tbuckley/cabot-search huggingface dataset:
Docetaxel clearance and cisplatin administration: Implications for toxicity of docetaxel, cisplatin, and fluorouracil (DCF) in gastric cancer
Authors: D. G. Power, N. Wu, W. Qin, D. Sully, C. Cisek, J. Randazzo, P. S. Ritch, M. P. Jhawer, D. P. Kelsen, M. A. Shah
Journal: Journal of Clinical Oncology (2008)

13502 Background: Although DCF is a standard option for advanced gastric cancer, its toxicity limits widespread use. D is both a substrate and inhibitor of CYP3A4, the enzyme responsible for its clearance. Aprepitant and palonosetron, both CYP3A4 inhibitors, are antiemetics used with C. We hypothesized that the concomitant use of these antiemetics with C administration affects D clearance and potentiates toxicity of the DCF regimen. Methods: We tested this hypothesis in a phase II random assignment clinical trial of parent DCF (D and C administered on d1) and modified DCF (mDCF, C and D administered on separate days). For both schedules, palonosetron, aprepitant and steroids are used with C as per standard guidelines. We examined D pharmacokinetics (PK) in both arms using non-linear mixed effects modelling. Standard PK parameters including AUC, Cmax, T1/2, Vdss and Clearance (CL), were calculated using Winonlin software. Both non- and two-compartment analyses were done. Serial blood draws were taken at 15 and 45 minutes, 1,2,4,6,8, and 24 hours post docetaxel initiation. Liver microsome studies were performed to examine in vitro metabolism of D. Results: Parent DCF had significantly more cycle 1 grade 3–4 toxicity, 7/8 pts vs. 1/5 pts with mDCF. PK data are available on 13 patients: 5 pts to mDCF and 8 to parent DCF. When C is given with D (parent DCF), dose adjusted D PK are as follows: AUC∞ 74.1 ng*hr/ml/mg/m2, CL 28.9 L/hr/m2, Vdss 27.8 L/m2, and T1/2 18.8hr. When D is given without C (mDCF), dose adjusted D PK are as follows: AUC∞ 46.1, CL 38.1, Vdss 17.1, and T1/2 12.1, suggesting higher clearance and reduced D exposure. Liver microsome studies demonstrate no difference in D metabolism in the presence or absence of C or F, suggesting that observed differences in D metabolism are due to drugs co-administered with C, i.e. palonosetron and aprepitant. Conclusions: These data suggest that Docetaxel clearance is reduced when C related antiemetics are given concomitantly with D. As a result of reduced D clearance, increased D exposure may be responsible for increased parent DCF toxicity. If validated these data would have significant implications for DC based therapies and their associated toxicity. D PK in additional patients is planned. No significant financial relationships to disclose.
Efficacy, safety, and tolerability of augmentation pharmacotherapy with aripiprazole for treatment-resistant depression in late life: a randomised, double-blind, placebo-controlled trial
Authors: Eric J Lenze, Benoit H Mulsant, Daniel M Blumberger, Jordan F Karp, John W Newcomer, Stewart J Anderson, Mary Amanda Dew, Meryl A Butters, Jacqueline A Stack, Amy E Begley, Charles F Reynolds
Journal: The Lancet (2015)
Glitazones are associated with reduced risk of COPD exacerbations and mortality among patients with diabetes
Authors: David Au, Thomas O'Riordan, Chuan-Fen Liu, Mark Perkins, John Toole, Christopher Bryson
Journal: European Respiratory Journal (2011)

