tbuckley/cabot-search huggingface dataset:
Abstract 2840: Dendritic cell-based immunotherapy targeting WT1 and MUC1 for advanced biliary tract cancer.
Authors: Masanori Kobayashi, Tomoyo Sakabe, Mitsugu Tanii, Hirofumi Abe, Hedenori Takahashi, Shun-ichi Tsujitani, Shigetaka Shimodaira, Yoshikazu Yonemitsu, Masato Okamoto, Masaki Nagaya
Journal: Cancer Research (2013)

Abstract Objectives:Despite intensive chemotherapy for biliary tract cancer (BTC), the outcome is not enough. Dendritic cells are the powerful antigen-presenting cells that have attracted attention from the efficacy of DC-based immunotherapy against many types of cancers. The objective of this study was to clarify the safety and efficacy of dendritic cell therapy for BTC.Methods: This retrospective study selected patients who underwent DC-based vaccine for BTC between May of 2009 and February of 2012. The safety of this treatment, median survival time (MST), 1-year survival rate, objective response rate (ORR), and disease control rate (DCR) were evaluated. The univariate and multivariate analyses were performed to identify the efficacy of DC by a Cox proportional hazards analysis.Results:Twenty-seven patients were selected for the study. The patients, and all but one patient had previous therapy, 13 patients had undergone prior surgical resection, and 21 patients went on to receive chemotherapy. No serious treatment-related adverse events were observed during the study period. One-year survival rate from 1st vaccination was 22 % and from the initial diagnosis was 67%. The MST from 1st vaccination and from the initial diagnosis were 8.2 months and 18.5 months, respectively. DCR and ORR were 37% and 11%,respectively. None of 27 patients showed complete response (CR), but we have found out 3 cases of partial responses (PR) and 7 cases of stable disease (SD).Furthermore, LDH, CRP, DTH, Performance Status (PS), combination with lymphokine-activated killer, chemotherapy were found to be statistically significant independent risk factors in multivariate analysis.Conclusion: DC-based immunotherapy for BTC was safe and prolonged the MST of the patients with BTC compared to chemotherapy alone,comparing the result from UK ABC-02 trial. DC-based immunotherapy for BTC may another option for BTC patient who has no chance for curative surgery. Citation Format: Masanori Kobayashi, Tomoyo Sakabe, Mitsugu Tanii, Hirofumi Abe, Hedenori Takahashi, Shun-ichi Tsujitani, Shigetaka Shimodaira, Yoshikazu Yonemitsu, Masato Okamoto, Masaki Nagaya. Dendritic cell-based immunotherapy targeting WT1 and MUC1 for advanced biliary tract cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2840. doi:10.1158/1538-7445.AM2013-2840
Esophagostomy vs. Esophagotomy.
Authors: L. J. Hammond
Journal: JAMA (1898)

Philadelphia, March 29, 1898. <h3>To the Editor:</h3> —I find the remarks made by me in the discussion of Dr. Roe's paper in the issue of theJournal(March 26, page 716), as reported, are so at variance with the idea that I wished to convey, that I hope you can find it possible to correct them. I distinctly said that<i>esophagostomy</i>is more desirable than esophagotomy, because the dangers of entering the posterior mediastinum are thus removed and we are enabled to remove the foreign body, if there be such, or divide the stricture through the external opening, thereby inflicting the minimum amount of force in the ulcerated region. Yours faithfully,
Diseases of affluence hit developing nations
Authors: S. Swafford
Journal: BMJ (1997)

“Diseases of affluence,” previously thought to affect only developed nations, are now becoming the leading killers in the developing world, according to a five year study-the global burden of disease-sponsored by the World Health Organisation and the World Bank.

