tbuckley/cabot-search huggingface dataset:
The use of biological control subjects to validate exercise testing with supplemental oxygen
Authors: Kevin De Soomer, K. Leemans, H. Vaerenberg, W. De Backer, E. Oostveen
Journal: European Respiratory Journal (2011)

Some patients desaturate during exercise due to diffusion limitation of O2-uptake in the lung. To measure their exercise tolerance and its limiting factor, cardiopulmonary exercise testing (CPET) can be performed with supplemental oxygen (O2). The aim of our study was to validate the High/Low FiO2 software option on the Jaeger Oxycon Pro (Jaeger, Wurzburg, Germany) using biological control subjects. Three healthy lung function technicians (2F: 1M) performed multiple exercise tests, breathing either room air or a gas mixture containing 30% O2 and 70% N2. The exercise test consisted of a 3 min rest period, 3 min unloaded pedaling followed by 5 min steady state exercise at 40 and 80 Watt for the female subjects and 60 and 120 Watt for the male subject, respectively. The mean values of minute ventilation (V9E), CO2 production (V9CO2), O2 consumption (V9O2) and heart rate (HR) as measured during the last two min of every steady state interval were used for further analysis. Each subject performed 7 tests while breathing FiO2= 21% and 4 tests while breathing FiO2= 30%. Bland-Altman analysis revealed no systematic differences in V9E, HR, V9CO2 and V9O2 at all work rates for all subjects between FiO2= 21% and FiO2= 30% (see figure).  We conclude that when using the High/Low FiO2 software option during CPET, V9CO2 and V9O2 are reliably measured while breathing 30% O2.
P147 Outcomes of pulmonary rehabilitation in severe asthma
Authors: J. Agbetile, S. Singh, P. Bradding, I. Pavord, R. Green
Journal: Thorax (2011)

<h3>Objectives</h3> Structured physical training programmes are a key component of pulmonary rehabilitation (PR) and have consistently been shown to be of significant benefit to patients with COPD. It is unclear whether the application of similar principles provides similar health improvements in patients with severe asthma. We aimed to assess this by studying the effects of pulmonary rehabilitation in a group of patients with severe asthma and significant disability who have completed our standard 7 week PR programme. <h3>Methods</h3> 111 patients with a physician diagnosis of severe asthma who have completed our standard PR programme were studied. Assessments including spirometry, chronic respiratory questionnaire (CRQ), hospital anxiety and depression scores (HAD) and incremental and endurance shuttle walk testing (ISWT, ESWT) were performed at baseline and completion to determine the effect of PR. Baseline demographic and spirometric data were compared with a larger population of patients with severe asthma attending our difficult asthma clinic (DAC). <h3>Results</h3> Following rehabilitation, statistically significant improvements were seen in MRC dyspnoea score (mean (95% CI) improvement −0.35 (−0.13 to −0.57), p=0.003); HADS anxiety (−1.4 (−0.4 to −2.3), p=0.007); HADS depression (−1.2 (−0.2 to −2.2), p=0.026); CRQ dyspnoea (+0.72 (+0.33 to +1.1), p=0.001); CRQ fatigue (+0.92 (+0.65 to +1.2), p&lt;0.001); CRQ Emotion (+0.64 (+0.36 to +0.92), p&lt;0.001); CRQ mastery (+0.47 (+0.13 to +0.81), p=0.007); Incremental shuttle walk test (ISWT) (+63 m (49.5 to 76.5), p&lt;0.001); and Endurance shuttle walk test (ESWT) (+339.7 m, (249.7 to 429.7), p&lt;0.001). Interestingly however, patients with severe asthma who completed pulmonary rehabilitation were older (66 vs 48 yrs p&lt;0.01), more likely to have smoked (69.5% vs 43.5%, p&lt;0.01), and tended to have more severe fixed airflow obstruction (FEV<sub>1</sub>% predicted 55.9 vs 71.9, p=0.28) than our DAC population. This may be because clinicians were more likely to refer patients with asthma who had a COPD-like phenotype or because patients with severe asthma were more likely to drop-out of the programme. <h3>Conclusion</h3> Pulmonary rehabilitation may offer significant benefit to patients with severe asthma though further work is needed to identify the patients mostly likely to benefit and the optimum training required.
Strategies for Culturally Effective End-of-Life Care
Authors: LaVera M. Crawley, Patricia A. Marshall, Bernard Lo, Barbara A. Koenig
Journal: Annals of Internal Medicine (2002)

