tbuckley/cabot-search huggingface dataset:
A randomized, double-blind comparison of intravenous ondansetron alone and in combination with intravenous dexamethasone in the prevention of high-dose cisplatin-induced emesis.
Authors: P J Hesketh, W H Harvey, W G Harker, T M Beck, T Ryan, L J Bricker, J A Kish, W K Murphy, J D Hainsworth, B Haley
Journal: Journal of Clinical Oncology (1994)

PURPOSE This study compares the efficacy and safety of ondansetron alone with that of ondansetron plus dexamethasone in the prevention of emesis induced by high-dose cisplatin (&gt; or = 100 mg/m2). PATIENTS AND METHODS This multicenter study used a randomized, double-blind, parallel-group design. Chemotherapy-naive patients were randomized to receive intravenous (IV) ondansetron (Zofran, Cerenex Pharmaceuticals, Research Triangle Park, NC) 0.15 mg/kg for three doses every 4 hours beginning 30 minutes before cisplatin administration either alone or in combination with dexamethasone 20 mg administered 45 minutes before cisplatin. Cisplatin (&gt; or = 100 mg/m2) was administered as a single infusion (&lt; or = 3 hours). Patients were monitored for emetic episodes (EEs), adverse events, and laboratory safety parameters for 24 hours after cisplatin administration. RESULTS A total of 275 patients were enrolled. Of these, 245 were assessable for efficacy. Patients who received ondansetron plus dexamethasone had a higher complete antiemetic response rate (61% v 46%, P = .02) and less nausea (posttreatment visual analog scale mean 18.2 v 32.8, P &lt; .001) than did those who received ondansetron alone. The time to the first EE was longer for patients in the group that received ondansetron plus dexamethasone (P = .005). Headache (12%), diarrhea (2%), and abdominal colic (1%) were the most common antiemetic-related adverse events reported. The incidence of adverse events was similar between the treatment groups. CONCLUSION IV ondansetron in combination with dexamethasone is safe and more effective than ondansetron alone in the prevention of emesis induced by high-dose cisplatin.
Control of the Acute Phase Response
Authors: Irving Kushner, Martin L. Broder, David Karp
Journal: Journal of Clinical Investigation (1978)

In order to investigate the magnitude and kinetics of the C-reactive protein (CRP) response after differing degrees of tissue injury, we studied changes in serum concentration of this acute phase protein in 19 patients after mild or extensive acute myocardial infarction. An increase in serum CRP concentration was seen in all patients. The rate of increase in concentration was found to be exponential, with a mean hourly rate constant for the entire group of patients of 0.085 (doubling time, 8.2 h). Patients with extensive infarction attained mean serum CRP levels about 4 times as great as did patients with mild infarction. No difference could be shown in the mean rate constant between these groups, the greater CRP response in the former group resulting principally from a more protracted period of rise in serum CRP concentration. A lag period before serum CRP levels began to rise was noted in only 4 of the 13 patients in whom this could be assessed. 7 of 10 patients with presumed unstable angina (coronary insufficiency) showed no rise in CRP concentration, while a small increase as noted in 3 patients. The data suggest that acute tissue injury, such as myocardial infarction, rapidly leads to acceleration in synthesis of CRP, and that the duration of this period of acceleration is related to the extent of tissue injury.
Acquired-cisplatin resistance by BRCA1-IRIS over-expression in human ovarian epithelial cells
Authors: Wael M. ElShamy
Journal: Clinical Cancer Research (2006)

B6   Evasion of apoptotic cell death plays a key role in cancer development, drug resistance and recurrence. BRCA1-IRIS, a product of BRCA1-locus alternative splicing, is over-expressed in multiple ovarian cancer cell lines. Its endogenous over-expression in ovarian cancer cell lines or ectopic overproduction in human ovarian surface epithelial cell lines induces the expression of two, known anti-apoptotic genes, AKT and survivin. Survivin too is over-expressed in ovarian cancer cell lines, in part through an AKT-driven mechanism. Survivin blocks apoptosis through inhibition of caspases. In this report, the role of BRCA1-IRIS in survivin/survival induction in ovarian cells is evaluated. Over-expression of BRCA1-IRIS induces AKT1/2 (not 3) over-expression/activation and thus survivin over-expression/activation. However, in the presence of high levels of BRCA1-IRIS, negative modulation of PI3`K (using pharmacological inhibitor, LY294002), or AKT (using siRNA or DN-AKT) only partially decreased survivin expression, suggesting that BRCA1-IRIS over-expression activates survivin up-regulation also by a PI3`K/AKT-independent mechanism. Interestingly, the cascade BRCA1-IRIS-> and/or AKT->survivin could be activated in ovarian cells by cisplatin treatment in a cell cycle-independent manner. This cascade inhibited cisplatin-induced apoptosis, whereas pre-treatment with siIRIS sensitized cells to it. We identified BRCA1-IRIS as an anti-apoptotic protein in ovarian cells and demonstrate that treatment with DNA damaging agent cisplatin activates the BRCA1-IRIS/AKT/survivin pathway that in part protects cells from drug-induced apoptosis.
Autoantibodies in psoriasis as predictors for loss of response and anti-infliximab antibody induction
Authors: J.H.O. Hoffmann, M. Hartmann, A.H. Enk, E.N. Hadaschik
Journal: British Journal of Dermatology (2011)