The report, the first of a series of four ( Lancet 1997;349:1269-76), says that the differences in diseases between developed and developing countries is not as great as previously thought. Developing nations continue to have major problems with infections, tuberculosis, and malaria. …
WHO urges introduction of single use syringes
Authors: A. Gulland
Journal: BMJ (2015)

Doctors and other healthcare workers should only use single use syringes, in a bid to stop the spread of infection through unsafe injections. In new guidance the World Health Organization is urging countries by 2020 to ditch syringes that can be reused, in favour of so called “smart” syringes that deliver a single dose and can be used only once.1

Research sponsored by WHO has shown that the number of infections caused by unsafe injections fell dramatically between 2000 and 2010 as injection practice improved.2 In 2009 the GAVI Vaccine Alliance reported that 66 of 71 developing countries receiving its financial support …
Allergen avoidance in infancy and allergy at 4 years of age
Authors: D. W. Hide, S. Matthews, S. Tariq, S. H. Arshad
Journal: Allergy (1996)

In an attempt to prevent or reduce the manifestations of atopic disease, a group of infants considered to be genetically at high risk of atopy was entered in a prenatally randomized, controlled study. A prophylactic group (n = 58) was either breast-fed with their mothers excluding foods regarded as highly antigenic from their diets, or given an extensively hydrolysed formula. In addition, strenuous efforts were made to reduce exposure to the house-dust mite by application of acaricide to the bedroom and living room carpets and upholstered furniture. A control group (n = 62) was fed conventionally by breast or on formula, and no specific environmental measures were taken. The results (previously reported) after 1 year showed significantly less total allergy, asthma, and eczema in the prophylactic group. Similar results were obtained at 2 years although the reduction in asthma no longer achieved statistical significance. However, there was significantly less sensitization, as shown by a battery of skin prick tests (SPTs), to both dietary allergens and aeroallergens in the prophylactic group. All the children have now been reviewed at the age of 4 years, and SPTs to a wide range of dietary allergens and aeroallergens have been performed. The control group continues to show more total allergy (odds ratio [OR] 2.73, 95% confidence interval [CI] 1.21-6.13, P < 0.02), definite allergy (allergic symptoms plus positive SPT) (OR 5.6, CI 1.8-17.9, P < 0.005), and eczema (OR 3.4, CI 1.2-10.1, P < 0.05). More control children have positive SPTs (OR 3.7, CI 1.3-10.0, P < 0.02). A dual approach to the prevention of allergic disease, avoiding as far as possible sensitization to food and aeroallergens, significantly reduces the risk of atopic disease. This should be reserved for infants considered at very high risk of atopy, and close medical and dietetic supervision must be available.
Sirolimus-Eluting Coronary Stents
Authors: Gregory D. Curfman
Journal: New England Journal of Medicine (2002)

The story of sirolimus began in 1975 on Easter Island, in the South Pacific, a remote, enigmatic place known for the prominent stone statues that punctuate its landscape. An actinomycete, Streptomyces hygroscopicus, cultured from a sample of the island's soil, was found to produce through natural fermentation a novel macrolide antibiotic with potent antifungal, immunosuppressive, and antimitotic activities. The generic name of the resulting drug is sirolimus (see Figure); it is also known as rapamycin, after Rapa Nui, the name given to Easter Island by its inhabitants.Twenty-five years of intensive research led, in 1999, to the approval of sirolimus . . .
Using Social Media in Research: New Ethics for a New Meme?
Authors: Eric S. Swirsky, Jinger G. Hoop, Susan Labott
Journal: The American Journal of Bioethics (2014)

Click to increase image sizeClick to decrease image size FUNDINGThis commentary was supported by the National Center for Advancing Translational Sciences (UL1 TR000050). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
Influence of Pre-PTCA Strategy and Initial PTCA Result in Patients With Multivessel Disease
Authors: Kevin E. Kip, Martial G. Bourassa, Alice K. Jacobs, Leonard Schwartz, Frederick Feit, Edwin L. Alderman, Bonnie H. Weiner, Melvin B. Weiss, Mirle A. Kellett, Barry L. Sharaf, Alexios P. Dimas, Robert H. Jones, George Sopko, Katherine M. Detre
Journal: Circulation (1999)

