tbuckley/cabot-search huggingface dataset:
Randomised controlled trial of non-invasive ventilation (NIV) for nocturnal hypoventilation in neuromuscular and chest wall disease patients with daytime normocapnia
Authors: S Ward, M Chatwin, S Heather, A K Simonds
Journal: Thorax (2005)

Long term non-invasive ventilation (NIV) reduces morbidity and mortality in patients with neuromuscular and chest wall disease with hypercapnic ventilatory failure, but preventive use has not produced benefit in normocapnic patients with Duchenne muscular dystrophy. Individuals with nocturnal hypercapnia but daytime normocapnia were randomised to a control group or nocturnal NIV to examine whether nocturnal hypoventilation is a valid indication for NIV.Forty eight patients with congenital neuromuscular or chest wall disease aged 7-51 years and vital capacity<50% predicted underwent overnight respiratory monitoring. Twenty six with daytime normocapnia and nocturnal hypercapnia were randomised to either nocturnal NIV or to a control group without ventilatory support. NIV was started in the control group if patients fulfilled preset safety criteria.Peak nocturnal transcutaneous carbon dioxide tension (Tcco2) did not differ between the groups, but the mean (SD) percentage of the night during which Tcco2 was >6.5 kPa decreased in the NIV group (-57.7 (26.1)%) but not in controls (-11.75 (46.1)%; p=0.049, 95% CI -91.5 to -0.35). Mean (SD) arterial oxygen saturation increased in the NIV group (+2.97 (2.57)%) but not in controls (-1.12 (2.02)%; p=0.024, 95% CI 0.69 to 7.5). Nine of the 10 controls failed non-intervention by fulfilling criteria to initiate NIV after a mean (SD) of 8.3 (7.3) months.Patients with neuromuscular disease with nocturnal hypoventilation are likely to deteriorate with the development of daytime hypercapnia and/or progressive symptoms within 2 years and may benefit from the introduction of nocturnal NIV before daytime hypercapnia ensues.
A comparative study of two- versus one-lung ventilation for needlescopic bleb resection
Authors: H. Kim, H.K. Kim, D-Y. Kang, D-K. Lee, Y.H. Choi, S.H. Lim
Journal: European Respiratory Journal (2010)

This prospective study was conducted to evaluate the feasibility of two-lung (TL) ventilation with low tidal volume anaesthesia compared with one-lung (OL) ventilation for needlescopic bleb resection. Patients with spontaneous pneumothorax that underwent bleb resection with a 2-mm thoracoscope were enrolled. During the operation, the tidal volume was set at 4.0 mL·kg −1 in the TL group and 8.0 mL·kg −1 in the OL group; the respiration rate was set at 23 and 12 breaths·min −1 , respectively, at the same inspiratory oxygen fraction (50%). A total of 108 patients (55 patients in the TL group and 53 in the OL group) were included in this study. Airway pressure was significantly lower in the TL group (mean± sd 8.0±3.3 versus 24.0±3.9 mmHg in the OL group; p&lt;0.001). The time from endotracheal intubation to the incision was 17.1±4.0 min in the TL group and 35.3±7.6 min in the OL group, which was significantly different (p&lt;0.001). However, the operation time was not different in comparisons between the two groups. Therefore, the total anaesthesia time was significantly longer in the OL group (77.9±21.6 versus 64.9±14.7 min in the TL group; p = 0.002). Needlescopic bleb resection using TL ventilation anaesthesia with low tidal volume was technically feasible, cost-effective and time-saving compared with OL ventilation anaesthesia.
Cytochrome P450 2C9 (CYP2C9) and vitamin K epoxide reductase (VKORC1) genotypes as determinants of acenocoumarol sensitivity
Authors: Laurent Bodin, Céline Verstuyft, David-Alexandre Tregouet, Annie Robert, Liliane Dubert, Christian Funck-Brentano, Patrice Jaillon, Philippe Beaune, Pierre Laurent-Puig, Laurent Becquemont, Marie-Anne Loriot
Journal: Blood (2005)
A Genome-wide siRNA Screen Identifies Proteasome Addiction as a Vulnerability of Basal-like Triple-Negative Breast Cancer Cells
Authors: Fabio Petrocca, Gabriel Altschuler, Shen Mynn Tan, Marc L. Mendillo, Haoheng Yan, D. Joseph Jerry, Andrew L. Kung, Winston Hide, Tan A. Ince, Judy Lieberman
Journal: Cancer Cell (2013)
Privatisation in Spain provokes protests among doctors
Authors: A. Garcia Rada
Journal: BMJ (2012)

A Spanish professional society of doctors has announced an indefinite strike in Madrid and healthcare workers have started sit-in protests at 12 hospitals over the increasing privatisation of the Madrid region’s health service and the levying of a €1 (£0.80; $1.30) charge on prescriptions.