Introduction: Moderators of systemic inflammation may reduce risk of exacerbations among patients with COPD. Glitazones, used in the treatment of diabetes, also have anti-inflammatory properties. We sought to assess whether glitazones were associated with a decreased risk of COPD exacerbations and mortality.  Study design: We performed a cohort study between 10/2005-09/2006 of all US veterans who received an oral antihypoglycemic medication (sulfonureas, biguanides, or glitazones) on more than one occasion. Our outcome measures included outpatient COPD exacerbations, hospitalization for COPD, and all cause mortality. Our primary exposure was glitazone use compared to sulfonureas and/or biguanides. We used GEE to estimate the effect of glitazones and to adjust for potential confounding factors.  Results: We identified 600,366 patients. Adjustment for age, sociodemographic characteristics, comorbidity, and markers of COPD severity had minimal effects on the point estimates. In comparison to either a sulfonylurea or biguanide, glitazones were associated with a significantly reduced risk of outpatient exacerbation (Adjusted relative likelihood (Adj-RL), 95%CI: 0.79 (0.72-0.86), hospitalization for COPD exacerbation (Adj-RL, 95%CI: 0.82 (0.69-0.97)) and all cause mortality (Adj-RL, 95%CI: 0.89 (0.85-0.93)). These estimates were robust to sensitivity analyses that imposed increasingly strict definitions of COPD.  Conclusion: Glitazones were associated with a significant reduction in COPD exacerbations and all cause mortality. We hypothesize that this association may be mediated through the anti-inflammatory properties of glitazones.  Funding: Gilead Sciences, Inc., & VA HSRD
Association between a functional TLR1 single nucleotide polymorphism and susceptibility to pulmonary tuberculosis
Authors: Diego Ferrer, Elena Puente, Fernando Ausin, Ramón Agüero, Jose Luis Arroyo, Manuel Gutierrez, Maria Carmen Fariñas, J. Gonzalo Ocejo
Journal: European Respiratory Journal (2013)

Background: Toll-like receptors (TLRs) are key sensors of mycobacterial infections and play a crucial role in the initiation and coordination of the antimycobacterial innate immune response. A functional TLR1 single nucleotide polymorphism (SNP), T1805G has been associated with susceptibility to pulmonary tuberculosis (PTB) but contradictory results among different populations have been reported.  Objectives: To assess if this functional TLR1 SNP could be associated with susceptibility or resistance to pulmonary tuberculosis in a genetically homogeneous population (Cantabria, Northern Spain).  Methods: Through a case-control study, DNA obtained from patients with PTB (n = 190) and age- and sex-matched healthy controls (n = 192) were analysed by polimerase chain reaction followed by restriction fragment length polymorphism (PCR-RFLP).  Results: We found a significant difference in the distribution of the two alleles between PTB patients and healthy controls. In this way, 1805G allele and GG genotype were significantly more frequent in PTB patients than in healthy controls [p = 0.02, OR (95%CI) 1.43 (1.07-1.90)] and [p = 0.005, OR (95%CI) 2.04, (1.26-3.31)] respectively.  Conclusions: Our results indicate that in our population, 1805G allele and GG genotype influence susceptibility to PTB, in contrast with data observed in other populations.
The kinase p38α serves cell type–specific inflammatory functions in skin injury and coordinates pro- and anti-inflammatory gene expression
Authors: Chun Kim, Yasuyo Sano, Kristina Todorova, Bradley A Carlson, Luis Arpa, Antonio Celada, Toby Lawrence, Kinya Otsu, Janice L Brissette, J Simon C Arthur, Jin Mo Park
Journal: Nature Immunology (2008)
A qualitative study of exceptional survivors of cancer
Authors: S. Meleth, L. Allen, E. Kvale, R. Meredith, S. Spencer, M. Heslin, L. Nabell, J. Posey, E. Partridge
Journal: Journal of Clinical Oncology (2009)

