tbuckley/cabot-search huggingface dataset:
Factors influencing the relative effect of leukotriene receptor antagonists (LTRA) and inhaled corticosteroids (ICS) as monotherapy in persistent asthma: A systematic review
Authors: Bhupendrasinh Chauhan, Francine Ducharme
Journal: European Respiratory Journal (2011)

Objectives: To compare the safety and efficacy of LTRA with ICS in patients with asthma across age groups, over time, baseline severity and ICS dose.

Methods: In a systematic review until Dec 2010, we included randomised controlled trials comparing LTRA to ICS for ≥30 days in children and adults with asthma. The primary outcome was exacerbation requiring systemic steroids. Secondary outcomes included lung function, asthma control, adverse effects and withdrawals.

Results: The 54 included trials comprised 13,460 patients (2,795 children) with mild (42%) or moderate (58%) airway obstruction. In 84% of trials, LTRA was compared to a low ICS dose over 4-52 weeks. Compared to ICS, 48% more patients treated with LTRA suffered exacerbations requiring systemic steroids (RR 1.48; 95% CI 1.18, 1.85). There was no significant difference in the magnitude of effect between children and adults, ICS dose, and over time. The benefit of ICS over LTRA was greater in patients with moderate vs. mild airway obstruction (RR=2.03 vs. 1.25, p<0.01). FEV1, symptoms, night awakenings, rescue β2-agonist use, symptom-free days, and quality of life favoured ICS at almost points of time. LTRA use was associated with more than a 2-fold increased risk of withdrawals due to poor asthma control (RR 2.58; 95% CI 2.01, 3.30). Both options were equivalent in the risk of overall side effects.

Conclusions: ICS remains superior to LTRA to prevent exacerbations and improve asthma control, irrespective of age group, ICS dose, and duration of treatment. However, the benefit of ICS is significantly greater in patients with moderate airway obstruction.
Interleukin-33 and Interferon-γ Counter-Regulate Group 2 Innate Lymphoid Cell Activation during Immune Perturbation
Authors: Ari B. Molofsky, Frédéric Van Gool, Hong-Erh Liang, Steven J. Van Dyken, Jesse C. Nussbaum, Jinwoo Lee, Jeffrey A. Bluestone, Richard M. Locksley
Journal: Immunity (2015)
Studies on Cellular and Humoral Immunity to Tumor-specific Antigens in Polyoma Virus-induced Tumors of Rats
Authors: Surjit K. Datta, Michel Vandeputte
Journal: Cancer Research (1971)

Cellular and humoral immunity against polyoma virus-induced tumors in rats was studied with the colony inhibition assay. Lymph node and spleen cells from syngeneic rats immunized by allogeneic polyoma tumors mediated the immune reaction and reduced the plating efficiency of polyoma target cells, whereas lymph node and spleen cells from syngeneic rats immunized by allogeneic chemical carcinogen [7,12-dimethylbenz(a)anthracene]-induced tumor did not exert an inhibitory effect on plated polyoma tumor cells. Both lymphocytes and sera (in the presence of complement) from animals inoculated at birth with polyoma virus and developing either primary polyoma tumors or no tumors inhibited the colony formation of plated polyoma tumor cells.

Serum from rats showing progressively growing polyoma tumors but not from rats developing no such tumors blocked the inhibitory effect of antipolyoma tumor-immune lymph node and spleen cells used in the colony inhibition assay. The blocking effect of this serum was specific, as it could be removed by absorption with polyoma tumor cells and not with 7,12-dimethylbenz(a)anthracene tumor cells. The sera from rats with primary polyoma tumors might contain blocking factor(s) (antibodies?), which abrogate the inhibitory action of immune lymphocytes, and mediate an efferent form of immunological enhancement, which facilitates the development of primary tumors.
The Science and Practice of Bone Health in Oncology: Managing Bone Loss and Metastasis in Patients With Solid Tumors
Authors: Allan Lipton, Robert Uzzo, Robert J. Amato, Georgiana K. Ellis, Behrooz Hakimian, G. David Roodman, Matthew R. Smith
Journal: Journal of the National Comprehensive Cancer Network (2009)