In PTCA patients with multivessel coronary artery disease, incomplete revascularization (IR) is the result of both pre-PTCA strategy and initial lesion outcome. The unique contribution of these components on long-term patient outcome is uncertain.From the Bypass Angioplasty Revascularization Investigation (BARI), 2047 patients who underwent first-time PTCA were evaluated. Before enrollment, all significant lesions were assessed by the PTCA operator for clinical importance and intention to dilate. Complete revascularization (CR) was defined as successful dilatation of all clinically relevant lesions. Planned CR was indicated in 65% of all patients. More lesions were intended for PTCA in these patients compared with those with planned IR (2.8 versus 2.1). Successful dilatation of all intended lesions occurred in 45% of patients with planned CR versus 56% with planned IR (P<0. 001). In multivariable analysis, planned IR (versus planned CR), initial lesions attempted (not all versus all intended lesions attempted), and initial lesion outcome (not all versus all attempted lesions successful) were unrelated to 5-year risk of cardiac death or death/myocardial infarction but were all independently related to risk of CABG.Overall, a pre-PTCA strategy of IR in BARI-like patients appears comparable to a strategy of CR except for a higher need for CABG. Whether the use of new devices may attenuate the elevated risk of CABG in patients with multivessel disease and planned IR remains to be determined.
Proximity to Crops and Residential Exposure to Agricultural Herbicides in Iowa
Authors: Mary H. Ward, Jay Lubin, James Giglierano, Joanne S. Colt, Calvin Wolter, Nural Bekiroglu, David Camann, Patricia Hartge, John R. Nuckols
Journal: Environmental Health Perspectives (2006)

Rural residents can be exposed to agricultural pesticides through the proximity of their homes to crop fields. Previously, we developed a method to create historical crop maps using a geographic information system. The aim of the present study was to determine whether crop maps are useful for predicting levels of crop herbicides in carpet dust samples from residences. From homes of participants in a case-control study of non-Hodgkin lymphoma in Iowa (1998-2000), we collected vacuum cleaner dust and measured 14 herbicides with high use on corn and soybeans in Iowa. Of 112 homes, 58% of residences had crops within 500 m of their home, an intermediate distance for primary drift from aerial and ground applications. Detection rates for herbicides ranged from 0% for metribuzin and cyanazine to 95% for 2,4-dichlorophenoxyacetic acid. Six herbicides used almost exclusively in agriculture were detected in 28% of homes. Detections and concentrations were highest in homes with an active farmer. Increasing acreage of corn and soybean fields within 750 m of homes was associated with significantly elevated odds of detecting agricultural herbicides compared with homes with no crops within 750 m (adjusted odds ratio per 10 acres = 1.06; 95% confidence interval, 1.02-1.11). Herbicide concentrations also increased significantly with increasing acreage within 750 m. We evaluated the distance of crop fields from the home at < 100, 101-250, 251-500, and 501-750 m. Including the crop buffer distance parameters in the model did not significantly improve the fit compared with a model with total acres within 750 m. Our results indicate that crop maps may be a useful method for estimating levels of herbicides in homes from nearby crop fields.
Don't take me to your leader
Authors: Tony Delamothe
Journal: BMJ (2010)

Medicine has suddenly discovered leadership, just as the rest of the world is moving on



If mentions of the word “leadership” in the BMJ keep increasing at the current exponential rate, then by 2034 every second journal article will include a reference to the term. Will that be enough?

Or is our average of three mentions a week already enough? Escaping the term has been virtually impossible since the publication of Ara Darzi’s final report on reforming the NHS, High Quality Care for All (2008). My own employer has played its part, setting up a course with Sweden’s Karolinska Institute on leadership for medical educators. This year a couple of the BMJ Group Awards saluted the “l” word. A keynote address at last month’s International Forum on Quality and Safety in Healthcare provided guidance on “Twenty-first century leadership.” And so on. “The range of courses, fellowships, and other entities linked to leadership in some way is vast,” despaired Douglas Noble in his recent letter to the journal. “What we are going to do with all these leaders in 5-15 years’ time is not clear” ( BMJ 2010;340:c914, doi:10.1136/bmj.c914).

