tbuckley/cabot-search huggingface dataset:
Improving Outcomes for Pulmonary Vascular Disease
Authors: Ivan M. Robbins, Timothy M. Moore, Carol J. Blaisdell, Steven H. Abman
Journal: American Journal of Respiratory and Critical Care Medicine (2012)

Recognizing the importance of improving lung health through lung disease research, the National Heart, Lung, and Blood Institute (NHLBI) convened a workshop of multidisciplinary experts for the following purpose: (1) to review the current scientific knowledge underlying the basis for treatment of adults and children with pulmonary vascular diseases (PVDs); (2) to identify gaps, barriers, and emerging scientific opportunities in translational PVD research and the means to capitalize on these opportunities; (3) to prioritize new research directions that would be expected to affect the clinical course of PVDs; and (4) to make recommendations to the NHLBI on how to fill identified gaps in adult and pediatric PVD clinical research. Workshop participants reviewed experiences from previous PVD clinical trials and ongoing clinical research networks with other lung disorders, including acute respiratory distress syndrome, chronic obstructive lung disease, and idiopathic pulmonary fibrosis, as well. Bioinformatics experts discussed strategies for applying cutting-edge health information technology to clinical studies. Participants in the workshop considered approaches in the following broad concept areas: (1) improved phenotyping to identify potential subjects for appropriate PVD clinical studies; (2) identification of potential new end points for assessing key outcomes and developing better-designed PVD clinical trials; and (3) the establishment of priorities for specific clinical research needed to advance care of patients with various subsets of PVDs from childhood through adulthood. This report provides a summary of the objectives and recommendations to the NHLBI concentrating on clinical research efforts that are needed to better diagnose and treat PVDs.
Incidence of systemic embolism before and after mitral valvotomy
Authors: P. B. Deverall, P. M. Olley, D. R. Smith, D. A. Watson, W. Whitaker
Journal: Thorax (1968)

Mitral valvotomy is of established value in improving the clinical condition and life expectancy of patients with rheumatic mitral stenosis. Its value in preventing or reducing the incidence of systemic arterial embolism is less certain. A comparison of pre- and post-operative embolic incidence can only be accepted if it is clear that the method of assessing the pre-operative figure is reliable. It is shown that the figure varies according to the length of the pre-operative study, and evidence is presented to show a changing incidence with increasing length of chronic rheumatic history. By studying patients in whom the time of onset of rheumatic heart disease is accurately known, a rising embolic incidence with the passage of time is shown. A comparison is made between groups of patients who have experienced the same length of chronic rheumatic history but who differ in respect of mitral valvotomy. We conclude from our comparison that this operation does not diminish the incidence of embolism, though only about a quarter of all our patients had atrial appendagectomy at the time of valvotomy. A reduction in the incidence of recurrent embolism in a given patient after mitral valvotomy is shown but may be more apparent than real. Operative embolism, defined here as that occurring either at or within 48 hours of operation, has an incidence of 3·8%. The factors related to pre-operative, operative, and post-operative embolism are presented.
Bronchial asthma due to <i>Cannabis sativa</i> seed
Authors: C. Vidal, R. Fuilnte, A. Iglesias, A. Sáez
Journal: Allergy (1991)

A 51‐year‐old man with asthmatic attacks due to Cannabis sativa seed inhalation was studied. Specific IgE against this seed was demonstrated by in vivo (skin and bronchial challenge tests) and in vitro methods (reverse enzyme immunoassay and histamine release from basophils), suggesting a Type I immunologic reaction.
Does the Recombination Rate Affect the Efficiency of Purifying Selection? The Yeast Genome Provides a Partial Answer
Authors: Csaba Pál, Balázs Papp, Laurence D. Hurst
Journal: Molecular Biology and Evolution (2001)