e17522 Background: An exceptional survivor of cancer is an individual who has outlived actuarial predictions for his/her particular form of cancer or experienced a complete regression. This pilot study was designed to determine if there were any biological, psychosocial, cultural or lifestyle characteristics exceptional survivors of cancer that can be measured and transferred through interventions to other cancer patients. Methods: The sample consisted of 21 survivors of cancer who were identified by oncologists at UAB as exceptional survivors. The study gathered qualitative data through semi-structured interviews and two validated scales measuring resilience, sense of coherence. A new cancer ‘catastrophizing’ scale based on the pain catastrophizing scale (PCS) was tested for its concordance with the two validated scales. The diagnosis and treatment information on these patients was collected through a questionnaire completed by the patient's oncologist. Results: Eight oncologists referred twenty-five patients to the study. Twenty-one patients agreed to participate. A unifying theme across all patient interviews was a deep spiritual connection with a supreme being. Praying for healing, intercessory prayer, and seeking guidance through faith with respect to best treatment options were common. The patients verbalized faith in physicians and were willing to seek more experimental treatments largely due to their spirituality. In general, the survivors were highly resilient as measured by the resilience scale and had a high sense of coherence as measured by the sense of coherence scale. They were also unlikely to conceptualize the diagnosis as a ‘catastrophe’ as measured by the new cancer catastrophizing scale. Conclusions: This study provides preliminary evidence of a relationship between spirituality and exceptional survivorship. Findings suggest exceptional survivors may be more willing to participate in clinical trials than other populations of cancer patients. Future studies should prospectively follow cancer patients to ascertain the temporal nature of the association between spirituality and exceptional survivorship. No significant financial relationships to disclose.
Use of acetylcysteinein the treatment of patients with exogenic allergic alveolitis (EAA)
Authors: Natalia Makaryants, Larisa Lepekha, Evgeny Shmelev
Journal: European Respiratory Journal (2013)

Aim: To evaluate effectiveness of a long-term treatment with high-dose acetylcysteine (NAC) in patients with chronic course of EAA.  Materials and methods: We studied 24 patients with chronic course of morphologically verified EAA. Group 1 (14 patients) received prednisolone, 15 mg/day, and NAC, 1800 mg/day.Group 2 (10 patients) received prednisolone, 15 mg/day, and cyclophosphamide, 0.2 g intravenously twice a week. We evaluated clinical symptoms (cumulative index), a 6-minute walk test, spirometry, computed tomography (CT) of the lungs by Kazerooni, before and after the treatment. The reliability of differences was established using the Wilcocson test.  Results: There was no reliable difference between the groups. The analysis of the data within the both groups revealed improvement of clinical symptoms, MEF 75 rates, longer distances in 6-minute walk tests, better CT results due to the alveolar component. In group 2 we also observed increasing rates of VCIN, FEV1, MEF50.  *p  Conclusion: Use of NACin the treatment of patients with chronic EAA is less effective versus cyclophosphamide.
Antioxodants attenuates alveolar epithelial cell damage induced by a component of essential oils
Authors: Yasuo Takano, Yuuya Hinode
Journal: European Respiratory Journal (2014)

Background : It is well known that essential oils extracted from plants have various biological effects. Some essential oils were shown to elicit cytotoxicity and induce apoptosis in cancer cells. However, little is known about the biological effects of essential oils on alveolar epithelial cells.  Objectives : In order to evaluate the biological effects of essential oils on alveolar epithelial cells, we have examined the cytotoxicity of essential oils toward alveolar type II cells  in vitro . Our final goal is to examine applications of a potent component of essential oils to respiratory health.  Method : Alveolar type II cells were exposed to a component of essential oils with antioxidants, such as superoxide dismutase (SOD), dimethylthiourea (DMTU), n-acetyl cysteine (NAC) and eugenol for 6 hrs. At the end of the experiment, lactate dehydrogenase (LDH) activity released into the culture medium was determined to reflect the cell damage.  Results : The cell damage of sesquiterpenes, such as nerolidol and cedrol were more severe than that of monoterpenes, such as geraniol and mentol. While, antioxidants like SOD, DMTU, NAC were significantly reduced the cell damage induced by these terpenes. Nerolidol and cedrol caused cell death characterized by phosphatidylserine externalization in alveolar type II cells.  Conclusions : The sensitivity of cell damage of alveolar type II cells is different depending on a type of terpenes and oxidative stress is associated with the cell damage. Nerolidol and cedrol may be induced apoptosis.
Abstract 453: Apelin Regulates Cardiac Contractility and Rescues Neurohormonal Heart Failure
Authors: Kavita V Ernst, Euan A Ashley, David Charo, Masataka Kawana, Giovanni Fajardo, Daniel Bernstein, Thomas Quertermous
Journal: Circulation (2006)

