tbuckley/cabot-search huggingface dataset:
A phase 2, randomized trial of GVAX pancreas and CRS-207 immunotherapy versus GVAX alone in patients with metastatic pancreatic adenocarcinoma: Updated results.
Authors: Dung T. Le, Andrea Wang-Gillam, Vincent Picozzi, Jr, Tim F. Greten, Todd S. Crocenzi, Gregory M. Springett, Michael Morse, Herbert Zeh, Deirdre Jill Cohen, Robert Lance Fine, Beth Onners, Jennifer N. Uram, Dan Laheru, Aimee Murphy, Justin Skoble, Ed Lemmens, John J. Grous, Thomas Dubensky, Dirk G. Brockstedt, Elizabeth M. Jaffee
Journal: Journal of Clinical Oncology (2014)

177^ Background: Immunotherapy for pancreatic ductal adenocarcinoma (PDA) is likely to require synergistic combinations. One approach is to use heterologous prime boost vaccinations to capitalize on immunostimulatory features of distinct vectors. GVAX is irradiated, GM-CSF-secreting allogeneic pancreatic cell lines given intradermally to elicit a broad antigenic response. Low-dose cyclophosphamide (CY) is given prior to GVAX to inhibit regulatory T-cells. CRS-207 is live-attenuated Listeria monocytogenes (Lm) which expresses mesothelin and stimulates innate and adaptive immunity. In mouse tumor models, Lm/GVAX vaccines are synergistic and in the Phase 1 study of CRS-207, 3 PDA patients who had received prior GVAX lived ≥15 months (mos). Methods: Metastatic PDA patients (ECOG 0-1; adequate organ function) who received or refused ≥1 prior chemotherapy were randomized 2:1 to receive either 2 doses of CY/GVAX followed by 4 doses of CRS-207 (Arm A) or 6 doses of CY/GVAX (Arm B) every 3 weeks. Courses could be repeated. The primary endpoint was to compare overall survival (OS) between the arms. Secondary endpoints were safety, clinical and immune responses. One-sided p-values are reported. Results: 90 patients (Full Analysis Set [FAS]; A: 61, B: 29), of which 51% had received ≥2 chemotherapy regimens for metastatic PDA, were treated. After a median follow-up of 7.8 mos, median OS in FAS was 6.1 vs 3.9 mos (A vs B; HR=0.54, p=0.011). Median OS in patients who received ≥3 doses (per protocol [PP] set: 2 doses of CY/GVAX and ≥1 dose of CRS-207 in A or ≥3 doses of CY/GVAX in B) was 9.7 vs 4.6 mos (A vs B; HR=0.44, p=0.0074). The treatment effect was particularly evident in patients who received ≥2 prior regimens for metastatic PDA with median OS of 5.1 vs 3.7 mos (A vs B; HR=0.34, p=0.001). OS in the PP set was 8.2 vs 4.0 mos (A vs B; HR=0.23, p=0.0003). CA19-9 stabilization was seen in 32% vs 13% of patients (A vs B; p=0.06). Toxicities included local reactions after GVAX and transient fevers, rigors and lymphopenia after CRS-207. Conclusions: CY/GVAX followed by CRS-207 shows extended survival with manageable toxicity in previously-treated metastatic PDA and warrants further study. Clinical trial information: NCT01417000.
The Changing Face of Chairmen of Psychiatry Departments in America: An Opinion
Authors: ARNOLD J. MANDELL
Journal: American Journal of Psychiatry (1974)

