tbuckley/cabot-search huggingface dataset:
Double-blind placebo-controlled study of long-term low-dose cyclosporin in the treatment of palmoplantar pustulosis
Authors: None Erkko, None Granlund, None Remitz, None Rosen, None Mobacken, None LindelÖF, None Reitamo
Journal: British Journal of Dermatology (1998)

We previously showed in a double-blind, placebo-controlled study that cyclosporin at a dose of 2.5 mg/kg per day is an effective treatment for palmoplantar pustulosis (PPP). In the present randomized, double-blind, placebo-controlled multicentre study we treated 58 PPP patients with placebo or cyclosporin at an initial dose of 1 mg/kg per day. Disease activity was calculated from the number of fresh pustules. Treatment success was defined as the number of fresh pustules not exceeding 50% of the patients' own baseline pustule number. In cases of treatment success the dose of the test medication was not increased and the treatment was kept blinded for a maximum of 12 months. Blinding was broken only on treatment failure of the initial test medication dose. The mean blinded treatment time was 5.1 months for the patients receiving cyclosporin and 2.1 months for placebo (P < 0.01). Treatment was kept blinded for 12 months for seven patients in the cyclosporin and two in the placebo group (P < 0.05). Patients whose treatment code was broken continued in an open dose-finding part of the study with dose adjustments of cyclosporin every second month. In cases of treatment failure the dose of cyclosporin was increased in steps of 1 mg/kg per day; in cases of treatment success the cyclosporin dose was decreased by 1 mg/kg per day. The minimum and maximum doses were 1 and 4 mg/kg per day, respectively. The mean effective dose during the dose-finding part was between 1.2 and 1.7 mg/kg per day. Two patients did not respond to the highest dose of 4 mg/kg per day. In two patients serum creatinine levels increased by > 30% of their own baseline. The other main adverse events were hypertension (seven patients) and hypertrichosis (six patients). After stopping cyclosporin treatment the mean number of fresh pustules showed a maximum after 2 weeks with a continuous decline after that. Twelve months after completing the treatment the mean number of pustules was reduced to 20.0 compared with 63.6 at baseline (P < 0.001); 11 patients were free from pustules and two of these were totally cleared. We conclude that cyclosporin at 1-2 mg/kg per day is an effective and well tolerated treatment for PPP in most patients.
Physician Attitudes and Practice in Cancer Pain Management: A Survey From the Eastern Cooperative Oncology Group
Authors: Jamie H. Von Roenn
Journal: Annals of Internal Medicine (1993)

Objective: The Eastern Cooperative Oncology Group (ECOG) conducted a groupwide survey to determine the amount of knowledge about cancer pain and its treatment among physicians practicing in ECOG-affiliated institutions and to determine the methods of pain control being used by these physicians. Design: Survey. Setting: A questionnaire was sent to all ECOG physicians with patient care responsibilities (medical oncologists, hematologists, surgeons, and radiation therapists), practicing in university institutions, Community Clinical Oncology Program (CCOP) institutions, and Cooperative Group Outreach Programs (CGOP) institutions. Measurements: A physician cancer pain questionnaire developed by the Pain Research Group at the University of Wisconsin was used. The questionnaire was designed to assess physicians' estimates of the magnitude of pain as a specific problem for cancer patients, their perceptions of the adequacy of cancer pain management, and their report of how they manage pain in their own practice setting. Results: The study analyzed responses to 897 of 1800 surveys. In regard to the use of analgesics for cancer pain in the United States, 86% felt that the majority of patients with pain were undermedicated. Only 51% believed pain control in their own practice setting was good or very good; 31% would wait until the patient's prognosis was 6 months or less before they would start maximal analgesia. Adjuvants and prophylactic side-effect management should have been used more frequently in the treatment plan. Concerns about side-effect management and tolerance were reported as limiting analgesic prescribing. Poor pain assessment was rated by 76% of physicians as the single most important barrier to adequate pain management. Other barriers included patient reluctance to report pain and patient reluctance to take analgesics (both by 62%) as well as physician reluctance to prescribe opioids (61%). Conclusions: Professional education needs to focus on the proper assessment of pain, focus on the management of side effects, and focus on the use of adjuvant medications. A better understanding of the pharmacology of opioid analgesics is also needed. Physicians also need to educate patients to report pain and to effectively use the medications that are prescribed for pain management.
Abstract 17375: Subnanomolar Concentrations of Urocortin Induce Expression and Release of IL-6 Leading to STAT3 Activation
Authors: Zhaokan Yuan, Carol Chen-Scarabelli, Giuseppe Faggian, Louis Saravolatz, Gabriele Scarabelli, Wen-Shi Shieh, Qureshi Waqas, Alessandro Mazzucco, Louis Saravolatz, Tiziano M Scarabelli
Journal: Circulation (2011)