Six hospitals in Madrid will shortly be taken over by private companies in the largest single step towards privatisation in Spain in the past year. The move was announced by Ignacio Gonzalez, the new president of the autonomous region of Madrid, who is a leading member of the conservative People’s Party.

All six hospitals (Infanta Leonor, Infanta Sofia, Infanta Cristina, del Henares, del Sureste, and del Tajo) had already privatised …
Plasma DNA Quantification in Lung Cancer Computed Tomography Screening
Authors: Gabriella Sozzi, Luca Roz, Davide Conte, Luigi Mariani, Francesca Andriani, Salvatore Lo Vullo, Carla Verri, Ugo Pastorino
Journal: American Journal of Respiratory and Critical Care Medicine (2008)

Free circulating plasma DNA has emerged as a potential biomarker for early lung cancer detection. In a previous case-control study we have shown that high levels of plasma DNA are a strong risk factor for lung cancer.To assess the diagnostic performance and prognostic value of plasma DNA levels in a cohort of 1,035 heavy smokers monitored by annual spiral computed tomography (CT) for 5 years.Plasma DNA levels were determined through real-time quantitative PCR at baseline and at time of lung cancer diagnosis. Screening performance of the assay was calculated through the area under the receiver-operating characteristic curve (AUC-ROC). Kaplan-Meier analyses were computed for association with prognosis.Median baseline concentration of plasma DNA was not different in individuals who developed CT-detected lung cancers in the 5-year period (n = 38) versus cancer-free control subjects (AUC-ROC, 0.496; P = 0.9330), and only slightly higher at the time of cancer diagnosis (AUC-ROC, 0.607; P = 0.0369). At surgery, plasma DNA was higher in tumors detected at baseline (AUC-ROC, 0.80; P < 0.0001) and in Stage II to IV tumors detected during the first 2 years of screening (AUC-ROC, 0.87; P < 0.0001). A longitudinal study of plasma DNA levels showed increased values approaching to lung cancer diagnosis (P = 0.0010). Higher plasma DNA was significantly associated with poorer 5-year survival (P = 0.0066).Baseline assessment of plasma DNA level does not improve the accuracy of lung cancer screening by spiral CT in heavy smokers. Higher levels of plasma DNA at surgery might represent a risk factor for aggressive disease.
Canakinumab in a patient with juvenile Behçet's syndrome with refractory eye disease: Figure 1
Authors: Serdal Ugurlu, Didar Ucar, Emire Seyahi, Gulen Hatemi, Sebahattin Yurdakul
Journal: Annals of the Rheumatic Diseases (2012)

Behcet's syndrome (BS) causes panuveitis and retinal vasculitis in about 50% of patients. Despite intensive treatment, up to 20% of patients may lose useful vision.1 Treatment consists of corticosteroids, immunosuppressive agents such as azathioprine (AZA) and ciclosporin A (CycA),1 and biological agents such as interferon-α (IFN) and antitumour necrosis factor agents.2 ,3 We describe a patient with juvenile BS whose refractory eye disease was treated successfully with canakinumab, a fully human anti-interleukin-1β antibody. Figure 1 shows the different treatment regimes used during the follow-up period.



Figure 1 
Different treatment regimes and eye flares during the follow-up period.



A 16-year-old girl was diagnosed with BS at the age of 9 years because …
Immunohistochemical study of lysozyme in lupus miliaris disseminatus faciei
Authors: K. MIHARA, M. ISODA
Journal: British Journal of Dermatology (1986)

The lysozyme activity in tissue samples from patients with lupus miliaris disseminatus faciei (LMDF), sarcoidosis and foreign body granuloma was investigated using the immunoperoxidase technique. The majority of epithelioid cells and giant cells in LMDF and sarcoidosis showed strong lysozyme staining in their cytoplasm. However, most macrophages and giant cells in foreign body granulomas, including granulomatous reactions to epidermal cysts and other foreign materials, stained weakly for lysozyme or were negative. These results suggest that LMDF is different from the foreign body reaction to inert substances, and may be induced by an immunological mechanism associated with cell-mediated immunity.
AN ANALYSIS OF GRAFT-VERSUS-HOST DISEASE IN SYRIAN HAMSTERS
Authors: J. Wayne Streilein, R. E. Billingham
Journal: The Journal of Experimental Medicine (1970)