Much attention has been focused on the effect of recombination on preservation of favorable variants and on reducing the mutational load (Muller 1964; Kondrashov 1993; Barton 1995; Hurst and Peck 1996; West, Lively, and Read 1999). As most amino acid changes are slightly deleterious (Li 1997), their accumulation is expected to depend on the efficiency of purifying selection. Theoretical models have revealed that recombination might prevent the accumulation of such slightly deleterious mutations. This is potentially of importance because it suggests that purifying selection is less effective in genomic regions of low recombination (Hill and Robertson 1966; Carvalho and Clark 1999; Comeron, Kreitman, and Aguade 1999; Comeron and Kreitman 2000; Williams and Hurst 2000). If purifying selection were more effective in regions of high recombination, accounting for within-genome variation, the rate of protein evolution should be lower in order to minimize the harmful effect of mutations on protein function. Furthermore, codon usage bias, which is at least partly influenced by selection, should be more pronounced in these genomic regions. Previous tests have employed this logic and shown that codon usage is slightly more biased under high recombination rates in Drosophila melanogaster (Comeron, Kreitman, and Aguade 1999). Two other studies (Carvalho and Clark 1999; Comeron and Kreitman 2000) have confirmed a negative relationship between intron size and recombination rate in the same organism (although the two groups give different interpretations of their results). One possible shortcoming of these works is that they did not control for variation in gene expression level. Some experimental works on yeast suggest that genomic regions with high transcription rates are also more prone to the initiation of meiotic doublestrand break (DSB) events (Gerton et al. 2000), and there are also some hints that this feature might be a general feature of eukaryotic organisms (e.g., Jones et al. 1997). As codon usage bias (e.g., Duret and Mouchiroud 1999) and intron size (Vinogradov 2001) are affected by differences in gene expression level in numerous model organisms, the conclusions drawn from the association of these parameters with recombination rate should be treated with caution. Yeast is currently a unique tool with which to address all of these issues owing to the availability of re-
Treatment of colorectal metastases: surgery, cryotherapy, or radiofrequency ablation
Authors: J N Primrose
Journal: Gut (2002)

The liver is the most common site of metastases from colorectal cancer. There has therefore been growing interest in how liver metastases may be ablated. The most common techniques for ablation of liver metastases are surgical resection, cryotherapy, and increasingly in recent years, radiofrequency ablation.
A new instrument for the assessment of patient-defined benefit in the treatment of allergic rhinitis
Authors: N. Franzke, I. Schäfer, K. Jost, C. Blome, S. J. Rustenbach, K. Reich, M. Reusch, M. Maurer, M. Augustin
Journal: Allergy (2010)

To cite this article: Franzke N, Schäfer I, Jost K, Blome C, Rustenbach SJ, Reich K, Reusch M, Maurer M, Augustin M. A new instrument for the assessment of patient-defined benefit in the treatment of allergic rhinitis. Allergy 2011; 66: 665–670. Background: Allergic rhinitis (AR) is a common disease that affects health-related quality of life (HRQoL). Current and future health policy demands the assessment of patient-relevant treatment benefit for evaluation of treatments. Methods: We developed, validated and tested a standardized instrument for the assessment of patient-relevant needs and benefits in AR. In an open survey of patients with AR, 100 need and benefit items were generated. The items were condensed to a 25-item list by an expert panel. On this list, patient rates the personal importance of 25 treatment needs on a scale ranging from 'not at all' to 'very' before treatment (Patient Needs Questionnaire, PNQ). At the end of the treatment, patient rates the extent, to which these needs were achieved by treatment from 'did not help at all' to 'helped a lot' (Patient Benefit Questionnaire). The patient benefit index (PBI) is computed to provide a global weighted benefit parameter. This disease-specific instrument was validated in n = 104 patients with AR. Results: The PBI-AR showed good acceptability and feasibility in clinical routine. Reduction in nose and eye symptoms was rated most important. The PBI amounted to 2.2 (PBI ranges from 0 = 'no benefit' to 4 = 'maximum benefit'). Reliability of the PNQ was high (Cronbach's alpha = 0.9).The PBI was significantly correlated with relevant external validation criteria, such as patient satisfaction (R = 0.54) and HRQoL (R = 0.26). Conclusion: The PBI-AR is a feasible, reliable and valid instrument for the standardized assessment of patient-relevant benefits in the treatment of AR.
Costs and Consequences of Additional Chest X-Ray in a Tuberculosis Prevention Program in Botswana
Authors: Taraz Samandari, David Bishai, Michiel Luteijn, Barudi Mosimaneotsile, Oaitse Motsamai, Maarten Postma, Gijs Hubben
Journal: American Journal of Respiratory and Critical Care Medicine (2010)

Isoniazid preventive therapy is effective in reducing the risk of tuberculosis (TB) in persons living with HIV (PLWH); however, screening must exclude TB disease before initiating therapy. Symptom screening alone may be insufficient to exclude TB disease in PLWH because some PLWH with TB disease have no symptoms. The addition of chest radiography (CXR) may improve disease detection.
"Non-alcoholic duct destructive chronic pancreatitis" or "primary chronic pancreatitis"?
Authors: L FRULLONI, P BOVO, V D. FRANCESCO, G CAVALLINI, G ZAMBONI
Journal: Gut (1999)

Editor,—We read with great interest the article by Ectors et al ( Gut 1997; 41 :263–8) in which the authors describe a particular form of chronic pancreatitis in patients without chronic alcohol intake. The authors suggest the term “non-alcoholic duct destructive chronic pancreatitis” for this type of pancreatic disease in order to stress: (1) the absence of any history of alcohol abuse; (2) the target of the chronic immunological reaction; and (3) the destructive nature of the process. Characteristically some of these cases were associated with an autoimmune disease, such as primary sclerosing cholangitis, ulcerative colitis, Crohn’s disease, or Sjogren’s syndrome. The authors conclude that the inflammatory changes in the pancreatic ducts observed in this particular form of chronic pancreatitis are suggestive of an autoimmune process.