Cancer and its treatment can compromise bone health, leading to fracture, pain, loss of mobility, and hypercalcemia of malignancy. Bone metastasis occurs frequently in advanced prostate and breast cancers, and bony manifestations are commonplace in multiple myeloma. Osteoporosis and osteopenia may be consequences of androgen-deprivation therapy for prostate cancer, aromatase inhibition for breast cancer, or chemotherapy-induced ovarian failure. Osteoporotic bone loss and bone metastasis ultimately share a pathophysiologic pathway that stimulates bone resorption by increasing the formation and activity of osteoclasts. Important mediators of pathologic bone metabolism include substances produced by osteoblasts, such as RANKL, the receptor activator of nuclear factor kappa B ligand, which spurs osteoclast differentiation from myeloid cells. Available therapies are targeted to various steps in cascade of bone metastasis.
Ifosfamide plus etoposide in newly diagnosed Ewing's sarcoma of bone.
Authors: W H Meyer, L Kun, N Marina, P Roberson, D Parham, B Rao, B Fletcher, C B Pratt
Journal: Journal of Clinical Oncology (1992)

PURPOSE We assessed the activity of ifosfamide plus etoposide against newly diagnosed Ewing's sarcoma of bone by administering this drug pair before standard induction therapy (the upfront window approach). PATIENTS AND METHODS Twenty-six children and adolescents with newly diagnosed, previously untreated Ewing's sarcoma of bone were enrolled onto this pilot study (EW-87). Eighteen were at a higher risk of treatment failure, with a primary tumor size of more than 8 cm or metastases at diagnosis. Window therapy with ifosfamide (1.6 g/m2/d with mesna uroprotection) and etoposide (100 mg/m2/d) was given in three 5-day cycles at 21-day intervals. Responses were evaluated clinically and radiologically. Subsequent induction therapy comprised three cycles of cyclophosphamide and doxorubicin. Radiation therapy was the primary local control modality; surgery was limited to biopsy or resection of expendable bones. After the local control phase, alternating courses of vincristine plus dactinomycin, ifosfamide plus etoposide, and cyclophosphamide plus doxorubicin were given as maintenance therapy. RESULTS There were four complete responses and 21 partial responses to ifosfamide/etoposide window therapy (overall response rate 96%; 95% confidence interval [CI], 80% to 99%). Disease progression was observed in four patients during the cyclophosphamide/doxorubicin phase. Chemotherapy was well tolerated; only 16% (20 of 125) of all ifosfamide/etoposide window and maintenance cycles resulted in hospitalization for fever and neutropenia. Two patients developed chemotherapy-induced cystitis. CONCLUSIONS The combination of ifosfamide and etoposide is highly active against previously untreated Ewing's sarcoma and generally is well tolerated. The ultimate impact of these two agents on outcome will be determined in randomized multicenter studies.
Current Issues in Cancer: Cancer of the head and neck
Authors: J S Tobias
Journal: BMJ (1994)

Cancers of the upper aerodigestive tract, collectively known as head and neck cancers, arise from a multiplicity of sites. In the West, excess tobacco and alcohol consumption are the most important of the known predisposing factors; elsewhere in the world, notably in India and China, the aetiology, pattern of primary sites, and clinical behaviour are different. Clinically these tumours pose exceptional problems in management, and skilled multidisciplinary teams are necessary in order to achieve the highest level of service and research. Historically, surgery and radiotherapy have been the most important treatment modalities; chemotherapy is now increasingly employed but not yet fully established. Successful rehabilitation of patients with head and neck cancers requires access to high quality speech therapists and other support staff with training in functional pharyngeal disorders. Current research efforts are largely directed towards defining the proper role of chemotherapy and assessing the possible advantage of unconventional radiation approaches. In recent years the roles of primary, reconstructive, and salvage surgery have also become better defined. Many patients are suitable for randomisation into ongoing prospective clinical trials which have been specifically designed to address these issues.
Platelets Play Differential Role During the Initiation and Progression of Autoimmune Neuroinflammation
Authors: Sarah C. Starossom, Tatyana Veremeyko, Amanda W.Y. Yung, Marina Dukhinova, Cheryl Au, Alexander Y. Lau, Howard L. Weiner, Eugene D. Ponomarev
Journal: Circulation Research (2015)

