that is three to five times less in this population. If N-ALT patients are treated at the same proportions as those with E-ALT, morbidity and mortality could be further reduced by 1400 cases of cirrhosis (13%, 1200-2200), 600 complications (9%, 600-1000), and 500 deaths (9%, 500-800).Treatment of N-ALT patients would decrease HCV morbidity and mortality. These patients should be considered candidates for treatment just as others are.
Whose risk is it anyway?
Authors: David A Waller
Journal: Thorax (2013)

Powell et al 1 have proposed the importance of 90-day mortality after lung cancer surgery, and have generated a predictive score using predominantly objective information. There are obvious advantages over the frequently quoted Thoracoscore2 which contains more subjective assessments of patient performance, and is based on data from a wide range of thoracic procedures including those for benign disease.

Their use of 90-day mortality as the outcome measure has merit, but its implications need further consideration. This measure may not reflect the standard of the operation. A lot can happen in that time: the risk of mortality in the first 3 months after surgery may be related to the side effects (direct or indirect) of adjuvant chemotherapy, or from comorbidity, that is, infective exacerbations of chronic obstructive pulmonary disease or even the natural history of the disease. The surgeon can only really influence the inhospital treatment; after discharge, the quality of primary care or medical care received from local referring physicians may also be important.

One wonders whether 90-day mortality was arbitrarily chosen for statistical reasons, and it is noted that no surgeon was involved as a coauthor of this paper. The parameter favoured for surgical performance would be inhospital mortality giving the patient an estimate of the chance of going home which must be their immediate priority.

When we report the apparent risk of an operation to remove a bronchogenic carcinoma the value is viewed by many parties involved in the interaction between patient and surgeon. This value means different things to different parties and begs the question: ‘whose risk is it anyway?’

The risk of the operation is, of course, a personal matter for each patient which suggests that the use of any fixed cut-offs ignores this variability and would be denying surgery to some patients for whom …
Therapeutic Restoration of Spinal Inhibition via Druggable Enhancement of Potassium-Chloride Cotransporter KCC2–Mediated Chloride Extrusion in Peripheral Neuropathic Pain
Authors: Kristopher T. Kahle, Arjun Khanna, David E. Clapham, Clifford J. Woolf
Journal: JAMA Neurology (2014)

Peripheral neuropathic pain, typified by the development of spontaneous pain or pain hypersensitivity following injury to the peripheral nervous system, is common, greatly impairs quality of life, and is inadequately treated with available drugs. Maladaptive changes in chloride homeostasis due to a decrease in the functional expression of the potassium-chloride cotransporter KCC2 in spinal cord dorsal horn neurons are a major contributor to the central disinhibition of γ-aminobutyric acid type A receptor- and glycine receptor-mediated signaling that characterizes neuropathic pain. A compelling novel analgesic strategy is to restore spinal ionotropic inhibition by enhancing KCC2-mediated chloride extrusion. We review the data on which this theory of alternative analgesia is based, discuss recent high-throughput screens that have searched for small-molecule activators of KCC2, and propose other strategies of KCC2 activation based on recent developments in the basic understanding of KCC2's functional regulation. Exploiting the chloride-dependent functional plasticity of the γ-aminobutyric acid and glycinergic system by targeting KCC2 may be a tenable method of restoring ionotropic inhibition not only in neuropathic pain but also in other "hyperexcitable" diseases of the nervous system such as seizures and spasticity.
Phosphorus-31 nuclear magnetic resonance analysis of transient changes of canine myocardial metabolism in vivo.
Authors: F W Heineman, R S Balaban
Journal: Journal of Clinical Investigation (1990)

The time course of the relative myocardial phosphocreatine and adenosine triphosphate contents (PCr/ATP) during step changes in heart rate in vivo was studied in 14 dogs using 31P nuclear magnetic resonance (NMR) to determine if transient changes in the high energy phosphates occur with changes in cardiac work. Coronary sinus blood flow (CF), oxygen consumption (MVO2), and NMR data were simultaneously measured during brief (approximately 3 min), paced increases in heart rate in these open chest animals. 31P spectra were collected with a time resolution of 15-16 s (PCr signal to noise 22-41:1). Paced tachycardia associated with increased CF and MVO2 had no significant transient or sustained effect on PCr/ATP. Higher heart rates, associated with decreased CF and blood pressure, caused rapid decreases of PCr/ATP that were reversible upon return to control rates. These data indicate that there are no transient changes in 31P metabolites (on a 15-16-s time base) during step changes in cardiac work associated with increased CF. This lack of change demonstrates that ATP hydrolysis and production are closely matched and that the feedback mechanism linking these processes occurs rapidly with no detectable transient change in the phosphate metabolites. In contrast, when the CF response to tachycardia is insufficient PCr is quickly depleted. This latter result suggests that the PCr/ATP ratio may be a sensitive, rapidly responding indicator of coronary supply/demand mismatching in vivo.
Reconstruction of Ancestral 16S rRNA Reveals Mutation Bias in the Evolution of Optimal Growth Temperature in the Thermotogae Phylum
Authors: Anna G. Green, Kristen S. Swithers, Jan F. Gogarten, Johann Peter Gogarten
Journal: Molecular Biology and Evolution (2013)

