tbuckley/cabot-search huggingface dataset:
Abstract CT411: Immune profiling of patients vaccinated with the survivin targeted therapeutic vaccine DPX-Survivac demonstrates durable polyfunctional CD4+ and CD8+ T cells in ovarian cancer patients
Authors: Yoav Peretz, Dominike Sauvé, Dominic Gagnon, Salim Ahmed Khan, Geneviève Lévesque, Nathalie Saha, Gilbert Croteau, Valérie Hébert, Karyne Savard, Bader Yassine Diab, Jean-Francois Poulin, Claire Landry, Mohan Karkada, Marc Mansour
Journal: Cancer Research (2014)

Abstract Survivin is a member of the inhibitor of apoptosis protein family and its over-expression has been reported in many cancer types such as melanoma, colon, brain, breast, and ovarian cancers making it a promising target for immunotherapy. DPX-Survivac is a Survivin multi-epitope vaccine that covers a broad range of HLA haplotypes (HLA-A1, A2, A3, A24, B7). The adjuvanted water free depot vaccine is designed to specifically induce CD8+ T cells. In a Phase I study in ovarian cancer patients (n=18), we aimed to evaluate one dose level of the vaccine (0.5 mL) without cyclophosphamide (Cohort A) and two dose levels (0.1 mL and 0.5 mL) combined with oral low dose cyclophosphamide as an immune modulator (Cohorts B and C). Using multiparametric flow cytometry, we measured the ex-vivo frequency, phenotype and function of Regulatory T cells (CD25+FoxP3+Ki67+) and Survivin-specific CD4 and CD8 T cells. Our data shows that cohort C preferentially mounted survivin-specific CD8 T cells which significantly peaked at one month following the third vaccination (study day 70) and persisted until at least day 126 post-vaccination. This polyfunctional T cell response was endowed with cytotoxic and proliferative functions as measured by the expression of IL-2, IFNγ, TNFα, Granzyme B and CD107a. The immune responses identified in this cohort functionally diversified over time and were distributed within the Effector memory (CD45RA-CD27-), Central Memory (CD45RA-CD27+) and Late Differentiated CD8 T cell pool (CD45RA+CD27-). Of note, polyfunctional CD4 helper responses directed against tetanus toxoid and Survivin were induced by DPX-Survivac and possibly contributed to the maintenance of the CD8 T cell response. Taken together, the data presented herein shows that DPX-Survivac induced durable polyfunctional CD4 helper and CD8 T cells providing a strong rationale for combining the targeted immune therapy with immune modulation using metronomic cyclophosphamide. Citation Format: Yoav Peretz, Dominike Sauvé, Dominic Gagnon, Salim Ahmed Khan, Geneviève Lévesque, Nathalie Saha, Gilbert Croteau, Valérie Hébert, Karyne Savard, Bader Yassine Diab, Jean-Francois Poulin, Claire Landry, Mohan Karkada, Marc Mansour. Immune profiling of patients vaccinated with the survivin targeted therapeutic vaccine DPX-Survivac demonstrates durable polyfunctional CD4+ and CD8+ T cells in ovarian 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 CT411. doi:10.1158/1538-7445.AM2014-CT411
Insufficient evidence to favour prednisolone over hydrocortisone in glucocorticoid replacement
Authors: S. H. S. Pearce
Journal: BMJ (2014)

Endocrine therapeutics is largely based on the principle that restoring the physiological pattern of hormonal secretion will control symptoms and have optimal long term health outcomes. People with adrenal insufficiency have increased morbidity and mortality from vascular disease and an increased risk of fracture.1 2 …
5-Fluorocytosine and Urinary Candidiasis
Authors: R. R. Davies, D. S. Reeves
Journal: BMJ (1971)

Two patients with urinary candidiasis were treated with 5-fluorocytosine. Serum levels of the drug and a study of its excretion in urine are recorded together with a brief account of its activity in body fluids. Evidence of toxicity was not observed with dosages of from 2 to 5 g a day.
In vivo class switch of B cells after cord blood stem cell transplantation in severe combined immune deficient (SCID) patient
Authors: Masayuki Nagasawa, Masako Imai, Kohsuke Imai, Sukeyuki Itoh, Michiko Kajiwara, Tomohiro Morio, Shigeaki Nonoyama
Journal: American Journal of Hematology (2000)
A Study of Ephedrine
Authors: K. K. Chen
Journal: BMJ (1927)