Infliximab is successfully used to treat psoriasis and psoriatic arthritis. However, some patients lose therapeutic response after several cycles. Antibodies to infliximab (infliximab-Abs) are induced during treatment in a subgroup of patients and are thought to be associated with loss of response (LOR). Routine screening for infliximab-Abs is expensive and not regularly performed. A reliable and affordable method for identifying patients who are at risk for LOR to infliximab is desirable.To analyse the development of antinuclear antibodies (ANA)/antidouble-stranded DNA antibodies (anti-dsDNA) over time in patients with psoriasis receiving infliximab. To analyse if there is an association between ANA titres/anti-dsDNA concentrations, infliximab-Ab status and LOR.A retrospective data analysis of 29 patients with psoriasis receiving infliximab was carried out. ANA titres and anti-dsDNA concentrations were regularly monitored in these patients and sera were tested for infliximab-Abs by enzyme-linked immunosorbent assay.Median ANA titres increased from 1 : 80 [interquartile range (IQR) 0 to 1 : 320, n = 29] pretreatment, to 1 : 1280 (IQR 1 : 640 to 1 : 1920, n = 15) after infusion 10, and 1 : 1920 (IQR 1 : 1280 to 1 : 2560, n = 10) after infusion 20. Infliximab-Abs were found in 21% of patients. Infliximab-Ab-positive patients and patients with LOR had significantly higher pretreatment anti-dsDNA concentrations and higher pretreatment ANA titres than infliximab-Ab-negative and responsive patients, respectively.The results of this study suggest a role for autoantibodies in the identification of patients with psoriasis at higher risk of developing infliximab-Abs and of LOR under treatment with infliximab.
Etoposide and Cisplatin/Etoposide, Methotrexate, and Actinomycin D (EMA) Chemotherapy for Patients With High-Risk Gestational Trophoblastic Tumors Refractory to EMA/Cyclophosphamide and Vincristine Chemotherapy and Patients Presenting With Metastatic Placental Site Trophoblastic Tumors
Authors: E.S. Newlands, P.J. Mulholland, L. Holden, M.J. Seckl, G.J. S. Rustin
Journal: Journal of Clinical Oncology (2000)

To evaluate the results of etoposide, cisplatin/etoposide, methotrexate, and actinomycin D (EP/EMA) chemotherapy in patients with gestational trophoblastic tumors (GTTs), who have relapsed after or who have become refractory to EMA/cyclophosphamide and vincristine (CO) chemotherapy, and in patients presenting with metastatic placental site trophoblastic tumors (PSTTs).We have treated a total of 34 patients with GTT and eight patients with metastatic PSTT with the EP/EMA chemotherapy schedule.Twenty-two patients received EP/EMA because of apparent drug resistance to EMA/CO, and because the human chorionic gonadotropin (hCG) was near normal, they were not assessable for response. Twenty-one of these patients (95%) are alive and in remission. In the group where the hCG was high enough to confirm a response (greater than one log fall in hCG) to EP/EMA, all 12 patients responded and nine of these patients (75%) are alive and in remission. We have treated three patients with PSTT where the interval from antecedent pregnancy was less than 2 years, and all patients (100%) are alive and in remission. We have treated five patients where the interval from antecedent pregnancy was greater than 2 years and one fifth (20%) remain in remission. The survival for patients with GTT is 30 (88%) out of 34 patients and four (50%) out of eight patients for PSTT, giving an overall survival for these two cohorts of 34 (81%) out of 42 patients. The toxicity of this schedule is significant, with grade 3 or 4 toxicity (National Cancer Institute common toxicity criteria) recorded in hemoglobin (21%), WBC (68%), and platelets (40%). The role of surgery in this group of patients is important and contributed to sustained remission in five patients (23%) and possibly helped an additional seven patients (32%).EP/EMA is an effective but moderately toxic regimen for patients with high-risk GTT who become refractory to or relapse from EMA/CO chemotherapy. Also, EP/EMA clearly has activity in patients with metastatic PSTT.
Early Detection of Relapse by Hypermetaphase Fluorescence In Situ Hybridization After Allogeneic Bone Marrow Transplantation for Chronic Myeloid Leukemia
Authors: Chy-Myong Seong, Sergio Giralt, Hagop Kantarjian, Jingping Xu, Jolynn Swantkowski, Kimberley Hayes, Armand B. Glassman, Issa Khouri, Martin Korbling, Peter Thall, Michael J. Siciliano, Richard E. Champlin
Journal: Journal of Clinical Oncology (2000)

