tbuckley/cabot-search huggingface dataset:
Relationship between sniff nasal inspiratory pressure and the multidimensional BODE index in patients with COPD
Authors: Leila Donária, Rafael Mesquita, Mônica Yosino, Larissa Martinez, Josiane Marques Felcar, Nidia A. Hernandes, Vanessa S. Probst, Fabio Pitta
Journal: European Respiratory Journal (2013)

Introduction  :  Inspiratory muscle force has been traditionally assessed by maximal inspiratory pressure (MIP). The sniff nasal inspiratory pressure (SNIP) is an alternative to the MIP and is considered as predictor of mortality in patients with chronic obstructive pulmonary disease (COPD). However, the relationship of SNIP with multidimensional indexes which predict mortality in COPD patients such as the Body mass index, airflow Obstruction, Dyspnea and Exercise capacity (BODE) has not yet been investigated.  Objective:  To investigate the relationship between SNIP and BODE index in COPD patients COPD.  Methods  :  Thirty-eight subjects with COPD (21 men, 66±8 years, FEV 1  42±16% of predicted) underwent assessments: SNIP, spirometry, degree of dyspnea (Medical Research Council scale) and 6-minute walk test. The BODE index was calculated and the patients were divided into four quartiles according to the BODE score.  Results  :  There was significant difference in the SNIP (cmH 2 O and %predicted) when patients in the different BODE quartiles were compared. The SNIP (cmH 2 O and %predicted) showed moderate correlation with the BODE and the updated BODE (-0.45 2 O (OR: 4.67, 95% CI 1.19 to 18.35, P= 0.03).  Conclusion  :  SNIP is moderately and significantly related with the BODE index in COPD patients. Moreover, the cutoff point of 63 cmH 2 O showed the best combination of sensitivity and specificity for predicting a higher ( i.e ., worse) score in the BODE index.
Safety data of MGN1601, a tumor vaccine, made of allogeneic, transfected, and irradiated tumor cells in combination with an immunomodulator for the treatment of metastatic renal cell carcinoma.
Authors: M. Schmidt, B. Volz, M. Schroff, K. Kapp, C. Kleuss, M. Tschaika, B. Wittig
Journal: Journal of Clinical Oncology (2010)

e15104 Background: The cell-based tumor vaccine MGN1601 for the treatment of renal cell carcinoma (RCC), consists of two active pharmaceutical ingredients: First, genetically modified allogeneic (human) cells in-vitro transiently transfected with four different MIDGE vectors encoding IL-7, GM-CSF, CD80 and CD154 and second, the synthetic DNA-based immunomodulatory molecule dSLIM-30L1, a TLR-9 agonist. The cells originate from primary RCC material. Methods: Studies of single-dose toxicity were performed with MGN1601 in rats (heterologous setting) by either subcutaneous or intradermal application (up to 300-fold or 60-fold of the amount of cells for patients/kg, respectively). Additionally, a single dose subcutaneous application of the murine homologue of MGN1601 in NMRI mice was performed (allogeneic setting, up to 2.900-fold of the amount of cells for patients/kg). Studies of repeated-dose toxicity (5- and 13-times, 28 days and 13 weeks, respectively) were performed in either the heterologous setting or the homologue setting. Furthermore, the local tolerance of MGN1601 was tested in rabbits. Results: The vaccine generally showed low to no toxicity at the tested doses. In all single-dose toxicity studies the NOEL was higher than the highest dose used. In the repeated-dose 28 days toxicity studies (5-times) only slight hematological changes in some female rats from the high-dose group (decrease of neutrophils and increase of lymphocytes) as well as minor changes at the injection site in some animals of all dose groups were observed. Conclusions: The murine homologue of MGN1601 applied to mice as well as MGN1601 in the heterologoues setting in rats showed excellent safety characteristics and was extremely well tolerated in all tested models up to very high multiples of the anticipated human therapeutic dose/kg. A clinical trial Phase I/II was initiated in November 2009. First patients will be included in the 1st Q/2010. The treatment duration will be 3 months. An extension treatment will last for further 2 years. In this clinical study safety and efficacy of MGN1601 in patients with metastatic RCC will be evaluated. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration MOLOGEN AG MOLOGEN AG MOLOGEN AG
Mode of action of abatacept in rheumatoid arthritis patients having failed tumour necrosis factor blockade: a histological, gene expression and dynamic magnetic resonance imaging pilot study
Authors: M H Buch, D L Boyle, S Rosengren, B Saleem, R J Reece, L A Rhodes, A Radjenovic, A English, H Tang, G Vratsanos, P O'Connor, G S Firestein, P Emery
Journal: Annals of the Rheumatic Diseases (2008)

