tbuckley/cabot-search huggingface dataset:
Palonosetron (PALO) versus granisetron (GRAN), both combined with dexamethasone (DEX) in preventing chemotherapy-induced nausea and vomiting (CINV) associated with cisplatin- or anthracycline plus cyclophosphamide-based regimens: Results of a phase III trial in Japanese patients
Authors: I. Sekine, M. Saito, K. Aogi, H. Yoshizawa, Y. Yanagita, H. Sakai, K. Inoue, C. Kitagawa, T. Ogura, S. Mitsuhashi
Journal: Journal of Clinical Oncology (2008)

20749 Background: PALO is a pharmacologically distinct 5-HT3 receptor antagonist with unique molecular interactions with the 5-HT3 receptor compared with GRAN. Methods: This multicenter, randomized, double-blind, stratified, phase III trial assessed the efficacy/safety of a single IV dose of PALO 0.75 mg vs IV GRAN 40 μg/kg (∼3mg) administered 30 min prior to cisplatin ≥50 mg/m2 (CDDP) or anthracycline + cyclophosphamide (AC/EC). Selection of the PALO dose was based on two Phase II dose-ranging trials and the dose of GRAN is the approved dose in Japan. DEX 16 mg IV was administered before chemotherapy (CT) on day 1, and 8 mg IV (CDDP) or 4 mg orally (AC/EC) on days 2–3. Stratification factors were gender, age and CT. The study was designed to demonstrate non-inferiority on day 1 and superiority on days 2–5 of PALO vs GRAN, combined with DEX. The primary endpoint was the complete response rate (CR = no emesis, no rescue medication). Adverse events (AEs) were assessed according to NCI-Common Toxicity Criteria. Results: A total of 1,114 pts (58% women; mean age 58) were evaluated; 57% received CDDP, 43% AC/EC. The CR rate for PALO was equivalent to GRAN in acute phase and significantly greater than GRAN in delayed phase (Table). Overall CR (0–120 h) was also greater for PALO (51.5%) vs GRAN (40.4%). Time to treatment failure was significantly longer for PALO with separation in the curves at 16 hrs after CT on day 1 (Hazard Ratio: 1.30, 95% CI: 1.106-1.526). The incidence, pattern or intensity of AEs did not differ between PALO and GRAN. Conclusions: A single dose of PALO resulted in a comparable prevention of CINV to GRAN at the end of day 1, and demonstrated superior long-lasting CINV prevention in the delayed phase in patients receiving highly emetogenic CT. CR rates Period CR (%) PALO vs GRAN p-value PALO 0.75 mg (N=555) GRAN 40 μg/kg (N=559) PALO minus GRAN Acute (0–24 hrs) § 77.5 75.2 2.29 [-2.70, 7.27]† Not done Delayed (24–120 hrs) 56.8 44.5 12.3 < 0.001* § : mean of minimum squared values adjusted with stratified factors (CT, gender and age) † : lower limit >-10% indicates non-inferiority of PALO against GRAN * : Cochran-Mantel-Haenszel test stratified with CT, gender and age No significant financial relationships to disclose.
OC-063 Relevance of routine post-cholecystectomy histopathological testing in different age demographics: a cost-benefit analysis
Authors: R Zakeri, P Latham, J Jackson, T Kingston, S Yeluri, C Kelty
Journal: Gut (2015)