MA HUANG has been identified as Ephedra vulgaris, var.7hCletical.It is a low, dioecious, practic-ally leafless shrub, 60 to 90 cm.high.The stem, which is green, ribbed, and channelled, is the part sold in Chinese drug stores.It is
The accuracy of Doppler ultrasound measurement of pressure gradients across irregular, dual, and tunnellike obstructions to blood flow.
Authors: P S Teirstein, P G Yock, R L Popp
Journal: Circulation (1985)

The accuracy of Doppler-estimated pressure gradients in the setting of irregular, multiple, and tunnellike stenoses was investigated. An in vitro model of the left ventricular outflow tract was designed to allow pulsatile flow of red cells in saline across valve orifices from 0.01 to 2.5 cm2. Simultaneous pressure gradients were estimated by both Doppler and direct-pressure manometer techniques. Gradients obtained by the two methods correlated well for valve areas in the range of clinical stenoses at pressure gradients of 10 to 150 mm Hg (r = .97 to .99). Model valves were constructed with a large orifice (0.75 to 1.25 cm2) placed beside a small orifice (0.02 to 0.25 cm2) in the same outflow tract. A distinct jet was recorded when the Doppler transducer was aligned with each orifice. Doppler-estimated gradients for each pair of large and small orifices were identical and correlated well with those measured by manometer (r = .97 to .99). Irregularly shaped orifices also provided good correlation between the two methods (r = .98 to .99). Pulsatile flow was generated through long tunnellike obstructions with cross-sectional areas varying from 0.06 to 1.25 cm2. Tunnel length varied from 0.1 to 4 cm. Tunnel areas above 0.25 cm2 gave good Doppler-to-manometer correspondence at all tunnel lengths. Doppler underestimated manometer-determined values in the 0.25 cm2 tunnel by 8% at 3 cm and by 15% at 4 cm. In the 0.06 cm2 tunnel, Doppler underestimated manometer gradients by 12%, 15%, 32%, and 42% at lengths of 1, 2, 3, and 4 cm, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
Access to Trauma Centers in the United States
Authors: Charles C. Branas
Journal: JAMA (2005)

Previous studies have reported that the number and distribution of trauma centers are uneven across states, suggesting large differences in access to trauma center care.To estimate the proportion of US residents having access to trauma centers within 45 and 60 minutes.Cross-sectional study using data from 2 national databases as part of the Trauma Resource Allocation Model for Ambulances and Hospitals (TRAMAH) project. Trauma centers, base helipads, and block group population were counted for all 50 states and the District of Columbia as of January 2005.Percentages of national, regional, and state populations having access to all 703 level I, II, and III trauma centers in the United States by either ground ambulance or helicopter within 45 and 60 minutes.An estimated 69.2% and 84.1% of all US residents had access to a level I or II trauma center within 45 and 60 minutes, respectively. The 46.7 million Americans who had no access within an hour lived mostly in rural areas, whereas the 42.8 million Americans who had access to 20 or more level I or II trauma centers within an hour lived mostly in urban areas. Within 45 and 60 minutes, respectively, 26.7% and 27.7% of US residents had access to level I or II trauma centers by helicopter only and 1.9% and 3.1% of US residents had access to level I or II centers only from trauma centers or base helipads outside their home states.Selecting trauma centers based on geographic need, appropriately locating medical helicopter bases, and establishing formal agreements for sharing trauma care resources across states should be considered to improve access to trauma care in the United States.
An Essential Role for RIG-I in Toll-like Receptor-Stimulated Phagocytosis
Authors: Ling Kong, Lei Sun, Hongxin Zhang, Qin Liu, Ye Liu, Linhua Qin, Guojun Shi, Jun-Hao Hu, Ajing Xu, Yue-Ping Sun, Dangsheng Li, Yu-Fang Shi, Jing-Wu Zang, Jiang Zhu, Zhu Chen, Zhu-Gang Wang, Bao-Xue Ge
Journal: Cell Host & Microbe (2009)
Medical Management of Benign Prostatic Hyperplasia — Are Two Drugs Better Than One?
Authors: E. Darracott Vaughan
Journal: New England Journal of Medicine (2003)

The prostate is a complex organ composed of epithelial cells and fibromuscular stroma. Benign prostatic hyperplasia is a true hyperplastic process, with an increase in the number of cells arising initially in the transition zone of the gland. Complex stromal–epithelial interactions lead to benign prostatic hyperplasia in 50 percent of men by the age of 50 years. This process requires testicular androgens and progresses with age. Aging is accompanied by an increase in symptoms of bladder obstruction or irritation attributable to benign prostatic hyperplasia. A prospective study showed that 24 percent of men with moderate symptoms of benign prostatic hyperplasia . . .
STUDIES ON IMMUNOLOGIC RECONSTITUTION OF THYMECTOMIZED MICE
Authors: Edmond J. Yunis, Henry R. Hilgard, Carlos Martinez, Robert A. Good
Journal: The Journal of Experimental Medicine (1965)