A few years ago our group postulated a new hypothesis for the pathogenesis of a particular form of chronic pancreatitis, which we defined as “primary chronic pancreatitis”.1 We suggested that the key step in the pathogenesis of this type of chronic pancreatitis may be …
Atypical chemokine receptor 1 deficiency reduces atherogenesis in ApoE-knockout mice
Authors: Wuzhou Wan, Qian Liu, Michail S Lionakis, Ana Paula M P Marino, Stasia A Anderson, Muthulekha Swamydas, Philip M Murphy
Journal: Cardiovascular Research (2015)

AimsAtypical chemokine receptor 1 (Ackr1; previously known as the Duffy antigen receptor for chemokines or Darc) is thought to regulate acute inflammatory responses in part by scavenging inflammatory CC and CXC chemokines; however, evidence for a role in chronic inflammation has been lacking. Here we investigated the role of Ackr1 in chronic inflammation, in particular in the setting of atherogenesis, using the apolipoprotein E-deficient (ApoE−/−) mouse model.
Effect of Nitric Oxide on Rhinovirus Replication and Virus-Induced Interleukin-8 Elaboration
Authors: POONAM KAUL, INDERJIT SINGH, RONALD B. TURNER
Journal: American Journal of Respiratory and Critical Care Medicine (1999)

Nitric oxide (NO) has been reported to have disparate effects in different viral infections. We conducted a study to determine whether rhinovirus (RV) infection is associated with production of NO, and to assess the effect of NO on RV-induced interleukin-8 (IL-8) elaboration both in vitro in monolayers of BEAS-2B cells, an immortalized respiratory epithelial cell line, and in MRC-5 cells, a diploid human embryonic lung fibroblast cell line, challenged with purified RV type 39, as well as in vivo, in experimental infections with RV type 23. Virus replication was not affected by pretreatment of cell monolayers with any of three different NO donors, and RV infection did not stimulate production of NO. Pretreatment of cell monolayers with either NO donors or inhibitors of NO synthase had no effect on RV-induced IL-8 elaboration measured either 6 or 24 h after virus challenge. Nasal wash specimens from RV-infected volunteers contained low concentrations of nitrite that were not different from the concentrations in specimens from sham-challenged subjects. The concentration of nitrite in these specimens did not change over the course of the subjects' rhinoviral illness. These results suggest that NO does not participate in the pathogenesis of RV infections.
Ventilation/perfusion lung scan in pulmonary veno-occlusive disease
Authors: Andrei Seferian, Badia Helal, Xavier Jaïs, Barbara Girerd, Laura C. Price, Sven Günther, Laurent Savale, Peter Dorfmüller, Florence Parent, Olivier Sitbon, Marc Humbert, Gérald Simonneau, David Montani
Journal: European Respiratory Journal (2011)

Pulmonary veno-occlusive disease (PVOD), a rare form of pulmonary arterial hypertension (PAH), requires histological proof for definitive diagnosis; however, lung biopsy is not recommended in PAH. Recent conjoint European Respiratory Society/European Society of Cardiology guidelines suggest that nonmatched perfusion defects on ventilation/perfusion ( V ′/ Q ′) lung scanning in PAH patients may suggest PVOD. The aim of our study was to evaluate V ′/ Q ′ lung scans in a large cohort of PVOD and idiopathic or heritable PAH patients. V ′/ Q ′ lung scans from 70 patients with idiopathic or heritable PAH and 56 patients with confirmed or highly probable PVOD were reviewed in a double-blind manner. The vast majority of V ′/ Q ′ lung scans were normal or without significant abnormalities in both groups. No differences in ventilation or perfusion lung scans were observed between PAH and PVOD patients (all p&gt;0.05). Furthermore, no differences were observed between confirmed (n=31) or highly probable PVOD (n=25). Nonmatched perfusion defects were found in seven (10%) idiopathic PAH patients and four (7.1%) PVOD patients (p&gt;0.05). Nonmatched perfusion defects were rarely seen in a large cohort of idiopathic or heritable PAH and PVOD patients. Future recommendations should be amended according to these results suggesting that V ′/ Q ′ lung scanning is not useful in discriminating PVOD from idiopathic PAH.
Hepatitis B core-related antigen (HBcrAg) levels in the natural history of hepatitis B virus infection in a large European cohort predominantly infected with genotypes A and D
Authors: B. Maasoumy, S.B. Wiegand, J. Jaroszewicz, B. Bremer, P. Lehmann, K. Deterding, A. Taranta, M.P. Manns, H. Wedemeyer, D. Glebe, M. Cornberg
Journal: Clinical Microbiology and Infection (2015)
The Decline of Androgen Levels in Elderly Men and Its Clinical and Therapeutic Implications
Authors: Jean M. Kaufman, Alex Vermeulen
Journal: Endocrine Reviews (2005)

