tbuckley/cabot-search huggingface dataset:
Novel vaccines targeting dendritic cells by coupling allergoids to nonoxidized mannan enhance allergen uptake and induce functional regulatory T cells through programmed death ligand 1
Authors: Sofía Sirvent, Irene Soria, Cristina Cirauqui, Bárbara Cases, Ana I. Manzano, Carmen M. Diez-Rivero, Pedro A. Reche, Juan López-Relaño, Eduardo Martínez-Naves, F. Javier Cañada, Jesús Jiménez-Barbero, Javier Subiza, Miguel Casanovas, Enrique Fernández-Caldas, José Luis Subiza, Oscar Palomares
Journal: Journal of Allergy and Clinical Immunology (2016)

Allergen immunotherapy (AIT) is the only curative treatment for allergy. AIT faces pitfalls related to efficacy, security, duration, and patient compliance. Novel vaccines overcoming such inconveniences are in demand.We sought to study the immunologic mechanisms of action for novel vaccines targeting dendritic cells (DCs) generated by coupling glutaraldehyde-polymerized grass pollen allergoids to nonoxidized mannan (PM) compared with glutaraldehyde-polymerized allergoids (P) or native grass pollen extracts (N).Skin prick tests and basophil activation tests with N, P, or PM were performed in patients with grass pollen allergy. IgE-blocking experiments, flow cytometry, confocal microscopy, cocultures, suppression assays, real-time quantitative PCR, ELISAs, and ELISpot assays were performed to assess allergen capture by human DCs and T-cell responses. BALB/c mice were immunized with PM, N, or P. Antibody levels, cytokine production by splenocytes, and splenic forkhead box P3 (FOXP3)(+) regulatory T (Treg) cells were quantified. Experiments with oxidized PM were also performed.PM displays in vivo hypoallergenicity, induces potent blocking antibodies, and is captured by human DCs much more efficiently than N or P by mechanisms depending on mannose receptor- and dendritic cell-specific intercellular adhesion molecule 3-grabbing nonintegrin-mediated internalization. PM endorses human DCs to generate functional FOXP3(+) Treg cells through programmed death ligand 1. Immunization of mice with PM induces a shift to nonallergic responses and increases the frequency of splenic FOXP3(+) Treg cells. Mild oxidation impairs these effects in human subjects and mice, demonstrating the essential role of preserving the carbohydrate structure of mannan.Allergoids conjugated to nonoxidized mannan represent suitable vaccines for AIT. Our findings might also be of the utmost relevance to development of therapeutic interventions in other immune tolerance-related diseases.
Oral versus Intravenous Empirical Antimicrobial Therapy for Fever in Patients with Granulocytopenia Who Are Receiving Cancer Chemotherapy
Authors: Winfried V. Kern, Alain Cometta, Robrecht de Bock, John Langenaeken, Marianne Paesmans, Giorgio Zanetti, Thierry Calandra, Michel P. Glauser, Françoise Crokaert, Jean Klastersky, Athanasios Skoutelis, Harry Bassaris, Stephen H. Zinner, Claudio Viscoli, Dan Engelhard, Andrew Padmos, Harold Gaya
Journal: New England Journal of Medicine (1999)

Intravenously administered antimicrobial agents have been the standard choice for the empirical management of fever in patients with cancer and granulocytopenia. If orally administered empirical therapy is as effective as intravenous therapy, it would offer advantages such as improved quality of life and lower cost.
Ocular motor signatures of cognitive dysfunction in multiple sclerosis
Authors: Joanne Fielding, Meaghan Clough, Shin Beh, Lynette Millist, Derek Sears, Ashley N. Frohman, Nathaniel Lizak, Jayne Lim, Scott Kolbe, Robert L. Rennaker, Teresa C. Frohman, Owen B. White, Elliot M. Frohman
Journal: Nature Reviews Neurology (2015)
Ether Inhalers in Early Use
Authors: William W. Ford
Journal: New England Journal of Medicine (1946)

ON A brick building at 17–19 Tremont Street, Boston, an inconspicuous bronze tablet commemorates the first of two events that served to introduce ether anesthesia and thereby changed the history of surgery. The tablet is inscribed as follows: "On Sept. 30, 1846, in a room in this building, Dr. William Thomas Green Morton first demonstrated the value of ether as an anaesthetic in a dental operation." A little more than two weeks from this date, on October 16, 1846, Morton, a successful dentist of twenty-seven who was also an enrolled student of medicine at Harvard, gave his epochal demonstration of . . .
Iatrogenic Prion Infection
Authors: Ian F. Laurenson, Andrew S. Whyte, Chris Fox
Journal: New England Journal of Medicine (2001)

