tbuckley/cabot-search huggingface dataset:
Influence of age in the functional status of COPD patients
Authors: Alexandru Corlateanu, Gloria Montanari, Victor Botnaru
Journal: European Respiratory Journal (2014)

Background:  It was demonstrated that COPD is the main cause of severe deterioration of quality of life, physical activity and functional status in elderly and in young patients. The impact of age on the functional status of COPD is not well characterized.  The  aim  of this study was to investigate possible age-related differences in a population of patients with similar severity of COPD by GOLD.   Methods:  139 consecutive patients with COPD were enrolled into the study. We measured demographics, co-morbidities and spirometry. Functional status was assessed by 6-minute walking test (6MWT) and by Karnofsky performance scaleand Barthel index.   Results:   The cohort consisted of 70 younger patients, mean age 50 ± 4.2 years and 69 elderly patients mean age 77 ± 6.8. The mean FEV1% for the groups were 42.8 ± 15% and 42.9 ± 11%, p=0.98.Mean 6-minute walking distance (6MWD) was significantly shorter (209.7 ± 82.27 m versus 255.4 ± 92.6 m, p   Conclusion:  Elderly COPD patients have a more severe deterioration of the functional status.Age is an independent risk factor for reducing functional capacity in COPD patients.
Kinetics of Responses to Tumor Antigens and Mouse Mammary Tumor Virus in BALB/cCrgl and BALB/cfC3H Mice&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: Diana M. Lopez, M. Michael Sigel, Vijaya L. Charyulu
Journal: JNCI Journal of the National Cancer Institute (1981)

Spleen cells from BALB/cCrgl mice responded to murine mammary tumor virus (MuMTV) in cell-mediated immune assays at higher levels than did the spleen cells from the syngeneic BALB/cfC3H mice. Implantation in BALB/cCrgl with a chemically induced mammary tumor and in BALB/cfCrgl mice with spontaneous mammary tumors (SMT) arising in the same strain resulted in sensitization of these animals to the antigens of their tumors. Reactivities peaked 3 weeks after transplantation, whereas no positive reactions could be detected when tumors reached maximum size. A kinetic study with the use of MuMTV antigen(s) showed that the responses of lymphocytes from BALB/cfC3H with SMT followed the same pattern as that obtained with tumor antigens, which indicated that this might be a de novo sensitization. In sharp contrast, a steady type of response to MuMTV was observed with the spleen cells from BALB/cCrgl mice; i.e., the levels of responsiveness to MuMTV did not significantly vary at any stage of tumor development. In vivo studies explored the possible relevance of the in vitro cell-mediated immunity to the host defenses. MuMTV-expressing mammary tumor cells were implanted in BALB/cCrgl and BALB/cfC3H mice. The total incidence of tumors was significantly reduced and a delay occurred in their time of appearance in BALB/cCrgl mice in relation to BALB/cfC3H animals. Thus the in vitro reactivity to MuMTV antigen(s) in BALB/cCrgl mice was found to be coincidental with a degree of protection against the development of MuMTV-expressing mammary tumors.
Gemcitabine and Cisplatin Versus Mitomycin, Ifosfamide, and Cisplatin in Advanced Non–Small-Cell Lung Cancer: A Randomized Phase III Study of the Italian Lung Cancer Project
Authors: L. Crinò, G. V. Scagliotti, S. Ricci, F. De Marinis, M. Rinaldi, C. Gridelli, A. Ceribelli, R. Bianco, M. Marangolo, F. Di Costanzo, M. Sassi, S. Barni, A. Ravaioli, V. Adamo, L. Portalone, G. Cruciani, A. Masotti, G. Ferrara, F. Gozzelino, M. Tonato
Journal: Journal of Clinical Oncology (1999)