<h3>Introduction</h3> Gallbladder cancer is an uncommon primary intra-abdominal malignancy, with around 800 new cases diagnosed in the UK each year.<sup>1</sup>Nevertheless, routine histopathological analysis of cholecystectomy specimens is current practice within many trusts. In our unit, a tertiary centre for hepatobiliary surgery, we perform approximately 1000 cholecystectomies per annum. Histological testing requires in the range of 15–60 min per gallbladder analysed, at a fixed cost of £64.95. We aim to determine the cost-benefit value of routine histopathological testing in light of current demographics and ever-increasing financial constraints. <h3>Method</h3> Retrospective analysis of all cholecystectomy cases performed over 1 year (October 2013–14). Histopathology reports were reviewed and case notes analysed in those identifying malignancy. All new diagnoses of gallbladder malignancy within the trust during the same time period were also analysed for patient demographics, clinical presentation and imaging findings. <h3>Results</h3> 983 cholecystectomies were performed, with 70 cases excluded due to known intra-abdominal malignancy or incorrect coding. Median age was 51 years (range 16–90 years) with female:male ratio 2.5:1. 90.7% of cases were elective, 45.0% day-case, with 91.5% performed laparoscopically (conversion rate = 5.5%). Gallbladders were sent for histological testing in 92.9%. Most were reported as chronic cholecystitis (85.0%). Malignancy was identified in 2 cases (0.22%) and dysplasia in a further 5 cases (0.55%), however no patients in this subgroup underwent further surgery or curative oncological treatment. During the same period, a total of 8 cases of gallbladder carcinoma were diagnosed within the trust. Median age was 68.5 years. 37.5% of patients had previous history of non-biliary malignancy and all patients had at least 1 feature of locally advanced disease on imaging performed at first presentation. <h3>Conclusion</h3> Our results show that cost and time implications for routine histopathological testing cannot be justified in the majority of cases of routine cholecystectomy for gallstone disease. Certainly in patients under 60 years of age with no risk factors, the probability of incidental diagnosis of gallbladder cancer is negligible. In our trust, this cohort comprises 592 cases per year, 65% of our total activity. Selective testing in these cases, based on risk factors, imaging and macroscopic examination of specimens, could give a saving of up to £38,450 per year. We combine our findings with concurrent analysis of gallbladder carcinoma patients to deduce guidelines for selective histopathological testing of cholecystectomy specimens. <h3>Disclosure of interest</h3> None Declared. <h3>Reference</h3> Cancer Research UK. <i>Risks and causes of gallbladder cancer</i>, 2014
Krüppel–Like Factor 15 Mediates Glucocorticoid-Induced Restoration of Podocyte Differentiation Markers
Authors: Sandeep K. Mallipattu, Yiqing Guo, Monica P. Revelo, Lucia Roa-Peña, Timothy Miller, Jason Ling, Stuart J. Shankland, Agnieszka B. Bialkowska, Victoria Ly, Chelsea Estrada, Mukesh K. Jain, Yuan Lu, Avi Ma’ayan, Anita Mehrotra, Rabi Yacoub, Edward P. Nord, Robert P. Woroniecki, Vincent W. Yang, John C. He
Journal: Journal of the American Society of Nephrology (2016)

Podocyte injury is the inciting event in primary glomerulopathies, such as minimal change disease and primary FSGS, and glucocorticoids remain the initial and often, the primary treatment of choice for these glomerulopathies. Because inflammation is not readily apparent in these diseases, understanding the direct effects of glucocorticoids on the podocyte, independent of the immunomodulatory effects, may lead to the identification of targets downstream of glucocorticoids that minimize toxicity without compromising efficacy. Several studies showed that treatment with glucocorticoids restores podocyte differentiation markers and normal ultrastructure and improves cell survival in murine podocytes. We previously determined that Krüppel-like factor 15 (KLF15), a kidney-enriched zinc finger transcription factor, is required for restoring podocyte differentiation markers in mice and human podocytes under cell stress. Here, we show that in vitro treatment with dexamethasone induced a rapid increase of KLF15 expression in human and murine podocytes and enhanced the affinity of glucocorticoid receptor binding to the promoter region of KLF15 In three independent proteinuric murine models, podocyte-specific loss of Klf15 abrogated dexamethasone-induced podocyte recovery. Furthermore, knockdown of KLF15 reduced cell survival and destabilized the actin cytoskeleton in differentiated human podocytes. Conversely, overexpression of KLF15 stabilized the actin cytoskeleton under cell stress in human podocytes. Finally, the level of KLF15 expression in the podocytes and glomeruli from human biopsy specimens correlated with glucocorticoid responsiveness in 35 patients with minimal change disease or primary FSGS. Thus, these studies identify the critical role of KLF15 in mediating the salutary effects of glucocorticoids in the podocyte.
The coming crisis in funding child psychiatry training
Authors: R S McKelvey
Journal: American Journal of Psychiatry (1990)

