tbuckley/cabot-search huggingface dataset:
Abstract IA31: Harnessing death for life.
Authors: Cassandra Vandenberg, Suzanne Cory, Rebecca Bilardi, Natasha Anstee, Phillipe Bouillet, Andreas Strasser
Journal: Clinical Cancer Research (2015)

Abstract Impaired apoptosis is a critical step in the development of cancer and a major impediment to effective therapy. Bcl-2, the oncoprotein activated by chromosome translocation in human follicular lymphoma, inhibits cells from undergoing apoptosis in response to many cytotoxic agents. Several close relatives (Bcl-xL, Bcl-w, Mcl-1 and A1) are also anti-apoptotic but others (Bax and Bak) are instead pro-apoptotic, despite strong sequence and structural homology. More distant pro-apoptotic family members, the ‘BH3-only proteins’, are largely unrelated, apart from the signature BH3 (Bcl-2 homology region 3) domain that is essential for their killing function. Using mouse models, we have shown that over-expression of Bcl-2 or Mcl-1, or loss of the BH3-only protein Bim, exacerbates a variety of lymphoid and myeloid neoplasias. Our recent preclinical studies suggest that small molecules mimicking BH3 domains will be effective cancer therapeutics. Citation Format: Cassandra Vandenberg, Suzanne Cory, Rebecca Bilardi, Natasha Anstee, Phillipe Bouillet, Andreas Strasser. Harnessing death for life. [abstract]. In: Proceedings of the AACR Special Conference on Hematologic Malignancies: Translating Discoveries to Novel Therapies; Sep 20-23, 2014; Philadelphia, PA. Philadelphia (PA): AACR; Clin Cancer Res 2015;21(17 Suppl):Abstract nr IA31.
Marrow Transplantation in Patients with Thalassemia Responsive to Iron Chelation Therapy
Authors: Guido Lucarelli, Maria Galimberti, Paola Polchi, Emanuele Angelucci, Donatella Baronciani, Claudio Giardini, Marco Andreani, Fabrizio Agostinelli, Federico Albertini, Reginald A. Clift
Journal: New England Journal of Medicine (1993)

Patients with homozygous beta-thalassemia, who have a good prognosis during treatment with conventional therapy, appear to have an especially high probability of hematologic cure with bone marrow transplantation, although the morbidity and mortality associated with such treatment are not established.
Granulomatous Colitis in Association with Diverticula
Authors: Richard H. Marshak, Henry D. Janowitz, Daniel H. Present
Journal: New England Journal of Medicine (1970)

Ten patients 45 years of age or older were initially believed, on the basis of clinical and radiologic findings, to have diverticulitis of the sigmoid and descending colon. At operation the same diagnosis was entertained in nine on the basis of the gross findings. Pathological examination of the resected specimens, however, revealed typical lesions of granulomatous colitis. The history, physical examination and laboratory studies did not aid in the differential diagnosis except for the past history of perirectal disease in four patients. Analysis of the radiographic findings, however, revealed some distinguishing features, particularly the presence of a longitudinal, intramural fistulous tract extending parallel to the lumen in the thickened bowel. This finding is pathognomonic for granulomatous colitis.
Misoprostol for the Treatment of Peptic Ulcer and Antiinflammatory-Drug–Induced Gastroduodenal Ulceration
Authors: Alastair J.J. Wood, Robert P. Walt
Journal: New England Journal of Medicine (1992)

MISOPROSTOL was the first analogue of prostaglandin E1 to be commercially available. It was developed after prostaglandins of the E series had been found to inhibit the secretion of acid and prevent gastric injury caused by various substances, with the hope that it would be useful for the prevention and treatment of gastrointestinal ulceration. The aim of this article is to review the use of the drug in clinical practice, with critical appraisal of its role in the prevention and management of upper gastrointestinal ulcers associated with the use of nonsteroidal antiinflammatory drugs (NSAIDs). In the United Kingdom, misoprostol . . .
Subcutaneous, Mediastinal and Probable Subpericardial Emphysema Treated with Recompression
Authors: J. C. Norman, P. J. Rizzolo
Journal: New England Journal of Medicine (1959)