<h3>Objectives:</h3> Abatacept is the only agent currently approved to treat rheumatoid arthritis (RA) that targets the co-stimulatory signal required for full T-cell activation. No studies have been conducted on its effect on the synovium, the primary site of pathology. The aim of this study was to determine the synovial effect of abatacept in patients with RA and an inadequate response to tumour necrosis factor alpha (TNFα) blocking therapy. <h3>Methods:</h3> This first mechanistic study incorporated both dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) and arthroscopy-acquired synovial biopsies before and 16 weeks after therapy, providing tissue for immunohistochemistry and quantitative real-time PCR analyses. <h3>Results:</h3> Sixteen patients (13 women) were studied; all had previously failed TNFα-blocking therapy. Fifteen patients completed the study. Synovial biopsies showed a small reduction in cellular content, which was significant only for B cells. The quantitative PCR showed a reduction in expression for most inflammatory genes (Wald statistic of p&lt;0.01 indicating a significant treatment effect), with particular reduction in IFNγ of −52% (95% CI −73 to −15, p&lt;0.05); this correlated well with MRI improvements. In addition, favourable changes in the osteoprotegerin and receptor activator of nuclear factor kappa B levels were noted. DCE–MRI showed a reduction of 15–40% in MRI parameters. <h3>Conclusion:</h3> These results indicate that abatacept reduces the inflammatory status of the synovium without disrupting cellular homeostasis. The reductions in gene expression influence bone positively and suggest a basis for the recently demonstrated radiological improvements that have been seen with abatacept treatment in patients with RA.
Enhanced chemosensitivity to gemcitabine and oxaliplatin by thymoquinone in pancreatic cancer
Authors: A. O. Kaseb, S. Banerjee, Z. Wang, F. H. Sarkar, M. Ramzi
Journal: Journal of Clinical Oncology (2008)

15565 Background: Most patients with pancreatic cancer (PC) present with an advanced, surgically-incurable disease which implies that the vast majority of patients will eventually be considered candidates for systemic treatment. Response rates to gemcitabine (Gem) and Oxaliplatin (Ox) remain quite low, which is partly due to chemo-resistance. Most recently, we reported targeted anti-cancer effects in prostate cancer using thymoquinone (TQ), an herbal agent that spares normal cells. Method: PC cells (HPAC, BxPC-3, Panc-1 and MDA Panc-28, COLO 357, L3.6pl) were treated with TQ (0–50μM) for 48hrs to examine antiproliferative and proapoptotic effects. Their response to chemosensitivity towards Gem and Ox was also assessed in vitro using MTT and quantifying cytoplasmic histone-DNA fragments upon pretreatment with TQ (5–50μM; 48 hrs) followed by cytotoxic drugs for 24hrs. The molecular mechanism for enhanced chemosensitivity was investigated by performing Western immunobloting targeting proapoptotic as well as, antiapoptotic signaling moieties. Additionally, gel shift assay was performed to elucidate whether activation of the basal NF-κB transcription factor is responsible in suppressing apoptosis. Results: All PC cells were found to be sensitive to TQ alone as deduced from reduced viability and undergoing apoptosis in the range between 30–50μM. TQ pretreatment also significantly (p<0.01) enhanced the anti-proliferative and apoptotic effect of Gem as well as, Ox in these cells relative to untreated control and single drug regimen. Additionally, constitutively active NF-κB and several of its downstream effector genes related to metastasis and invasion were down-regulated by TQ, suggestive of an important molecular target in reversing PC chemoresistance. Conclusion: Our studies that clearly demonstrates that TQ inhibits proliferation of PC cells, and enhances growth inhibition, and apoptosis induced by Gem and oxaliplatin. This is first report on therapeutic effect of TQ suggestive of chemosensitization of human pancreatic cancer cells. Based on our current research findings in vivo animal studies are currently under progress so as to obtain better clue for its efficacy for future phase-1clinical trial. No significant financial relationships to disclose.
18F-FDG PET/CT Diagnosis of Bronchopulmonary Carcinoids Versus Pulmonary Hamartomas
Authors: Natalja Uhlén, Oscar Grundberg, Hans Jacobsson, Anders Sundin, Katalin Dobra, Alejandro Sánchez-Crespo, Rimma Axelsson, Karl-Gustaf Kölbeck
Journal: Clinical Nuclear Medicine (2016)