As a result of profound worldwide demographic change, physicians will increasingly care for patients from cultural backgrounds other than their own. Differences in beliefs, values, and traditional health care practices are of particular relevance at the end of life. Health care providers and patients and families may not have shared understandings of the meaning of illness or death and may not agree on the best strategies to plan for the end of life or to alleviate pain and suffering. Good end-of-life care may be complicated by disagreements between physicians and patients, difficult interactions, or decisions the physician does not understand. Challenges may result from cultural differences between the patient's background and traditional medical practice. Values so ingrained in physicians as to be unquestioned may be alien to patients from different backgrounds. Physicians need to be sensitive to cultural differences and to develop the skills necessary to work with patients from diverse backgrounds. Community and cultural ties provide a source of great comfort as patients and families prepare for death. This paper describes two cases that raise issues about cross-cultural end-of-life practice and suggests strategies for negotiating common problems. Physicians should assess the cultural background of each patient and inquire about values that may affect care at the end of life. They should become aware of the specific beliefs and practices of the populations they serve, always remembering to inquire whether an individual patient adheres to these cultural beliefs. Attention to cultural difference enables the physician to provide comprehensive and compassionate palliative care at the end of life.
Anchored FRET sensors detect local caspase activation prior to neuronal degeneration
Authors: Ricardo A Figueroa, Veronica Ramberg, Tom Gatsinzi, Malin Samuelsson, Mu Zhang, Kerstin Iverfeldt, Einar Hallberg
Journal: Molecular Neurodegeneration (2011)

Abstract Background Recent studies indicate local caspase activation in dendrites or axons during development and in neurodegenerative disorders such as Alzheimer's disease (AD). Emerging evidences point to soluble oligomeric amyloid-β peptide as a causative agent in AD. Results Here we describe the design of fluorescence resonance energy transfer (FRET)-based caspase sensors, fused to the microtubule associated protein tau. Specific caspase sensors preferentially cleaved by caspase-3, -6 or -9 were expressed in differentiated human neuroblastoma SH-SY5Y cells. The anchoring of the sensors resulted in high FRET signals both in extended neurites and soma and made analysis of spatiotemporal signal propagation possible. Caspase activation was detected as loss of FRET after exposure to different stimuli. Interestingly, after staurosporine treatment caspase-6 activation was significantly delayed in neurites compared to cell bodies. In addition, we show that exposure to oligomer-enriched amyloid-β peptide resulted in loss of FRET in cells expressing sensors for caspase-3 and -6, but not -9, in both soma and neurites before neurite degeneration was observed. Conclusions Taken together, the results show that by using anchored FRET sensors it is possible to detect stimuli-dependent differential activation of caspases and to distinguish local from global caspase activation in live neuronal cells. Furthermore, in these cells oligomer-enriched amyloid-β peptide induces a global, rather than local activation of caspase-3 and -6, which subsequently leads to neuronal cell death.
SPECIFICITY OF THE REACTION BETWEEN RHEUMATOID FACTORS AND GAMMA GLOBULIN
Authors: Hugh H. Fudenberg, Henry G. Kunkel
Journal: The Journal of Experimental Medicine (1961)

Rheumatoid factors in the sera of patients with rheumatoid arthritis appear to be specifically directed against genetically determined "antigens" in human gamma-globulin. At least eight rheumatoid factors of differing specificity exist; usually several are present in combination in the same serum. The different rheumatoid factors can be readily detected through their pattern of reactivity with anti-Rh antibodies from different individuals. Rheumatoid factors in diseases other than rheumatoid arthritis were found to have a more restricted specificity, contrasted to the broader reactivity of the factors in most rheumatoid arthritis sera. A specificity similar to that for incomplete antibodies was not demonstrated for the reaction of rheumatoid factors with aggregated gamma-globulin or with gamma-globulin to form the "22S complex." In certain instances, using the anti-Rh system, rheumatoid factors were found to react poorly with the patient's own gamma-globulin, compared to that of other individuals of different genetic gamma-globulin types. These results, as well as additional indirect evidence, indicate that the rheumatoid factors can possess isospecificity. However, a certain degree of autospecificity was also found which was most clearly evident through complex formation with the patients own gamma-globulin and in the reaction with aggregates. The relevance of these findings to possible isoantibody as well as autoantibody concepts is discussed.
Whole-genome sequencing to establish relapse or re-infection with Mycobacterium tuberculosis: a retrospective observational study
Authors: Josephine M Bryant, Simon R Harris, Julian Parkhill, Rodney Dawson, Andreas H Diacon, Paul van Helden, Alex Pym, Aziah A Mahayiddin, Charoen Chuchottaworn, Ian M Sanne, Cheryl Louw, Martin J Boeree, Michael Hoelscher, Timothy D McHugh, Anna L C Bateson, Robert D Hunt, Solomon Mwaigwisya, Laura Wright, Stephen H Gillespie, Stephen D Bentley
Journal: The Lancet Respiratory Medicine (2013)

