tbuckley/cabot-search huggingface dataset:
The role of the asthma nurse specialist in optimising the management of acute asthma according to British Thoracic Society guidelines
Authors: Philip Coakley, Karina Virdee, Ajitha Jayaratnam, Bernadette Hawkes
Journal: European Respiratory Journal (2012)

Introduction & aims: Asthma affects over 5 million people in the UK and accounts for one hospital admission every 7.5 minutes. The British Thoracic Society (BTS) has evidence-based guidelines on the management of acute asthmatics which have been shown to reduce readmission rates. This study aims to audit the management of acute asthmatic admissions against BTS guidelines and establish whether or not intervention by an asthma nurse specialist (ANS) improves the audit criteria outcomes.

Methods: In a busy Outer London district general hospital, retrospective case note audit was carried out on all patients admitted with acute asthma in September and October 2011. The patients were then divided into those who were jointly managed by the medical team and ANS with those who were managed by the medical team alone.

Results: 50 patients were admitted over the 2 month period, of which 50% had been reviewed by the ANS. Across all 16 BTS audit criteria, the achieval rates in the group of patients who received the intervention of ANS was either equal to or higher than those who were managed by physicians alone. The average achieval rate of all audit criteria in patients who did not see the ANS was 29.3% compared to 60.1% for those who were seen by the ANS.

Conclusions: The intervention of the ANS in the inpatient management of acute asthmatics increases the adherence to national guidelines, thus improving standards in overall management. This audit also demonstrates the importance of the continuing education of junior doctors in the guidelines in the management of acute asthmatics to improve overall adherence.
Paradoxical response to bronchodilators: Radiologic correlates and clinical implications
Authors: Surya Bhatt, James Wells, Victor Kim, Gerard Criner, Craig Hersh, Megan Hardin, William Bailey, Hrudaya Nath, Douglas Stinson, Carla Wilson, Barry Make, Mark Dransfield
Journal: European Respiratory Journal (2014)

Background   Bronchodilator response is seen in a significant proportion of patients with chronic obstructive pulmonary disease (COPD). However, there are also reports of a paradoxical response to bronchodilators, resulting in bronchoconstriction and significant respiratory distress. Asymptomatic bronchoconstriction is likely far more common; however there has been no systematic study of this paradoxical response (PR).   Methods   Subjects from a large multicenter study (COPDGene) that included current and former smokers, were categorized into two groups based on PR defined as at least a 12% and 200ml reduction in FEV 1  and/or FVC post-bronchodilator.   Results:   9986 subjects were included. PR was seen in 4.54%, and the frequency was similar in those with COPD and smokers without airflow obstruction. Those with PR were younger, more likely to be current smokers, and had worse airflow obstruction. Compared to Caucasians, PR was twice as common in African Americans (6.9% vs. 3.4%;p l0.001). On multivariate analyses, African American race (adjusted OR 1.89, 95%CI 1.50 to 2.39), reduced emphysema (OR 0.996,95%CI 0.992 to 0.999) and increased wall area% of segmental airways (OR 1.04,95%CI 1.01 to 1.08) were independently associated with PR. PR was also independently associated with worse dyspnea, lower six minute walk distance, higher BODE index, and greater frequency of exacerbations (adjusted RR 1.33, 95%CI 1.06 to 1.66). These relationships held true when PR was defined by other %FEV 1  change criteria.   Conclusions   Paradoxical response to bronchodilators is associated with distinct clinical and radiologic features, and may represent a novel COPD phenotype associated with worse outcomes.
Isolated increase in pollen sensitization over 20 years among Swedish adults
Authors: Anders Bjerg, Jonas Eriksson, Linda Ekerljung, Göran Wennergren, Jan Lötvall, Bo Lundbäck
Journal: European Respiratory Journal (2013)