THE purpose of this paper is to report a case of mediastinal, subcutaneous and probable subpericardial emphysema treated by recompression, with subsequent recovery.Spontaneous mediastinal emphysema and its bizarre auscultatory "crunch," first described by Hamman1 in 1939, is a well known clinical and radiologic entity. Subpericardial emphysema resulting from the presence of gases within the pericardial sac after penetrating wounds, infections by gas-forming bacilli, rupture of hollow viscus or rupture of the pulmonary parenchyma into and through the pericardium during the course of granulomatous fibroadherent infections, though admittedly rare, has previously been reported. However, subpericardial emphysema associated with mediastinal and . . .
S98 Effectiveness of home maintenance tele-rehabilitation on COPD exacerbations
Authors: G Kaltsakas, AI Papaioannou, M Vasilopoulou, S Spetsioti, SA Gennimata, AF Palamidas, N Chynkiamis, E Kortianou, T Vasilogiannakopoulou, I Vogiatzis, NG Koulouris
Journal: Thorax (2015)

<h3></h3> Acute exacerbations are cardinal events in the natural history of chronic obstructive pulmonary disease (COPD) and are associated with increased morbidity and mortality. Tele-monitoring interventions are a relatively new field in COPD research and management. Furthermore, the effect of home tele-rehabilitation on COPD exacerbation has not been thoroughly studied. Therefore, we set out to investigate whether a home tele-rehabilitation program would be as beneficial as an outpatient maintenance rehabilitation program, in the context of COPD exacerbations, following completion of a 3-month course of supervised pulmonary rehabilitation. We studied 137 Caucasian, ambulatory COPD patients. Forty seven patients were assigned to home maintenance tele-rehabilitation (FEV<sub>1</sub>,%pred = 50 ± 22, mean±SD). Fifty patients were assigned to twice weekly hospital-based maintenance rehabilitation (FEV<sub>1</sub>,%pred = 52 ± 17). Forty COPD patients (FEV<sub>1</sub>, %pred = 52 ± 21), were not assigned to any rehabilitation program and served as controls. Tele-rehabilitation included home exercise reconditioning, self-management techniques, dietary, and psychological advice. Patients were provided with tablets and wireless devices to record and transmit data, related to symptoms, lung function, and vital signs, to a tele-health platform. Patients were followed up for 12 months. At baseline there were no significant differences amongst the tele-rehabilitation (3.3 ± 3.1), hospital-based rehabilitation (3.4 ± 1.9), or control (3.3 ± 1.6), groups in terms of COPD exacerbations. After 12 months, COPD exacerbations in the group of home tele-rehabilitation were significantly reduced to 1.7 ± 1.7. In the group of hospital-based rehabilitation COPD exacerbations were also significantly reduced to 1.8 ± 1.4. In contrast, in the control group COPD exacerbations remained unchanged (3.5 ± 1.7). There were significant difference amongst the two rehabilitation groups (tele-rehabilitation and hospital-based) and the control group in terms of COPD exacerbations (p &lt; 0.001). In conclusion, ongoing home tele-rehabilitation with the use of tele-monitoring could significantly reduce COPD exacerbations and seems to be as beneficial as an outpatient hospital-based maintenance rehabilitation program in the context of COPD exacerbations. Thus, tele-rehabilitation may constitute a satisfactory alternative rehabilitative strategy to diminish health care costs.
Impaired Lung Function in Patients with IgA Deficiency and Low Levels of IgG2 or IgG3
Authors: Janne Björkander, Björn Bake, Vivi-Anne Oxelius, Lars Å. Hanson
Journal: New England Journal of Medicine (1985)

We examined the relation between serum levels of IgG subclasses and lung function, as determined by spirometry, lung volumes, the single-breath nitrogen test, and static recoil pressures, in 29 patients with IgA deficiency and repeated upper or lower respiratory tract infections. Four of the patients had decreased levels of IgG2, and two had decreased levels of IgG3. Two or more lung-function values were abnormal in each of these six patients and also in three others with normal levels of IgG subclasses. Low levels of IgG2 and IgG3 were significantly related to abnormal lung function (P less than 0.01). The 20 patients with normal lung function all had IgG-subclass levels above the lower range. There may be a causal relation between low levels of IgG subclasses and deterioration in lung function, suggesting that patients with combined IgA and IgG-subclass deficiencies may benefit from immunoglobulin prophylaxis.
PTH-169 Global inverse associations between gastric and oesophageal adenocarcinoma supports h. pylori infection protecting from latter
Authors: MH Derakhshan, M Arnold, DH Brewster, JJ Going, DR Mitchell, D Forman, KE McColl
Journal: Gut (2015)