What, …
Twist1 Is a Key Regulator of Cancer-Associated Fibroblasts
Authors: Keun-Woo Lee, So-Young Yeo, Chang Ohk Sung, Seok-Hyung Kim
Journal: Cancer Research (2014)

Cancer-associated fibroblasts (CAF) are key contributors to malignant progression, but their critical regulators remain largely unknown. In this study, we examined the role of Twist1, a central regulator of epithelial-mesenchymal transition in carcinoma cells, in the transdifferentiation of normal quiescent fibroblasts to CAF and we defined its upstream controls and downstream effectors. Primary human gastric fibroblast and CAF cultures were established from gastrectomy specimens and validated as nontumor cells by somatic mutation analyses. In these cultures, exposure to the proinflammatory cytokine IL6 commonly expressed in tumors was sufficient to induce Twist1 expression in normal fibroblasts and transdifferentiate them into CAFs via STAT3 phosphorylation. In xenograft models, tumor infiltration of Twist1-expressing CAFs was enhanced strongly by ectopic IL6 expression in gastric or breast cancer cells. We found that Twist1 expression was necessary and sufficient for CAF transdifferentiation. Enforced expression of Twist1 in normal fibroblasts was also sufficient to drive CAF marker expression and malignant character in gastric cancer cells both in vitro and in vivo. Conversely, silencing the expression of Twist1 in CAFs abrogated their tumor-promoting properties. Downstream of Twist1, we defined the chemokine CXCL12 as a transcriptional target. Clinically, CXCL12 and Twist1 expression were correlated in CAFs present in gastric tumor specimens. Finally, ectopic expression of Twist1 in normal fibroblasts suppressed premature senescence, whereas Twist1 attenuation accelerated senescence in CAFs. Our findings define Twist1 as a compelling target to deprogram the tumor-supporting features of the cancer microenvironment.
Biomedical Research Enters the Marketplace
Authors: Barbara J. Culliton
Journal: New England Journal of Medicine (1981)

THE past few years have witnessed a virtual explosion of "technology transfer" as researchers and industrialists have moved with unprecedented speed and determination to exploit molecular biology in a search for useful and profitable products based on recombinant DNA and monoclonal antibodies—technologies whose conceptual roots are in university-based science. One anticipates the rapid development of much-needed therapeutic agents including human insulin, hepatitis B antigen, somatostatin, human growth hormone, and interferon. New applications of enzymes in industrial chemistry and of hormones in agriculture are also near. Universities are warily but hopefully looking at industry as an untapped source of support for . . .
What determines glomerular capillary permeability?
Authors: William M. Deen
Journal: Journal of Clinical Investigation (2004)

There have been exciting recent advances in our understanding of the structural and molecular biology of the glomerular slit diaphragm, as described in a report in this issue of the JCI. These findings, combined with data on the permeability of the basement membrane and evidence that the endothelium may be a more important barrier than often supposed, are allowing a clearer understanding to emerge of how the 3 parts of the glomerular capillary wall jointly determine its functional properties.
THE EFFECT OF INTRACUTANEOUS GLUCOCORTICOIDS ON PLASMA CORTISOL LEVELS
Authors: Gerald N. Wachs
Journal: British Journal of Dermatology (1973)

Journal Article THE EFFECT OF INTRACUTANEOUS GLUCOCORTICOIDS ON PLASMA CORTISOL LEVELS Get access Gerald N. Wachs Gerald N. Wachs Schering Corporation Kenilworth New Jersey 07033, U.S.A Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 89, Issue 6, 1 December 1973, Page 647, https://doi.org/10.1111/j.1365-2133.1973.tb07593.x Published: 01 December 1973
Needling doubts about where to vaccinate.
Authors: J. Piggot
Journal: BMJ (1988)

American Society of Anaesthesiologists' (ASA) grade system (ASA I, healthy patient; ASA II, mild systemic disease; ASA III, severe, non- incapacitating systemic disease; ASA IV, severe, incapacitating systemic disease which is a constant threat to life; and ASA V, moribund patient, not expected to live for 24 hours with or without surgery) abnormal values were found in 1-5% of patients in grade I, 17% in grade II, 35% in grade III, and 48% in grades IV and V.' In addition, most abnormal values in patients in grade II were minor and not clinically important.Therefore patients in grades I and II do not need routine estimations of urea and electrolyte concentrations whereas those in grades III, IV, and V do, as the results are much more likely to be abnormal.I therefore suggest that this grading system, which could be easily learnt by junior medical staff, would be more appropriate than age as an indicator of the need for biochemical screening preoperatively.
Does Familial Hypertriglyceridemia Predispose to NIDDM?
Authors: Timo Sane, Marja-Riitta Taskinen
Journal: Diabetes Care (1993)