Background: The increases in the prevalence of asthma and rhinoconjunctivitis are well documented. Yet few studies have assessed trends in sensitization to aeroallergens in the general adult population.  Aim: To characterize allergic sensitization in a general population of adults, and study trends in sensitization over two decades.  Methods: Out of 18072 participants in the West Sweden Asthma Study, a random sample of 1472 aged 16-60 years were invited to skin prick testing (SPT) against 11 common aeroallergens during 2009-12. Complete SPTs were performed in 783 subjects (57.3% women). The 375 subjects aged 20-46 and living in Gothenburg were compared to a similar sample from ECRHS in 1991-2 (n=589).  Results: Sensitization was seen in 42.0%, and 20.0% were sensitized to three or more allergens. The dominating allergens were timothy (24.8%), birch (21.3%), cat (17.9%) and dog (14.9%). Any mite sensitization was seen in 12.6% while only 2.0% were sensitized to molds. In Gothenburg sensitization to pollen had increased significantly since 1991-2: timothy +12.5% (p  Discussion: In this general sample of Swedish adults sensitization to aeroallergens was common. The isolated increase in sensitization to pollens points toward allergen-specific causes such as air pollution, which specifically increases the allergenicity of pollens.
Blocking rpS6 Phosphorylation Exacerbates Tsc1 Deletion–Induced Kidney Growth
Authors: Huijuan Wu, Jianchun Chen, Jinxian Xu, Zheng Dong, Oded Meyuhas, Jian-Kang Chen
Journal: Journal of the American Society of Nephrology (2015)

The molecular mechanisms underlying renal growth and renal growth–induced nephron damage remain poorly understood. Here, we report that in murine models, deletion of the tuberous sclerosis complex protein 1 (Tsc1) in renal proximal tubules induced strikingly enlarged kidneys, with minimal cystogenesis and occasional microscopic tumorigenesis. Signaling studies revealed hyperphosphorylation of eukaryotic translation initiation factor 4E-binding protein 1 (4E-BP1) and increased phosphorylation of ribosomal protein S6 (rpS6) in activated renal tubules. Notably, knockin of a nonphosphorylatable rpS6 in these Tsc1-mutant mice exacerbated cystogenesis and caused drastic nephron damage and renal fibrosis, leading to kidney failure and a premature death rate of 67% by 9 weeks of age. In contrast, Tsc1 single-mutant mice were all alive and had far fewer renal cysts at this age. Mechanistic studies revealed persistent activation of mammalian target of rapamycin complex 1 (mTORC1) signaling causing hyperphosphorylation and consequent accumulation of 4E-BP1, along with greater cell proliferation, in the renal tubules of Tsc1 and rpS6 double-mutant mice. Furthermore, pharmacologic treatment of Tsc1 single-mutant mice with rapamycin reduced hyperphosphorylation and accumulation of 4E-BP1 but also inhibited phosphorylation of rpS6. Rapamycin also exacerbated cystic and fibrotic lesions and impaired kidney function in these mice, consequently leading to a premature death rate of 40% within 2 weeks of treatment, despite destroying tumors and decreasing kidney size. These findings indicate that Tsc1 prevents aberrant renal growth and tumorigenesis by inhibiting mTORC1 signaling, whereas phosphorylated rpS6 suppresses cystogenesis and fibrosis in Tsc1-deleted kidneys.
Alterations in the T-Cell Receptor Variable β Gene–Restricted Profile of CD8+ T Lymphocytes in the Peripheral Circulation of Patients with Squamous Cell Carcinoma of the Head and Neck
Authors: Andreas E. Albers, Carmen Visus, Takashi Tsukishiro, Robert L. Ferris, William Gooding, Theresa L. Whiteside, Albert B. De Leo
Journal: Clinical Cancer Research (2006)