Radiological characterization of pulmonary tumors may be difficult and invasive. Needle biopsy may produce false-negative results. 18F-FDG PET/CT is an established noninvasive procedure for lung tumor characterization and staging. This study was aimed at differentiating bronchopulmonary carcinoids from hamartomas and typical from atypical bronchopulmonary carcinoids by means of 18F-FDG PET/CT.In a retrospective analysis of 118 patients, with surgically resected pulmonary carcinoid tumors and hamartomas, 87 of those selected had also undergone 18F-FDG PET/CT preoperatively and constituted the study population. To better assess the tracer accumulation, especially in small lesions, the 18F-FDG uptake (SUV) in the tumors was corrected for partial volume effect by applying recovery coefficients corresponding to the respective various specific tumor volumes, as extrapolated from those obtained from experiments in a NEMA phantom.The SUVmax was higher in the pulmonary carcinoids (mean, 3.9) than in the hamartomas (mean, 1.4; P ≤ 0.00001) and higher in the subgroup of peripheral carcinoids than in hamartomas (P ≤ 0.00001). The SUVmax was similar for the atypical and typical carcinoids, 5.0 and 3.8, respectively, because of the large variation in the data (P = 0.11).Using PET measurements of the 18F-FDG uptake (SUVmax) in the tumors, corrected for partial volume effects, it was possible to differentiate the carcinoids from the hamartomas, but the clinically more aggressive atypical carcinoids could not be differentiated from the typical carcinoids.
Mental health implications and consequences following sport-related concussion
Authors: Anthony P Kontos, Jamie McAllister Deitrick, Erin Reynolds
Journal: British Journal of Sports Medicine (2015)

Concussion is a heterogeneous injury involving a myriad of physical (eg, dizziness, headache), cognitive (eg, memory problems, difficulty concentrating), sleep-related and affective (eg, depression, anxiety) symptoms, and impairment (eg, cognitive, vestibular, oculomotor). Consequently, clinical researchers have advocated for a more comprehensive and targeted approach to assessing and treating sport-related concussion (SRC).1 Some athletes experience mood-related consequences including anxiety and depression following SRC.2 In the extreme, these consequences if ignored or improperly managed can lead to clinical depression, anxiety, and even suicidal ideation and intent. As such, it is important to assess mood-related changes following SRC in all athletes and to properly treat those athletes who may be experiencing more pervasive affective symptoms.

In this paper, we aim to highlight the current research on the mental health consequences of SRC and explore their implications for assessment and treatment of SRC. We also discuss potential directions for future research on mental health-related outcomes following SRC.