PURPOSE: To compare gemcitabine and cisplatin (GC) with mitomycin, ifosfamide, and cisplatin (MIC) chemotherapy in patients with stage IIIB (limited to T4 for pleural effusion and N3 for supraclavicular lymph nodes) or stage IV non–small-cell lung cancer (NSCLC). The end points were the evaluation of quality of life (QoL), response rates, survival, and toxicity. PATIENTS AND METHODS: Three hundred seven patients were randomized to receive either gemcitabine 1,000 mg/m 2 on days 1, 8, and 15 plus cisplatin 100 mg/m 2 on day 2, every 28 days, or mitomycin 6 mg/m 2 , ifosfamide 3,000 mg/m 2 , and mesna on day 1 plus cisplatin 100 mg/m 2 on day 2, every 28 days. The whole-blood cell count was repeated on day 1 in both arms and weekly in the GC arm before each gemcitabine administration. RESULTS: No major differences in changes in QoL were observed between the two treatment arms. The objective response rate was 38% in the GC arm compared with 26% in the MIC arm (P = .029). The median survival time was 8.6 months in the GC arm and 9.6 months in the MIC arm (P = .877, log-rank test). Grade 3 and 4 thrombocytopenia was significantly worse in the GC arm (64% v 28%, P &lt; .001), whereas grade 3 and 4 alopecia was reported more commonly in the MIC arm (39% v 12%, P &lt; .001). CONCLUSION: We report an increased response rate without changes in QoL and a similar overall survival, time to progression, and time to treatment failure for the GC when compared with the MIC regimen in the treatment of advanced NSCLC.
Intractable Pain: A Neglected Area of Medical Education in the UK
Authors: D Marcer, S Deighton
Journal: Journal of the Royal Society of Medicine (1988)

Unease over the previous management of 67 patients referred for treatment to 3 pain relief clinics led us to investigate the current state of education in pain and pain control in the UK. Twenty-seven medical schools provided data which revealed; (i) in 4 schools no teaching whatsoever is given in these subjects; (ii) in the remainder it is accorded an average of 3.5 hours during the 5 year course, with little evidence of multidisciplinary teaching; (iii) only 10 schools (37%) regularly set questions on pain control in formal examinations. A survey of 219 general practitioners revealed a wide-ranging lack of knowledge about the facilities and approach to treatment at their local pain relief clinic. These findings have wide reaching implications for medical education. At the undergraduate level they demonstrate a need for more multidisciplinary teaching and practical experience in specialist units. Thereafter specialists in pain control must enable practising doctors to keep abreast of new developments. This may require them to devote more time writing for a non-specialist audience and devising short, postgraduate courses.
The effect of treatment on right ventriculo-arterial coupling in idiopathic pulmonary arterial hypertension
Authors: C.E.E. van der Bruggen, P. Trip, F.S. de Man, H.J. Bogaard, N. Westerhof, A. Vonk Noordegraaf
Journal: European Respiratory Journal (2013)

Introduction: Right heart failure is the main cause of death in idiopathic pulmonary arterial hypertension (IPAH). Current medication aims to reduce right ventricular (RV) afterload, but the effect on RV function is unknown. Therefore, we aimed to assess the influence of PAH-specific treatment on load-independent RV systolic function and RV-arterial coupling.  Methods: In 39 IPAH patients we determined RV end-systolic elastance (Ees), arterial elastance (Ea) and RV-arterial coupling (Ees/Ea) at baseline and follow-up. Maximal isovolumic pressure (Piso) was estimated from RV pressure curves with the single-beat method. Ees=(Piso-mPAP)/SV and Ea=mPAP/SV. (SV=stroke volume, mPAP=mean pulmonary artery pressure, both measured using right heart catheterization)  Results: Median follow-up (FU) time was 0.8 years (interquartile range 0.5-1.0). PAH-therapy lowers mPAP, pulmonary vascular resistance and mean right atrial pressure and increases cardiac index (p  Conclusions: PAH-specific treatment decreases both arterial and end-systolic elastance. Whether the improvement in RV-arterial coupling results from an RV-specific treatment effect or is secondary to the decreased afterload, is a subject for further research.
Dose-intensity meta-analysis of chemotherapy regimens in small-cell carcinoma of the lung.
Authors: R J Klasa, N Murray, A J Coldman
Journal: Journal of Clinical Oncology (1991)