Targets of acute heart failure (HF) therapy include vascular resistance, contractility, the renin-angiotensin system, and arginine vasopressin. We have reported a role for the G protein coupled ape...
High-dose carboplatin in refractory ovarian cancer patients.
Authors: R F Ozols, Y Ostchega, G Curt, R C Young
Journal: Journal of Clinical Oncology (1987)

Thirty previously treated refractory ovarian cancer patients, all of whom received prior therapy with cisplatin, were treated in a phase II trial with high-dose carboplatin (800 mg/m2 per cycle with cycles administered every 35 days). Patients were treated with high-dose carboplatin when they were no longer responding to prior therapy or had relapsed after an initial response. Objective responses were achieved in eight of 30 patients (27%) while ten patients had minor responses or stable disease. No responses were observed from high-dose carboplatin in patients who had progressive disease during prior therapy with a cisplatin-based regimen. The primary toxicity of high-dose carboplatin was myelosuppression with a median WBC nadir of 0.6 and a median platelet nadir of 6,500 after the first cycle of therapy. Myelosuppression was not particularly cumulative as 78% of patients were able to receive either 100% or 75% of the projected dose even with the fourth cycle of high-dose carboplatin. The gastrointestinal (GI) toxicity of carboplatin was mild and there was no clinically apparent nephrotoxicity or neurotoxicity. These results demonstrate that: there is marked cross-resistance between cisplatin and carboplatin, and high-dose carboplatin may be a potential alternative to high-dose cisplatin in the treatment of ovarian cancer patients.
Mesangial Function in Ureteral Obstruction in the Rat
Authors: Leopoldo Raij, William F. Keane, Hartmuth Osswald, Alfred Michael
Journal: Journal of Clinical Investigation (1979)

The kinetics for mesangial uptake and transport of radiolabeled aggregated human immunoglobulin (Ig)G (AHIgG125I) deviated markedly from normal in male Sprague-Dawley rats with ureteral obstruction. Four experimental groups, each containing 25 rats, were used: (a) bilateral ureteral ligation (BUL) with release of one ureter 24 h later; (b) unilateral ureteral ligation with release 24 h later [UUL(R)]; (c) unilateral ureteral ligation without release (unreleased) [UUL(U)]; (d) uremia-control, which consisted of rats with ligated left ureter and a severed right ureter. A similar number of sham-operated rats served as control for each group. AHIgG125I (45 mg/100 g body wt) was given intravenously 1 h after release of the ureteral obstruction (25 h after ureteral obstruction or sham surgery). Groups of five control and five experimental animals were sacrificed at 2, 4, 8, 16, and 24 h after injection.
Incapacity to increase pulmonary blood flow determines 6 minutes walking distance in pulmonary hypertension
Authors: Gael Deboeck, Robert McKenzie Ross, Linda Sharples, Joanna Pepke-Zaba
Journal: European Respiratory Journal (2011)