Two decades ago psychiatrists were trained by a few charismatic, humanistic clinicians who did not have much to do with laboratories or fund raising. After World War II academic psychiatry was transformed, largely by federal money, into a multidimensional scientific enterprise, the leaders of which needed to be scientific entrepreneurs as well as persuasive humanists. But, the author believes, since the fantastic promise of a technology for universal well-being could not be fulfilled before the sources of financial support began to dry up, department chairmen are evolving from humanistic scientists into corporate executives who haven't the time or energy to pursue clinical elegance or rigorous laboratory research firsthand.
N-(phosphonacetyl)-l-aspartate and calcium leucovorin modulation of fluorouracil administered by constant rate and circadian pattern of infusion over 72 hours in metastatic gastrointestinal adenocarcinoma
Authors: J.L. Grem, L.K. Yee, B. Schuler, J.M. Hamilton, A.P. Chen, C. Chabuk, F. Grollman, M. Grabenc, C.J. AJlegra, C.H. Takimoto
Journal: Annals of Oncology (2001)
Endemic meningococcal disease in Cerdanyola, Spain, 1987–93: molecular epidemiology of the isolates of Neisseria meningitidis
Authors: M. Esther Verdú, Pere Coll, Dionisia Fontanals, Francesca March, Immaculada Pons, Isabel Sanfeliu, Guillem Prats
Journal: Clinical Microbiology and Infection (1996)
Effect of Hyperthermia on Epithelial Microneoplastic Cell Populations Induced by Irradiation of Rat Skin&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN3"&gt;3&lt;/xref&gt;
Authors: N J Gragtmans, J F McGregor
Journal: JNCI Journal of the National Cancer Institute (1983)

Two groups of male rats of the Charles River CD stock received a dose of 1,600 rad beta-radiation (700 rad/min) on the skin of the dorsum. Two months later, the site of irradiation of one of the groups was treated with hyperthermia at 44 degrees C for 2.5 minutes. A third control group received only the hyperthermic treatment. Over 90% of the animals in the 2 irradiated groups developed skin tumors (benign and malignant epithelial) at the irradiated site. There was no significant difference between these 2 groups in incidence of animals with tumors, incidence of tumors, distribution of tumor types, or rate of tumor appearance. The incidence of animals with tumors in the control group was less than 4% at any time.
High-dose therapy with autologous hematopoietic rescue for follicular low-grade non-Hodgkin's lymphoma.
Authors: P J Bierman, J M Vose, J R Anderson, M R Bishop, A Kessinger, J O Armitage
Journal: Journal of Clinical Oncology (1997)

PURPOSE This study evaluated the results of high-dose therapy followed by autologous bone marrow or peripheral-blood stem-cell transplantation for patients with follicular low-grade non-Hodgkin's lymphoma. PATIENTS AND METHODS We performed a retrospective review of 100 patients undergoing autologous transplantation for follicular low-grade lymphoma between April 22, 1983 and December 31, 1993. RESULTS Sixty-seven patients remained alive and 48 were failure-free. The median follow-up duration of surviving patients was 2.6 years (range, 1.0 to 11.7). There were eight (8%) deaths within 100 days of transplantation. Six additional patients died of nonrelapse causes up to 912 days after transplantation. Overall survival at 4 years was estimated to be 65% (95% confidence interval [CI], 54% to 75%) and failure-free survival was estimated to be 44% (95% CI, 33% to 55%). There was no definite evidence of a plateau in the failure-free survival curve. The only factor significantly associated with overall survival and failure-free survival was the number of chemotherapy regimen received before transplantation. No significant differences in outcome were observed between patients with follicular small cleaved-cell lymphoma and follicular mixed lymphoma, or between patients who received peripheral-blood stem-cell transplants and unpurged autologous bone marrow transplants. CONCLUSION Prolonged failure-free survival is possible following high-dose therapy and autologous hematopoietic rescue for follicular low-grade lymphoma. It is unclear whether patients are cured with this therapy or if survival is prolonged.
Differences in Response of Hamster Tumor Cells Induced by Polyoma Virus to Interfering Virus and Interferon&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Gertrude Henle, Werner Henle
Journal: JNCI Journal of the National Cancer Institute (1963)