Affective symptoms (eg, depression, anxiety) following traumatic brain injuries including concussion are common.2 However, it is estimated that only 6% of patients experience some form of depression following the concussion.3 Recent consensus statements on SRC have called for more research exploring the emotional sequelae that may accompany SRC as well as appropriate assessment and treatment approaches.2 ,4 Researchers have indicated that affective responses, particularly depression, are common following concussion.5–9 However, it is important to note that most affective responses occur at a subclinical level that does not meet diagnostic criteria for a clinical disorder. Additionally, it is important for the clinician to be aware of any pre-existing psychological conditions that may affect the emotional responses following SRC.

Both psychosocial and neurobiological factors may help to explain affective responses following SRC. For example, individuals with clinical depression have been found …
A longitudinal follow-up study of seasonal affective disorder
Authors: K Sakamoto, S Nakadaira, K Kamo, T Kamo, K Takahashi
Journal: American Journal of Psychiatry (1995)

The purposes of this study were to evaluate the long-term stability of a seasonal pattern of recurrent depression, identify possible factors associated with alteration of the seasonal pattern, and determine whether atypical vegetative symptoms during early seasonal depressive episodes predict future seasonal relapses.The subjects were 41 patients satisfying the criteria used in the Japanese multicenter study of seasonal affective disorder who were consistently treated at the same outpatient clinic. Their longitudinal courses were evaluated by using case records and the Schedule for Affective Disorder and Schizophrenia--Life-time Version; the mean follow-up period was 10.4 years.Nine subjects (22.0%) consistently showed a fall-winter pattern of recurrence throughout follow-up. Seventeen patients with an initial fall-winter pattern subsequently tended to shift seasons or show less seasonality. This alteration in pattern was possibly associated with antidepressant therapy or life events. Eleven patients with an initial diagnosis of nonseasonal affective disorder subsequently developed seasonal affective disorder; no specific factors were associated with this change. Atypical vegetative symptoms were significantly more common in patients with stable seasonal patterns of recurrence than in those who lost seasonality.Although seasonal affective disorder appeared to be altered by antidepressant treatment, the presence of a core group of patients with a consistent seasonal pattern of recurrent depression suggests the validity of seasonal affective disorder as a distinct subtype of recurrent affective illness. The findings also suggest that atypical vegetative symptoms during early seasonal depressive episodes predict the subsequent seasonality of depression.
CD4+ T cell anergy prevents autoimmunity and generates regulatory T cell precursors
Authors: Lokesh A Kalekar, Shirdi E Schmiel, Sarada L Nandiwada, Wing Y Lam, Laura O Barsness, Na Zhang, Gretta L Stritesky, Deepali Malhotra, Kristen E Pauken, Jonathan L Linehan, M Gerard O'Sullivan, Brian T Fife, Kristin A Hogquist, Marc K Jenkins, Daniel L Mueller
Journal: Nature Immunology (2016)
Impact of intensive enteral nutrition in association with corticosteroïds in the treatment of severe alcoholic hepatitis: a multicenter randomized controlled trial
Authors: C Moreno, E Trepo, A Louvet, D Degre, B Bastens, A Hittelet, MA Piquet, W Laleman, H Orlent, L Lasser, T Serste, P Starkel, X Dekoninck, S Negrin, Jean Delwaide, I Colle, C de Galocsy, S Francque, P Langlet, Putzeys, H Reynaert, T Gustot, P Deltenre
Journal: Hepatology (2014)
Combination of cetuximab and chemotherapy in the first-line treatment of metastatic colorectal cancer: Slovakian experience.
Authors: T. Salek, E. Sebo, D. Mazalova, J. Chovanec, M. Stresko, A. Thomkova, I. Andrasina, R. Barilla, Z. Hlavata, M. Mego
Journal: Journal of Clinical Oncology (2011)