PURPOSE: Standard G-band cytogenetic analysis (CG) provides information on approximately 25 metaphases for monitoring the presence of Philadelphia chromosome positive (Ph+) cells in chronic myelogenous leukemia (CML) patients, making the detection of a low frequency of Ph+ cells problematic. The purpose of this study was to improve the detection of a low frequency of Ph+ cells. PATIENTS AND METHODS: We combined fluorescence in situ hybridization (FISH) with long-term colcemid exposure, capturing several hundred metaphases in bone marrow cultures (hypermetaphase FISH [HMF]). Using probes that identify Ph+ cells, HMF was compared with CG analysis in the follow-up evaluations of 51 patients with CML at various time points after allogeneic bone marrow transplant (BMT). RESULTS: Thirty-five patients never showed the presence of Ph+ cells by either method. In four patients, high frequencies of Ph+ cells were detected by both methods. In the remaining 12 patients, Ph+ cells were detected by HMF at time points after BMT when they were not detected by CG. In seven of the 12 patients, low but statistically significant frequencies of Ph+ cells (0.37% to 5.20%) were detected 3 months or later after BMT, and when no intervention was initiated, all seven patients later relapsed. Based on those data, an eighth patient with mixed chimerism and a similar HMF-detected Ph+ frequency (1.8% at 27 months after BMT) was reinfused with donor lymphocytes and achieved remission with 0% Ph+ cells studied by HMF (up to 50 months after BMT). Ph+ cells detected by HMF but not by CG less than 3 months after BMT disappeared on later examination in two of four patients. After detection of Ph+ cells by HMF only, the median time to cytogenetic progression (detection of Ph+ cells by CG) was 101 days. CONCLUSION: The results demonstrate the ability of HMF to detect low but clinically relevant levels of leukemic cells not detected by CG in transplant patients. The data indicate that HMF can detect low levels of Ph+ cells before standard cytogenetics at a time that may be useful in monitoring disease status and planning clinical interventions.
Homocysteine-Induced Endoplasmic Reticulum Stress and Growth Arrest Leads to Specific Changes in Gene Expression in Human Vascular Endothelial Cells
Authors: P. Andrew Outinen, Sudesh K. Sood, Sabine I. Pfeifer, Sushmita Pamidi, Thomas J. Podor, Jun Li, Jeffrey I. Weitz, Richard C. Austin
Journal: Blood (1999)
Assessment of facemask seal leakage from six VHC systems on two pediatric simulated anatomical models under simulated breathing conditions
Authors: Zhen Xu, Dirk Von Hollen, Wenchi Hsu, Ashwin Viswanath, Kurt Nikander, Richard Dalby
Journal: European Respiratory Journal (2012)

Facemasks establish the vital patient-device interface to facilitate drug delivery from a pressurized metered dose inhaler (pMDI) with an attached valved holding chamber (VHC). Leakage from a VHC facemask seal can reduce the delivered dose. We used two pediatric simulated anatomical models (SAMs, Figure 1 Right) to test the leakage from six VHC facemasks. Testing was conducted using an apparatus which allowed reproducible facemask placement with a constant applied force of 1.9kg. 1  Each facemask with associated VHC (Figure 1 Left) was applied to each SAM in turn. A constant flow of 15 L/min was extracted from the rear of the SAM. The difference (ΔTSI, L/min) between flow into the VHC and flow exiting the SAM was measured using two flow meters (TSI Inc, Shoreview, MN). The vertical location of the SAM in relation to the VHC was altered by 1 mm increments until the minimum ΔTSI (leakage) was found. Figure 1 Left shows the minimum leakage for each VHC/facemask combination with each SAM.  Figure 1. Left - Facemask seal leakage (%), Top Right - SAM 0, Bottom Right - SAM 1.  There was a wide variation in leakage from different VHC facemasks and also between SAMs. The smallest amount of leakage for both SAMs was seen with the OptiChamber Diamond VHC with LiteTouch facemask.  1) Hsu et al. Proceedings of Respiratory Drug Delivery Europe 2011; www.rddonline.com.
Asthma control is reached in a large majority of asthmatics treated with omalizumab. An Italian observational study
Authors: Federica Novelli, Giulia Lenzini, Manuela Latorre, Laura Malagrinò, Federico Lorenzo Dente, Pier Luigi Paggiaro
Journal: European Respiratory Journal (2013)