Two cell lines, derived from tumors induced by inoculation of hamsters at birth with polyoma virus, were compared with respect to their responses to interfering virus and interferon preparations. Both lines, H-1 and H-2, were free from, and resistant to, polyoma virus. They were similar in morphology, cultural growth pattern, capacity to produce tumors in weanling hamsters, and susceptibility to Newcastle disease virus (NDV) and vesicular stomatitis virus (VSV). They differed slightly in acid production and strikingly in the degrees of resistance to NDV and VSV, which could be induced in them by ultraviolet-inactivated NDV (NDVuv) or interferon, and in their capacities to synthesize interferon. With reduction in cytopathic effects, immunofluorescence, and viral yields as criteria, H-1 cells and their various sublines showed moderate or no protection after exposure to NDVuv when challenged with NDV and VSV, respectively; they could not be rendered resistant by any interferon tested and produced irregularly an interferon ineffective in homologous and H-2 cultures but active in hamster embryo and Earle's strain L cell population. In contrast, H-2 cells were readily protected by NDVuv and interferon preparations, whether derived from homologous, hamster embryo, or L cell cultures; they yielded a potent interferon which, in turn, made hamster embryo and L cells resistant. Protection was more pronounced in the homologous than in heterologous systems. A third tumor line (H-3) reacted, as far as ascertained, like the H-2 cells. Apparently, lack of response to interfering virus and interferon is not a reliable criterion for the malignant state of cells.
Effect of metformin pretreatment on myocardial injury during coronary artery bypass surgery in patients without diabetes (MetCAB): a double-blind, randomised controlled trial
Authors: Saloua El Messaoudi, Rianne Nederlof, Coert J Zuurbier, Henry A van Swieten, Peter Pickkers, Luc Noyez, Hendrik-Jan Dieker, Marieke J Coenen, A Rogier T Donders, Annemieke Vos, Gerard A Rongen, Niels P Riksen
Journal: The Lancet Diabetes & Endocrinology (2015)
Slow-Flow Phenomenon During Carotid Artery Intervention With Embolic Protection Devices
Authors: Ivan P. Casserly, Alex Abou-Chebl, Robert B. Fathi, David S. Lee, Jacqueline Saw, Jose E. Exaire, Samir R. Kapadia, Christopher T. Bajzer, Jay S. Yadav
Journal: Journal of the American College of Cardiology (2005)
The boy who sewed his lips together in protest
Authors: T. Delamothe
Journal: BMJ (2015)

The former UK prime minister Tony Blair described the Freedom of Information Act 2000 as one of the biggest mistakes of his career. Perhaps history will judge it his greatest legacy, a worthy addendum to the Magna Carta.

Benjamin Dean used the act to force the General Medical Council to disclose secret meetings it had held throughout the Shape of Training review of UK postgraduate medical training, as he explained in his personal view a few weeks ago (doi:10.1136/bmj.h2400). After the GMC and then the Information Commissioner’s Office refused his request for documentation of these meetings, he appealed successfully to the General Regulatory Chamber of the Courts and Tribunals Service. Without his efforts, the issue …
Comparison of 2011 and 2007 GOLD guidelines for predicting mortality and hospitalization
Authors: Ane Johannessen, Roy Miodini Nilsen, Michael Storebø, Amund Gulsvik, Tomas Eagan, Per Bakke
Journal: European Respiratory Journal (2013)