Abstract Purpose: Apoptosis of activated CD8+ T cells is often seen in tumor-infiltrating lymphocytes and circulating peripheral blood mononuclear cells (PBMC) in patients with squamous cell carcinoma of the head and neck (SCCHN). We investigated whether T-cell receptor (TCR) variable β chain (Vβ)–restricted T cells were more sensitive to apoptosis than non–TCR Vβ-restricted T cells. Experimental Design: Flow cytometry analysis with anti-TCR Vβ antibodies was used to define expansions and contractions of Vβ-restricted T cells in patients with SCCHN relative to normal donors. This staining was combined with Annexin V binding to indicate early T-cell apoptosis. Results: The TCR Vβ profiles of CD3+ T cells in tumor-infiltrating lymphocytes and PBMCs of patients with SCCHN were altered relative to controls, with one to five expansions and numerous contractions of TCR Vβ-restricted T cells detected. These types of alterations were significantly greater in CD8+ than CD4+ T cells. Enhanced Annexin V binding to CD8+ T cells was evident in PBMCs obtained from all patients, with 3 of 13 showing preferential targeting for apoptosis of TCR Vβ-restricted T cells. Conclusions: TCR Vβ profiles of CD8+ T cells were altered in patients with SCCHN relative to normal controls. This may reflect increased apoptosis of expanded or contracted CD8+ T cells, which define the TCR Vβ profile of antigen-responsive T-cell populations in patients with cancer.
Reflux associated cough is usually not associated with reflux: role of reduced cough threshold.
Authors: L Benini, M Ferrari, G Talamini, I Vantini
Journal: Gut (2006)

We read with great interest the article by Sifrim and colleagues ( Gut 2005; 54 :449–54) addressing the issue of the importance of weakly acidic reflux (as measured by 24 hour ambulatory pressure and pH impedance monitoring) in patients with chronic cough. The presence of asthma, postnasal drip, or use of angiotensin converting enzyme inhibitors was ruled out so that an association with gastro-oesophageal reflux was probable. They found that only 15% of cough bursts were preceded by reflux episodes, which in 4% of cases were weakly acidic and therefore not detectable by conventional automated analysis of oesophageal pH tracings. Although the temporal relationship between acid or weakly acidic reflux and cough was highly significant, it could not be demonstrated in most episodes. In this respect their findings are in agreement with a previous study by Laukka and colleagues,1 who also used manometry for a more accurate timing of cough. Taken together, the results of the two studies suggest that the pathogenetic mechanisms usually proposed as a link between reflux and cough (micro/macroaspiration of refluxate into the airways and vagally mediated cough reflex) may be involved, at best, in a minority of cough episodes.

A different explanation has therefore to be formulated, not requiring a …
An isotopic assay for NADPH oxidase activity and some characteristics of the enzyme from human polymorphonuclear leukocytes.
Authors: L R DeChatelet, L C McPhail, D Mullikin, C E McCall
Journal: Journal of Clinical Investigation (1975)

An isotopic assay for NADPH ixodase that measures the amount of NADP formed by the 6-phosphogluconate dehydrogenase reaction has been developed. Under appropriate conditions, the amount of NADP present is directly proportional to the amount of 14CO2 released from [1-14C]6-phosphogluconic acid. Because this assay employs radioisotopes, it is far more sensitive than conventional assays for the enzyme. The human granule NADPH oxidase, as measured by this assay, is active in the presence of CN minus, is stimulated by Mn-2+, and has a pth optimum of 5.5. Granules isolated from cells that have been allowed to ingest zymosan consistently exhibited more enzyme activity than did granules isolated from either resting cells or cells challenged with zymosan that was not preopsonized. This effect was observed over a wide range of substrate concentrations and could not be explained by differences in protein concentrations between the various samples. If whole homogenates are used in place of isolated granules, the enzyme activity can be observed only with a homogenate of phagocytizing cells and even then only at a high concentration of NADPH. This suggests that an inhibitor of the enzyme might be present within the cell. One patient with chronic granulomatous disease was studied. There was no difference in tnadph oxidase activity of the patients' cells when granules from resting and phagocytizing cells were compared. In contrast, the enzyme activity in granules from two control patients doubled upon phagocytosis. These results are consistent with a role for NADPH oxidase in the initiation of the respiratory burst accompanying phagocytosis by human neutrophils.
The Beginning of the End for Laparoscopic Banding
Authors: Justin B. Dimick, Jonathan F. Finks
Journal: JAMA Surgery (2014)

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Phase I Trial of 2-Methoxyestradiol NanoCrystal Dispersion in Advanced Solid Malignancies
Authors: Amye J. Tevaarwerk, Kyle D. Holen, Dona B. Alberti, Carolyn Sidor, Jamie Arnott, Check Quon, George Wilding, Glenn Liu
Journal: Clinical Cancer Research (2009)