<h3>Introduction</h3> H.pylori atrophic gastritis and associated hypochlorhydria have been suggested to protect against oesophageal adenocarcinoma (OAD), so that the falling incidence of the former might be linked to the rising incidence of the latter seen recently. If so, a negative association should exist between the incidences of OAD and non-cardia gastric cancer, mediated by atrophic gastritis. <h3>Method</h3> In a cross-sectional study, world age-standardised incidences rates (WASR), for the period 2003–07, were abstracted from “Cancer Incidence in Five Continents” Volume X together with 2012 estimates from GLOBOCAN 2012. Relevant ICD-10 codes were used to locate oesophageal and gastric cancers anatomically, and ICD-O3 codes for the histological diagnosis of OAD. In a longitudinal study, trends in WASRs of OAD and total gastric cancer (TGC) were extracted from Cancer in Five Continents Plus (CI5C-Plus). Average annual percentage change (AAPC) in WASRs were calculated for the period 1989–2007 using joinpoint regression. <h3>Results</h3> WASRs for the year 2012 were available for 51 countries and showed a negative correlation between OAD and both TGC (men: CC=-0.38, p = 0.006, women: CC=-0.41, p = 0.003) and non-cardia gastric cancer (men: CC=-0.41, p = 0.003 and women: CC=-0.43, p = 0.005). AAPCs were analysed for 38 populations and showed a significant decrease of TGC in 89% and increase of OAD in 66% of the populations, with no population showing a fall in the latter. Significant negative correlations between the incidences of the two cancers were observed in 28 of the 39 populations over the 18–49 years of available observation time. Super-imposition of the longitudinal and cross-sectional data indicated that populations with currently high incidence of OAD and low incidence of gastric cancer had previously resembled countries with high incidence of gastric cancer and low incidence of oesophageal adenocarcinoma. <h3>Conclusion</h3> The negative association between OAD and gastric cancer in both recent incidence and over time supports the hypothesis of atrophic gastritis protecting against OAD and also the falling incidence of the gastritis contributing to the rise in the incidence of OAD. Our study also demonstrates the value of the global cancer registry network in identifying disease trends and their implications. <h3>Disclosure of interest</h3> None Declared.
Experimental Intracardiac Visualization
Authors: Walter J. Gamble, Robert E. Innis
Journal: New England Journal of Medicine (1967)

INTRACARDIAC visualization differs from conventional endoscopic examinations because of unique conditions present within the heart and the great vessels. First of all, the blood filling these spaces is opaque to all visible wavelengths of light. Secondly, blood cannot safely be excluded from any chamber of the heart for more than a brief interval without the use of complex bypass mechanisms. Finally, most structures are in a state of motion too rapid to be followed by the naked eye.Doubtless, the direct inspection of intracardiac defects would be of value, both to the diagnostician and to the surgeon. With such a . . .
Romiplostim in children with immune thrombocytopenia: a phase 3, randomised, double-blind, placebo-controlled study
Authors: Michael D Tarantino, James B Bussel, Victor S Blanchette, Jenny Despotovic, Carolyn Bennett, Ashok Raj, Bronwyn Williams, Donald Beam, Jaime Morales, Melissa J Rose, Nancy Carpenter, Kun Nie, Melissa Eisen
Journal: The Lancet (2016)
CD3 immunotoxin therapy of cutaneous T cell lymphoma
Authors: A. E. Frankel, J. Woo, S. L. Zuckero, A. A. Mankin, M. Grable, K. Mitchell, Y. Lee, D. M. Neville
Journal: Journal of Clinical Oncology (2009)