622 Background: Cetuximab is an EGFR-targeting IgG1 monoclonal antibody that is active against EGFR-expressing Kras wild type metastatic colorectal cancer (mCRC) in monotherapy or in combination with chemotherapy. Here, we report efficacy and safety of combination of cetuximab and chemotherapy in patients (pts) with mCRC treated in major cancer centers in Slovakia from 01/2009 to 07/2010. Methods: Forty consecutive pts (28F/12M) with EGFR expressing Kras wild type mCRC (14 pts-rectal cancer, 26 pts-colon cancer) treated with irinotecan-based (29 pts-73%) and oxaliplatin-based (11 pts-27%) chemotherapy were evaluated. Median age was 59 years (44-77).17 pts were pretreated with adjuvant therapy. No of metastatic sites: 1 mts -22 pts (55%), 2 mts-13 pts (32.5%), 3 mts -5pts (12.5%). Median CEA level before therapy 13.5 (1-1,800). Results: 10 pts achieved complete remission (25%), 21 pts partial remission (52.5%), 8pts disease stabilization, 1pt disease progression. Median progression-free survival (mPFS) was 16 months, 1 year survival 65%-95% CI (50-80), median follow-up was 13 months (range 4-20m). The main Gr 3-4 toxicity was skin rash 2pts (5%) and diarrhea 2 pts (5%). Any grade toxicity: rash 32 pts (80%), diarhea 8pts (20%), neuropathy 8pts (20%), weakness 3pts (7.5%), neutropenia 2pts (5%), trombocytopenia 2pts (5%). Conclusions: Our experience confirms the efficacy and acceptable safety profile of combination chemotherapy and cetuximab in first line mCRC patients. No significant financial relationships to disclose.
Nijmegen breakage syndrome 1 (NBS1) gene polymorphism and chemotherapy-induced neutropenic fever in breast cancer patients
Authors: A. Sun, T. Yu, L. Wang, J. Lu, G. Gonzales, L. Pusztai, S. Singletary, M. I. Ross, Q. Wei, T. A. Buchholz
Journal: Journal of Clinical Oncology (2007)

574 Background: Neutropenic fever (NF) is a serious complication of the chemotherapies given to breast cancer patients and often limits their use. Hence, identifying which patients are at increased risk to develop NF is very important. The NBS1 gene product is important for the repair of double-strand DNA breaks and is activated by chemotherapy. The objective of this study was to determine if genetic variations of NBS1 polymorphisms predict the risk of chemotherapy-induced NF in breast cancer patients. Methods: Blood from 306 newly diagnosed breast cancer patients treated with chemotherapy were prospectively collected on a study approved by the institutional review board. The relationship of chemotherapy administration (e.g. dose, timing) and growth factor use were correlated with the absolute neutrophil count (ANC) and NF development. For each patient, we assessed three polymorphisms (924T&gt;C, 8360G&gt;C, and 30537G&gt;C) of NBS1 gene using polymerase chain reaction-restriction fragment length polymorphism method. Two-sided Chi-square test was used for univariate analysis and a multivariable logistical regression analysis was used to calculate odds ratios. Results: In total, 167 (55%) patients experienced ANC less than 1,000 cells/microliter (CIN1000) and 30 (10%) patients developed NF. For 8360G&gt;C polymorphism, 9.7% of patients had a 8360CC variant genotype and these patients had increased risk of NF than the other genotypes (NF in CC 20.7% vs. in others 8.1%; Odds Ratio [OR] = 3.0; 95% confidence interval [CI] = 1.1 - 8.0, p = 0.034). In multivariable logistic regression model, 8360CC genotype (OR = 5.0, 95% CI = 1.6 - 16.1, p = 0.007) and growth factor support (OR = 19.6, 95% CI = 4.4 - 87.6, p &lt; 0.001) were significantly associated with NF development. No genotypes of 924T&gt;C and 30537G&gt;C polymorphisms increased the risk of NF and there was no statistical association between the three NBS1 gene polymorphisms and CIN1000. Conclusions: Breast cancer patients with 8360CC variant polymorphism in NBS1 gene have increased risk in developing NF with systemic chemotherapy. Analysis of polymorphisms of NBS1 and other DNA repair genes could potentially help identify who will develop chemotherapy-induced bone marrow toxicities. No significant financial relationships to disclose.
Conditioning regimen-dependent disposition of cyclophosphamide and hydroxycyclophosphamide in human marrow transplantation patients.
Authors: J T Slattery, T F Kalhorn, G B McDonald, K Lambert, C D Buckner, W I Bensinger, C Anasetti, F R Appelbaum
Journal: Journal of Clinical Oncology (1996)