Background: Few data are available on the proportion of asthmatics achieving a good asthma control during omalizumab treatment (OT).  Aim: To assess the level of control (according GINA guidelines) achieved in a group of asthmatics on OT, characterize what influences the lack of control and correlate the level of control with the treatment duration.  Method and Results: We studied 281 asthmatics on OT from a median of 32 months (range 4-96). 70.1% of patients showed a good or partial control of asthma (37.5% of these showed a well control). Comparison between poorly controlled (PC) and partially or well controlled asthmatics showed a significant higher prevalence in the first group of comorbidities [obesity: 33.8% vs 17.9%, gastro-oesophageal reflux (GERD): 47.9% vs 33.5%, aspirin intolerance:32.9% vs 16.1%] and a lower post-BD FEV1 (70.9±19.9 vs 81.1±18.3 % of pred, p  Conclusions: OT allows a high percentage of asthmatics to obtain a well or partial control of asthma, even after several months of therapy. Among patients who remain with PC asthma or continue to have exacerbations, there is a higher prevalence of comorbidities which are probably not optimally treated.
Vaccination Against Strontium-90-Induced Bone Tumors&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN3"&gt;3&lt;/xref&gt;
Authors: A E Reif, W E Triest
Journal: JNCI Journal of the National Cancer Institute (1983)

The thesis was tested that immunization against a murine osteosarcoma virus can reduce the incidence of bone tumors induced by 90Sr. C57BL/6J female mice (190) were divided into three sets of 2 groups. Each set consisted of a control group and an experimental group treated ip with 1.0 muCi 90Sr at 66 days of age. The three sets of groups received the following additional treatments: none (controls), 6 injections of Formalin-inactivated FBJ osteosarcoma virus (vaccinated group), or 6 injections of active FBJ virus (active virus controls). Only 1 bone tumor developed in a mouse not treated with 90Sr in the active virus controls. In 90Sr-treated mice, vaccination reduced bone tumor deaths during the first 600 days from 9 of 36 in controls to 1 of 33 in vaccinated mice (P less than .01), but bone tumor deaths during the entire life-span, 10 of 36 and 5 of 33, respectively, were not significantly different (P = .07). Thus the vaccination procedure delayed the development of bone tumors. In contrast, injection of active virus into 90Sr-treated mice increased the lifetime incidence of bone tumors from 10 of 36 in controls to 19 of 32 (P = .01).
Tumor Metastases and Cell-Mediated Immunity in a Model System in DBA/2 Mice. VII. Interaction of Metastasizing and Nonmetastasizing Tumors With Normal Tissue In Vitro2
Authors: Marie-Luise Lohmann-Matthes, Annelies Schleich, Geraldine Shantz, Volker Schirrmacher
Journal: JNCI Journal of the National Cancer Institute (1980)

Three mouse tumors known to metastasize in vivo and 3 nonmetastasizing mouse tumors that grow only locally in vivo were examined for their ability to adhere to and invade normal syngeneic lung organ cultures in vitro. All 3 metastasizing tumors adhered to and invaded the normal lung cultures. In contrast, tumors that grow only locally in vivo neither adhered to nor invaded the normal lung tissue. The described system is ideally suited to correlate the in vivo invasiveness of a given tumor with its potential to metastasize in vivo and to study in vitro how to influence the interaction of metastasizing tumor cells with normal tissue.
Aquoaporin-1 expression in idiopathic pulmonary fibrosis
Authors: César Gutiérrez, Álvaro Donate, Lourdes Gómez Izquierdo, María Molina-Molina, Miriam Echevarría, Jose Antonio Rodriguez Portal
Journal: European Respiratory Journal (2013)