Introduction:  Pulmonary hypertension (PH) is a disease of elevated pulmonary artery pressure leading to the inability of the overloaded right ventricle to adapt pulmonary blood flow (PBF) and systemic oxygen delivery to peripheral tissue oxygen demand. 6 minutes walk test (6MWT) is a submaximal, well tolerated but strenuous test regularly used for the assessment of PH functional status and is strongly associated to survival.   Aim:  To study the adaptation of PBF during a 6MWT.   Methods:  We measured heart rate (HR) and PBF with a rebreathing device (INNOCOR) before and directly after a 6MWT in 28 patients with chronic thromboembolic pulmonary hypertension and 8 with pulmonary arterial hypertension. The relation between increase (after – before 6MWT) in PBF (ΔPBF) in response to 6MWdistance (6MWD) was plotted and different mathematical model applied to describe the relation (Akaike test).   Results/Discussion:  The best fitting model is a polynomial cubic model, showing a small and constant ΔPBF for patients walking less than 300-350 m but more rise in ΔPBF is observed with increased distance.  We notice that the rise in ΔPBF occurs at comparable 6MWD that is associated with better survival in PH. The stroke volume (PBF/HR) is not increased whatever the distance covered.   Conclusions:  Ability to substantially increase PBF determines 6MWD and is dependent on chronotropic response in patient with PH.
Quantitative Analysis of Melanoma-Induced Cytokine-Mediated Immunosuppression in Melanoma Sentinel Nodes
Authors: Jonathan H. Lee, Hitoe Torisu-Itakara, Alistair J. Cochran, Alan Kadison, Young Huynh, Donald L. Morton, Richard Essner
Journal: Clinical Cancer Research (2005)

Melanoma sentinel nodes (SN) show evidence of immunosuppression prior to tumor metastasis. Interleukin (IL)-10 and IFN-gamma can induce dendritic cells (DC) that express immunosuppressive enzyme indoleamine 2,3-dioxygenase (IDO). The goals of this study are to evaluate the role of melanoma in SN immunosuppression and to assess reversibility of SN immunosuppression by a cytokine therapy.Fifty-seven clinical stage I/II melanoma patients underwent wide local excision and sentinel lymphadenectomy (WLE/SL), with removal of non-SN. In 21 patients, nodal RNA was analyzed by quantitative real-time PCR for expression levels of IL-2, IL-10, IL-12, IFN-gamma, and IDO genes. Among the remaining 36 patients, 15 received peritumoral injection of recombinant human granulocyte macrophage colony-stimulating factor (rhGM-CSF) 2 to 5 days prior to WLE/SL. Lymph nodes (LN) from these 36 patients were assessed for T-cell area, DC area, and DC density.Of 21 patients whose nodal RNA was analyzed, 13 had residual melanoma at the primary site or a tumor-positive SN. In these patients, expression levels of IL-10 (P = 0.05), IFN-gamma (P < 0.05), and IDO (P = 0.06) were dramatically higher in SNs than non-SNs. This difference was not evident in the 8 patients without residual melanoma or SN metastasis. Of the 36 patients whose LNs were examined for histologic features, the 15 patients who received rhGM-CSF had significantly higher SN values of T-cell area, DC area, and DC density than those who did not receive rhGM-CSF.Our data provide molecular evidence of cytokine-mediated SN immunosuppression that is associated with presence of melanoma. Furthermore, SN immunosuppression can potentially be reversed by a cytokine therapy.
A randomized, phase III study of carboplatin and pegylated liposomal doxorubicin versus carboplatin and paclitaxel in relapsed platinum-sensitive ovarian cancer (OC): CALYPSO study of the Gynecologic Cancer Intergroup (GCIG)
Authors: E. Pujade-Lauraine, S. Mahner, J. Kaern, V. Gebski, M. Heywood, P. Vasey, A. Reinthaller, I. Vergote, S. Pignata, A. Ferrero
Journal: Journal of Clinical Oncology (2009)

LBA5509 The full, final text of this abstract will be available in Part II of the 2009 ASCO Annual Meeting Proceedings, distributed onsite at the Meeting on May 30, 2009, and as a supplement to the June 20, 2009, issue of the Journal of Clinical Oncology. No significant financial relationships to disclose.
Common drugs can affect moral decision making, study finds:
Authors: Jacqui Wise
Journal: BMJ (2015)

Some commonly prescribed drugs can influence moral decisions, a double blind randomised controlled trial published in Current Biology has found.

Researchers from University College London1 found that healthy people given the selective serotonin reuptake inhibitor citalopram (Celexa) were more likely to avoid harming themselves or others than those given placebo—whereas the Parkinson’s disease drug levodopa tended to make healthy people more selfish, eliminating the usual altruistic tendency to prefer harming oneself over others.