Abstract Purpose: 2-Methoxyestradiol (2ME2; Panzem) is an endogenous, estradiol-17β metabolite that at pharmacologic doses exerts antimitotic and antiangiogenic activities. Studies with a 2ME2 capsule formulation showed limited oral bioavailability. We report the results of a phase I study using a NanoCrystal Dispersion formulation of 2ME2 (2ME2 NCD). Experimental Design: Patients with refractory solid tumors received 2ME2 NCD orally. Patients received drug either every 6 hours (part A) or every 8 hours (part B). Doses were escalated in successive cohorts until the maximum tolerated dose (MTD) was identified. The primary objective was identifying the MTD. Secondary objectives were to evaluate the plasma pharmacokinetics of 2ME2 and efficacy. Results: In part A, 16 patients received a median of 4 cycles of 2ME2 NCD. Dose-limiting toxicities (DLT) included fatigue (2), hypophosphatemia (2), increased alanine aminotransferase (1), and muscle weakness (1). Trough levels at steady-state reached the minimum effective concentration in all cohorts. The MTD was determined to be 1,000 mg orally every 6 hours. In part B, 10 patients received a median of 1 cycle. DLTs included elevated γ-glutamyltransferase (1), hyponatremia (1), fatigue (1), and anorexia (1). An MTD could not be defined for part B because 4 of 10 patients had DLTs at the initial dose level and dose reduction was not pursued. Thirteen patients had stable disease (A, 11; B, 2); there were no confirmed responses. Conclusion: For 2ME2 NCD, the MTD and recommended phase II regimen is 1,000 mg orally every 6 hours. Treatment was generally well-tolerated.
Prognosis and sleep disordered breathing in heart failure
Authors: I Wilcox, S G McNamara, T Wessendorf, G N Willson, A J Piper, C E Sullivan
Journal: Thorax (1998)

The ability to detect and compensate for errors is crucial in producing effective, goal-directed behavior. Human error processing is reflected in two event-related brain potential components, the error-related negativity (Ne/ERN) and error positivity (Pe), but the functional significance of both components remains unclear. Our approach was to consider error detection as a decision process involving an evaluation of available evidence that an error has occurred against an internal criterion. This framework distinguishes two fundamental stages of error detection—accumulating evidence (input), and reaching a decision (output)—that should be differentially affected by changes in internal criterion. Predictions from this model were tested in a brightness discrimination task that required human participants to signal their errors, with incentives varied to encourage participants to adopt a high or low criterion for signaling their errors. Whereas the Ne/ERN was unaffected by this manipulation, the Pe varied consistently with criterion: A higher criterion was associated with larger Pe amplitude for signaled errors, suggesting that the Pe reflects the strength of accumulated evidence. Across participants, Pe amplitude was predictive of changes in behavioral criterion as estimated through signal detection theory analysis. Within participants, Pe amplitude could be estimated robustly with multivariate machine learning techniques and used to predict error signaling behavior both at the level of error signaling frequencies and at the level of individual signaling responses. These results suggest that the Pe, rather than the Ne/ERN, is closely related to error detection, and specifically reflects the accumulated evidence that an error has been committed.
Dynamic Nano‐Interfaces Enable Harvesting of Functional 3D‐Engineered Tissues
Authors: Akihiro Nishiguchi, Michiya Matsusaki, Shigeru Miyagawa, Yoshiki Sawa, Mitsuru Akashi
Journal: Advanced Healthcare Materials (2015)

Functional 3D-engineered tissues are successfully harvested from a substrate using stimuli-responsive hydrogel films with dynamic nano-interface. The dynamic wettability control at the interfaces allows cellular detachment, leading to tissue harvesting without serious damage and remaining polymers. This method can be applied to various types of organs and used for tissue transplantation in regenerative medicine.
Homoeopathy for sports, exercise and dance.: Emlyn Thomas. (Pp 337; soft cover; pound25.00.) Beaconsfield, Bucks: Beaconsfield Publishers, 2000. ISBN 0-906584-48-5.
Authors: Patricia Fearon
Journal: British Journal of Sports Medicine (2001)