To the Editor: Prusiner1 and Roos2 (May 17 issue) do not mention the spread of prions by contaminated surgical instruments. Since prions are not inactivated by the usual methods of sterilization, surgical procedures may account for some cases of sporadic Creutzfeldt–Jakob disease.3 Responding to this concern, the United Kingdom Department of Health has mandated that all tonsillectomy procedures be carried out with single-use instruments and has identified other procedures in which single-use instruments must be used. Instruments should not be reused after use in a patient with known or suspected Creutzfeldt–Jakob disease. Since it is unrealistic to expect that all . . .
Is tumor board relevant?
Authors: D. S. Dizon, J. Gass, R. D. Legare, B. J. Sakr, T. Rizack
Journal: Journal of Clinical Oncology (2010)

e19654 Background: There are limited studies looking at whether tumor board (TB) recommendations are followed into practice and whether they follow guidelines set forth by the National Comprehensive Cancer Network (NCCN). This study seeks to investigate the implementation of TB recommendations to patient care in breast cancer patients and adherence to NCCN guidelines. Methods: Breast tumor board records were retrospectively collected from January 1 to September 30, 2005 from Women and Infants Hospital in Providence, Rhode Island. Data on recommendations from the TB were compared to provider recommendations. In addition, data was collected on women with hormone receptor (HR) positive disease and those with node positive breast cancer to determine the proportion of cases recommended for treatment per NCCN Guidelines. Results: Over nine months, data was collected on 242 patients: median age 57 years; 69% HR positive; 44% node positive. Regarding overall concordance, the TB and provider recommendations were similar in 195/198 cases (98.5%). Looking at the group with HR positive disease (n=167) the TB was concordant with NCCN Guidelines in 73% of cases. In those with node-positive disease, a chemotherapy recommendation consistent with NCCN guidelines was made in 88% of cases. Conclusions: A multidisciplinary breast TB made recommendations that were consistent with NCCN Guidelines in the vast majority of cases. In addition, the TB recommendations were concordant with those of the provider the majority of the time (p<.0001). Prospective TB presentation enabled our breast center to follow NCCN Guidelines to ensure quality care. In addition, the TB recommendations were ultimately reflected in the provider's recommendations. This supports the finding that the majority of patients seen were followed in a standard fashion as outlined by national guidelines. The TB's ability to promote adherence to national standards may be useful to address other priority areas, including the identification of patients for genetic testing and eligibility in clinical trials. No significant financial relationships to disclose.
The Effects of a Single Dose of 2000 Units of Protamine Zinc Insulin Taken by a Diabetic Patient with Suicidal Intent
Authors: Alfred Vogl, Sol H. Youngwirth
Journal: New England Journal of Medicine (1949)

THE effects of exceedingly large doses of protamine zinc insulin are known chiefly from patients who have taken excessive amounts by error.1 The literature, however, also lists 2 cases in which huge quantities were taken with suicidal intent, 490 units in the first case and "one bottle" in the other.2 These observations indicate that overdosage with protamine zinc insulin is characterized by a definite sequence of symptoms.Since the effect of protamine zinc insulin on the blood sugar level develops much more slowly than that of unmodified insulin, there is a considerable initial period during which the compensatory mechanisms (chiefly . . .
Comprehensive assessment of truncated HER2 in formalin-fixed paraffin embedded breast cancer tissue by chromogenic duplex immunohistochemistry.
Authors: M. Pickl, C. Rutz, H. Nicolai, M. Hasmann, G. Brockhoff, F. Feuerhake
Journal: Journal of Clinical Oncology (2011)