Background: We recently showed that short-term treatment with urocortin (Ucn) of HL-1 cells induces Src-mediated phosphorylation and subsequent nuclear translocation of Signal Transducer and Activator of Transcription (STAT)3. In breast cancer cells, STAT3 was found to be activated by IL-6, while Ucn was shown to stimulate IL-1β and IL-6 secretion from mononuclear inflammatory cells. Aim: To verify whether cardiac myocytes can express and secrete IL-6, and, if so, to investigate the role of IL-6 in Ucn-mediated STAT3 activation. Methods and Results: Immortalized mouse atrial HL-1 cardiomyocytes were cultured in Claycomb medium supplemented with 10% fetal bovine serum, before being serum-starved for 16 to 20 hours. IL-6 enzyme-linked immunosorbent assay (ELISA) of the conditioned medium from starved HL-1 cells showed that 16 and 24 hours treatment with 10 nM Ucn increased the secretion of IL-6 to 162.9±8.0% and 235.3±34.5%, respectively, as compared to control cells. Conversely, Ucn did not induce the release in the culture medium of IL-1β, as documented by IL-1β ELISA. Quantitative real-time PCR also confirmed the increased expression of IL-6 at the mRNA level. Interestingly, a concentration of Ucn as low as 0.01 nM, which was not sufficient to activate Src kinase, could indeed induce the expression and secretion of IL-6 by 275.7±9.4%. Moreover, transAM STAT3 transcription factor assay (ELISA) and Western blot analysis of HL-1 nuclear extracts showed that 100 nM Ucn increased the nuclear translocation of STAT3 by 132.2±10.9% and 2.6 folds, respectively. STAT3 nuclear translocation was significantly reduced, though not abrogated, by incubation of HL-1 cells with 2 μ g/ml of anti-IL-6 polyclonal antibody (109.1±10.2% and 1.1 folds, respectively). Conclusions: We report for the first time that incubation of HL-1 cells with subnanomolar concentrations of Ucn induced the expression and secretion of IL-6, which resulted in STAT3 activation via an autocrine/paracrine mechanism, independent from Src activation.
Abstract 12587: An Improved Approach to Cardiac Volumetrics: A Cardiac MRI Technique to Further Augment Accuracy
Authors: Geetha Rayarao, Robert W Biederman, Diane V Thompson, Sahadev T Reddy, June Yamrozik, Ronald B Williams, Mark Doyle
Journal: Circulation (2014)

Introduction: In cardiac MRI (CMR), heart volumes are traditionally measured using contouring methods applied to contiguous image data. Herein, we introduce a new approach, Automatic Threshold and Manual Trimming (ATMT), which is applied to the same contiguous data set. Potentially, the ATMT method can be applied by seed/region-growing algorithms with minimal user supervision. We sought to establish its clinical validity. Hypothesis: We hypothesize that the ATMT approach is more accurate as compared to conventional 'gold standard', cardiac contouring. Methods: Hearts from two populations (N=74) were evaluated: explanted heart transplant (Tx) and a clinical validation cohort ( in vivo ). The transplanted hearts were imaged ex vivo using CMR and then weighed on a high-fidelity scale. Cardiac volume/mass was compared (N=54) to the patient cohort (N=20) and measured non-invasively with stroke volume, independently measured via CMR phase velocity technique. Bland-Altman was applied in a 3-way manner for each group. Results: Bland-Altman analysis for Standard Deviation (SD), Bias and Correlation (R) are summarized in Table 1. When compared with independent measurements (weight/flow), ATMT has lower Bias (close to zero) and SD. Further, any comparison involving cardiac contours has a substantially larger bias term and a higher SD. From the table below, ATMT has consistently higher correlations with the independent measurement than does the contour method. Conclusions: Based on multiple comparison metrics with independent measures, the ATMT approach is more accurate and reproducible for quantification of cardiac volume (integral for EF determination) as compared to standard contouring. Furthermore, ATMT accommodates trabeculae and papillary structures more intuitively than the contouring method. This intrinsic accuracy coupled with the potential for more rapid analysis gives a valid impetus to further develop the ATMT approach further increasing CMR accuracy.
Abstract P348: A Novel Antioxidant Score Independently Predicts CVD Mortality Better than Any Single Antioxidant: Longitudinal Data from the Third National Health and Nutrition Examination Survey (1988-94)
Authors: Cindy E McCrea, Jacqueline A Vernarelli, Penny M Kris-Etherton, Katherine A Sauder, Sheila G West
Journal: Circulation (2014)