Recurrence of tuberculosis after treatment makes management difficult and is a key factor for determining treatment efficacy. Two processes can cause recurrence: relapse of the primary infection or re-infection with an exogenous strain. Although re-infection can and does occur, its importance to tuberculosis epidemiology and its biological basis is still debated. We used whole-genome sequencing-which is more accurate than conventional typing used to date-to assess the frequency of recurrence and to gain insight into the biological basis of re-infection.We assessed patients from the REMoxTB trial-a randomised controlled trial of tuberculosis treatment that enrolled previously untreated participants with Mycobacterium tuberculosis infection from Malaysia, South Africa, and Thailand. We did whole-genome sequencing and mycobacterial interspersed repetitive unit-variable number of tandem repeat (MIRU-VNTR) typing of pairs of isolates taken by sputum sampling: one from before treatment and another from either the end of failed treatment at 17 weeks or later or from a recurrent infection. We compared the number and location of SNPs between isolates collected at baseline and recurrence.We assessed 47 pairs of isolates. Whole-genome sequencing identified 33 cases with little genetic distance (0-6 SNPs) between strains, deemed relapses, and three cases for which the genetic distance ranged from 1306 to 1419 SNPs, deemed re-infections. Six cases of relapse and six cases of mixed infection were classified differently by whole-genome sequencing and MIRU-VNTR. We detected five single positive isolates (positive culture followed by at least two negative cultures) without clinical evidence of disease.Whole-genome sequencing enables the differentiation of relapse and re-infection cases with greater resolution than do genotyping methods used at present, such as MIRU-VNTR, and provides insights into the biology of recurrence. The additional clarity provided by whole-genome sequencing might have a role in defining endpoints for clinical trials.Wellcome Trust, European Union, Medical Research Council, Global Alliance for TB Drug Development, European and Developing Country Clinical Trials Partnership.
Atypical Teratoid/Rhabdoid Tumors (ATRT): Improved Survival in Children 3 Years of Age and Older With Radiation Therapy and High-Dose Alkylator-Based Chemotherapy
Authors: Tanya M. Tekautz, Christine E. Fuller, Susan Blaney, Maryam Fouladi, Alberto Broniscer, Thomas E. Merchant, Matthew Krasin, James Dalton, Gregory Hale, Larry E. Kun, Dana Wallace, Richard J. Gilbertson, Amar Gajjar
Journal: Journal of Clinical Oncology (2005)

To describe clinical features, therapeutic approaches, and prognostic factors in pediatric patients with atypical teratoid/rhabdoid tumors (ATRT) treated at St Jude Children's Research Hospital (SJCRH).Primary tumor samples from patients diagnosed with ATRT at SJCRH between July 1984 and June 2003 were identified. Pathology review included histologic, immunohistochemical analysis, and fluorescence in situ hybridization for SMARCB1 (also known as hSNF5/INI1) deletion. Clinical records of patients with pathologic confirmation of ATRT were reviewed.Thirty-seven patients were diagnosed with ATRT at SJCRH during the 19-year study interval. Six patients were excluded from this clinical review based on pathologic or clinical criteria. Of the remaining 31 patients, 22 were younger than 3 years. Posterior fossa primary lesions and metastatic disease at diagnosis were more common in younger patients with ATRT. All patients underwent surgical resection; 30 received subsequent chemotherapy. The majority of patients aged 3 years or older received postoperative craniospinal radiation. Two-year event-free (EFS) and overall survival (OS) of children aged 3 years or older (EFS, 78% + 14%; OS, 89% +/- 11%) were significantly better than those for younger patients (EFS, 11% +/- 6%; OS, 17% +/- 8%); EFS, P = .009 and OS, P = .0001. No other clinical characteristics were predictive of survival. Three of four patients 3 years or older with progressive disease were successfully rescued with ifosfamide, carboplatin, and etoposide therapy.Children presenting with ATRT before the age of 3 years have a dismal prognosis. ATRT presenting in older patients can be cured using a combination of radiation and high-dose alkylating therapy. Older patients with relapsed ATRT can have salvage treatment using ICE chemotherapy.
Health Care for Prisoners in Haiti
Authors: John P. May
Journal: Annals of Internal Medicine (2010)

