tbuckley/cabot-search huggingface dataset:
The saviour of Hunter's collection
Authors: W. Moore
Journal: BMJ (2013)

When, during Great Britain’s war with revolutionary France, Prime Minister William Pitt was asked to buy John Hunter’s anatomical collection for the nation, he thundered, “What! Buy preparations! I have not got money enough to buy gunpowder!” That the Hunterian Museum celebrates its bicentenary this year despite Pitt’s apathy is due to the tenacity of William Clift (1775-1849).⇑

Clift was born near Bodmin, the youngest of seven children. Orphaned at 11, he worked in a plant nursery but was sacked for drawing a caricature of the owner. Luckily his artistic skills were spotted …
Allergen induced gene expression of airway epithelial cells shows a possible role for TNF‐α
Authors: A. B. Vroling, D. Duinsbergen, W. J. Fokkens, C. M. Van Drunen
Journal: Allergy (2007)

Epithelium is more than a physical barrier for pathogens and allergens, as it is also capable of producing mediators in response to these environmental factors. Some of these mediators have an immuno-modulatory function, suggesting that epithelium is an active component of the immune response. Here, we fully characterize the expression profile of airway epithelial cells in response to house dust mite (HDM) allergen.H292 cells were exposed to HDM extract for 24 h, RNA and supernatant was used for microarray analysis and multiplex enzyme-linked immunosorbent assay (ELISA) respectively.A total of 38,500 genes, 813 were differentially expressed by more than twofold and 116 even more than fivefold. Interestingly, among the most up-regulated genes, a large number are involved in cell-to-cell communication. These include chemokines (CCL-8 and -20, CXCL-1, -2 and -3), cytokines (IL-1alpha, -6 and -11), anti-inflammatory factors [PTX-3, interleukin (IL)-13Ralpha, tumour necrosis factor (TNF)-alphaIP3], and factors that are involved in repair of the mucosal tissue (LOXL-2, NID-2, HBEGF, MUC-5AC and MUC-5B). Pathway analysis showed that a number of these genes are transcriptionally regulated by TNF-alpha, which we could detect by quantitative polymerase chain reaction at earlier time points after HDM exposure. In addition, we could detect increased protein levels for TNF-alpha, IL-6, IL8, granulocyte-macrophage colony-stimulating factor, granulocyte colony stimulating factor and interferon (IFN)-gamma using ELISA.Our data show that a broad range of mediators produced upon allergen exposure by these mediators' epithelial cells can participate in the immune response via recruitment and activation of cells of the immune system.
Spreading the Safety Net — Obstacles to the Expansion of Community Health Centers
Authors: John K. Iglehart
Journal: New England Journal of Medicine (2008)

During the presidency of George W. Bush, his administration's agenda of “compassionate conservatism” — with its emphasis on market-based, rather than government-sponsored, approaches to health care services and income support — has been rejected by Democrats innumerable times. This philosophical conflict has resulted in stalemates on many health care issues, and the administration's proposed 2009 budget, which calls for reductions of $200.9 billion in Medicare and Medicaid spending over the next 5 years, only deepens the political divide between the parties. Amidst this partisan standoff, however, Bush has remained resolute in fulfilling one early campaign pledge that most Democrats enthusiastically . . .
Enhanced Effector Responses in Activated CD8+ T Cells Deficient in Diacylglycerol Kinases
Authors: Matthew J. Riese, Liang-Chuan S. Wang, Edmund K. Moon, Rohan P. Joshi, Anjana Ranganathan, Carl H. June, Gary A. Koretzky, Steven M. Albelda
Journal: Cancer Research (2013)