Rationale : The Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2011 update on COPD bases disease classification on level of dyspnea, exacerbation history and FEV 1 , while the previous GOLD categorized disease severity according to FEV 1  only.  Objectives : To examine how GOLD2011 predicts hospitalizations and mortality in an 8-yr-period, and assess differences in predictive ability between GOLD2011 and GOLD2007.  Methods : The GenKOLS study comprised 954 COPD patients (FEV 1 /FVC 1  Measurements and Main Results : 20% were classified as GOLD2011 group A, 30% group B, 6% group C and 44% group D. Patients in GOLD2011 group D had OR (95% CI) of 4.1 (2.5, 6.7), 9.6 (3.4, 27.0), and 3.0 (0.7, 13.2) relative to group A for all-cause, respiratory and cardiovascular mortality, respectively, and 3.8 (2.4, 5.9) and 13.0 (6.6, 25.6) for all-cause and respiratory hospitalizations. Associations were similar also for GOLD2007. Adjusted AUC for GOLD2011 and GOLD2007 were 0.82/0.82 for respiratory mortality (p=0.87) and 0.77/0.76 for respiratory hospitalizations (p=0.51).  Conclusions : The predictive ability of GOLD2011 did not differ significantly from GOLD2007 in terms of hospitalizations and mortality.
Pyoderma gangrenosum with liver, spleen and btone involvement in a patient with chronic myelomonocytic leukaemia
Authors: None Vadillo, None Jucgla, None Podzamczer, None Rufi, None Domingo
Journal: British Journal of Dermatology (1999)

Pyoderma gangrenosum is a neutrophilic dermatosis of unknown aetiology. Visceral involvement by pyoderma gangrenosum is rare, the lung being the most frequent site of extracutaneous disease. We describe a 73-year-old man with pyoderma gangrenosum and chronic myelomonocytic leukaemia in whom aseptic hepatosplenic abscesses and bony lesions were associated.
Bronchial provocation testing (BPT) of pre-school children by acoustic respiratory monitoring (ARM) of wheeze (Wz) and cough (C)
Authors: Galit Livnat, Claudia Katz, Moshe Rotschild, Yazeed Toukan, Lea Bentur
Journal: European Respiratory Journal (2011)

Background: Unequivocal diagnosis of asthma in pre-school children is limited by their inability to perform spirometry. We evaluated the feasibility of BPT using an automatic ARM system.

Methods: We performed doubling-dose methacholine BPT in 41 children age 2 to 7 to confirm asthma. Provoking Concentration by wheeze-endpoint (PCWz) was declared when Wz was heard by physician auscultation, SpO2 fell by 5% or respiratory rate (RR) increased by >50%. ARM of Wz and C (PulmoTrack®, KarmelSonix, Israel) was recorded in parallel and reviewed off-line.

Results: Endpoint by ARM was the same as clinical PCWz in 25/41 (60.9%) and preceded PCWz in 8/41 (19.5%) patients by 1-4 doubling doses. In 4 patients (9.8%) PCWz preceded ARM endpoint and in 4 patients (9.8%) the test was inconclusive due to poor patient cooperation. Of the 4 tests where ARM lagged behind PCWz, 2 were due to ARM not detecting Wz and 2 were possibly stopped prematurely by the physician. In 6 of the patients there were false positive ARM Wz detections due to ambient noise. In 9/41 patients (22%) there was excessive cough towards the endpoint.

Discussion and conclusions: ARM-based BPT was as good as or better than PCWz in 80% of tests. Improved sensitivity and specificity of wheeze detection and automatic detection of increased RR are needed to facilitate physician-unattended use of the ARM for a BPT.

Acknowledgement: S Godfrey, N Gavriely and the KarmelSonix Technical Team assisted in data recording and analysis. M Meriach, RT, performed the BPTs.
Abstract 10375: Rupture of Non-Thin Cap Fibroatheroma in Culprit Lesions of Acute ST Elevation Myocardial Infarction: A Virtual Histology Intravascular Ultrasound analysis
Authors: Sang-Wook Kim, Wang Soo Lee, Gary S Mintz, Akiko Maehara, Young Joon Hong, Sung Yun Lee, Seong Hoon Lim, Kwang Je Lee, Tae Ho Kim, Chee Jeong Kim, Wang Seong Ryu, August D Pichard, Neil J Weissman
Journal: Circulation (2010)