Rapid changes in health care financing and delivery systems will adversely affect child psychiatry training. Reductions in teaching hospitals' patient revenues and in federal support for graduate medical education have made the development of strong academic and research programs more difficult. Training programs must search for innovative ways to fund clinical training if they are to survive and grow. The authors review major sources for funding, such as state governments, future employers of trainees, endowments, faculty practice plans, and residents paying for training, and discuss opportunities for increasing their contributions.
Bowel obsessions responsive to tricyclic antidepressants in four patients
Authors: M A Jenike, H L Vitagliano, J Rabinowitz, D C Goff, L Baer
Journal: American Journal of Psychiatry (1987)

The authors report on four patients with disabling bowel obsessions who responded to tricyclic antidepressant medication despite the absence of depressive symptoms. The relationship of this symptom constellation to DSM-III obsessive-compulsive disorder and social phobia is discussed.
Should psychic studies be included in psychiatric education? An opinion survey
Authors: S R Dean, C O Plyler, M L Dean
Journal: American Journal of Psychiatry (1980)

The authors received 228 response to a questionnaire on psychic phenomena mailed to professors and residents in psychiatry, other medical faculty, and deans of medical schools. Fifty-eight percent of the respondents believed that an understanding of psychic phenomena is important to future graduates of psychiatry, and 44% believed that psychic factors are important in the healing process. The authors believe that including psychic studies in psychiatric education would attract more medical students to psychiatry.
Abstract 3529: BET bromodomain proteins regulate the canonical WNT signaling and drug resistance in colorectal cancer
Authors: Lihong Wang, Yufang Ma, Ethan Lee, Jialiang Wang
Journal: Cancer Research (2015)

Abstract The canonical WNT signaling is aberrantly activated in the vast majority of colorectal cancer (CRC) and results in activation of beta-catenin and its downstream target MYC. These two oncogenic transcription factors play central roles in CRC pathogenesis, but are refractory to direct pharmacological interventions. The recurrent mutations of APC or β-catenin in CRC also limit the utilities of currently available WNT inhibitors that mostly target upstream regulators. The bromodomain and extra-terminal domain (BET) family epigenetic readers recently emerged as a key regulator of MYC expression. In the present study, we demonstrated that BET proteins regulated beta-catenin-mediated MYC expression in CRC. Inhibition of BET proteins repressed activities of both wild type and constitutively active β-catenin mutants. Pharmacological or genetic targeting of BET proteins broadly impaired proliferation and survival in CRC cells, including KRAS or BRAF-mutant lines. Furthermore, BET bromodomain inhibitors synergistically sensitized CRC cells to inhibitors of the MAPK pathway. The ability of BET inhibitors to augment the efficacy of the MAPK pathway inhibitors is potentially secondary to altered balance among pro-survival and pro-apoptotic regulators. Using KRAS- or BRAF-mutant CRC xenograft models, we showed that a combination of BET inhibitor and MEK inhibitor, but not either agent alone, induced significant tumor regression. Our findings suggest that BET-based epigenetic therapy can be utilized as an alternative approach to block the canonical WNT signaling in CRC and potentially other human cancers, in particular those carrying APC or beta-catenin mutations. Our results also identify a novel combination therapy for treating CRCs, including those refractory to currently available therapeutic options. Citation Format: Lihong Wang, Yufang Ma, Ethan Lee, Jialiang Wang. BET bromodomain proteins regulate the canonical WNT signaling and drug resistance in colorectal cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3529. doi:10.1158/1538-7445.AM2015-3529
Testicular Cancer
Authors: Janet M. Torpy
Journal: JAMA (2008)

Testicular Cancer Cancer of the testicle, the male reproductive organ responsible for making sperm, is common, especially among younger men.In developed nations, the chance of a man developing testicular cancer during his life is 1 in 300.The risk of dying from testicular cancer is very low because it can be treated and even cured when found early.Regular selfexamination of the testicles is the best way for a man to detect testicular cancer as early as possible.Treatment and prognosis (chances of cure) depend on the type of cancer found in the testicle.The February 13, 2008, issue of JAMA includes an article about treating advanced testicular cancer.
An outbreak of airborne tularaemia in France, August 2004
Authors: V Siret, D Barataud, M Prat, V Vaillant, S Ansart, A Le Coustumier, J Vaissaire, F Raffi, M Garré, I Capek
Journal: Eurosurveillance (2006)