Aging in men is accompanied by a progressive, but individually variable decline of serum testosterone production, more than 20% of healthy men over 60 yr of age presenting with serum levels below the range for young men. Albeit the clinical picture of aging in men is reminiscent of that of hypogonadism in young men and decreased testosterone production appears to play a role in part of these clinical changes in at least some elderly men, the clinical relevancy of the age-related decline in sex steroid levels in men has not been unequivocally established. In fact, minimal androgen requirements for elderly men remain poorly defined and are likely to vary between individuals. Consequently, borderline androgen deficiency cannot be reliably diagnosed in the elderly, and strict differentiation between "substitutive" and "pharmacological" androgen administration is not possible. To date, only a few hundred elderly men have received androgen therapy in the setting of a randomized, controlled study, and many of these men were not androgen deficient. Most consistent effects of treatment have been on body composition, but to date there is no evidence-based documentation of clinical benefits of androgen administration to elderly men with normal or moderately low serum testosterone in terms of diminished morbidity or of improved survival or quality of life. Until the long-term risk-benefit ratio for androgen administration to elderly is established in adequately powered trials of longer duration, androgen administration to elderly men should be reserved for the minority of elderly men who have both clear clinical symptoms of hypogonadism and frankly low serum testosterone levels.
Propranolol-induced reduction in recurrent variceal hemorrhage in schistosomiasis
Authors: Harold O. Conn
Journal: Hepatology (1990)

Fifty patients with non–cirrhotic portal fibrosis who were admitted to hospital because of upper gastrointestinal bleeding were randomly assigned to treatment with either oral propranolol given in does that reduced the resting pulse rate by 25% (25 patients) or with a placebo (25 patients). One year after the start of the study 20 patients in the propranolol group and five patients in the placebo group were free from recurrent gastrointestinal bleeding (p &lt; 0.0001). Giving continuous oral propranolol treatment is therefore effective in preventing recurrent upper gastriontestinal bledding in patients with noncirrhotic portal fibrosis.
A feasibility study evaluating docetaxel-based sequential and combination regimens in the adjuvant therapy of node-positive breast cancer
Authors: A. Di Leo, J. Crown, J.-M. Nogaret, K. Duffy, S. Bartholomeus, S. Dolci, S. Rowan, N. O'Higgins, M. Paesmans, D. Larsimont, A. Riva, M.J. Piccart
Journal: Annals of Oncology (2000)
Scotland opts for a more integrated approach to health care
Authors: B. Christie
Journal: BMJ (2003)

Scotland's 23 acute and primary care trusts are to be abolished in the latest set of NHS reforms, which are designed to create services that are more integrated. Clinical staff are to be given greater responsibility for redesigning services.

The changes are contained in a white paper on health, and they mark a clear difference in emphasis from the development of health services in England. Scotland has rejected the idea of creating foundation hospitals, which are seen as potentially divisive.

The Scottish health minister, Malcolm Chisholm, said: …
Cell-Autonomous and Non–Cell-Autonomous Mechanisms of Transformation by Amplified <i>FGFR1</i> in Lung Cancer
Authors: Florian Malchers, Felix Dietlein, Jakob Schöttle, Xin Lu, Lucia Nogova, Kerstin Albus, Lynnette Fernandez-Cuesta, Johannes M. Heuckmann, Oliver Gautschi, Joachim Diebold, Dennis Plenker, Masyar Gardizi, Matthias Scheffler, Marc Bos, Danila Seidel, Frauke Leenders, André Richters, Martin Peifer, Alexandra Florin, Prathama S. Mainkar, Nagaraju Karre, Srivari Chandrasekhar, Julie George, Steffi Silling, Daniel Rauh, Thomas Zander, Roland T. Ullrich, H. Christian Reinhardt, Francois Ringeisen, Reinhard Büttner, Lukas C. Heukamp, Jürgen Wolf, Roman K. Thomas
Journal: Cancer Discovery (2013)