e11059 Background: Truncated forms of HER2, previously described in subsets of HER2 positive breast cancer, lack the extracellular domain (ECD) but may retain intracellular domain (ICD) functionality and may render tumors less sensitive to HER2 targeted therapy. Herein, we describe a workflow to comprehensively detect truncated HER2 forms regardless of their putative origin (e.g., from alternative initiation of translation, or proteolytic cleavage) in formalin-fixed paraffin embedded tissue (FFPET). Methods: Multispectral unmixing of chromogenic duplex immunohistochemistry (IHC) was used to generate ECD and ICD specific images. Mean ECD/ICD ratios were calculated per case and related to those of full-length HER2 overexpressing SKBR3 cells as standard. The quantitative assessment of staining intensities was restricted to membranes of morphologically intact, vital tumor cells, using Definiens Developer – based image analysis. Technical validation was performed in various cell models reflecting both proteolytic ECD cleavage as well as alternative translation initiation resulting in the truncated HER2 variant CTF-611. Results: The IHC – based workflow accurately detected HER2 ECD and ICD in cell based models, regardless of the origin of the truncated membrane-bound protein. In a pilot series of FFPET breast cancer samples, 5/14 showed decreased mean ECD/ICD ratios at levels comparing to SKBR3 cells pretreated with a metalloproteinase activating compound. 9/14 had a ECD/ICD ratio within the normal range observed in full-length HER2 overexpressing SKBR3 cells. An unexpected heterogeneity of ECD/ICD ratios was observed in some cases, suggesting that focal loss of ECD may occur in a subset of breast cancer cases. Conclusions: Duplex IHC in FFPET accurately detects truncated HER2 in the context of full length HER2 and therefore captures potential co-existence of different HER2 variants lacking the ECD. This approach preserves tumor morphology, enabling pathologists to relate local loss of ECD to potential tumor heterogeneity. The biological relevance of global or focal decrease of HER2 ECD/ICD ratio remains to be evaluated in clinically annotated samples.
Integrating health and mental health services: historical obstacles and opportunities
Authors: H H Goldman
Journal: American Journal of Psychiatry (1982)

Historically, health and mental health services have been separated by a variety of forces, including specialization; ideological, attitudinal, and financial barriers; the professionalization of psychiatry; and functional and organizational differentiation. Recently, several models of integration and coordination have been proposed. If they are to succeed, health planners will have to be aware of the essential ingredients of interorganizational cooperation and work to eliminate the obstacles to integration of health and mental health services.
Induction of Tumors by a Guinea Pig Herpesvirus-Transformed Hamster Cell Line2
Authors: F. J. Michalski, C. K. Y. Fong, G. D. Hsiung, R. D. Schneider
Journal: JNCI Journal of the National Cancer Institute (1976)

Journal Article Induction of Tumors by a Guinea Pig Herpesvirus-Transformed Hamster Cell Line Get access F. J. Michalski, F. J. Michalski Search for other works by this author on: Oxford Academic PubMed Google Scholar C. K. Y. Fong, C. K. Y. Fong Search for other works by this author on: Oxford Academic PubMed Google Scholar G. D. Hsiung, G. D. Hsiung Search for other works by this author on: Oxford Academic PubMed Google Scholar R. D. Schneider R. D. Schneider Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 56, Issue 6, June 1976, Pages 1165–1170, https://doi.org/10.1093/jnci/56.6.1165 Published: 01 June 1976 Article history Received: 15 July 1975 Accepted: 10 December 1975 Published: 01 June 1976
P130 Effectiveness and safety of initiating treatment with fluticasone/salmeterol via MDI versus DPI in COPD: Abstract P130 Table 1
Authors: R Jones, J Martin, V Thomas, D Skinner, J Marshall, D Price
Journal: Thorax (2015)

<h3>Introduction and objectives</h3> Fluticasone propionate/salmeterol (FP/SAL), can be delivered by metered-dose inhaler (MDI) or dry powder inhaler (DPI). The choice of device may affect adherence to and effectiveness of treatment. Although only 1000 mcg/day DPI is licensed for the treatment of COPD in the UK, the MDI and lower doses are regularly used in real-world practice. The aim of this study was to compare the effectiveness and safety of FP/SAL MDI or DPI at two doses (500 and 1000 mcg/day) in COPD patients. <h3>Methods</h3> Historical, matched cohort study using the Optimum Patient Care Research Database in patients with COPD, aged ≥35 years and initiating with FP/SAL via either MDI or DPI. Conditional Poisson regression and conditional logistic regression were used respectively to compare the rate of moderate/severe COPD exacerbations and the odds of diagnosis of pneumonia and diabetes mellitus (including anti-diabetic drug prescriptions) between MDI and DPI during one year outcome period. Models were adjusted for the respective baseline values of the outcome variable of interest where possible. Addition of LAMA therapy during the outcome period was compared using conditional logistic regression. <h3>Results</h3> 472 and 1172 patients initiated on FP/SAL at 500 mcg/day and 1000 mcg/day, respectively. The rate of moderate/severe COPD exacerbations was significantly lower for patients prescribed MDI versus DPI initiating with 500 mcg/day of FP/SAL; no significant difference was observed between MDI and DPI for those initiating at 1000 mcg/day. There were no significant differences in the odds of diagnosis of diabetes mellitus or pneumonia between MDI and DPI, irrespective of the initiation dose of FP/SAL (Table 1). LAMA prescription during the outcome period was significantly lower for patients prescribed MDI versus DPI initiating at 1000 mcg/day; no significant difference was observed between MDI and DPI for those initiating at 500 mcg/day. <h3>Conclusions</h3> This study showed greater reduction in exacerbations for patients using MDI than those using DPI when initiating with FP/SAL 500 mcg/day; no differences in exacerbation reduction and safety were seen for FP/SAL at 1000 mcg/day. Fewer patients using MDIs than DPIs at 1000 mcg/day were prescribed LAMAs, suggesting less need for treatment intensification.
Case 36-1987
Authors: Richard C. Cabot, Robert E. Scully, Eugene J. Mark, William F. McNeely, Betty U. McNeely, Joseph I. Wolfsdorf, Eugene J. Mark
Journal: New England Journal of Medicine (1987)