To determine if chemotherapy dose intensity (DI) influences treatment outcome, 60 published studies in limited- and extensive-stage small-cell carcinoma of the lung (SCCL) were retrospectively analyzed for relationship between intended DI and response (complete response [CR] or partial response [PR]) or median survival (MS). Agents used in the regimens included cyclophosphamide (C), doxorubicin (A), vincristine (V), etoposide (E), and cisplatin (P). Relative DI (RDI) of each study regimen was calculated against a reference regimen, and weighted regression analysis was used. Additionally, analysis of individual drug RDI within combinations was performed. For CAV, increasing RDI of the regimen showed no correlation with outcome. For the individual drugs, C RDI correlated positively, while A RDI correlated negatively with attainment of CR in limited disease, but both only after unduly influential observations were eliminated. In extensive-stage disease, A RDI correlated positively with CR+, PR but only in randomized trials, and this correlation lost statistical significance after unduly influential observations were eliminated. For CAE and CAVE, the RDI of the regimens correlated positively with MS in extensive-stage disease as did the C RDI. In limited disease, the C RDI correlated negatively with MS. For EP, no significant correlations were seen. We conclude that DI-outcome correlations are not consistent for these chemotherapy regimens in SCCL. Meta-analysis of retrospective data can generate hypotheses for testing in prospective clinical trials, but study sample and method of analysis can appreciably affect conclusions.
Survival and Neurodevelopmental Outcome of Young Children With Medulloblastoma at St Jude Children's Research Hospital
Authors: Andrew W. Walter, Raymond K. Mulhern, Amar Gajjar, Richard L. Heideman, David Reardon, R. Alex Sanford, Xiaoping Xiong, Larry E. Kun
Journal: Journal of Clinical Oncology (1999)

Young children treated for medulloblastoma are at especially high risk for morbidity and mortality from their disease and therapy. This study sought to assess the relationship, if any, between patient outcome and M stage. Neuropsychologic and endocrine outcomes were also assessed.Twenty-nine consecutively diagnosed infants and young children were treated for medulloblastoma at St Jude Children's Research Hospital between November 1984 and December 1995. All patients were treated with the intent of using postoperative chemotherapy to delay planned irradiation.The median age at diagnosis was 2.6 years. Six patients completed planned chemotherapy without progressive disease and underwent irradiation at completion of chemotherapy. Twenty-three children experienced disease progression during chemotherapy and underwent irradiation at the time of progression. The 5-year overall survival rate for the entire cohort was 51% +/- 10%. The 5-year progression-free survival rate was 21% +/- 8%. M stage did not impact survival. All patients lost cognitive function during and after therapy at a rate of -3.9 intelligence quotient points per year (P =.0028). Sensory functions declined significantly after therapy (P =.007). All long-term survivors required hormone replacement therapy and had growth abnormalities.The majority of infants treated for medulloblastoma experienced disease progression during initial chemotherapy. However, more than half of these patients can be cured with salvage radiation therapy, regardless of M stage. The presence of metastatic disease did not increase the risk of dying from medulloblastoma. All patients treated in this fashion have significant neuropsychologic deficits. Our experience demonstrates that medulloblastoma in infancy is a curable disease, albeit at a significant cost.
Relationship of Hormone Dependency to Estrogen Receptor and Adenosine 3′5′-Cyclic Monophosphate-Binding Proteins in Rat Mammary Tumors2
Authors: Jeffrey S. Bodwin, Timothy Clair, Yoon Sang Cho-Chung
Journal: JNCI Journal of the National Cancer Institute (1980)

Estrogen-binding activity and the binding activity of adenosine 3′,5′-cyclic monophosphate (cAMP) were assayed in the cytosol of biopsy specimens from 70 rat mammary tumors. The response of these tumors to host ovariectomy was followed. The hormone dependency of the tumors was closely related to the relative concentrations of estrogen receptor (ER) and cAMP-binding protein (CR) in the tumor cytosol. When ER and CR were expressed as the ER/CR ratio, 36 of 38 (95%) hormone-dependent tumors had ratios of 35×10−3 or more, whereas 31 of 32 (97%) hormone-independent tumors had ratios of less than 35×10−3. When ER alone was measured, hormone dependency could be correctly predicted in only 60% of the tumors because the ER range for individual tumors of both types greatly overlapped. Ratios of ER/CR were also elevated in normal estrogen target tissues as compared to those in normal estrogen nontarget tissues. Thus determination of the ER/CR ratio in tumor cytosols appeared to be a more reliable method of predicting hormone dependency than was determination of ER alone.
Thyroid Function in a Uremic Rat Model
Authors: Victoria S. Lim, Carlos Henriquez, Hisao Seo, Samuel Refetoff, Enio Martino
Journal: Journal of Clinical Investigation (1980)

The main objective of this study was to determine whether the principal abnormality of thyroid function observed in patients with chronic renal failure, low serum triiodothyronine (T3) concentration, causes hypothyroidism at the tissue level. A partially nephrectomized (Nx) uremic rat model was developed and the following parameters of thyroid function were assessed: serum total thyroxine (TT4), total T3 (TT3), and thyrotropin and liver T3 content, and activity of two thyroid hormone-dependent enzymes, mitochondrial α-glycerophosphate dehydrogenase (α-GPD) and cytosol malate dehydrogenase (MDH). The results were compared to those of intact control (C), thyroidectomized (Tx), and nephrectomized-thyroidectomized (NxTx) littermates.
Applied Comparative Anatomy of the Avian Middle Ear
Authors: Robert Mills
Journal: Journal of the Royal Society of Medicine (1994)