Recent clinical trials have shown promise in the use of chimeric antigen receptor (CAR)-transduced T cells; however, augmentation of their activity may broaden their clinical use and improve their efficacy. We hypothesized that because CAR action requires proteins essential for T-cell receptor (TCR) signal transduction, deletion of negative regulators of these signaling pathways would enhance CAR signaling and effector T-cell function. We tested CAR activity and function in T cells that lacked one or both isoforms of diacylglycerol kinase (dgk) expressed highly in T cells, dgkα and dgkζ, enzymes that metabolize the second messenger diacylglycerol (DAG) and limit Ras/ERK activation. We found that primary murine T cells transduced with CARs specific for the human tumor antigen mesothelin showed greatly enhanced cytokine production and cytotoxicity when cocultured with a murine mesothelioma line that stably expresses mesothelin. In addition, we found that dgk-deficient CAR-transduced T cells were more effective in limiting the growth of implanted tumors, both concurrent with and after establishment of tumor. Consistent with our studies in mice, pharmacologic inhibition of dgks also augments function of primary human T cells transduced with CARs. These results suggest that deletion of negative regulators of TCR signaling enhances the activity and function of CAR-expressing T cells and identify dgks as potential targets for improving the clinical potential of CARs.
Graded associations between cardiorespiratory fitness, fatness, and blood pressure in children and adolescents
Authors: L Klasson-Heggebø, L B Andersen, A H Wennlöf, L B Sardinha, M Harro, K Froberg, S A Anderssen
Journal: British Journal of Sports Medicine (2005)

Objective: To measure the graded relation between cardiorespiratory fitness and sum of skinfolds, waist circumference, and blood pressure in children and adolescents participating in the European youth heart study. Methods: The participants were 4072 children and adolescents (aged 9 and 15) from Denmark, Portugal, Estonia, and Norway. Cardiorespiratory fitness was indirectly determined using a maximal ergometer cycle test. The sum of four skinfolds, waist circumference, and blood pressure were assessed with a standardised protocol. Linear regression analysis was used to test the graded relation between cardiorespiratory fitness and the dependent variables adjusted for pubertal stage, sex, and country. Results: A significant curvilinear graded relation was found between cardiorespiratory fitness and waist circumference and sum of skinfolds (partial r 2 for cardiorespiratory fitness was 0.09–0.26 for the different sexes and age groups). Systolic and diastolic blood pressure also showed a curvilinear relation with cardiorespiratory fitness, and fitness explained 2% of the variance in systolic blood pressure. The difference in systolic blood pressure between the least and most fit was 6 mm Hg. Conclusion: A curvilinear graded relation was found between cardiorespiratory fitness and waist circumference, sum of skinfolds, and systolic blood pressure. The greatest difference in these health variables was observed between low and moderate fitness levels.
Successful en bloc resection of superficial esophageal cancer treated by endoscopic submucosal dissection with a splash needle
Authors: M. Fujishiro, S. Kodashima, O. Goto, S. Ono, Y. Muraki, N. Kakushima, M. Omata
Journal: Endoscopy (2008)

Endoscopic submucosal dissection (ESD) enables resection of large or nonlifting gastrointestinal epithelial neoplasms in an en bloc fashion. However, the high frequency of complications and the complexity of the procedure need to be improved [1–4]. In collaboration with the Pentax Corporation, Tokyo, Japan, we have therefore invented a novel electrosurgical knife for ESD, called the splash needle (DN-2618A; Pentax Corp.), which has an ultra-thin short needle with a water-jet function ([Fig. 1]. The advantages are: (i) the short needle is adjustable in length (maximum 2.5mm); (ii) the thinness of the needle (0.3 mm diameter) makes it possible to resect using only coagulation current from mucosal incision to submucosal dissection, to reduce the risk of heavy bleeding, or to resect sharply with minimal tissue damage by using cutting or Endocut current; (iii) the water-jet function from the knife itself allows the endoscopic view field to be kept clean, bleeding vessels to be easily identified, and additional submucosal injection to be done without changing the device. A disadvantage could be that a sharper cutting ability could lead to perforation if the knife is used incorrectly. A 64-year-old gentleman with a semicircular non-Lugol-staining area diagnosed as squamous cell carcinoma in the lower esophagus was referred for ESD. With a preoperative diagnosis of type 0-IIc intramucosal squamous cell carcinoma (m2), 3 cm in size, ESD was performed with a splash needle without complications in an operating time of 65 minutes, in a similar way to that described previously, with some modification [5] ([Fig. 2], [Video 1]). The main modifications were:
Digital Dialogue
Authors: R Peters, R Sikorski
Journal: JAMA (1997)