The 8p12 locus (containing the FGFR1 tyrosine kinase gene) is frequently amplified in squamous cell lung cancer. However, it is currently unknown which of the 8p12-amplified tumors are also sensitive to fibroblast growth factor receptor (FGFR) inhibition. We found that, in contrast with other recurrent amplifications, the 8p12 region included multiple centers of amplification, suggesting marked genomic heterogeneity. FGFR1-amplified tumor cells were dependent on FGFR ligands in vitro and in vivo. Furthermore, ectopic expression of FGFR1 was oncogenic, which was enhanced by expression of MYC. We found that MYC was coexpressed in 40% of FGFR1-amplified tumors. Tumor cells coexpressing MYC were more sensitive to FGFR inhibition, suggesting that patients with FGFR1-amplified and MYC-overexpressing tumors may benefit from FGFR inhibitor therapy. Thus, both cell-autonomous and non-cell-autonomous mechanisms of transformation modulate FGFR dependency in FGFR1-amplified lung cancer, which may have implications for patient selection for treatment with FGFR inhibitors.Amplification of FGFR1 is one of the most frequent candidate targets in lung cancer. Here, we show that multiple factors affect the tumorigenic potential of FGFR1, thus providing clinical hypotheses for refinement of patient selection.
The Role of Iron in Diabetes and Its Complications
Authors: Sundararaman Swaminathan, Vivian A. Fonseca, Muhammad G. Alam, Sudhir V. Shah
Journal: Diabetes Care (2007)

The central importance of iron in the pathophysiology of disease is derived from the ease with which iron is reversibly oxidized and reduced. This property, while essential for its metabolic functions, makes iron potentially hazardous because of its ability to participate in the generation of powerful oxidant species such as hydroxyl radical (1). Oxygen normally accepts four electrons and is converted directly to water. However, partial reduction of oxygen can and does occur in biological systems. Thus, the sequential reduction of oxygen along the univalent pathway leads to the generation of superoxide anion, hydrogen peroxide, hydroxyl radical, and water (1,2). Superoxide and hydrogen peroxide appear to be the primary generated species. These species may then play a role in the generation of additional and more reactive oxidants, including the highly reactive hydroxyl radical (or a related highly oxidizing species) in which iron salts play a catalytic role in a reaction. This reaction is commonly referred to as the metal catalyzed Haber-Weiss reaction (1): \batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \[\frac{\mathrm{Fe}^{3{+}}{+}\mathrm{O}\_{{\dot{2}}}^{{\mbox{--}}}   \mathrm{Fe}^{2{+}}{+}\mathrm{O}\_{2} \mathrm{Fe}^{2{+}}{+}\mathrm{H}\_{2}\mathrm{O}\_{2}   \mathrm{Fe}^{3{+}}{+}{\cdot}\mathrm{OH}{+}\mathrm{OH}{-}}{\mathrm{O}\_{{\dot{2}}}^{{\mbox{--}}}{+}\mathrm{H}\_{2}\mathrm{O}\_{2}   \mathrm{O}\_{2}{+}{\cdot}\mathrm{OH}{+}\mathrm{OH}{-}}\] \end{document} Because iron participates in the formation of reactive oxygen species, organisms take great care in the handling of iron. Indeed, iron sequestration in transport and storage proteins may contribute to antioxidant defenses. It is now well established that oxidants can cause the release of catalytic iron (1); thus, a vicious cycle is initiated that leads to the formation of more reactive oxygen species.

In this review, we discuss the role tissue iron and elevated body iron stores play in causing type 2 diabetes and the pathogenesis of its important complications, particularly diabetic nephropathy and cardiovascular disease (CVD). In addition, we emphasize that iron overload is not a prerequisite for iron to mediate either diabetes or its complications. Important in its pathophysiology is the availability of so-called catalytic iron or iron that is available to …
THE SERUM CALCIUM IN EXPERIMENTAL TUBERCULOSIS
Authors: J. C. Hoyle
Journal: BMJ (1928)

The statistics for the United States Registration Area for deaths show that the fall in the case mortality rate preceded that of Enigland.While, up to the end of the nineteenth cenitury, the case mortality is known to have been about 20 per cenit. in the States belonging at the time to the riegistration area, it had already fallen to between 3 and 4 per cent.during the first five years of the twentieth