Despite the implication of oxidative stress in CVD development, neither blood levels of nor supplementation with any one individual antioxidant is consistently related to CVD incidence and death. Thus, the relationship between diet-derived antioxidants and CVD remains unclear. However, many analyses consider the predictive value of only a few antioxidant markers in isolation, which may not reflect overall antioxidant status. We developed an antioxidant score and tested the hypothesis that it would be a more robust predictor of CVD death than concentrations of single antioxidants in aging adults. Quintiles of 10 serum antioxidant concentrations (α-carotene, β-carotene, β-cryptoxanthin, lutein, lycopene, vitamins A, C, E, retinyl esters and selenium), collected at baseline from 7094 (weighted N = 58,875,272) adults aged 50+ years enrolled in the Third National Health and Nutrition Examination Survey (1988-1994) were used as predictors in a time-to-death analysis using Cox regression modeling. Forty-two percent (N=3695, weighted to 26189208) of the sample was deceased at 12-18 year follow-up, with 1362 deceased due to CVD. In models adjusted for known demographic, behavioral and biological risk factors, concentration quintiles of the individual antioxidants α-carotene, lycopene, selenium and retinyl ester were significantly associated with CVD death (ps for trend ranged from 0.015 to 0.042, HRs of quintile 1 vs 5 ranged from 1.34 to 1.52). A stepwise regression method was used to identify the best combination of candidate markers, and an antioxidant score was computed using only those 6 markers (vitamins C and E, lycopene, selenium, α and β-carotene). Quintiles of the antioxidant score were also significantly associated with risk of death (p for trend = 0.004, HR for Q1 vs. Q5 = 1.88) and in a more predictive manner than a score using all 10 antioxidants (p for trend = 0.016, HR for Q1 vs. Q5 = 1.69). After controlling for traditional risk factors, an antioxidant score including vitamins C and E, lycopene, selenium, α and β-carotene was more strongly associated with rates of CVD death than individual antioxidants in a large nationally representative sample of aging adults. An antioxidant score may more closely reflect oxidative status than measures of single dietary antioxidants, and therefore be more useful when assessing risk of CVD death.
Abstract 157: Randomized Controlled Trial of the Impact of Ultra-Brief Chest Compression-Only CPR Video Training on Responsiveness, Compression Rate, and Hands-Off Time Interval Among Bystanders in a Shopping Mall
Authors: Ashish R Panchal, Omar Meziab, Uwe Stolz, Wes Anderson, Mitchell Bartlett, Daniel W Spaite, Bentley Bobrow, Karl B Kern
Journal: Circulation (2013)

Background: Recent studies have demonstrated higher quality chest compressions (CCs) following a 60 sec ultra-brief video (UBV) on compression-only CPR (CO-CPR). However, the effectiveness of UBVs as a CPR teaching tool for lay bystanders in public venues remains unknown. Objective: Determine whether: 1) UBV is an effective instrument to teach laypersons CO-CPR in a public setting and 2) viewing leads to superior responsiveness and CPR skills in simulated arrest scenarios versus untrained controls. Methods: Study setting was a shopping mall. Adult (age ≥18) bystanders with no CPR training in the last 24 months were enrolled and randomized into two arms: (1) Control (CTR): sat idle for 60 sec; (2) UBV: watched a 60 sec UBV on CO-CPR. Subjects were taken to a private area where a Laerdal Skillreporter™ mannequin was on the ground and read a simulated scenario detailing a sudden collapse in the mall and asked to do what they “thought was best”. Performance measures were recorded for 2 min: responsiveness (ti...
An Outbreak of cepacia Respiratory Tract Colonization and Infection Associated with Nebulized Albuterol Therapy
Authors: Richard J. Hamill
Journal: Annals of Internal Medicine (1995)