A 65-year-old man with newly diagnosed Alzheimer disease comes to a physician's office with several members of his family. The family is apprehensive about what to expect in the coming months and unsure of whether they can take care of the patient at home. The patient's son says that he has been subscribing to an Internet newsgroup on Alzheimer disease to find out more about his father's illness. He asks the physician what she thinks about receiving advice through online forums.
Computerized ECG Analysis-Reply
Authors: Mario Ariet
Journal: JAMA (1978)

<h3>In Reply.—</h3> We apologize for the ambiguity of our statement in our report. We intended to say that (1) the diagnostic accuracy of an electrocardiographer would be enhanced if he had a computerized interpretation as a second opinion to suggest abnormalities he might have overlooked and to force him to resolve discrepancies, and (2) a computerized ECG system saves time, particularly in reporting, by generating typed reports, and even when physician corrections may be required, the report can be edited and retyped automatically. We did not mean to imply that physicians' time would necessarily be saved by a computerized ECG system, although many physicians who use such systems believe that some of their time is saved.
Langerhans cells protect from allergic contact dermatitis in mice by tolerizing CD8+ T cells and activating Foxp3+ regulatory T cells
Authors: Mercedes Gomez de Agüero, Marc Vocanson, Fériel Hacini-Rachinel, Morgan Taillardet, Tim Sparwasser, Adrien Kissenpfennig, Bernard Malissen, Dominique Kaiserlian, Bertrand Dubois
Journal: Journal of Clinical Investigation (2012)

Allergic contact dermatitis is the most frequent occupational disease in industrialized countries. It is caused by CD8+ T cell–mediated contact hypersensitivity (CHS) reactions triggered at the site of contact by a variety of chemicals, also known as weak haptens, present in fragrances, dyes, metals, preservatives, and drugs. Despite the myriad of potentially allergenic substances that can penetrate the skin, sensitization is relatively rare and immune tolerance to the substance is often induced by as yet poorly understood mechanisms. Here we show, using the innocuous chemical 2,4-dinitrothiocyanobenzene (DNTB), that cutaneous immune tolerance in mice critically depends on epidermal Langerhans cells (LCs), which capture DNTB and migrate to lymph nodes for direct presentation to CD8+ T cells. Depletion and adoptive transfer experiments revealed that LCs conferred protection from development of CHS by a mechanism involving both anergy and deletion of allergen-specific CD8+ T cells and activation of a population of T cells identified as ICOS+CD4+Foxp3+ Tregs. Our findings highlight the critical role of LCs in tolerance induction in mice to the prototype innocuous hapten DNTB and suggest that strategies targeting LCs might be valuable for prevention of cutaneous allergy.
Sir William Osler and Robert Burton's Anatomy of Melancholy
Authors: Nicholas Dewey
Journal: JAMA (1969)

We are commemorating this month not only the semicentennial of Sir William Osler's death, but also the 100th anniversary of a formative event in his life. It was during the winter of 1869-1870 that Osler became a resident member of the Bovell household in Toronto, where Dr. James Bovell, his inspiring mentor, provided the young medical student with his first serious opportunity "for browsing in a large library." As Osler gratefully recalled at the end of his long career, it was this valuable early experience which aroused in him "an enduring interest in books"—of which Dr. Bovell had collected only "the best [that] the human mind has afforded...."<sup>1(ppxvi-xvii)</sup>The precise content of that library is not known, but it certainly influenced the growth of his own lifelong avocation, the fruits of which (splendidly housed in the Osler Library at McGill University), reflect the humanistic sympathies of the great physician
A common LRRK2 mutation in idiopathic Parkinson's disease
Authors: William P Gilks, Patrick M Abou-Sleiman, Sonia Gandhi, Shushant Jain, Andrew Singleton, Andrew J Lees, Karen Shaw, Kailash P Bhatia, Vincenzo Bonifati, Niall P Quinn, John Lynch, Daniel G Healy, Janice L Holton, Tamas Revesz, Nicholas W Wood
Journal: The Lancet (2005)
Mild Cognitive Impairment — No Benefit from Vitamin E, Little from Donepezil
Authors: Deborah Blacker
Journal: New England Journal of Medicine (2005)