Rationale : Platelets are known to participate in vascular pathologies; however, their role in neuroinflammatory diseases, such as multiple sclerosis (MS), is unknown. Autoimmune CD4 T cells have been the main focus of studies of MS, although the factors that regulate T-cell differentiation toward pathogenic T helper-1/T helper-17 phenotypes are not completely understood. Objective : We investigated the role of platelets in the modulation of CD4 T-cell functions in patients with MS and in mice with experimental autoimmune encephalitis, an animal model for MS. Methods and Results : We found that early in MS and experimental autoimmune encephalitis, platelets degranulated and produced soluble factors serotonin (5-hydroxytryptamine), platelet factor 4, and platelet-activating factor, which specifically stimulated differentiation of T cells toward pathogenic T helper-1, T helper-17, and interferon-γ/interleukin-17–producing CD4 T cells. At the later stages of MS and experimental autoimmune encephalitis, platelets became exhausted in their ability to produce proinflammatory factors and stimulate CD4 T cells but substantially increased their ability to form aggregates with CD4 T cells. Formation of platelet–CD4 T-cell aggregates involved the interaction of CD62P on activated platelets with adhesion molecule CD166 on activated CD4 T cells, contributing to downmodulation of CD4 T-cell activation, proliferation, and production of interferon-γ. Blocking of formation of platelet–CD4 T-cell aggregates during progression of experimental autoimmune encephalitis substantially enhanced proliferation of CD4 T cells in the central nervous system and the periphery leading to exacerbation of the disease. Conclusion : Our study indicates differential roles for platelets in the regulation of functions of pathogenic CD4 T cells during initiation and progression of central nervous system autoimmune inflammation.
Gemcitabine Plus Cisplatin, an Active Regimen in Advanced Urothelial Cancer: A Phase II Trial of the National Cancer Institute of Canada Clinical Trials Group
Authors: Malcolm J. Moore, Eric W. Winquist, Nevin Murray, Ian F. Tannock, Susan Huan, Katherine Bennett, Wendy Walsh, Lesley Seymour
Journal: Journal of Clinical Oncology (1999)

PURPOSE: To evaluate the efficacy and toxicity of gemcitabine (2′,2′-difluorodeoxycytidine) plus cisplatin in previously untreated patients with advanced transitional-cell carcinoma. PATIENTS AND METHODS: Thirty-one patients with measurable advanced transitional-cell carcinoma who had received no prior chemotherapy for metastatic disease were scheduled to receive gemcitabine 1,000 mg/m 2 intravenously over 30 minutes on days 1, 8, and 15 and cisplatin 70 mg/m 2 over 1 hour on day 2 of a 28-day cycle. Prior adjuvant or neoadjuvant therapy for locally advanced disease was allowed if this was completed more than 1 year before study entry. RESULTS: There were six complete responses and 10 partial responses in 28 assessable patients, for anoverall response rate of 16 of 28 (57%). The response rate on an intent-to-treat basis was 16 of 31 patients (52%). The median survival is 13.2 months, with 18 patients still alive at this time. Toxicity was primarily hematologic, with 12 of 31 patients (39%) having ≥ grade 3 granulocytopenia and 17 of 31 (55%) having ≥ grade 3 thrombocytopenia. Two patients had febrile neutropenia. All patients required a dose modification of gemcitabine at some point in their therapy; the primary reason was thrombocytopenia and/or neutropenia. CONCLUSION: Gemcitabine plus cisplatin is an active regimen for the treatment of urothelial cancer.
A phase I dose escalation trial of the VEGFR tyrosine kinase inhibitor, PTK787/ ZK222584 (PTK/ZK), used in combination with paclitaxel in patients with advanced solid tumors with pharmacokinetic (PK) analysis
Authors: S. R. Malireddy, E. Chiorean, A. Foster, D. Jones, M. Waddell, M. Margol, S. Hall, B. Schneider, C. J. Sweeney
Journal: Journal of Clinical Oncology (2007)

14012 Background: The aim of this study was to define the maximum tolerated dose (MTD) for weekly paclitaxel administered in combination with daily PTK/ZK and assess for a potential PK drug interaction. Methods: 17 patients (pts) with refractory metastatic solid tumors, were enrolled. During cycle 1 (C1) paclitaxel was given on days 1 and 15 in combination with PTK/ZK on days 3 to 28. PTK/ZK was administered once daily each night. During cycle 2 (C2) and beyond, paclitaxel was given on days 1, 8 and 15 every 28 days. PTK/ZK was taken orally each night. A “3+3” design was used. In addition to the standard definitions of dose limiting toxicity (DLT) occurring in C1 and C2, the inability to give day 8 or 15 of paclitaxel or &gt; 7 days of missed PTK/ZK due to toxicity was also deemed dose limiting. Therapy was given until disease progression. Results: 60 cycles (range: 1 to 8) have been administered to 16 evaluable pts. No DLTs were observed when 75 mg/m 2 of paclitaxel was combined with PTK/ZK doses of 250 mg, 500 mg and 750 mg. Two of 5 pts treated with paclitaxel 85 mg/m 2 and PTK/ZK 1,000 mg had Grade 3 transaminase elevation (defined DLT) in C1 after day 15. The MTD was therefore 75 mg/m 2 paclitaxel and 750 mg PTK/ZK. Paclitaxel PK was obtained in 14 patients: 13 of 14 patients had a faster clearance (L/hr) of paclitaxel on C1 day 15 versus day 1 (average % increase: 79%, range 14–256%, SD: 69). Only one patient had a slower clearance: 26% decrease. Activity included 2 partial responses (prostate and esophageal cancer), and 8 pts had stable disease lasting 2–9+ months, including ovarian cancer pts previously treated with paclitaxel. Conclusion: The MTD for weekly paclitaxel plus daily PTK/ZK is 75 mg/m 2 and 750 mg. DLTs were liver transaminase elevation. This combination was well tolerated, and responses and prolonged disease stabilization were seen. PK analysis revealed an increase in rate of paclitaxel clearance in most patients. No significant financial relationships to disclose.
Health care in the US and Canada
Authors: A Watson, J Halpin
Journal: BMJ (1994)