INTRODUCTION: Idiopathic pulmonary fibrosis (IPF) is an interstitial lung disease. IPF is the result of alveolar reepitalization and interstitial fibroblasts proliferation. Aquaporin-1 is a membrane protein that helps to the water transport between alveolar space and lung parenquima. AQP1 could contribute in cellular proliferative process in IPF. Our objective was to determine AQP1 expression in different lung cellular types in patients with IPF.  METHODS: we studied by immunohistochemistry with AQP1 antibodies various histological sections corresponding to diverse lung diseases. They were included normal lung, hypersensitivity pneumonitis, sarcoidosis and IPF samples. The stain analysis was cualitative, and it was made by two independent observers. We gave 0: no stain, + (25% of the sample), ++ (50% of the sample), +++ (75% of the sample) and ++++ (100% of the sample). It was analyzed which cells showed AQP1 on their surface.  RESULTS:  IPF: type II pneumocytes hyperplasia, which show AQP1 on their surface, a 75% of visual field (+++). Type I pneumocytes did not show AQP1 on their surface. Plenty of collagen fibers and fibroblasts without AQP1 expression.  Hypersensitivity Pneumonitis: type II pneumocytes with AQP1 expression on their surface. AQP1 with a 5% by field (0/+).  Sarcoidosis: 0% cuantitative AQP1 expression.  Normal lung: almost absolute type I pneumocytes predominance, without AQP1 expression.  We noticed AQP1 expression in all erytrocites and endotellium cells, in all analyzed samples.  CONCLUSIONS: In IPF, hyperplasic type II pneumocytes show AQP1 on their surface. For this reason, these hyperplastic cells and the regulation of AQP1 could be implicated in the physiopathology of IPF.
Exercise, Pulmonary Physiology and Pathophysiology
Journal: Thorax (1991)

sweeping, in the enclosed atmosphere ofa hut and tent.These activities have been considered to be responsible for the fact that desert lung is predominantly a disease of women.2"It would be interesting to know whether the woman farmer with massive fibrosis in the paper by Dr Norboo and others had performed any of these traditional chores.Furthermore, being a farmer, had she engaged in ploughing, or earth or well dig- ging, occupations which generate considerable dust exposure during the dry season?Are we truly dealing with progressive massive fibrosis of purely environmental origin?
Endoscopic Insertion of Celestin Tubes in Carcinoma of the Oesophagus
Authors: J Beynon, T Winston, M H Thompson
Journal: Journal of the Royal Society of Medicine (1991)

‘Carcinoma of the oesophagus is by no means uncommon, and few conditions are more distressing. If left to himself the patient has nothing to look forward to but death by slow starvation … The problem of his relief is the purely mechanical one of relieving his obstruction.’ Sir Henry S Souttar 1924
Incidence of Recurrent Thromboembolic and Bleeding Complications Among Patients With Venous Thromboembolism in Relation to Both Malignancy and Achieved International Normalized Ratio: A Retrospective Analysis
Authors: Barbara A. Hutten, Martin H. Prins, Michael Gent, Jeff Ginsberg, Jan G. P. Tijssen, Harry R. Büller
Journal: Journal of Clinical Oncology (2000)

Initial heparinization followed by vitamin K antagonists is the treatment of choice for patients with venous thromboembolism. There is controversy whether known malignancy is a risk factor for recurrences and bleeding complications during this treatment. Furthermore, the incidence of such events in these patients is dependent on the achieved International Normalized Ratio (INR). The aim of this study was to assess the incidence of venous thromboembolic recurrence and major bleeding among patients with venous thromboembolism in relation to both malignancy and the achieved INR.In a retrospective analysis, the INR-specific incidence of venous thromboembolic and major bleeding events during oral anticoagulant therapy was calculated separately for patients with and without malignancy. Eligible patients participated in two multicenter, randomized clinical trials on the initial treatment of venous thromboembolism. Patients were initially treated with heparin (standard or low-molecular weight). Treatment with vitamin K antagonists was started within 1 day and continued for 3 months, with a target INR of 2.0 to 3.0.In 1,303 eligible patients (264 with malignancy), 35 recurrences and 12 bleeds occurred. Patients with malignancy, compared with nonmalignant patients, had a clinically and statistically significantly increased overall incidence of recurrence (27.1 v 9.0, respectively, per 100 patient-years) as well as bleeding (13.3 v 2.1, respectively, per 100 patient-years). In both groups of patients, the incidence of recurrence was lower when the INR was above 2.0 compared with below 2.0.Although adequately dosed vitamin K antagonists are effective in patients with malignant disease, the incidence of thrombotic and bleeding complications remains higher than in patients without malignancy.