Optimal growth temperature is a complex trait involving many cellular components, and its physiology is not yet fully understood. Evolution of continuous characters, such as optimal growth temperature, is often modeled as a one-dimensional random walk, but such a model may be an oversimplification given the complex processes underlying the evolution of continuous characters. Recent articles have used ancestral sequence reconstruction to infer the optimal growth temperature of ancient organisms from the guanine and cytosine content of the stem regions of ribosomal RNA, allowing inferences about the evolution of optimal growth temperature. Here, we investigate the optimal growth temperature of the bacterial phylum Thermotogae. Ancestral sequence reconstruction using a nonhomogeneous model was used to reconstruct the stem guanine and cytosine content of 16S rRNA sequences. We compare this sequence reconstruction method with other ancestral character reconstruction methods, and show that sequence reconstruction generates smaller confidence intervals and different ancestral values than other reconstruction methods. Unbiased random walk simulation indicates that the lower temperature members of the Thermotogales have been under directional selection; however, when a simulation is performed that takes possible mutations into account, it is the high temperature lineages that are, in fact, under directional selection. We find that the evolution of Thermotogales optimal growth temperatures is best fit by a biased random walk model. These findings suggest that it may be easier to evolve from a high optimal growth temperature to a lower one than vice versa.
Radiation therapy as a curative treatment in extraocular sebaceous carcinoma
Authors: C. Conill, I. Toscas, I. Morilla, J.M. Mascaro
Journal: British Journal of Dermatology (2003)

Sir, Sebaceous carcinoma is a rare malignant neoplasm derived from the sebaceous glands of the skin. Only 25% are extraocular. We report our experience in the treatment of an extraocular sebaceous carcinoma with radiation therapy. An 87‐year‐old white male presented in February 1997 with an irregular, ulcerative, exophitic and erythematous tumour extending to the left side of the face in the cheek. The lesion had appeared 6 months previously, and had initially been diagnosed as a nodular malignant hydroadenoma. It was then treated with radiation therapy with a single field directly on the lesion to a total dose of 70 Gy/35 fractions with Co60 photons in another hospital, achieving a complete response. In August 1997 the patient was referred because he presented a marginal local recurrence. On physical examination, he presented with large ulcerative, exophitic, firm and erythematous nodules on the left of the face from the periorbital area to the labial comisure caudally, around the anterior border of the previous treatment (Fig. 1a).
Inhibition of signal transducer and activator of transcription 1 attenuates allergen-induced airway inflammation and hyperreactivity
Authors: David Quarcoo, Silke Weixler, David Groneberg, Ricarda Joachim, Birgit Ahrens, Andreas H. Wagner, Markus Hecker, Eckard Hamelmann
Journal: Journal of Allergy and Clinical Immunology (2004)
Arsenic-induced skin lesions among Atacameño people in Northern Chile despite good nutrition and centuries of exposure.
Authors: A H Smith, A P Arroyo, D N Mazumder, M J Kosnett, A L Hernandez, M Beeris, M M Smith, L E Moore
Journal: Environmental Health Perspectives (2000)

It has been suggested that the indigenous Atacameño people in Northern Chile might be protected from the health effects of arsenic in drinking water because of many centuries of exposure. Here we report on the first intensive investigation of arsenic-induced skin lesions in this population. We selected 11 families (44 participants) from the village of Chiu Chiu, which is supplied with water containing between 750 and 800 microg/L inorganic arsenic. For comparison, 8 families (31 participants) were also selected from a village where the water contains approximately 10 microg/L inorganic arsenic. After being transported to the nearest city for blind assessment, participants were examined by four physicians with experience in studying arsenic-induced lesions. Four of the six men from the exposed village, who had been drinking the contaminated water for more than 20 years, were diagnosed with skin lesions due to arsenic, but none of the women had definite lesions. A 13-year-old girl had definite skin pigmentation changes due to arsenic, and a 19-year-old boy had both pigmentation changes and keratoses on the palms of his hands and the soles of his feet. Family interviews identified a wide range of fruits and vegetables consumed daily by the affected participants, as well as the weekly intake of red meat and chicken. However, the prevalence of skin lesions among men and children in the small population studied was similar to that reported with corresponding arsenic drinking water concentrations in both Taiwan and West Bengal, India--populations in which extensive malnutrition has been thought to increase susceptibility.
Pathologic Correlates of Primary Central Nervous System Lymphoma Defined in an Orthotopic Xenograft Model
Authors: Cigall Kadoch, Eduard B. Dinca, Ramona Voicu, Lingjing Chen, Diana Nguyen, Seema Parikh, Juliana Karrim, Marc A. Shuman, Clifford A. Lowell, Patrick A. Treseler, C. David James, James L. Rubenstein
Journal: Clinical Cancer Research (2009)