EDITOR,-I read the section on sports medicine education in the August issue of the journal with great interest because of the issues raised for all of us involved.It stimulated me to raise two points.Firstly, although it is desirable for undergraduate medical students to be introduced to sports medicine, it does seem to be an area of practice that seems very appropriate for continuing medical education and for postgraduate qualifications.Although a case can be made out for medical practitioners who wish to practice full time in sports medicine, the number of such practitioners will be relatively few.The much greater need is for the "up-skilling" in sports medicine of medical practitioners whatever their practice-family medicine, emergency medicine, rehabilitation medicine, paediatrics, orthopaedics.There is a great need for much better "duty of care" in sports medicine practice by local medical practitioners with regard to promotion of physical activity, recreational sport, school and regional sporting teams, and community sporting and physical activity events.Secondly, the useful article by Professor Peter Fricker on sports medicine education in Australia does contain statements that require correction for the public record.He states that there are two classes of medical practitioners with an interest in the practice of sports medicine in Australia: sports physicians and "sports medicine practitioners".In fact, there are now two discipline bodies representing medical practitioners in Sports Medicine Australia, the Australian College of Sports Physicians and Sports Doctors Australia, members of which quite properly refer to themselves as sports doctors, either possessing a Masters of Sports Medicine or demonstrating a continuing involvement in sports medicine.This new body was formed two years ago in response to a request from Sports Medicine Australia to represent doctors who wished to incorporate sports medicine into their existing practice.In referring to the sports medicine programmes at the University of New South Wales in Sydney, Professor Fricker states that the teaching in these programs is carried out by "sports physicians and researchers".In fact, in the distance delivery postgraduate programs (MSpMed, GradDipSpMed, GradCertSpMed), teaching is conveyed in weekly video presentations in which the contribution of sports physicians is 20%, valuable particularly in the area of musculoskeletal medicine.As is to be expected in the multidisciplinary area of sports medicine, 80% of teaching is provided by medical physiologists such as myself, cardiologists, rehabilitation physicians, rheumatologists, ophthalmologists, anatomists, respiratory physiologists,
GM-CSF Gene Expression Is Normal but Protein Release Is Absent in a Patient with Pulmonary Alveolar Proteinosis
Authors: KAM-MENG TCHOU-WONG, TIMOTHY J. HARKIN, CHUANXIANG CHI, MARION BODKIN, WILLIAM N. ROM
Journal: American Journal of Respiratory and Critical Care Medicine (1997)

Pulmonary alveolar proteinosis (PAP) is a rare disease characterized by an excessive accumulation of surfactant lipids and proteins in the alveolar space. In mice with a homozygous deletion of granulocyte macrophage-colony stimulating factor (GM-CSF), their phenotype mimics PAP. To evaluate whether the knockout mouse model mimics human disease, we evaluated GM-CSF expression in alveolar macrophages from a patient with PAP. We performed multiple whole lung lavages on a patient with PAP, and cultured BAL cells in the presence or absence of LPS. In contrast to the GM-CSF knockout mouse, human BAL cells from a patient with PAP expressed mRNA for GM-CSF following LPS stimulation. However, similar to the knockout mouse, GM-CSF protein release from BAL cells was undetectable with or without LPS. BAL cells from normal human controls released GM-CSF in abundance after LPS stimulation. In BAL cells from the patient with PAP, neutralization of interleukin-10 (IL-10) by anti-IL-10 antibody, resulted in enhanced GM-CSF production. Thus, alveolar macrophages from a PAP lung have deficient GM-CSF production analogous to the GM-CSF knockout mice; in contrast, human cells from a PAP lung have an intact GM-CSF gene. This case report illustrates an important difference between the knockout mouse model of PAP and the human disease. Tchou-Wong K-M, Harkin TJ, Chi C, Bodkin M, Rom WN. GM-CSF gene expression is normal but protein release is absent in a patient with pulmonary alveolar proteinosis.