Presentation of CaseA 14-year-old girl was admitted to the hospital because of diabetic ketoacidosis and pneumonitis.She was generally well until two years before admission, when diabetes mellitus was found and insulin therapy was begun. The child's compliance and diabetic control were poor. Five months before admission she entered this hospital because of diabetic ketoacidosis and gastroenteritis. She was provided with an apparatus to estimate her own blood glucose level, but she monitored the level rarely and never adjusted her dose of insulin because of illness.Thirty-four days before entry the child was seen by a physician because of . . .
Hyponatremia in Hypopituitarism
Authors: John E. Bethune, Don H. Nelson
Journal: New England Journal of Medicine (1965)

IN recent years several patients with panhypopituitarism and serum sodium concentrations as low as 106 milliequiv. per liter have been seen by us. These patients have usually had associated stressful situations and unrecognized panhypopituitarism. Present physiologic concepts suggest that the pituitary gland is of definite secondary importance in the control of aldosterone secretion and therefore a mechanism for production of hyponatremia in hypopituitarism is not readily apparent. The lack of information on the frequency and genesis of this problem was recently discussed in a clinicopathological conference in this journal.1 It is the purpose of this article, therefore, to present evidence . . .
Cancer Health Disparities and the Cost of Cancer Care: Payment Model Issues
Authors: Pallavi Kumar, Beverly Moy
Journal: Journal of the National Comprehensive Cancer Network (2013)

Despite major advances in cancer research, screening, and treatment over the past few decades, not all Americans with cancer have benefited equally.Although the rate of cancer-related death has decreased 14% between 1991 and 2004, racial and ethnic minority patients continue to die disproportionately from cancer, even after adjusting for insurance status and income. 1 Factors contributing to cancer health disparities include limited access to cancer care because of lack of insurance or underinsurance, lower quality of cancer care, lower socioeconomic status, and cultural and social factors. 2 In 2010, the Affordable Care Act (ACA) was signed into law, marking the most comprehensive health care reform since the creation of Medicare and Medicaid in 1965.The major provisions of the ACA serve to decrease the number of uninsured Americans, partly by expanding Medicaid coverage to an additional 20 million individuals.Other reforms set forth by the ACA are aimed at improving health care outcomes and streamlining health care delivery via several mechanisms: the creation of accountable care organizations (ACOs), a shift away from fee-for-service payment structures to payment bundling, and increased funding for comparative-effectiveness research.Although the ACA provides several opportunities to reduce or eliminate cancer health disparities, very little in the law actually addresses the affordability of care.In fact, current political and economic climates have placed major aspects of health care reform in peril.National health expenditures as a percent of the US gross domestic product (GDP) totaled 5% in 1965 but are expected to total 20% by the middle of this decade. 3Although spending on cancer care constitutes only 5% of the overall health care budget, 4 these costs continue to rise at a more rapid pace than any other area of health care. 5 Debates over entitlement reform and sequestration cuts have brought health care costs to the forefront.In the current climate of cost-consciousness, how can health care reform simultaneously address health disparities and the cost of cancer care?With sequestration in place and looming cuts to entitlements, we focus on forthcoming changes to Medicaid, Medicare, and payment structures and how these will affect disparities in cancer care.
Roentgen Therapy in Acne
Authors: G. Marshall Crawford, Ralph H. Luikart, Robert F. Tilley
Journal: New England Journal of Medicine (1951)