Abstract Purpose: The prospect for advances in the treatment of patients with primary central nervous system lymphoma (PCNSL) is likely dependent on the systematic evaluation of its pathobiology. Animal models of PCNSL are needed to facilitate the analysis of its molecular pathogenesis and for the efficient evaluation of novel therapeutics. Experimental Design: We characterized the molecular pathology of CNS lymphoma tumors generated by the intracerebral implantation of Raji B lymphoma cells in athymic mice. Lymphoma cells were modified for bioluminescence imaging to facilitate monitoring of tumor growth and response to therapy. In parallel, we identified molecular features of lymphoma xenograft histopathology that are evident in human PCNSL specimens. Results: Intracerebral Raji tumors were determined to faithfully reflect the molecular pathogenesis of PCNSL, including the predominant immunophenotypic state of differentiation of lymphoma cells and their reactive microenvironment. We show the expression of interleukin-4 by Raji and other B lymphoma cell lines in vitro and by Raji tumors in vivo and provide evidence for a role of this cytokine in the M2 polarization of lymphoma macrophages both in the murine model and in diagnostic specimens of human PCNSL. Conclusion: Intracerebral implantation of Raji cells results in a reproducible and invasive xenograft model, which recapitulates the histopathology and molecular features of PCNSL, and is suitable for preclinical testing of novel agents. We also show for the first time the feasibility and accuracy of tumor bioluminescence in the monitoring of a highly infiltrative brain tumor.
Benefit-risk assessment of tumour necrosis factor antagonists in the treatment of psoriasis
Authors: R.G. Langley, B.E. Strober, Y. Gu, S.J. Rozzo, M.M. Okun
Journal: British Journal of Dermatology (2010)

Journal Article Benefit‐risk assessment of tumour necrosis factor antagonists in the treatment of psoriasis Get access R.G. Langley, R.G. Langley Queen Elizabeth II Health Sciences Centre, Division of Dermatology, Department of Medicine, Dalhousie University, Halifax, NS B3H 2Y9, Canada Richard G. Langley. E‐mail: richard.langley@dal.ca Search for other works by this author on: Oxford Academic Google Scholar B.E. Strober, B.E. Strober New York University, New York, NY, U.S.A. Search for other works by this author on: Oxford Academic Google Scholar Y. Gu, Y. Gu Abbott Laboratories, Abbott Park, IL, U.S.A. Search for other works by this author on: Oxford Academic Google Scholar S.J. Rozzo, S.J. Rozzo Abbott Laboratories, Abbott Park, IL, U.S.A. Search for other works by this author on: Oxford Academic Google Scholar M.M. Okun M.M. Okun Abbott Laboratories, Abbott Park, IL, U.S.A. Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 162, Issue 6, 1 June 2010, Pages 1349–1358, https://doi.org/10.1111/j.1365-2133.2010.09707.x Published: 01 June 2010
Intraoperative autologous blood transfusion: report of a technique.
Authors: R M Khan, H F Bassett
Journal: Thorax (1975)

Using a simple and relatively inexpensive technique, blood was salvaged during major thoracic and cardiovascular surgery in 34 cases. Detailed haematological, biochemical, and bacteriological studies were carried out, with red cell survival studies. It has been shown that cellular as well as non-cellular elements of the blood were well preserved with little or nor bacterial contamination. It has been suggested that this form of autologous blood is a more suitable form of blood replacement than donor blood.
Na+ transport in cystic fibrosis respiratory epithelia. Abnormal basal rate and response to adenylate cyclase activation.
Authors: R C Boucher, M J Stutts, M R Knowles, L Cantley, J T Gatzy
Journal: Journal of Clinical Investigation (1986)

The transepithelial potential difference (PD) of cystic fibrosis (CF) airway epithelium is abnormally raised and the Cl- permeability is low. We studied the contribution of active Na+ absorption to the PD and attempted to increase the Cl- permeability of CF epithelia. Nasal epithelia from CF and control subjects were mounted in Ussing chambers and were short-circuited. The basal rate of Na+ absorption was raised in CF polyps compared with control tissues. Whereas beta agonists induced Cl- secretion in normal and atopic epithelia, beta agonists further increased the rate of Na+ absorption in CF epithelia without inducing Cl- secretion. This unusual effect is not due to an abnormal CF beta receptor because similar effects were induced by forskolin, and because cAMP production was similar in normal and CF epithelia. We conclude that CF airway epithelia absorb Na+ at an accelerated rate. The abnormal response to beta agonists may reflect a primary abnormality in a cAMP-modulated path, or a normal cAMP-modulated process in a Cl- impermeable epithelial cell.
Relapsing Fever in Addis Ababa
Authors: P. Robinson
Journal: BMJ (1942)

MEDICAL JOURN~AL rectal treatment.This patient has no conscious memory of rectal trauma, yet an unconscious one is suggested by her showing great indignation concerning a pre-operative enema, and by the fact that at 17 years she was rectally examined by a woman specialist and suddenly fainted.Such histories may perhaps be taken as direct support of the theory that vaginismus is caused by early trauma-and further indirect evidence may be deduced by the method of resolution of the disorder.