In this issue of the Journal, Petersen et al. present the long-awaited results of a randomized, placebo-controlled trial of donepezil, a standard therapy for Alzheimer's disease, and the widely used antioxidant vitamin E as an early intervention for mild cognitive impairment — essentially the prodromal phase of Alzheimer's disease.1 The implications of this study for primary care medicine and for public health are enormous. The clear-cut negative findings for vitamin E, which is widely used despite the dearth of evidence of its efficacy, are especially noteworthy. The findings for donepezil, on the other hand, are much less clear.Mild cognitive . . .
Human ethology: concepts and implications for the sciences of man
Authors: Irenäus Eibl-Eibesfeldt
Journal: Behavioral and Brain Sciences (1979)

Abstract Human ethology is defined as the biology of human behavior. The methods it employs and the questions it poses are elaborations of those generally used in the various fields of biology, but especially adapted to the study of man. Observation and experimentation in the natural and seminatural setting as well as the comparative method derived from morphology play important roles in human ethology, and the exploration of phylogenetic adaptations constitutes one of its focal interests. On the basis of observations on experientially deprived and nondeprived children, comparative primate and animal behavior studies, and cross-cultural investigations, certain universal phylogenetic adaptations (in terms of fixed action patterns, innate releasing mechanisms, releasers, innate motivating mechanisms, and innate learning dispositions) have been found to occur. However, human ethology does not restrict itself to the investigation of phylogenetic adaptations. The question as to how a behavior pattern contributes to survival can be posed with respect to cultural patterns as well. Similar selection pressures have shaped both culturally and phylogenetically evolved patterns. Through cross-cultural studies a number of universal social interaction strategies have been discovered.
Bile acid secretion in cystic fibrosis.
Authors: G P Davidson, T A Robb
Journal: Gut (1987)

Eosinophilic colitis SIR, When we read the report by Moore et al on eosinophilic gastroenteritis with isolated colonic involvement (Gut 1986; 27: 1219-22) we were re- minded of a similar patient we have been following for five years.In November 1981 a 12 year old girl was seen with an eight week history of crampy lower abdominal pain, diarrhoea, and intermittent rectal bleeding.She averaged four bowel movements per day and occasionally a bowel movement at night.The stool was watery, brown in colour, and malodorous.The bleeding occurred with bowel movements, was bright red in colour and was mixed in with the stool.It varied in quantity.She denied fever, chills, anorexia, nausea or vomiting.Past health was unremarkable and functional inquiry was normal.Physical examina- tion, upper gastrointestinal series and follow through, and barium enema were normal.Colonoscopy to the mid-transverse colon revealed numerous haemorrhagic blebs 1-2 mm in diameter.Some were intact and looked like 'blood blisters', while others had ruptured.The intervening mucosa was endoscopically normal and the rectum was spared.Multiple biopsies were obtained and reported as showing moderately severe inflammation with a high proportion of inflam- matory cells being eosinophils.The inflammation did not extend past the muscularis mucosa.Crypt abscesses were not present, but sporadic cryptitis was seen.An unusual feature was that there was separa- tion of the superficial mucosal epithelium from the underlying lamina propria.Stools were negative for ova and parasites and no enteric pathogens were identified.Scotch tape test for pinworm was negative.Mild iron deficiency anaemia was present.The white blood cell count was normal without eosinophilia.Serum immunoglobulins including IgE were normal.Skin tests using the prick technique against milk, eggs, and wheat were negative.Complement studies were normal.A
Influence of Chlorothiazide upon Arterial Responsiveness to Nor-Epinephrine in Hypertensive Subjects
Authors: D. Aleksandrow, W. Wysznacka, J. Gajewski
Journal: New England Journal of Medicine (1959)