X-RAY therapy has been employed in the treatment of acne vulgaris since Gautier1 reported its efficacy in 1897. Pusey2 was the first to utilize this mode of therapy in the United States. Technics were rapidly established, and it was soon evident that an efficient tool had been discovered.Although the majority of adolescent boys and about half of the girls develop some degree of acne, the condition spontaneously clears in a year or two in most young patients. Proper medical and dermatologic management relieves many others. There remains a small group whose condition is singularly recalcitrant, and who may develop . . .
Value of ECGs in identifying heart failure due to left ventricular systolic dysfunction
Authors: S. Khandekar, J. J Murphy, C. M Bossingham
Journal: BMJ (1996)

lack of evidence showing that such improved respi- ratory function is associated with a diminished incidence of clinically significant episodes of atelectasis.The central issue is that, despite optimum pain control and aggressive physio- therapy, about 10-15% of patients undergoing abdominal surgery develop a postoperative respiratory complication.There is a clear need to look beyond the simplistic paradigms relating to the pathophysiology of atelectasis that are implied in the letters by Sabanathan and colleagues, Haigh and Eden, and Quinn and Mallick.Higgs commented on the possibility of random confounding-that is, that randomisation may have resulted in groups that differ in regard to major risk factors.2However, as discussed above, differences in beliefs about the cause of atelectasis result in differing perceptions about the relative importance of various risk fac- tors.The selection of risk factors in the clinical trial was based on the results of our multivariate analysis of 1000 patients undergoing abdominal surgery.3Higgs can be reassured that there was good equivalence between the groups for the body mass index and the incidence of upper abdominal surgery.An attempt was made to measure "early ambulation" in an earlier study, but we found it impossible to reliably define and measure this important activity.Other issues must go unanswered as we neither evaluated patients undergoing thoracotomy nor made rec- ommendations about laparoscopic surgery.
MRI-Guided Diagnosis and Treatment of Prostate Cancer
Authors: Anthony V. D'Amico, Robert A. Cormack, Clare M. Tempany
Journal: New England Journal of Medicine (2001)

To the Editor: We congratulate Valenzuela et al. and Page et al. (Oct.26 issue) on their studies of defibrillation in casinos 1 and airplanes. 2 The advantage of immediate diagnosis and treatment is certain.However, the authors missed the opportunity to demonstrate sustained preservation of neurologic, neuropsychological, and behavioral brain function.Discharge from the hospital is a crude criterion for survival with a healthy brain. [1]2][3] The best function, according to another commonly used standard, the Glasgow Cerebral Performance Scale, includes "minor psychological or neurological defects (mild dysphasia, non-incapacitating hemiparesis, or minor cranial nerve abnormalities)."Memory testing is not specified.This level of function is not likely to be sufficient to allow one to resume running a business or pursuing a profession.In our review of studies of cardiopulmonary resuscitation (CPR) that provided even crude, varied measures of extended outcome, at least 50 percent of survivors had neuropsychological impairment and pathologic depression. 3 A reluctance to acknowledge that neurologic injury occurs need not diminish enthusiasm for CPR.Most persons who undergo CPR out of the hospital do not provide informed consent in advance.We believe that follow-up assessments of both the benefits and the risks of out-of-hospital CPR should be made widely available.The value of reliable mental-function tests has been well demonstrated in studies of degenerative brain disease, obstructive sleep apnea, the acute respiratory distress syndrome, and coronary by-pass surgery. 4,5 We have proposed that such evaluations be included in all new trials of CPR. 6
Arachnoid Cyst
Authors: Balakrishna Valluru, Ray Raj
Journal: New England Journal of Medicine (2015)

A 22-year-old man presented after a motor vehicle collision in which his head struck the windshield of a bus. A CT scan showed an incidental finding of grossly dilated occipital and temporal horns of the right lateral ventricle. MRI confirmed the presence of a large cystic lesion.
Pattern of Dihydropyrimidine Dehydrogenase Genetic Variants in Patients with Various Degrees of Tolerability of Fluoropyrimidine Treatment
Authors: M. Del Re, F. Pietrantonio, M. Palombi, S. Sameen, F. Loupakis, C. Barbara, T. Latiano, P. Ulivi, E. Zafarana, A. Passardi, E. Maiello, A. Brandes, F. Cappuzzo, S. Siena, F.G.M. De Braud, A. Falcone, R. Labianca, C. Zamagni, C. Pinto, R. Danesi
Journal: Annals of Oncology (2014)