We assessed ruptured plaques with Virtual Histology Intravascular Ultrasound (VH-IVUS) in 150 pts with acute ST elevation myocardial infarction (STEMI). Methods and Results: VH-thin-capped fibroath...
日本人心臓機器療法登録(JCDTR)に基づく最近5年間の植込み型除細動療法の実情
Authors: Shimizu Akihiko, Nitta Takashi, Kurita Takashi, Imai Katsuhiko, Kobayashi Yoshinori, Soejima Kyouko, Niwano Shinichi, Watanabe Shigeyuki, Abe Haruhiko, Aizawa Yoshifusa
Journal: Circulation (2011)
Robotic-assisted thymectomy by da Vinci II versus sternotomy in the surgical treatment of non thymomatous myasthenia gravis
Authors: Stéphane Renaud, Mathilde Renaud, Nicola Santelmo, Marie Fleury, Jérôme De Seze, Christine Tranchant, Gilbert Massard
Journal: European Respiratory Journal (2011)

Introduction: Thymectomy in myasthenia gravis is controversial. Remission rate 5 years after surgery in literature varies from 13 to 51%. Sternotomy is the standard technique, not acceptable because of significant esthetic sequelae. Our objective was to demonstrate that the robot-assisted technique is at least as efficient and leaves less scars than sternotomy.

Methods: We retrospectively reviewed data of 30 patients with myasthenia gravis operated on in our center from January 1998 to December 2009. Two groups were formed: group 1 corresponding to patients who received a sternotomy, group 2 patients the robotic-assisted technique. Hospital stay, pain on D1, 1 year improvement according to De Filippi, frequency of relapses, peri-operative treatment, have been particularly studied.

Results: We identified 13 women and 7 men. The mean age was 31 years old. The mean delay before surgery was 24,8 m. Group 1 consisted of 15 patients, group 2 of 5. Complete remission rate at 1 year was 5%. Surgery decreased the frequency of relapses equally in the 2 groups. Hospitalization stay and pain on D1 in group 2 were significantly lower than those in group 1 (p=0.04, p=0.001). Postoperative improvement was not significantly different between the 2 groups.

Conclusion: Results at 1 year of the 2 techniques are fully comparable. Robot provides additional benefits: minimal esthetic sequelae, less parietal morbidity, shorter hospital stays. Our complete remission rate, lower than those in the literature, must take into account the early nature of these results. The surgical robot appears to be a promising technique and should facilitate the early management of these patients.
Phase I Trial of Concurrent Tirapazamine, Cisplatin, and Radiotherapy in Patients With Advanced Head and Neck Cancer
Authors: Danny Rischin, Lester Peters, Rodney Hicks, Peter Hughes, Richard Fisher, Rosetta Hart, Maree Sexton, Ieta D’Costa, Reinhard von Roemeling
Journal: Journal of Clinical Oncology (2001)