Fifteen tularaemia cases were identified after a holiday spent at a converted mill in the Vendee region in France, between 9 and 12 August 2004. The mill was visited, and descriptive, retrospective cohort and environmental investigations were conducted. The 39 people who had stayed at the mill between 24 July and 11 August were asked about symptoms, exposure to food and animals, and leisure activities. A case was defined as a person with evidence of fever and a positive serology (seroconversion or significant rise in antibody titre, or a single titre) = 40. Culture for Francisella tularensis and polymerase chain reaction (PCR) diagnosis was carried out for drinking water, firewood, and domestic animals at the mill. Fifteen cases of tularaemia (38%) were confirmed. Twelve of the cases (80%) had the pulmonary form. None of the patients was admitted to hospital. There was a strong association between infection and participation in a dinner at the mill on 4 August (p < 10(-8)). One of the three dogs present in the dining room was serologically positive for F. tularensis. Results of analysis of environmental samples were negative. These investigations confirmed the occurrence of a cluster of 15 tularaemia cases, in patients who were infected on the evening of 4 August, in a mill in VendAe, an endemic area for tularaemia. The investigations highlight the existence of nonspecific and benign pulmonary forms of the illness in France. The pulmonary form of infection in the human cases and the positive serology of the dog suggest contamination by inhalation of contaminated particles from the dogos fur disseminated by the dog shaking itself.
AB1133 Epidemiological Comparative Analysis in a Large Cohort of Psoriatic Arthritis Patients: Results of the Spanish IMID Consortium
Authors: J. Cañete, J. Rodriguez, J. Gratacos, R. Queiro, C. Montilla, J.C. Torre-Alonso, J.J. Pérez-Venegas, S. Muñoz, A. Fernández-Nebro, C. González, D. Roig, A. Erra, R. Tortosa, R. Juverdeanu, A. Alonso, M. Lόpez-Lasanta, S. Marsal
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background</h3> Psoriatic Arthritis (PsA) is a complex disease of unknown etiology, involving both genetic and environmental factors. <h3>Objectives</h3> To analyze the more relevant epidemiological characteristics in a large cohort of patients with PsA and controls in the Spanish population. <h3>Methods</h3> A cross-sectional, comparative, multicenter study of patients with PsA and hypernormal healthy subjects for IMID diseases was performed. All patients were recruited through the <i>Immune-Mediated Inflammatory Diseases</i> Consortium (IMIDC).The IMIDC is a network of Spanish biomedical researchers focused in the study of the molecular basis of immune-mediated inflammatory diseases. All patients included in the present study were selected from the outpatient clinics of 13 Rheumatology Departments at different Spanish University Hospitals. An epidemiological questionnaire developed by experts at DNA National Bank was applied to obtain all data. <h3>Results</h3> 1,602 PsA patients and 1,558 healthy subjects were included. 53% of PsA patients and 60% of controls were male. The mean age of patients PsA patients and controls was 52±13 years and 49±7 years respectively. In the univariate analysis, we observed that the height and weight of the control subjects was significantly higher than in patients with PsA.The level of statistical significance was decreased by introducing gender and age as covariates.In our cohort,55% of patients with PsA had no education or only primary education. Control subjects mostly had secondary or higher education.The physical exercise was significantly more frequent among controls. The gender and age affect the assessment of physical activity performed by both groups of patients.Regarding employment status, most patients with PsA (29%) and controls (44%) were external employers.Both PsA patients and controls (52%) most frequently use their private cars.The mean consumption of tobacco and alcohol was higher in the control group and the statistical significance was maintained in multivariate analysis.In both univariate and multivariate analysis,statistical differences in the average number of children and consumption of coffee were observed. <h3>Conclusions</h3> In this large comparative study we describe for the first time the general epidemiological characteristics in patients with PsA and healthy subjects representative of the Spanish population.PsA patients are older, have an average number of children higher and lower consumption of alcohol and tobacco than controls. The influence of gender confirms the significance level of variables such as physical activity, weight and height. <h3>Disclosure of Interest</h3> None declared
Accumulation, Intracellular Metabolism, and Antitumor Activity of High- and Low-Dose Methotrexate in Human Osteosarcoma Xenografts
Authors: William H. Meyer, Susan K. Loftin, Janet A. Houghton, Peter J. Houghton
Journal: Cancer Communications (1990)