F(1) hybrid hamsters derived from genetically disparate strains develop a severe and often lethal cutaneous disorder when inoculated intracutaneously with immunologically competent lymphoid cells from either parental strain, The disease is characterized clinically by extensive epidermal necrolysis, and histologically by a complete dissolution of the dermal-epidermal junction. The requisites for elicitation of this syndrome were determined to be: (a) the parental strains must differ from each other at a major histocompatibility locus, and (b) the donor inoculum must contain immunologically competent parental strain cells. In addition it was found that specifically sensitized cells surpassed normal unsensitized ones in their ability to elicit the disease, and that the disease can be transferred adoptively from affected to normal F(1) hosts by means of lymphoid cells. On the basis of these observations, it was concluded that the disease was immunologic in nature, and graft-versus-host in type. However, a series of critical studies failed to demonstrate that the epidermolysis had an immunogenetically specific basis, thus invalidating the provisional assumption that this lesion resulted from a direct immunologic attack upon parenchymal cells of the epidermis and dermis. With the aid of radiation chimeras, it was clearly established that typical epidermolysis could be induced in skin of the same genetic constitution as the attacking donor lymphoid cells. This paradox was taken into account by the possibility that, amid the intense local cutaneous graft-versus-host reactions, "skin-specific" antigenic determinants are bared which incite a quasi autoimmune response that in turn is responsible for the epidermolytic lesions.
Minimal Residual Disease in Breast Cancer: In Blood Veritas
Authors: Giulia Siravegna, Alberto Bardelli
Journal: Clinical Cancer Research (2014)

Abstract A blood-based molecular test might direct recommendations for systemic therapies in patients with early-stage breast cancer undergoing surgery with curative intent. A new study suggests that droplet digital PCR (ddPCR) can be used to detect cancer-specific DNA alterations in plasma with sensitivity suitable for monitoring minimal residual disease. Clin Cancer Res; 20(10); 2505–7. ©2014 AACR.
p53 Mutation and Locoregional Treatment Failure in Head and Neck Squamous Cell Carcinoma
Authors: W. M. Koch, J. A. Brennan, M. Zahurak, S. N. Goodman, W. H. Westra, D. Schwab, G. H. Yoo, D. J. Lee, A. A. Forastiere, D. Sidransky
Journal: JNCI Journal of the National Cancer Institute (1996)

The p53 gene (also known as TP53) may be the most common genetic target involved in the malignant transformation of human cells. Direct sequence analysis has demonstrated that alteration of this gene occurs in approximately 45% of head and neck squamous cell carcinomas. The consequences of p53 mutations in these cancers with respect to tumor behavior and patient survival have not been rigorously determined.We evaluated the implications of p53 mutations in relation to the control of locoregional disease and overall survival following radiation therapy.Data from 110 consecutive patients with invasive disease who were treated with primary radiation therapy (given with curative intent) or with adjuvant radiation therapy (following complete surgical extirpation of gross disease) were included in the analysis. A 1.8-kilobase fragment of the p53 gene encompassing exons 5-9 was amplified from the DNA of stored (frozen) tumor specimens; the amplified DNA was cloned and sequenced by use of standard techniques. Overall survival and locoregional disease-free survival after the completion of radiation therapy were estimated by the Kaplan-Meier method; survival comparisons were made by use of the logrank test or proportional hazards regression models. Reported P values are two-sided.Fortyeight (44%) of the 110 tumors had cells bearing p53 mutations. The risk of locoregional recurrence following either primary or adjuvant radiation therapy was significantly greater (i.e., the time to recurrence was shorter) for patients whose tumors contained mutant p53 genes (univariate model hazard ratio [HR] for p53 mutation versus wild-type = 2.2; 95% confidence interval [CI] = 1.2-4.1; P = .02). The presence of regional lymph node metastases (presence versus absence, HR = 2.0; 95% CI = 1.0-4.2; P = .05) and treatment type (primary radiation therapy versus surgery plus adjuvant radiation therapy, HR = 2.3; 95% CI = 1.2-4.3; P = .01) were also associated with greater risks of locoregional failure. The presence of p53 mutations and lymph node metastases and treatment with primary, as opposed to adjuvant, radiation therapy remained significant risk factors in multivariate regression analysis. No relationship was demonstrated between p53 status and overall survival (mutant versus wild-type, HR = 1.1; 95% CI = 0.6-2.1; P = .66); however, a relationship was shown for tumor stage and overall survival (stages III and IV [more advanced] versus stages I and II [less advanced], HR = 3.3; 95% CI = 1.0-10.8; P = .05). Mutation of the p53 gene was not associated with patient age, sex, tumor stage, primary tumor site, regional lymph node status, degree of tumor cell differentiation, or treatment method.Mutation of the p53 gene is associated with an increased risk of locoregional failure in patients with invasive head and neck squamous cell carcinoma who are treated with radiation therapy.
Chemoimmunotherapy With a Modified Hyper-CVAD and Rituximab Regimen Improves Outcome in De Novo Philadelphia Chromosome–Negative Precursor B-Lineage Acute Lymphoblastic Leukemia
Authors: Deborah A. Thomas, Susan O'Brien, Stefan Faderl, Guillermo Garcia-Manero, Alessandra Ferrajoli, William Wierda, Farhad Ravandi, Srdan Verstovsek, Jeffrey L. Jorgensen, Carlos Bueso-Ramos, Michael Andreeff, Sherry Pierce, Rebecca Garris, Michael J. Keating, Jorge Cortes, Hagop M. Kantarjian
Journal: Journal of Clinical Oncology (2010)