1. Immunologic function, growth, and longevity of neonatally thymectomized mice was restored by intraperitoneal administration of 100 to 400 million syngeneic, hemiallogeneic, or ailogeneic thymus cells from newborn or adult donors. Assays of the graft versus host capabilities of spleen cells from the animals restored with allogeneic cells showed that their immunologically competent cells are of donor histocompatibility characteristics. Such animals accepted skin grafts from mice of the cell donor strain, but rejected skin from a third strain. 2. Similar results were obtained when the neonatally thymectomized animals were treated with 10 to 100 million syngeneic, hemiallogeneic, or allogeneic cells from adult spleen. 3. In one strain combination, C(3)H recipients and A donors, injected thymus or spleen cells apparently attacked host tissues, since the animals died very early of wasting disease. When this combination was reversed, A strain recipients treated with C(3)H cells were reconstituted immunologically and physiologically. 4. Syngeneic or allogeneic adult spleen, grafted in the newborn period, reconstituted neonatally thymectomized mice, but all experiments involving grafting of newborn spleen failed. Immunogenetic analysis of the host spleen cells from two allogeneic spleen-grafted animals previously thymectomized showed that the reconstitution was entirely of donor histocompatibility characteristics. 5. Postthymectomy wasting disease was reversed by administration of 200 million adult syngeneic spleen or thymus cells. Immunologic recovery was confirmed by graft versus host assays of the spleens of the recovered animals and by application of allogeneic skin grafts. Some of the animals have been under observation for 42 weeks and appear to be normal. 6. The wasting syndrome in neonatally thymectomized mice was also reversed by injection of 200 million hemiallogeneic or allogeneic spleen cells. 7. Thymus grafts did not reverse wasting disease, whether the donors were adult or newborn, of the same strain or a different one. 8. Spleen, lymph node, and Peyer's patches from representative animals of the reconstituted groups were examined and compared with the tissues of untreated neonatally thymectomized mice and intact animals of the same strain. Tissues of normal cellularity and follicular organization were found in some of the reconstituted animals and also in mice with reversed wasting disease. Extreme deficit of the lymphoid tissues was rare in either group.
Recollections of My Life
Authors: Frank R. Freemon
Journal: JAMA (1990)

Santiago Ramón y Cajal (1852-1934) was one of the founders of modern neuroscience. His autobiography, written over many years and translated into English in 1937, is now reissued by the MIT Press as a paperback. Thomas Henry Huxley said that autobiography is a special branch of fiction, and Cajal's recollections of his childhood certainly strain credulity. But when he recounts his career in science, the reader is entranced by his fairness and his romantic language. Cajal attributed his initial success to perseverance ("the virtue of the less brilliant") in the dreary technical details of the Golgi method of staining nervous tissue. He felt that international recognition of his startling histological studies was delayed because he published in the Spanish language. At the turn of the century, said Cajal, any person who wanted an international audience had to publish in English, French, or German. "Educated people of other countries have no
Chewing the fat
Authors: F. Godlee
Journal: BMJ (2014)

What role does fast food play in the world’s obesity epidemic, and how can we moderate its effect? This week’s journal offers several new insights into the complex interplay between dietary intake, environmental exposure, and genetic risk. We know that eating fried and other energy dense foods increases the risk of obesity, even if the role of certain types of fat in raising cardiovascular risk is uncertain (doi:10.1136/bmj.g2238). We also know that some people are at increased genetic risk of obesity. Qibin Qi and colleagues have now found an interaction between high intake of fried food and high genetic risk, as measured by pooling the effects of common genetic variants (doi:10.1136/bmj.g1610). In an analysis …
Individualized treatment duration for hepatitis C genotype 1 patients: A randomized controlled trial
Authors: Alessandra Mangia, Nicola Minerva, Donato Bacca, Raffaele Cozzolongo, Giovanni L. Ricci, Vito Carretta, Francesco Vinelli, Gaetano Scotto, Giuseppe Montalto, Mario Romano, Giuseppe Cristofaro, Leonardo Mottola, Fulvio Spirito, Angelo Andriulli
Journal: Hepatology (2007)