High doses of methotrexate with leucovorin rescue are routinely used in the treatment of patients with osteosarcoma; the rationale for this application is controversial. Using human osteosarcoma xenografts growing in mice as a clinically relevant model, we compared the accumulation, intracellular metabolism, and tumor response of methotrexate administered as either high-dose (2400 mg/kg) or low-dose (150 mg/kg) infusions. The high-dose regimen, which included i.v. hydration and leucovorin rescue, resulted in plasma methotrexate levels that approximated those in patients receiving the drug at 12 g/m2. The low-dose infusion produced essentially the same toxicity as the higher dose level, without use of leucovorin. The HxOs33 tumor line was moderately sensitive to the high-dose infusion (55-day delay in tumor volume doubling time), whereas the second line, HxOs2, did not respond. Neither xenograft had a measurable response to low-dose methotrexate. Methotrexate was present in both tumors for up to 72 hr post-infusion, regardless of the dosage regimen. Only shorter-chain polyglutamates (MTXglu2 and MTXglu3) were detected over this period in the high-dose trial, and levels of these derivatives were uniformly higher in the resistant HxOs2 xenograft. Low-dose infusions were associated with formation of longer-chain polyglutamate species, with more abundant production in the HxOs2 line. Methotrexate polyglutamates exceeded baseline [3H]MTX binding of dihydrofolate reductase, as measured in tumor homogenates, at all testing intervals through 72 hr in both tumor lines. Nonetheless, high-dose methotrexate-induced suppression of [14C]formate incorporation into DNA was greater in the drug-sensitive HxOs33 tumor than in HxOs2. These results suggest a therapeutic advantage for high-dose methotrexate regimens in the treatment of human osteosarcoma but show that formation of tumor MTX polyglutamates is not the sole determinant of response to this agent.
Federal Employees' experience as a guide to the cost of insuring psychiatric services in the various states
Authors: J Krizay
Journal: American Journal of Psychiatry (1982)

The two largest plans in the Federal Employees Health Benefits Program-Blue Cross and Blue Shield and Aetna - have reported benefit payments and the number of people who have used psychiatric services on a state-by-state basis for two decades. The author translates this experience into per capita utilization rates in a constant dollar terms and compares the benefit costs of the two plants over a 4-year period (1976-1979). Within each state, utilization rates did not change much over the 4 years, and the rank ordering among states by rate of utilization was quite similar for both plants. The author believes that the consistency noted can be useful in estimating costs of psychiatric coverage at the state level.
The Effect of Ultracentrifugation and Hyaluronidase on the Filtrability of Chick-Embryo Extract for Tissue Culture&lt;xref ref-type="fn" rid="fn1"&gt;2&lt;/xref&gt;
Authors: J C BRYANT, W R EARLE, E V PEPPERS
Journal: JNCI Journal of the National Cancer Institute (1953)

Journal Article The Effect of Ultracentrifugation and Hyaluronidase on the Filtrability of Chick-Embryo Extract for Tissue Culture Get access Jay C. Bryant, Jay C. Bryant Tissue Culture Section, Laboratory of Biology, National Cancer Institute,3Bethesda 14, Md. Search for other works by this author on: Oxford Academic PubMed Google Scholar Wilton R. Earle, Wilton R. Earle Tissue Culture Section, Laboratory of Biology, National Cancer Institute,3Bethesda 14, Md. Search for other works by this author on: Oxford Academic PubMed Google Scholar Ellison V. Peppers Ellison V. Peppers Tissue Culture Section, Laboratory of Biology, National Cancer Institute,3Bethesda 14, Md. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 14, Issue 1, August 1953, Pages 189–225, https://doi.org/10.1093/jnci/14.1.189 Published: 01 August 1953 Article history Received: 07 July 1952 Published: 01 August 1953