EDITOR, - Minerva1 refers to a paper in the New England Journal of Medicine that compares expenditure in the United States and Canada.2 The authors note the greater expenditure on health care and poorer outcomes in the United States. Per capita expenditure is 40% higher in the United States despite the higher numbers of doctors, beds, and admissions (and longer lengths of stay) in Canada. There was also greater variation of expenditure within the United States.

Examination of admissions by diagnostic related groups suggests that American patients require slightly more complex care. Although …
EAACI Position Paper: Prevention of work-related respiratory allergies among pre-apprentices or apprentices and young workers
Authors: G. Moscato, G. Pala, M. A. Boillat, I. Folletti, R. Gerth van Wijk, D. Olgiati-Des Gouttes, L. Perfetti, S. Quirce, A. Siracusa, J. Walusiak-Skorupa, S. M. Tarlo
Journal: Allergy (2011)

To cite this article: Moscato G, Pala G, Boillat MA, Folletti I, Gerth van Wijk R, Olgiati-Des Gouttes D, Perfetti L, Quirce S, Siracusa A, Walusiak-Skorupa J, Tarlo SM. EAACI Position Paper: Prevention of work-related respiratory allergies among pre-apprentices or apprentices and young workers. Allergy 2011; 66: 1164–1173. Apprenticeship is a period of increased risk of developing work-related respiratory allergic diseases. There is a need for documents to provide appropriate professional advice to young adults aiming to reduce unsuitable job choices and prevent impairment from their careers. The present document is the result of a consensus reached by a panel of experts from European and non-European countries addressed to allergologists, pneumologists, occupational physicians, primary care physicians, and other specialists interested in this field, which aims to reduce work-related respiratory allergies (rhinoconjunctivitis and asthma) among allergic or nonallergic apprentices and other young adults entering the workforce. The main objective of the document is to issue consensus suggestions for good clinical practice based on existing scientific evidence and the expertise of a panel of physicians.
Interactive Big Data Resource to Elucidate Human Immune Pathways and Diseases
Authors: Dmitriy Gorenshteyn, Elena Zaslavsky, Miguel Fribourg, Christopher Y. Park, Aaron K. Wong, Alicja Tadych, Boris M. Hartmann, Randy A. Albrecht, Adolfo García-Sastre, Steven H. Kleinstein, Olga G. Troyanskaya, Stuart C. Sealfon
Journal: Immunity (2015)
Management of Breast Cancer After Hodgkin’s Disease
Authors: Suzanne L. Wolden, Steven L. Hancock, Robert W. Carlson, Don R. Goffinet, Stefanie S. Jeffrey, Richard T. Hoppe
Journal: Journal of Clinical Oncology (2000)