It was hypothesized that in hepatitis C virus (HCV) genotype 1 patients, variable treatment duration individualized by first undetectable HCV RNA is as effective as standard 48-week treatment. Patients (n = 696) received peginterferon alfa-2a, 180 mg/week, or peginterferon alfa-2b, 1.5 mg/kg/week, plus ribavirin, 1000-1200 mg/day, for 48 weeks (standard, n = 237) or for 24, 48, or 72 weeks if HCV-RNA–negative at weeks 4, 8, or 12, respectively (variable, n = 459). Sustained virologic response (SVR) was achieved in 45.1% [95% confidence interval (CI) 38.8-51.4] of the patients in the standard group and in 48.8% (CI 44.2-53.3) of the patients in the variable group ( P = 0.37). The percentages of patients who first achieved undetectable HCV RNA at weeks 4, 8, or 12 were 26.7%, 27.8%, and 11.3%, respectively. In the standard treatment group, 87.1%, 70.3%, and 38.1% of patients who first achieved undetectable HCV RNA at 4, 8, or 12 weeks attained SVRs, respectively. In the variable group, corresponding SVR rates were 77.2%, 71.9%, and 63.5%. Low viremia levels and young age were independent predictors of response at week 4 [rapid virologic response (RVR)]. RVR patients with baseline viremia ≥400,000 IU/mL achieved higher SVR rates when treated for 48 weeks rather than 24 weeks (86.8% versus 73.1%, P = 0.14). The only predictive factor of SVR in RVR patients was advanced fibrosis. Conclusion: Variable treatment duration ensures SVR rates similar to those of standard treatment duration, sparing unnecessary side effects and costs. (Hepatology 2007.)
POISON GAS FOR MOSQUITOES
Authors: Hulussi Mustafa
Journal: JAMA (1926)

To the Editor:  —Some time ago, I used to be in touch here with the late Dr. Carlos John Finlay, before he returned to Cuba and the Hawaiian Islands. I decided therefore to write to you about my discovery. One of the worst diseases in our country is malarial fever, which, of course, is caused by the bite of mosquitoes. Some time ago, I conceived the idea that the best agent for their destruction would be poison gas. All swamps could be treated with gas, and the mosquitoes, together with the larvae and nymphs that live in the water, could be destroyed. I thought the matter was of sufficient importance to present it to the president of Turkey, Mustapha Kemal Pasha, and in March, 1925, the health department of Constantinople was asked to render its opinion in the matter. Laboratory experiments were made and my observations were confirmed and my
Screening for Lung Cancer Has No Proven Utility-Reply
Authors: Albert Y. Lin
Journal: JAMA (1992)

In Reply.  —The routine chest roentgenogram in our patient was performed by referring physicians. The case was chosen for presentation to illustrate that distant metastases are a major threat even to patients with localized lung cancer who undergo complete surgical resection.  The characteristics of a disease that is suitable for periodic health evaluation among asymptomatic subjects are well described. 1 The fact that there is no highly effective treatment modality available for treating occult distant metastases hampers the effectiveness of periodic screening for lung cancer. Major studies have addressed this specific issue. 2-4 We agree that at present there is no proven utility in screening for lung cancer.
Atresia of the Left Coronary Artery Ostium
Authors: C. E. MULLINS, G. EL-SAID, D. G. MCNAMARA, D. A. COOLEY, B. TREISTMAN, E. GARCIA
Journal: Circulation (1972)

Symptoms and electrocardiographic changes of acute myocardial ischemia in a 10-year-old boy resulted from congenital atresia of the ostium of the left coronary artery. At 14 years of age persistence of symptoms and a positive exercise test prompted surgical treatment by aortocoronary artery saphenous vein bypass graft. Two months postoperatively, the symptoms and the abnormal findings on exercise test had subsided and forward flow through the graft to the left coronary artery was demonstrated by contrast angiography.
Attenuated Expression of Xeroderma Pigmentosum Group C Is Associated with Critical Events in Human Bladder Cancer Carcinogenesis and Progression
Authors: Zhiwen Chen, Jin Yang, Gan Wang, Bo Song, Jin Li, Zhigang Xu
Journal: Cancer Research (2007)