PURPOSE The pharmacokinetics of cyclophosphamide (CY) and 4-hydroxycyclophosphamide (HCY) were studied in 14 patients being prepared for bone marrow transplantation with either busulfan (BU)/CY (n = 7) or CY/total-body irradiation (TBI) (n = 7) to determine whether exposure to CY and its proximate toxic metabolite HCY is modulated by other agents used in the preparative regimen. PATIENTS AND METHODS HCY was assayed by a new method that stabilized the metabolite at bedside. In BU/CY patients (who also received phenytoin), CY clearance was 112% greater (P = .0014), half-life 54% less (P = .0027), peak HCY concentration in plasma/CY dose 113% greater (P = .0006), and the ratio of area under the plasma concentration-time curves (AUCs) of HCY to CY 166% greater (P = .0116) than in CY/TBI patients. The ratio of the AUC of HCY/CY dose was 48% greater in BU/CY patients than in CY/TBI patients when one CY/TBI patient with an apparent impaired ability to eliminate HCY was excluded from analysis. In CY/TBI patients, there was an inverse correlation between the AUC of HCY and that of CY (R2 = .740, P = .028). Also, the ratio of the AUC of HCY/CY dose was correlated with the average concentration of BU at steady-state (Css, Bu) (R2 = .646, P = 0.29). Variability in CY and HCY pharmacokinetics among the 14 patients overall was pronounced, with the highest variability (15-fold) observed in the ratio of the AUC of HCY to that of CY. CONCLUSION Prior administration of BU and/or phenytoin significantly alters exposure to CY and HCY. Interpatient variability in HCY exposure at a given CY dose is substantial.
Tumorigenic Effect of 3-Amino-1 H -1,2,4-triazole on Rat Thyroid 2
Authors: Hiroyuki Tsuda, Motoo Hananouchi, Masae Tatematsu, Masao Hirose, Kazuya Hirao, Michihito Takahashi, Nobuyuki Ito
Journal: JNCI Journal of the National Cancer Institute (1976)

Journal Article Tumorigenic Effect of 3-Amino-1H-1,2,4-triazole on Rat Thyroid Get access Hiroyuki Tsuda, Hiroyuki Tsuda Search for other works by this author on: Oxford Academic PubMed Google Scholar Motoo Hananouchi, Motoo Hananouchi Search for other works by this author on: Oxford Academic PubMed Google Scholar Masae Tatematsu, Masae Tatematsu Search for other works by this author on: Oxford Academic PubMed Google Scholar Masao Hirose, Masao Hirose Search for other works by this author on: Oxford Academic PubMed Google Scholar Kazuya Hirao, Kazuya Hirao Search for other works by this author on: Oxford Academic PubMed Google Scholar Michihito Takahashi, Michihito Takahashi Search for other works by this author on: Oxford Academic PubMed Google Scholar Nobuyuki Ito Nobuyuki Ito Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 57, Issue 4, October 1976, Pages 861–864, https://doi.org/10.1093/jnci/57.4.861 Published: 01 October 1976 Article history Received: 24 November 1975 Accepted: 12 March 1976 Published: 01 October 1976
Evaluation of Met Staining in Gastric/Gastroesophageal Junction (G/Gej) Tumor Samples As a Biomarker for Rilotumumab (R) Benefit
Authors: M.D. Hale, K.S. Oliner, R. Tang, J.G. Vallone, I. Klement, S. Webster, L. Chen, E. Loh, S.D. Patterson
Journal: Annals of Oncology (2014)