e19511 Background: T cell lymphomas represent 12% of lymphoma cases in the U.S. Cytotoxic chemotherapies, radiation therapies, monoclonal antibodies, transcription modulators and topical therapies yield remissions, but over half of patients relapse and die with progressive disease. Patients ineligible for allogeneic transplant need additional therapeutic options. One class of T cell directed agents are immunotoxins composed of protein synthesis inactivating peptide toxins covalently linked to antibodies or hormone ligands. We prepared a new immunotoxin, A-dmDT390-bisFv(UCHT1) composed of the catalytic and translocation domains of diphtheria toxin fused to two single chain antibody fragments reactive with an acidic loop on the extracellular domain of CD3epsilon. We prepared a clinical batch of drug and obtained FDA approval for a phase I trial (IND#100712). Methods: Cohort of three-six CTCL patients were treated with immunotoxin via 15min IV infusion twice daily for four days at 2.5–5ug/kg. CTCAEv3.0 toxicity grading, blood samples counts, chemistries, CMV/EBV PCR, PK, immune response and flow cytometry, and disease assessments by CT scans, skin mapping and bone marrow biopsies were done. Results: Six patients received all eight 2.5ug/kg doses. Toxicities were mild- moderate with fever, chills, nausea, transaminasemia, hypoalbuminemia, lymphopenia and reactivation of EBV and CMV. Side effects responded to antipyretics, anti-emetics, albumin infusions, rituximab and valgancyclovir. Lymphopenia was marked at the end of treatment (99.9% reduction) and was followed by partial recovery at two weeks. Circulating T regulatory cells doubled. Cmax occured 5 min post-infusion and was 18ng/mL. Half-life was 49 min. All patient had anti-immunotoxin antibodies at a median of 1.3ug/mL which increased after 30 days to 9–1700ug/mL. Two of five evaluable patients had PRs lasting one and 6+ months. Conclusions: This novel immunotoxin has dramatic clinical activity even at the lowest dose in CTCL patients and merits applications at higher doses in CTCL and other CD3+ T cell leukemia/lymphoma patients. The lymphodepletion with recovery of T regulatory cells suggests the drug may be beneficial for immunosuppression of T cell autoimmune disorders. No significant financial relationships to disclose.
Cerebral dysfunction secondary to high-dose methotrexate.
Authors: N Jaffe
Journal: Journal of Clinical Oncology (1987)

Article Tools Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.1987.5.4.681 Journal of Clinical Oncology - published online before print September 22, 2016 PMID: 3559659 Cerebral dysfunction secondary to high-dose methotrexate. N JaffexN JaffeSearch for articles by this author https://doi.org/10.1200/JCO.1987.5.4.681 PDF "Cerebral dysfunction secondary to high-dose methotrexate.." Journal of Clinical Oncology, 5(4), pp. 681–682© 1987 by American Society of Clinical Oncology
A Cluster of<i>Pneumocystis carinii</i>Pneumonia in Adults without Predisposing Illnesses
Authors: Jonathan L. Jacobs, Daniel M. Libby, Robert A. Winters, David M. Gelmont, Ethan D. Fried, Barry J. Hartman, Jeffrey Laurence
Journal: New England Journal of Medicine (1991)

PNEUMOCYSTIS CARINII pneumonia is the most common infection complicating the acquired immunodeficiency syndrome (AIDS),1 , 2 but before 1981 it was a rare condition. P. carinii pneumonia was first reported in the United States in 1955,3 and only 107 cases were reported during the subsequent decade.4 Before the AIDS epidemic, more than 99 percent of patients with P. carinii pneumonia had a predisposing condition, such as lymphoma, leukemia, organ transplantation, or a disorder treated with corticosteroids or cytotoxic drugs.4 , 5 Reports of P. carinii pneumonia in nonimmunocompromised adults are extremely rare.6 7 8 9 10 Serologic but not histopathological evidence of latent subclinical P. carinii infection has . . .
PTH-298 Pre-operative neutrophil lymphocyte ratio (NLR) is a poor predictor of response to neo-adjuvant chemo-radiotherapy in rectal cancer resection
Authors: MAS Khan, AR Hakeem, N Scott, I Botterill
Journal: Gut (2015)