Purpose The adverse prognosis of CD20 expression in adults with de novo precursor B-lineage acute lymphoblastic leukemia (ALL) prompted incorporation of monoclonal antibody therapy with rituximab into the intensive chemotherapy regimen hyper-CVAD (fractionated cyclophosphamide, vincristine, doxorubicin, dexamethasone). Other modifications (irrespective of CD20 expression) included early anthracycline intensification, alterations in number of risk-adapted intrathecal chemotherapy treatments for CNS prophylaxis, additional early and late intensifications, and extension of maintenance phase chemotherapy by 6 months. Patients and Methods Two hundred eighty-two adolescents and adults with de novo Philadelphia chromosome (Ph)–negative precursor B-lineage ALL were treated with standard or modified hyper-CVAD regimens. The latter incorporated standard-dose rituximab if CD20 expression ≥ 20%. Results The complete remission (CR) rate was 95% with 3-year rates of CR duration (CRD) and survival (OS) of 60% and 50%, respectively. In the younger (age &lt; 60 years) CD20-positive subset, rates of CRD and OS were superior with the modified hyper-CVAD and rituximab regimens compared with standard hyper-CVAD (70% v 38%; P &lt; .001% and 75% v 47%, P = .003). In contrast, rates of CRD and OS for CD20-negative counterparts treated with modified versus standard hyper-CVAD regimens were similar (72% v 68%, P = not significant [NS] and 64% v 65%, P = NS, respectively). Older patients with CD20-positive ALL did not benefit from rituximab-based chemoimmunotherapy (rates of CRD 45% v 50%, P = NS and OS 28% v 32%, P = NS, respectively), related in part to deaths in CR. Conclusion The incorporation of rituximab into the hyper-CVAD regimen appears to improve outcome for younger patients with CD20-positive Ph-negative precursor B-lineage ALL.
Participatory Epidemiology: Use of Mobile Phones for Community-Based Health Reporting
Authors: Clark C. Freifeld, Rumi Chunara, Sumiko R. Mekaru, Emily H. Chan, Taha Kass-Hout, Anahi Ayala Iacucci, John S. Brownstein
Journal: PLoS Medicine (2010)

The Health in Action section is a forum for individuals or organizations to highlight their innovative approaches to a particular health problem.
Long term follow up of radiosynovectomy with yttrium-90 silicate in haemophilic haemarthrosis.
Authors: M.E van Kasteren, I.R Nováková, A.M Boerbooms, J.A Lemmens
Journal: Annals of the Rheumatic Diseases (1993)

The aim of this study was to evaluate the long term effect of radiation synovectomy with yttrium-90 silicate in haemophiliac patients with recurrent haemarthrosis. The bleeding frequency and the mobility of the joint were recorded in 16 joints of 14 patients 1 year before radiosynovectomy and during follow up, which ranged from 3 to 6 years. Patients evaluated the effect of their own treatment by completing a questionnaire. Radiographs of the joints were scored by an independent radiologist before treatment. A satisfactory reduction of the frequency of haemorrhage was achieved in 94% of joints during the first year after treatment and was maintained in 63% until the end of the follow up period. In general there was no decrease in mobility attributable to radiosynovectomy, and the patients' own evaluations agreed with the evaluations based on the frequencies of haemarthrosis in 75%. Patients who had only minor, or no, radiological abnormalities of the joints before treatment showed the best results. One patient developed synovitis as a complication of the radiosynovectomy. Radiosynovectomy is an effective and safe treatment for recurrent haemarthrosis in haemophiliac patients, especially in those who have joints with no or minor radiological damage.
Rescue of murine silica-induced lung injury and fibrosis by human embryonic stem cells
Authors: P. Spitalieri, M.C. Quitadamo, A. Orlandi, L. Guerra, E. Giardina, V. Casavola, G. Novelli, C. Saltini, F. Sangiuolo
Journal: European Respiratory Journal (2011)