PURPOSE: To evaluate the incidence, detection, pathology, management, and prognosis of breast cancer occurring after Hodgkin’s disease. PATIENTS AND METHODS: Seventy-one cases of breast cancer in 65 survivors of Hodgkin’s disease were analyzed. RESULTS: The median age at diagnosis was 24.6 years for Hodgkin’s disease and 42.6 years for breast cancer. The relative risk for invasive breast cancer after Hodgkin’s disease was 4.7 (95% confidence interval, 3.4 to 6.0) compared with an age-matched cohort. Cancers were detected by self-examination (63%), mammography (30%), and physician exam (7%). The histologic distribution paralleled that reported in the general population (85% ductal histology) as did other features (27% positive axillary lymph nodes, 63% positive estrogen receptors, and 25% family history). Although 87% of tumors were less than 4 cm, 95% were managed with mastectomy because of prior radiation. Two women underwent lumpectomy with breast irradiation. One of these patients developed tissue necrosis in the region of overlap with the prior mantle field. The incidence of bilateral breast cancer was 10%. Adjuvant systemic therapy was well tolerated; doxorubicin was used infrequently. Ten-year disease-specific survival was as follows: in-situ disease, 100%; stage I, 88%; stage II, 55%; stage III, 60%; and stage IV, zero. CONCLUSION: The risk of breast cancer is increased after Hodgkin’s disease. Screening has been successful in detecting early-stage cancers. Pathologic features and prognosis are similar to that reported in the general population. Repeat irradiation of the breast can lead to tissue necrosis, and thus, mastectomy remains the standard of care in most cases.
The effect of coexisting chronic heart failure (CHF) in exercise ventilatory inefficiency in patients with COPD
Authors: Flávio Ferlin Arbex, Maria Clara N. Alencar, Mayron F. Oliveira, Aline S. Souza, Wladimir M. Medeiros, Adriana Mazzuco, Gabriela O. Siqueira, Frederico J.A. Mancuso, Luiz Eduardo Nery, Dirceu R. Almeida, J. Alberto Neder
Journal: European Respiratory Journal (2013)

Background: Increase in “wasted” ventilation (VE) during exercise – as a consequence of large dead space to tidal volume ratio – is a common feature of chronic obstructive pulmonary disease (COPD) and CHF. Coexistence of COPD and CHF, therefore, could be associated with greater increases in exercise VE relative to both oxygen uptake (VO2) and carbon dioxide output (VCO2) compared to COPD alone. Objective: To investigate the role of ventilatory inefficiency during incremental exericse in suggesting the presence of CHF in patients with established COPD. Methods: Twenty-four males (13 with COPD-CHF (FEV1= 59.6 ± 17.5 % pred; left ventricle ejection fraction (LVEF) = 34 ± 6 %) and 10 with COPD alone (FEV1= 48.6 ± 16.0 % pred; LVEF= 64 ± 4 %) were submitted to a ramp-incremental cardiopulmonary exercise test. Results : COPD-CHF patients had shallower Δ VO2 /Δ work rate (WR) and lower peak VO2 than their counterparts ( p <0.05). In line with our hypotheses, measures of excessive exercise ventilation relative to both VO2 and VCO2 were more disturbed in COPD-CHF than COPD patients (ΔVE/ΔVCO2= 39± 10 vs . 30 ± 6 ( p <0.05) and VO2 efficiency slope (OUES, L/min/log)= 1.35± 0.38 vs. 1.76 ± 0.42 ( p <0.01), respectively. In addition, decreases in ΔVO2 /ΔWR and OUES were more closely related to peak VO2 in COPD-CHF than in COPD (r= 0.72 vs. 0.24 and 0.80 vs. 0.68, respectively). Conclusions : Pulmonary ventilation increases out of proportion of both VCO2 and VO2 during progressive exercise in COPD plus CHF patients compared to COPD alone. These results suggest that ventilatory inefficiency variables might be helpful in indicating the coexistence of CHF in COPD patients.
Guidelines of the National Comprehensive Cancer Network on the Use of Myeloid Growth Factors with Cancer Chemotherapy: A Review of the Evidence
Authors: Gary H. Lyman
Journal: Journal of the National Comprehensive Cancer Network (2005)

The prophylactic use of myeloid growth factors reduces the risk of chemotherapy-induced neutropenia and its complications, including febrile neutropenia and infection-related mortality. Perhaps most importantly, the prophylactic use of colony-stimulating factors (CSFs) has been shown to reduce the need for chemotherapy dose reductions and delays that may limit chemotherapy dose intensity, thereby increasing the potential for prolonged disease-free and overall survival in the curative setting. National surveys have shown that the majority of patients with potentially curable breast cancer or non-Hodgkin's lymphoma (NHL) do not receive prophylactic CSF support. In this issue, the National Comprehensive Cancer Network presents guidelines for the use of myeloid growth factors in patients with cancer. These guidelines recommend a balanced clinical evaluation of the potential benefits and harms associated with chemotherapy to define the treatment intention, followed by a careful assessment of the individual patient's risk for febrile neutropenia and its complications. The decision to use prophylactic CSFs is then based on the patient's risk and potential benefit from such treatment. The routine prophylactic use of CSFs in patients receiving systemic chemotherapy is recommended in patients at high risk (&gt;20%) of developing febrile neutropenia or related complications that may compromise treatment. Where compelling clinical indications are absent, the potential for CSF prophylaxis to reduce or offset costs by preventing hospitalization for FN should be considered. The clinical, economic, and quality of life data in support of these recommendations are reviewed, and important areas of ongoing research are highlighted.