Abstract Xeroderma pigmentosum group C (XPC) is an important DNA damage recognition protein that binds to damaged DNA at a very early stage during DNA repair. The XPC protein is also involved in DNA damage–induced cell cycle checkpoint regulation and apoptosis. XPC defects are associated with many types of solid tumors. The mechanism of the XPC protein in cancer progression, however, remains unclear. In this report, we showed the strong correlation between bladder cancer progression and attenuated XPC protein expression using tissues derived from patients with bladder cancer. The results obtained from our immunohistochemical studies further revealed a strong correlation of XPC deficiency, p53 mutation, and the degree of malignancy of bladder tumors. In addition, the results obtained from our studies have also shown that HT1197 bladder cancer cells, which carry a low-level XPC protein, exhibited a decreased DNA repair capability and were resistant to cisplatin treatment. When an XPC gene cDNA-expression vector was stably transfected into the HT1197 cells, however, the cisplatin treatment–induced apoptotic cell death was increased. Increased p53 and p73 responses following cisplatin treatment were also observed in HT1197 cells stably transfected with XPC cDNA. Taken together, these results suggest that XPC deficiency is an important contributing factor in bladder tumor progression and bladder cancer cell drug resistance. [Cancer Res 2007;67(10):4578–85]
Tc-99m-MDP Bone Scanning Detection of Gastric Calcification
Authors: ERIC DELCOURT, MICHEL BAUDOUX, PIERRE NEVE
Journal: Clinical Nuclear Medicine (1980)

A 50-year-old man with hypercalcemia related to Cope syndrome was referred for bone scintigraphy. There was a clear accumulation of the technetium-phosphate complex in the stomach. The condition was reversible with treatment of the underlying cause.
Esophageal Dislodgment of a Reused Variceal Ligator Cap: A Complication of Endoscopic Variceal Ligation
Authors: A. O. Silvério, J. C. Resplande, F. H. Ramos
Journal: Endoscopy (2004)

We read with interest the article by Wai et al. on esophageal dislodgment of a variceal ligator cap [1]. Recent issues of Endoscopy have carried reports of esophageal dislodgment of ligator caps that has occurred because of a mismatch of sizes between the ligator cap and the endoscope diameter [1] [2].
Efficacy and safety of omalizumab in patients with chronic urticaria who exhibit IgE against thyroperoxidase
Authors: Marcus Maurer, Sabine Altrichter, Thomas Bieber, Tilo Biedermann, Matthias Bräutigam, Stefan Seyfried, Randolf Brehler, Jürgen Grabbe, Nicolas Hunzelmann, Thilo Jakob, Andreas Jung, Jörg Kleine-Tebbe, Martin Mempel, Michael Meurer, Kristian Reich, Franziska Ruëff, Knut Schäkel, Kaushik Sengupta, Christian Sieder, Jan C. Simon, Bettina Wedi, Torsten Zuberbier, Vera Mahler, Petra Staubach
Journal: Journal of Allergy and Clinical Immunology (2011)
Neonatal effects of maternal administration of acebutolol.
Authors: Y Dumez, C Tchobroutsky, H Hornych, C Amiel-Tison
Journal: BMJ (1981)

Systolic blood pressure, heart rate, and blood glucose concentration were measured in the first three days of life in 10 infants born to mothers who had received acebutolol, a cardioselective beta-adrenergic-blocking agent, for hypertension in pregnancy and compared with values in 10 infants whose mothers had received methyldopa. The blood pressure was expressed as a percentage of the expected value. Blood pressure was significantly lower in the infants of the mothers given acebutolol (p less than 0.02, less than 0.01, and less than 0.01 respectively during the three days of observation). Heart rate was also lower, but the significance was only at the 0.05 level. Blood glucose was not significantly different between the two groups. These results suggest that care should be taken in prescribing beta-adrenergic-blocking drugs during pregnancy.
A controlled trial of heparin therapy in the coagulation defect of paracetamol-induced hepatic necrosis
Authors: B. G. Gazzard, R. Clark, V. Borirakchanyavat, R. Williams
Journal: Gut (1974)

Treatment of the coagulation disturbances developing with hepatic damage following a paracetamol overdose was assessed in a controlled trial of 22 patients, one half being given heparin and fresh frozen plasma and the other fresh frozen plasma alone.No significant difference was observed either in the speed of correction of the coagulation defect or in the clinical outcome.Two- thirds of the patients had evidence of disseminated intravascular coagulation, but despite the presence of a severe coagulation defect, significant bleeding occurred in only five patients.This may be because with paracetamol-induced hepatic necrosis both the coagulation defect (and possibly other features attributable to severe hepatic insufficiency) are of shorter duration than in hepatic necrosis due to causes such as viral hepatitis in which the liver damage may be a continuing process.on July 6,
Impaired ribosome biogenesis in Diamond-Blackfan anemia
Authors: Valérie Choesmel, Daniel Bacqueville, Jacques Rouquette, Jacqueline Noaillac-Depeyre, Sébastien Fribourg, Aurore Crétien, Thierry Leblanc, Gil Tchernia, Lydie Da Costa, Pierre-Emmanuel Gleizes
Journal: Blood (2006)