Alveolar type II pneumocytes (ATII cells) are considered putative alveolar stem cells. Since no treatment is available to repair damaged epithelium and prevent lung fibrosis, novel approaches to induce regeneration of injured alveolar epithelium are desired. The objective of this study was to assess both the capacity of human embryonic stem cells (HUES-3) to differentiate in vitro into ATII cells and the ability of committed HUES-3 cells (HUES-3-ATII cells) to recover in vivo a pulmonary fibrosis model obtained by silica-induced damage. In vitro differentiated HUES-3-ATII cells displayed an alveolar phenotype characterised by multi-lamellar body and tight junction formation, by the expression of specific markers such as surfactant protein (SP)-B, SP-C and zonula occludens (ZO)-1 and the activity of cystic fibrosis transmembrane conductance regulator-mediated chloride ion transport. After transplantation of HUES-3-ATII cells into silica-damaged mice, histological and biomolecular analyses revealed a significant reduction of inflammation and fibrosis markers along with lung function improvement, weight recovery and increased survival. The persistence of human SP-C, human nuclear antigen and human DNA in the engrafted lungs indicates that differentiated cells remained engrafted up to 10 weeks. In conclusion, cell therapy using HUES-3 cells may be considered a promising approach to lung injury repair.
Essential Role for OspA/B in the Life Cycle of the Lyme Disease Spirochete
Authors: Xiaofeng F. Yang, Utpal Pal, Sophie M. Alani, Erol Fikrig, Michael V. Norgard
Journal: The Journal of Experimental Medicine (2004)

The molecular basis of how Borrelia burgdorferi (Bb), the Lyme disease spirochete, maintains itself in nature via a complex life cycle in ticks and mammals is poorly understood. Outer surface (lipo)protein A (OspA) of Bb has been the most intensively studied of all borrelial molecular constituents, and hence, much has been speculated about the potential role(s) of OspA in the life cycle of Bb. However, the precise function of OspA (along with that of its close relative and operonic partner, outer surface [lipo]protein B [OspB]) heretofore has not been directly determined, due primarily to the inability to generate an OspA/B-deficient mutant from a virulent strain of Bb. In this study, we created an OspA/B-deficient mutant of an infectious human isolate of Bb (strain 297) and found that OspA/B function was not required for either Bb infection of mice or accompanying tissue pathology. However, OspA/B function was essential for Bb colonization of and survival within tick midguts, events crucial for sustaining Bb in its natural enzootic life cycle.
Some Aspects of the Role of Vitamin B&lt;sub&gt;12&lt;/sub&gt; and Folic Acid in DNA-Thymidine Synthesis in a Neoplastic C3H Mouse Cell Strain
Authors: Jean Rotherham, Floyd M. Price, Theodore T. Otani, Virginia J. Evans
Journal: JNCI Journal of the National Cancer Institute (1971)

In chemically defined medium containing adenine, deoxyuridine, and 0.57 × 10−6 M folate, but no vitamin B12, the amount of DNA synthesized by a neoplastic C3H mouse cell strain, NCTC 5905, was comparatively limited. It was increased by substitution of thymidine for deoxyuridine or by addition of B12. When B12 was present, but the folate concentration was lowered to 0.57 × 10−7 M and other components were unchanged, less DNA was synthesized; the decrease was partly reversed when deoxyuridine was replaced by thymidine. A further similar limitation was observed when adenine was left out of the B12-containing medium. Incorporation of radioactivity from both 14C-formate and deoxyuridine-2-14C into DNA-thymidine was limited without B12. Under conditions of culture requiring B12 for continuous cell proliferation, the requirement was met by B12, methylcobalamin, or hydroxocobalamin at a concentration of 0.7 × 10−6 M. It appeared, however, that methylcobalamin does not provide a pool of methyl groups for DNA-purine or DNA-thymidine synthesis. That B12 functions, in part, to increase DNA-thymidine synthesis in 5905 cells in culture by raising limiting levels of folate coenzymes required in the metabolism of “one-carbon fragments” seems the most probable explanation of these findings. Additional data related to our previous studies concerning other aspects of the metabolism of nucleic acid precursors in cells of this strain are included.