The anatomy of the middle ear has been studied in nine species of birds, with particular reference to the structure of the ossicle and its relationship to the tympanic membrane. The morphology of the avian middle ear has been compared to that of the reconstructed human middle ear. Drum to stapes foot plate assemblies created during ossiculoplasty operations differ from the pattern found in the avian middle ear in a number of important respects and this may help to explain why they are often unsuccessful. It is not technically feasible to reproduce the avian middle ear pattern exactly in the human middle ear and developments in reconstructive technique should therefore be directed towards reproducing the three ossicle pattern of the mammalian ear.
Drug-Induced Immunogenic Changes of Murine Leukemia Cells: Dissociation of Onset of Resistance and Emergence of Novel Immunogenicity&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: M. C. Fioretti, R. Bianchi, L. Romani, E. Bonmassar
Journal: JNCI Journal of the National Cancer Institute (1983)

n vivo exposure of tumor-bearing mice to the antineoplastic agent 5-(3,3-dimethyl-1-triazenyl)-1H-imidazole-4-carboxamide (DTIC) results in increased immunogenicity of tumor cells, an event often referred to as "chemical xenogenization" (CX). To verify the hypothesis of DTIC-induced somatic mutation(s) as the major mechanism underlying CX, studies were performed to dissociate CX from the onset of drug resistance, which was invoked in the past as an event leading to selection of preexisting immunogenic clones. Therefore, experiments were done with a DTIC-susceptible tumor line treated with DTIC and quinacrine dihydrochloride (Q), an antimutagenic compound, according to selected experimental schedules. At different transplant generations, the CX and the onset of drug resistance were evaluated. The results show that a) Q does not prevent the onset of DTIC resistance, b) DTIC-resistant clones arising after treatment with DTIC plus Q are not immunogenic, and c) CX is selectively antagonized by Q. The present data confirm that DTIC-induced immunogenicity is not the result of a selection mechanism mediated by the drug and give further support to the hypothesis that the molecular mechanism of CX may be related to somatic mutation(s).
Cisplatin plus etoposide consolidation following cyclophosphamide, doxorubicin, and vincristine in limited small-cell lung cancer.
Authors: L H Einhorn, J Crawford, R Birch, G Omura, D H Johnson, F A Greco
Journal: Journal of Clinical Oncology (1988)

From June 1982 through October 1985, the Southeastern Cancer Study Group randomized patients with limited small-cell lung cancer (SCLC) to cyclophosphamide plus doxorubicin (Adriamycin, Adria Laboratories, Columbus, OH) plus vincristine (CAV) for six cycles v CAV plus concomitant thoracic irradiation as induction therapy. Patients achieving either a complete or partial response and remaining in remission after completion of induction therapy were subsequently randomized to consolidation chemotherapy consisting of cisplatin 20 mg/m2 X 4 plus etoposide (VP-16) 100 mg/m2 X 4 every 4 weeks for two courses v no further therapy. There were 160 patients entered on the consolidation phase and 148 were fully evaluable. The median survival for patients randomized to cisplatin plus VP-16 (PVP16) from start of CAV chemotherapy was 97.7 weeks, compared with 68 weeks for the no-consolidation arm (P = .0094). PVP16 consolidation also significantly increased the duration of remission, with median durations of 49 weeks v 28 weeks (P = .0008). The median durations for partial remission were 41 weeks v 23 weeks (P = .013), and for complete remission, 52 weeks v 30.5 weeks (P = .0091). Furthermore, 18 patients on PVP16 consolidation remain in a continuous complete remission for 12+ months and 13 of these are continuously disease free 2+ years. Eight patients randomized to no consolidation remain in a continuous complete remission, with only four patients disease free 2+ years. PVP16 consolidation has significantly improved the duration of remission and overall survival and appears capable of improving the cure rate in limited SCLC.
Long-term bortezomib treatment decreases allergen-specific IgE but fails to amend chronic asthma in mice
Authors: Michael Wegmann, Lars Lunding, Zane Orinska, David M. Wong, Rudofh A. Manz, Heinz Fehrenbach
Journal: European Respiratory Journal (2012)