Levodopa boosts dopamine levels, whereas citalopram enhances serotonin levels. Serotonin and dopamine levels have …
Neoplastic and Life-Span Effects of Chronic Exposure to Tritium. I. Effects on Adult Rats Exposed During Pregnancy
Authors: D F Cahill, J F Wright, J H Godbold, J M Ward, J W Laskey, E A Tompkins
Journal: JNCI Journal of the National Cancer Institute (1975)

Female Sprague-Dawley rats were continuously exposed to equilibrium levels of tritiated water (HTO) during pregnancy. The tritium activities were 1, 10, 50, and 100 muCi HTO/ml body water which provided cumulative, whole-body radiation doses of approximately 6.6, 66, 330, and 660 rads. Administration of the radioisotope was terminated at parturition. Throughout their life-spans and at autopsy, the dams showed an increased incidence of mammary fibroadenomas at exposure to 330 and 660 rads. Although the data for the incidence of malignant mammary neoplasms were consistent with a linear dose response, the small numbers of tumors preclude specific definition of the dose-response curve. Postexposure life-spans for dams chronically exposed to 66, 330, and 660 rads during pregnancy were reduced by 14, 24, and 22%, respectively. Accelerated aging was also demonstrated in these rats: The mean age for mammary fibroadenoma onset decreased with an increasing dose of radiation.
Does cognitive behavior therapy assist slow-taper alprazolam discontinuation in panic disorder?
Authors: D A Spiegel, T J Bruce, S F Gregg, A Nuzzarello
Journal: American Journal of Psychiatry (1994)

The authors investigated whether cognitive behavioral treatment could facilitate discontinuation of alprazolam therapy and maintenance of drug abstinence among panic disorder patients treated with alprazolam doses sufficient to suppress spontaneous panic attacks.Twenty-one outpatients who met DSM-III-R criteria for panic disorder with mild to severe agoraphobia were made panic-free with alprazolam (mean dose = 2.2 mg/day) and were then randomly assigned to receive either supportive drug maintenance and slow, flexible drug taper or an identical medication treatment plus 12 weeks of concurrent, individual cognitive behavioral treatment. Taper in the combined treatment group was sequenced to conclude before cognitive behavioral treatment ended.Twenty subjects completed the study. There was no significant difference between groups in the rate of alprazolam discontinuation (80% and 90%, respectively, in the alprazolam-only group and the combined treatment group). However, during the 6-month follow-up period, half of the subjects who discontinued alprazolam without cognitive behavior therapy, but none of those who were given cognitive behavior therapy, relapsed and resumed alprazolam treatment.Cognitive behavioral treatment administered in parallel with alprazolam maintenance and taper was effective in preventing relapse after drug discontinuation. The results warrant further research on the thoughtful integration of these two therapeutic modalities.
Identification Of AML Subtype-Selective Drugs By Functional Ex Vivo Drug Sensitivity and Resistance Testing and Genomic Profiling
Authors: Tea Pemovska, Mika Kontro, Bhagwan Yadav, Henrik Edgren, Samuli Eldfors, Agnieszka Szwajda, Henrikki Almusa, Maxim Bespalov, Pekka Ellonen, Erkki Elonen, Bjorn T Gjertsen, Riikka Karjalainen, Evgeny Kulesskiy, Sonja Lagström, Anna Lehto, Maija Lepistö, Tuija Lundan, Muntasir Mamun Majumder, Jesus Maria Lopez Marti, Pirkko Mattila, Astrid Murumägi, Satu Mustjoki, Aino Palva, Alun Parsons, Tero Pirttinen, Maria E Rämet, Minna Suvela, Laura Turunen, Imre Västrik, Maija Wolf, Jonathan Knowles, Tero Aittokallio, Caroline A Heckman, Kimmo Porkka, Olli Kallioniemi, Krister Wennerberg
Journal: Blood (2013)