Prisoners have disproportionate health care needs. Meeting those needs in a prison environment is challenging, especially in such resource-poor countries as Haiti. Even so, before the January 2010 earthquake, local and international organizations, in collaboration with the Haitian government, had been making significant progress to provide for the health needs of prisoners. The effort screened and identified prisoners for infectious disease, initiated appropriate care and treatment, and prepared prisoners for release to the community. Not only is it possible to establish an adequate prison health care program in a resource-poor country, it is necessary. Without adequate management of prisoners' health needs, especially for such infectious diseases as HIV and tuberculosis, disease burden increases. Infectious disease can spread among prisoners and impact the public's health. Recovery for postearthquake Haiti, as any nation rebuilding following natural disaster or conflict, requires respect for rule of law. This includes humane detention and the delivery of justice and adequate health care for prisoners.
Characterization of clinical photosensitivity in cutaneous lupus erythematosus
Authors: Kristen Foering, Aileen Y. Chang, Evan W. Piette, Andrew Cucchiara, Joyce Okawa, Victoria P. Werth
Journal: Journal of the American Academy of Dermatology (2013)

Photosensitivity (PS) in lupus erythematosus (LE) is frequently determined by patient report.
Interleukin 10 (IL-10) upregulates functional high affinity IL-2 receptors on normal and leukemic B lymphocytes.
Authors: A C Fluckiger, P Garrone, I Durand, J P Galizzi, J Banchereau
Journal: The Journal of Experimental Medicine (1993)

Interleukin 10 (IL-10) has recently been shown to induce normal human B lymphocytes to proliferate and differentiate into immunoglobulin (Ig)-secreting cells. Herein, we show that IL-10 also promotes DNA synthesis and IgM production by anti-CD40 activated B cell chronic lymphocytic leukemia (B-CLL). Most strikingly, IL-2 and IL-10 were found to synergize to induce the proliferation and differentiation of B-CLL cells. This synergy between IL-2 and IL-10 was also observed with normal B cells which proliferated strongly and secreted large amounts of IgM, IgG, and IgA. The observed synergy is likely to be due to the IL-10-induced increase of high affinity IL-2 receptors on both normal and leukemic B cells. This increase of high affinity receptor is associated to an increase of Tac/CD25 expression that can be detected by flow cytometric analysis. Taken together, these results indicate that IL-10 permits anti-CD40 activated B cells to respond to IL-2 through an induction of high affinity IL-2 receptors. This effect of IL-10 may partly explain how T cells, which activate B cells in a CD40-dependent fashion, induce B cell proliferation and differentiation mostly through IL-2.
Antimyeloperoxidase antibodies are a useful marker of disease activity in antineutrophil cytoplasmic antibody-associated vasculitides
Authors: B Terrier, D Saadoun, D Sène, P Ghillani, Z Amoura, G Deray, B Fautrel, J-C Piette, P Cacoub
Journal: Annals of the Rheumatic Diseases (2008)