<h3>Introduction</h3> Previous studies have reported a pre-operative elevated neutrophil lymphocyte ratio (NLR) is associated with poor prognosis in colorectal cancer (CRC) patients. The aim of this study was to assess if elevated NLR can predict the response to neo-adjuvant long course chemo-radiotherapy (CRT) in rectal cancer as assessed by Mandard Regression score and its ultimate outcome of disease free survival (DFS) and overall survival (OS). <h3>Method</h3> Patients who received neo-adjuvant long course chemo-radiotherapy followed by resection for primary rectal cancer from January 2005 till December 2010 were identified from prospectively maintained cancer database. The NLR was calculated from pre-treatment blood tests. The relationship between the NLR and clinicopathological parameters was analysed. Modified receiver operating characteristic curve were constructed to determine the optimum cut-off NLR to dichotomise the data for pathological response, DFS and OS. The measured cut-off was 2.7. <h3>Results</h3> There were 143 male and 76 female patients with a median age at diagnosis of 65 (Range 25–85 years). Patients were grouped into favourable response with Mandard regression score of 1 and 2 and unfavourable response with Mandard regression score of 3, 4 and 5. The sensitivity and specificity of NLR to predict complete pathological response or favourable response was 66% and 46%, for disease recurrence was 60% and 39% and for survival was 70% and 50%. NLR did not prove to be a significant predictor of tumour response to CRT and ultimate oncological outcomes. Kaplan Meier survival graph showed a little better OS (p = 0.001) for patients with NLR &lt;2.7 but it had no impact on DFS (p = 0.180). <h3>Conclusion</h3> Pre-operative NLR does not appear to offer useful predictive ability for response to CRT, disease free survival and overall survival following rectal cancer resection in patients who received neo-adjuvant long course chemo-radiotherapy. <h3>Disclosure of interest</h3> None Declared.
Patterns of imatinib resistance mutation analysis in chronic myeloid leukemia (CML) patients on imatinib at the time of loss of response to the drug in Asian Indian subjects
Authors: K. Prabhash, T. Vora, N. S. Ghadyalpatil, B. Rangarajan, S. S. Hingmire, H. Menon, P. Jain, P. A. Kurkure, P. M. Parikh
Journal: Journal of Clinical Oncology (2009)

7079 Background: The treatment of (CML) has undergone major changes in the past decade with the introduction of tyrosine kinase inhibitors (TKI). However the initial enthusiasm is waning with increasing recognition of drug resistance. There is an urgent need to identify the types of receptor mutations which lead to drug resistance and their significance in salvage therapy. Methods: We identified 17 males and 8 female patients with median age 40 yrs (range 9–55 years) with CML who were on imatinib at the time of loss of hematologic response (HR), cytogenetic (CyR), or molecular response (MR) and performed imatinib-resistance mutation analysis. The sequencing was done on ABI machine by direct sequencing method. Results: This group included 22 patients with chronic phase (CP) disease, 2 patients with accelerated phase (AP), and 1 patient with extramedullary blast crisis (BC). Fourteen patients received treatment with agents other than imatinib as the first-line therapy due to either nonavailability of the drug at the time of diagnosis in India, but were started on imatinib when drug became available. The other 11 patients received imatinib as first-line therapy. The best response to imatinib included major CyR in 14 patients which included 3 patients with complete CyR and minor CyR in 6 patients. Lack of HR was noted in 2 patients in whom CyR was not evaluated. Imatinib resistance mutation analysis was prompted by no HR (n = 2); loss of HR after achieving CyR (n = 9); failure to achieve CyR milestones (n = 3); loss of CyR (n = 9); development of extramedullary BC (n = 1). The analysis revealed no mutations-11 patients, M351T-4 patients, G250E-3 patients, F317L-2 patients, M244V- 1 patient, T315I-1 patient, F382L-1 patient, results awaited in 4 patients with 2 patients showing 2 mutations. Conclusions: The majority of patients 11/25 had no detectable mutations while T315I which confers resistance to all TKIs was detected only in 1/25 patients who demonstrated loss of response in our population. The correlation of the other mutations to loss of response and the response to second line TKI needs to be studied in further detail. In addition analysis of mutation patterns at baseline may help in stratifying patients for treatment. No significant financial relationships to disclose.