To investigate an outbreak of Burkholderia (formerly Pseudomonas) cepacia respiratory tract colonization and infection in mechanically ventilated patients.A retrospective case-control and bacteriologic study.Veterans Affairs medical center.42 mechanically ventilated patients who developed respiratory tract colonization or infection with B. cepacia and 135 ventilator-dependent controls who were not colonized and did not develop infections.Clinical and demographic data; benzalkonium chloride concentrations and pH levels in albuterol sulfate solutions; repetitive-element polymerase chain reaction (PCR)-mediated molecular fingerprinting on eight patient isolates and three environmental B. cepacia isolates that were available for study.42 patients had B. cepacia respiratory tract colonization or infection. Observation of intensive care unit and respiratory care personnel showed faulty infection control procedures (for example, the same multiple-dose bottle of albuterol was used for many mechanically ventilated patients). More case patients (39 [92.9%]) than controls (95 [70.4%]; P = 0.006) received nebulized albuterol, and case patients (67.5 treatments) received more treatments than controls (18 treatments; P < 0.001). In-use albuterol solutions had pH values that were unstable, and benzalkonium chloride concentrations declined over time to levels capable of supporting bacterial growth. Medication nebulizers and in-use bottles of albuterol harbored B. cepacia. Molecular fingerprints of patient isolates and environmental B. cepacia isolates were identical using repetitive-element PCR. No further isolates of B. cepacia were identified after institution of appropriate infection control procedures.Multiple-dose medications and reliance on benzalkonium chloride as a medication preservative provide a mechanism for nosocomial spread of microorganisms, particularly if infection control procedures are not carefully followed. Repetitive-element PCR is a useful fingerprinting technique for molecular epidemiologic studies of B. cepacia.
Abstract 4094: Identification of co-inhibitory receptor expression on T cells from gastric cancer patients
Authors: Yunhui Zong, Fuliang Chu, Songbing He, Yu Jing, Sally A Hunsucker, Tina Yang, Ming Zhang, Sisi Ye, Yafen Li, Bin Liu, Jinle Tang, Huimin Meng, Gangli An, Lin Yang
Journal: Cancer Research (2014)

Abstract The critical role of tumour antigen-specific immune responses to restrain tumour growth in patients with gastric cancer furthers the need to dissect the co-inhibitory pathways involved in tumour infiltrating lymphocyte (TIL) exhaustion/dysfunction. It was previously reported that PD-1 expression was significantly increased on CD4+ and CD8+ T cells from patients with gastric cancer and in gastric cancer tissues, compared to normal donors. In this study, we observed up-regulation of TIM-3 and PD-1 expression on peripheral T cells and up-regulation of CTLA-4, TIGIT, TIM-3 and PD-1 expression on TILs from gastric cancer patients; however TIGIT was down-regulated on CD8+ TILs and TIM-3 up-regulation on CD8+ TILs was not statistically significant. Furthermore, the percentages of PD-1+/TIM-3+ and PD-1+/TIM-3- peripheral T cells was significantly higher in gastric cancer patients than normal donors, and the percentage of PD-1+/TIM-3+ TILs was significantly higher than the percentage of PD-1+/TIM-3+ peripheral T cells in gastric cancer patients. PD-1+/TIM-3+ cells represent the predominant fraction of TILs. PD-1 blockade enhanced cytokine production and the cytotoxicity of TILs and exhibited a synergistic effect with TIM-3 blockade. Collectively, our results suggest that the use of anti-PD-1 blockade in combination with anti-TIM-3 blockade could restore the cytotoxic activity of TILs in patients with gastric cancer. Citation Format: Yunhui Zong, Fuliang Chu, Songbing He, Yu Jing, Sally A Hunsucker, Tina Yang, Ming Zhang, Sisi Ye, Yafen Li, Bin Liu, Jinle Tang, Huimin Meng, Gangli An, Lin Yang. Identification of co-inhibitory receptor expression on T cells from gastric cancer patients. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4094. doi:10.1158/1538-7445.AM2014-4094
Precision pulmonary trans-arterial chemoembolization (PPTACE) plus percutaneous RFA for unresectable lung neoplasms: Initial experience in twelve cases
Authors: C. Gadaleta, A. Catino, G. Rubini, G. Ranieri, V. Fazio, G. Gadaleta-Caldarola, G. Vinciarelli, F. Armenise, A. Gaudiano, V. Mattioli
Journal: Journal of Clinical Oncology (2009)