OBJECTIVE To determine the 10 -yr incidence of impaired glucose tolerance and NIDDM in families with a clustering of endogenous hypertriglyceridemia. RESEARCH DESIGN AND METHODS The prospective population study, where the oral glucose tolerance test and the measurement of serum lipids and lipoproteins were performed at the baseline examination and after the 10-yr followup, was conducted on 56 subjects (17–60 yr of age at the baseline). The subjects were from six pedigrees with a clustering of endogenous hypertriglyceridemia, and 47 of these subjects attended the follow-up 10 yr later. RESULTS In the study families, the prevalence of glucose intolerance and NIDDM increased from 15 to 49% (P &amp;lt; 0.001) and from 2 to 21% (P &amp;lt; 0.001), respectively, over the 10-yr period. When grouped according to the baseline serum triglyceride tertiles, 76% (P &amp;lt; 0.01) of the family members with highest serum triglycerides were glucose intolerant (29% impaired glucose tolerance, 47% NIDDM) at follow-up compared with 20% of those with lowest serum triglycerides. In discriminant analysis, including age, body mass index, treatment with thiazides and β-blocking agents, and 2-h serum insulin concentration, the baseline serum triglycerides still remained as an independent predictor of development of impaired glucose tolerance and NIDDM. CONCLUSIONS Families with a clustering of hypertriglyceridemia are at increased risk of NIDDM, and in these families elevation of serum triglycerides serves as a risk marker of glucose intolerance and NIDDM.
The Importance and Purpose of Medical Psychology in the Study of Medicine
Authors: S. Rossmanith
Journal: Psychotherapy and Psychosomatics (1990)

Medical psychology is to be understood both as an interdisciplinary science, orientated to the bio-psychosocial concept of illness as well as a basic medical attitude that encompasses the whole of a doctor's activity. In the curriculum the students must be provided with a medico-psychological training that is specific to individual phases of study. This requires a didactic process that is centered on the student, both in the teaching of medical psychology as well as in medico-psychological hospital practice, which is to be achieved in close cooperation with other medical subjects. Medical psychology is mostly described as a newer scientific discipline. It does have a history, however, that has evolved over time. Although medical psychology has always been a building block in the thinking and actions of the medical profession, it is now explicitly anchored in the training (i.e. in the curriculum) of doctors.
The initiation of embryonic-like collagen fibrillogenesis by adult human tendon fibroblasts when cultured under tension
Authors: Monika L. Bayer, Chin-Yan C. Yeung, Karl E. Kadler, Klaus Qvortrup, Keith Baar, René B. Svensson, S. Peter Magnusson, Michael Krogsgaard, Manuel Koch, Michael Kjaer
Journal: Biomaterials (2010)

Tendon fibroblasts synthesize collagen and form fibrils during embryonic development, but to what extent mature fibroblasts are able to recapitulate embryonic development and develop normal tendon structure is unknown. The present study examined the capability of mature human tendon fibroblasts to initiate collagen fibrillogenesis when cultured in fixed-length fibrin gels. Fibroblasts were dissected from semitendinosus and gracilis tendons from healthy humans and cultured in 3D linear fibrin gels. The fibroblasts synthesized an extracellular matrix of parallel collagen fibrils that were aligned along the axis of tension. The fibrils had a homogeneous narrow diameter that was similar to collagen fibrils occurring in embryonic tendon. Immunostaining showed colocalization of collagen type I with collagen III, XII and XIV. A fibronectin network was formed in parallel with the collagen, and fibroblasts stained positive for integrin α5. Finally, the presence of cell extensions into the extracellular space with membrane-enclosed fibrils in fibripositors indicated characteristics of embryonic tendon. We conclude that mature human tendon fibroblasts retain an intrinsic capability to perform collagen fibrillogenesis similar to that of developing tendon, which implies that the hormonal/mechanical milieu, rather than intrinsic cellular function, inhibits regenerative potential in mature tendon.