<h3>Objective:</h3> To evaluate the relevance of monitoring antimyeloperoxidase antibody levels in the management of antimyeloperoxidase-associated vasculitides. <h3>Methods:</h3> Thirty-eight patients with antimyeloperoxidase-associated vasculitides were included: microscopic polyangiitis (n = 18), Wegener's granulomatosis (n = 15) and Churg–Strauss syndrome (n = 5). Baseline characteristics and outcomes were recorded. Serial measurements of antimyeloperoxidase antibody levels were performed (ELISA, positive ⩾20 IU/ml). <h3>Results:</h3> All patients achieved vasculitis remission after a mean time of 2.0 months (SD 0.9), with a significant decrease in the mean antimyeloperoxidase antibody level at remission (478 vs 41 IU/ml (SD 598 vs 100); p&lt;0.001). Twenty-eight (74%) patients became antimyeloperoxidase antibody negative. After a mean follow-up of 54 months (SD 38), 12 cases of clinical relapse occurred in 11/38 (29%) patients. Relapses were associated with an increase in antimyeloperoxidase antibody levels in 10/11 (91%) patients (34 vs 199 IU/ml (88 vs 314); p = 0.002). The reappearance of antimyeloperoxidase antibodies after achieving negative levels was significantly associated with relapse (odds ratio 117; 95% CI 9.4 to 1450; p&lt;0.001). Antimyeloperoxidase antibodies showed a positive predictive value of 90% and a negative predictive value of 94% for relapse of vasculitis. Up to 60% of cases of relapse occurred less than 12 months after the reappearance of antimyeloperoxidase antibodies. Relapse-free survival was significantly worse for patients who exhibited a reappearance of antimyeloperoxidase antibodies than in those with persistent negative antimyeloperoxidase antibodies (p&lt;0.001). The antimyeloperoxidase antibodies serum level was strongly correlated with the Birmingham vasculitis activity score and the disease extent index (r = +0.49; p = 0.002). <h3>Conclusion:</h3> Through monitoring, antimyeloperoxidase antibodies are a useful marker of disease activity and a good predictor of relapse in antimyeloperoxidase-associated vasculitides.
Analysis of C1q polymorphisms suggests association with systemic lupus erythematosus, serum C1q and CH50 levels and disease severity
Authors: H A Martens, M W Zuurman, A H M de Lange, I M Nolte, G van der Steege, G J Navis, C G M Kallenberg, M A Seelen, M Bijl
Journal: Annals of the Rheumatic Diseases (2008)

Several findings link systemic lupus erythematosus (SLE) with C1q, the first molecule of the classical complement pathway. Polymorphisms of the C1qA gene are associated with low serum C1q levels in patients with cutaneous LE, but C1q polymorphisms have not been studied in patients with systemic lupus.To determine whether polymorphisms of the C1q genes are associated with SLE, disease phenotypes, serum C1q and CH50 levels.DNA for genetic analysis was obtained from 103 Caucasian patients with SLE and their family members. Five tag single nucleotide polymorphisms (tag SNPs) served as unique markers for underlying SNPs in the genes of the C1q protein. The pedigree disequilibrium test (PDT) was applied to trios to determine association of markers with SLE, SLE phenotypes, low serum C1q and low CH50. Single SNP association and haplotype analysis was also performed.The PDT revealed a significant association of the tag SNP rs631090 (covering the C1qB gene) with SLE (p = 0.02). Rs631090 was moderately associated with low serum C1q levels (p = 0.06). In addition, the tag SNPs rs292001 and rs294183 were associated with more severe SLE (Systemic Lupus Erythematosus International Collaborating Clinics (SLICC) damage index score>0; p = 0.007 and p = 0.02, respectively). Haplotype analysis and single SNP association analysis showed no significant associations, but additional analyses revealed that marker rs587585 is associated with low serum C1q and CH50 levels.C1q polymorphisms are associated with SLE, serum C1q and CH50 levels in a stable founder population of patients with SLE. Although the studied population was small and allele frequencies were low, this is the first study to suggest an association of C1q polymorphisms with SLE.
Effect of a "stop smoking" booklet on smokers attending for chest radiography: a controlled study.
Authors: I A Campbell, M Hansford, R J Prescott
Journal: Thorax (1986)

At two chest clinics 1206 cigarette smokers referred by their general practitioners for chest radiography only either were dealt with in the normal way or in addition were given a How to Stop Smoking booklet by the clinic receptionist or nurse. Follow up one year later showed that 3.2% of all patients had successfully given up smoking, older patients doing better than younger ones and men doing better than women. Overall 3.9% of the group receiving a booklet were successful compared with 2.7% of the controls (p = 0.14). At one clinic the groups were not well matched for age but at the other, where there was no such imbalance, there was a suggestion that the booklet group did better than the controls (6.5% v 2.7% success), although the difference did not achieve conventional statistical significance (p = 0.09). If this can be confirmed as a real effect then this cheap, simple strategy could easily be applied on a large scale.