Since allergen-specific immuno-globulin E (IgE) enables mast cells and eosinophils to react on allergen-contact it plays a critical role in the formation of allergic inflammation and has been identified as a target for asthma therapy. By inhibiting the proteasome complex Bortezomib efficiently depletes Ig-secreting plasma cells and, thus, reduces Ig-serum titers. The present study evaluates the therapeutic potential of Bortezomib in a mouse model of chronic experimental asthma.  Therefore, BALB/c mice were sensitized to ovalbumin (OVA) and challenged with OVA-aerosol for twelve weeks. Bortezomib treatment was started after six weeks of challenge, and continued for one week (short-term) or six weeks (long-term), respectively, with a dosage of 0.75 mg/kg body weight with two intra-venous injections weekly. Airway responsiveness to metacholine, lung histology, Ig serum titers, and plasma cell numbers were assessed.  In mice with chronic experimental asthma short-term treatment resulted in decreased eosinophil numbers in BAL fluids, while long-term treatment significantly lowered serum titers of anti-OVA IgE. Nevertheless, neither short-term nor long-term treatment significantly diminish ed plasma cell numbers, anti-OVA IgG1 serum titers, allergic airway inflammation or improved lung function.  These results demonstrate that Bortezomib has no therapeutic effect on chronic experimental asthma in mice. Therefore, Bortezomib treatment could have only limited value as plasma cell depleting therapy against allergic bronchial asthma.
A Phase 3 Open-Label, Randomized, Multicenter Study of Imprime Pgg in Combination with Cetuximab in Patients with Kras Wild Type Metastatic Colorectal Cancer
Authors: M.L. Patchen, M. Gargano, M. Grady, J. Lowe, R.D. Huhn, A. Braun
Journal: Annals of Oncology (2014)
Increased Expression of HER2, HER3, and HER2:HER3 Heterodimers in HPV-Positive HNSCC Using a Novel Proximity-Based Assay: Implications for Targeted Therapies
Authors: Netanya I. Pollock, Lin Wang, Gerald Wallweber, William E. Gooding, Weidong Huang, Ahmed Chenna, John Winslow, Malabika Sen, Kara A. DeGrave, Hua Li, Yan Zeng, Jennifer R. Grandis
Journal: Clinical Cancer Research (2015)

Abstract Purpose: In other cancer types, HPV infection has been reported to coincide with overexpression of HER2 (ERBB2) and HER3 (ERBB3); however, the association between HER2 or HER3 expression and dimer formation in HNSCC has not been reported. Overexpression of HER2 and HER3 may contribute to resistance to EGFR inhibitors, including cetuximab, although the contribution of HPV in modulating cetuximab response remains unknown. Determination of heterodimerization of HER receptors is challenging and has not been reported in HNSCC. The present study aimed to determine the expression of HER proteins in HPV+ versus HPV− HNSCC tumors using a proximity-based protein expression assay (VeraTag), and to determine the efficacy of HER-targeting agents in HPV+ and HPV− HNSCC cell lines. Experimental Design: Expression of total HER1, HER2, and HER3, p95HER2, p-HER3, HER1:HER1 homodimers, HER2:HER3 heterodimers, and the HER3–PI3K complex in 88 HNSCC was determined using VeraTag, including 33 baseline tumors from individuals treated in a trial including cetuximab. Inhibition of cell growth and protein activation with cetuximab and afatinib was compared in HPV+ and HPV− cetuximab-resistant cell lines. Results: Expression of total HER2, total HER3, HER2:HER3 heterodimers, and the HER3:PI3K complex were significantly elevated in HPV+ HNSCC. Total EGFR was significantly increased in HPV− HNSCC where VeraTag assay results correlated with IHC. Afatinib significantly inhibited cell growth when compared with cetuximab in the HPV+ and HPV− cetuximab-resistant HNSCC cell lines. Conclusions: These findings suggest that agents targeting multiple HER proteins may be effective in the setting of HPV+ HNSCC and/or cetuximab resistance. Clin Cancer Res; 21(20); 4597–606. ©2015 AACR.
White Paper AGA: Advanced Imaging in Barrett’s Esophagus
Authors: Prateek Sharma, Joel Brill, Marcia Canto, Daniel DeMarco, Brian Fennerty, Neil Gupta, Loren Laine, David Lieberman, Charles Lightdale, Elizabeth Montgomery, Robert Odze, Jeffrey Tokar, Michael Kochman
Journal: Clinical Gastroenterology and Hepatology (2015)