PURPOSE: To determine the maximum-tolerated dose of tirapazamine when combined with cisplatin and radiation in patients with T3/4 and/or N2/3 squamous cell carcinoma of the head and neck. PATIENTS AND METHODS: The starting schedule was conventionally fractionated radiotherapy (70 Gy in 7 weeks) with concomitant cisplatin 75 mg/m 2 and tirapazamine 290 mg/m 2 (before cisplatin) in weeks 1, 4, and 7 and tirapazamine alone 160 mg/m 2 three times a week in weeks 2, 3, 5, and 6. Positron emission tomography scans for tumor hypoxia ( 18 F misonidazole) were performed before and during radiotherapy. RESULTS: We treated 16 patients with predominantly oropharyngeal primary tumors, including 10 patients with T4 or N3 disease. Febrile neutropenia occurred toward the end of radiotherapy in three out of six patients treated on the initial dose level. Two of these patients also developed grade 4 acute radiation reactions. Another 10 patients were treated with the same doses, but the week 5 and week 6 tirapazamine doses were omitted. This resulted in less neutropenia and only one dose-limiting toxicity (DLT) (febrile neutropenia), and eight out of 10 patients completed treatment without any dose omissions. In these 10 patients, the acute radiation toxicities were not obviously enhanced compared with chemoradiotherapy regimens using concurrent platinum and fluorouracil. 18 F misonidazole scans detected hypoxia in 14 of 15 patients at baseline, with only one patient having detectable hypoxia at the end of treatment. With a median follow-up of 2.7 years, the 3-year failure-free survival rate was 69% (SE, 12%), the 3-year local progression-free rate was 88% (SE, 8%), and the 3-year overall survival rate was 69% (SE, 12%). CONCLUSION: DLT was due unexpectedly to febrile neutropenia, which could be overcome by omitting tirapazamine in weeks 5 and 6. The combination of tirapazamine, cisplatin, and radiotherapy resulted in remarkably good and durable clinical responses in patients with very advanced head and neck cancers. It warrants further investigation.
Population genetic differentiation of height and body mass index across Europe
Authors: Matthew R Robinson, Gibran Hemani, Carolina Medina-Gomez, Massimo Mezzavilla, Tonu Esko, Konstantin Shakhbazov, Joseph E Powell, Anna Vinkhuyzen, Sonja I Berndt, Stefan Gustafsson, Anne E Justice, Bratati Kahali, Adam E Locke, Tune H Pers, Sailaja Vedantam, Andrew R Wood, Wouter van Rheenen, Ole A Andreassen, Paolo Gasparini, Andres Metspalu, Leonard H van den Berg, Jan H Veldink, Fernando Rivadeneira, Thomas M Werge, Goncalo R Abecasis, Dorret I Boomsma, Daniel I Chasman, Eco J C de Geus, Timothy M Frayling, Joel N Hirschhorn, Jouke Jan Hottenga, Erik Ingelsson, Ruth J F Loos, Patrik K E Magnusson, Nicholas G Martin, Grant W Montgomery, Kari E North, Nancy L Pedersen, Timothy D Spector, Elizabeth K Speliotes, Michael E Goddard, Jian Yang, Peter M Visscher
Journal: Nature Genetics (2015)
Treatment of recurrent gliomas and metastatic brain tumors with a polydrug protocol designed to combat nitrosourea resistance.
Authors: V A Levin, M D Prados
Journal: Journal of Clinical Oncology (1992)

The study was undertaken to evaluate a chemotherapy protocol against recurrent malignant gliomas that was designed to combat presumed chloroethyl-nitrosourea (NU) resistance.All patients had malignant gliomas and had failed prior therapy. Patients were stratified as having either glioblastoma multiforme (GM) or anaplastic gliomas (AG) and as having failed radiotherapy (RT) only or both RT and chemotherapy. Chemotherapy consisted of six drugs: before lomustine (CCNU), thioguanine (TG), dibromodulcitol (mitolactol; DBD), and procarbazine (PCB) were given to enhance CCNU-induced tumor-cell kill and to reduce alkyltransferase repair of ethylated DNA. A fluorouracil-hydroxyurea (FUHU) combination was given 2 weeks later to kill cells that began to cycle after the challenge of the first four drugs (TPDC-FUHU chemotherapy).Of the 88 assessable patients, 37 had GM, 38 had AG, and 13 had other primary and metastatic brain tumors. For GM patients, 61% had a partial response (PR) or stable disease (SD) for a median of 9.3 months if RT only failed, and 58% had a PR or SD for a median of 5.1 months if they had previously been treated with an NU. For AG patients, 92% had a PR or SD for a median of 15 months if RT only had failed, but only 38% had a PR or SD for a median of 10.6 months if they had been previously treated with a NU. Activity was also seen against other recurrent or progressive primary and metastatic brain tumors.TDPC-FUHU chemotherapy is a highly effective form of chemotherapy for both recurrent GM and AG patients. This study suggests but does not prove that this combination may be superior to other NU-based treatments for recurrent malignant glioma patients who fail RT. Because of the activity of this chemotherapy, we intend to evaluate more fully this approach in a randomized study.