7593 Background: The study aimed to evaluate the feasibility and safety of precision pulmonary arterial chemoembolization (PPTACE) followed by percutaneous RFA in patients with unresectable lung neoplasms Methods: From November 2007 to October 2008, twelve patients (5 male, 7 female, median age 57) and 20 nodules were treated in 14 sessions. Patients had lung metastases from the following tumors: uterine cancer (2), colorectal carcinoma (7), breast carcinoma (1) and two patients had primary unresectable NSCLC. Median diameter of neoplasms was 2 cm. Both RFA and pulmonary TACE were performed under general anesthesia. Two patients underwent two sessions of treatment due to bilateral disease. After subclavian vein puncture and mapping of arterial vascularization of the segment including the tumoral nodule, antiblastic agents loaded on microspheres (Hepasphere, 50–100 micron in diameter) were selectively perfused in a subsegmental sector. Doxorubicin was used in 3 sessions, as well as mitomycin C, while irinotecan was administered in six cases and cisplatin in one case (one session was performed only with microspheres). Percutaneous CT-guided RFA of lung nodules was performed 2–7 days after PPTACE. Pretreatment work-up included: contrast-enhanced CT-scan, (18-F)Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography (18F-FDG PET/CT) and Ventilation Lung Single Photon Emission Tomography (VL-SPET). Results: The treatment was well tolerated; pneumothorax, requiring chest- tube placement, occurred in two sessions (14%). Technical success was achieved in all treated nodules. In all cases, the impedance during RFA decreased from 30 to 50%, with an increase of the delivered energy (expressed by Watts). Morphological response showed a necrotic area, without contrast-enhancement at CT scan, including the neoplasm plus a large safety zone. VL-SPET showed a wide area without ventilation in lung parenchyma submitted to PPTACE and extending over it; the changes on alveolar ventilation detected by VL- SPET after PPTACE could explain the better heat conduction during RFA. Conclusions: Lung RFA after pulmonary TACE is feasible and safe. These preliminary data deserve further investigation. No significant financial relationships to disclose.
Abstract 2985: In vivo evaluation of regorafenib and liposomal-doxorubicin in a panel of low passage uterine START-PDX tumor models
Authors: Justin Meade, Michael J. Wick, Teresa Vaught, Lizette Gamez, Roger Chavez, Anthony Tolcher, Drew Rasco, Amita Patnaik, Allan J. White, Kyriakos Papadopoulos
Journal: Cancer Research (2014)

Abstract Background: Uterine and ovary cancers account for a majority of gynecologic cancer-related deaths in Western countries. While initial cure rates are high, recurrent disease is often chemoresistant with few treatment options. Regorafenib is a recently approved multi-tyrosine kinase targeting VEGFR2 and Tie2. As Tie2 has been implicated in the pathogenesis of uterine cancers, we evaluated regorafenib as a potential therapy in our panel of uterine PDX models and compared activity to the approved therapy liposomal-doxorubicin. Methods: PDX uterine models were established in immune-deficient mice from primary or metastatic patient tissue and once established were confirmed by histologic comparative analysis with patient tumor tissue, linked with patient treatment and outcome data and characterized for activating mutations and known amplifications. Drug sensitivity studies were performed in each model evaluating daily oral regorafenib or weekly intravenous liposomal-doxorubicin versus control; group sizes were n=2-3 for control and n=1 for treatment arms. Study endpoints included a set day following treatment initiation with tumor growth inhibition or delay and regression reported at study completion. Results: For this project we evaluated twenty-five uterine models. Statistically significant (p&amp;lt;0.05) regorafenib activity was reported in a subset of evaluated endometrial models; however, activity was not limited to a particular tumor subtype or mutation profile. Liposomal-doxorubicin also demonstrated differential but significant tumor growth inhibition towards models in the evaluated panel. Conclusion: We have screened preclinical activity of regorafenib and liposomal-doxorubicin towards a panel of uterine START-PDX models and identified sensitive and resistant models. Additional genomic and characterization studies are underway to better understand activity of regorafenib with the goal of identifying a sensitivity profile for patient stratification. Citation Format: Justin Meade, Michael J. Wick, Teresa Vaught, Lizette Gamez, Roger Chavez, Anthony Tolcher, Drew Rasco, Amita Patnaik, Allan J. White, Kyriakos Papadopoulos. In vivo evaluation of regorafenib and liposomal-doxorubicin in a panel of low passage uterine START-PDX tumor models. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2985. doi:10.1158/1538-7445.AM2014-2985