THE pressor effect of a given dose of nor-epinephrine is greater in hypertensive than in normotensive patients.1 , 2 A similar increase in the responsiveness to nor-epinephrine has been observed in hypertension in laboratory animals.3 4 5 In 1952 Raab and his colleagues6 reported that a low-sodium diet weakened or even abolished the increased responsiveness to nor-epinephrine in hypertensive subjects, and they suggested that the observed effect might be due to sodium loss from the arteriolar walls. Dahl,7 however, in a similar study, was unable to confirm such an effect of the low-sodium diet.The purpose of the present work has been to determine . . .
Primary Hyperparathyroidism With 31 Years of Hypercalcemia
Authors: Katharine Kosinski
Journal: JAMA (1976)

BIOCHEMICAL screening during the course of routine medical examinations has led to the discovery of increasing numbers of patients with asymptomatic primary hyperparathyroidism.<sup>1,2</sup>There is a paucity of clinical data as to the natural history of primary hyperparathyroidism, and though recent studies,<sup>2,3</sup>as well as Robert Neer, MD, in an oral communication (Jan 2, 1976), have indicated that a significant number of these patients may be observed without danger, many physicians feel obligated to operate on these asymptomatic individuals in order to correct the biochemical abnormality. There have been numerous reports of patients whose first symptom of primary hyperparathyroidism, usually a renal stone, has occurred as much as 40 years prior to the establishment of the diagnosis of primary hyperparathyroidism and the treatment of this disease.<sup>4,5</sup>Fahey and Meyers<sup>6</sup>reported a patient with chemically proved hypercalcemia of 36 years' duration that persisted 30 years after removal
Primary Chemotherapy of Advanced Head and Neck Cancer: Where Do We Go From Here?
Authors: B. S. Glisson, W. K. Hong
Journal: JNCI Journal of the National Cancer Institute (1996)

Despite nearly two decades of intense investigation, the role of chemotherapy as an adjunct to definitive local treatment (either surgery and/or radiation) of locoregionall y advanced squamous cell carcinoma of the head and neck is still being defined. Three ways of integrating chemotherapy into the primary management of this disease have been evaluated: 1) neoadjuvant or induction therapy (chemotherapy preceding local treatment), 2) adjuvant therapy (chemotherapy following local treatment), and 3) concomitant therapy (chemotherapy and local treatment [radiation] given simultaneously). As reviewed previously {12), the medical literature is replete with randomized clinical trials that have attempted to demonstrate the value of these different approaches with regard to two major goals: 1) improving survival through enhanced locoregional and systemic control and 2) preserving normal organ function. Although much of the extant literature is marred by flaws in design or execution that limit an interpretation of the data, a few consistent observations have been gleaned from the best-run studies. In general, neoadjuvant and adjuvant approaches have been associated with modest decreases in the incidence of distant metastases, and neoadjuvant therapy followed by radiotherapy now has an established role in organ preservation of the larynx and hypopharynx (3-9). Thus far, however, a survival benefit for adjunctive chemotherapy has been consistently observed only in studies of concomitant chemotherapy and radiotherapy. With the exception of a recent trial of both concomitant and adjuvant chemotherapy (compared with radiotherapy alone) in the treatment of advanced nasopharyngeal carcinoma, which demonstrated a striking survival advantage
Strategies for Prolonged Therapy in Patients With Advanced Non–Small-Cell Lung Cancer
Authors: Panos Fidias, Silvia Novello
Journal: Journal of Clinical Oncology (2010)

A key challenge in the treatment of advanced non-small-cell lung cancer (NSCLC) is improving outcomes for patients who have achieved at least stable disease after standard first-line therapy. Although current guidelines recommend a maximum of six cycles of first-line therapy, even in responding patients, recent trials have shown benefit with maintenance therapy.We reviewed the English literature for randomized controlled trials on prolonged therapy for NSCLC conducted between January 1999 and January 2010. The search was supplemented by a review of abstracts presented at the American Society of Clinical Oncology annual meetings (2004 to 2010), the World Lung Cancer Conference (2007 to 2009), and the 2009 Joint European CanCer Organisation-European Society for Medical Oncology conference.Several alternative strategies for prolongation of chemotherapy have been tested: these can be broadly categorized as continuation (prolongation of the first-line regimen until disease progression, unacceptable toxicity, or administration of a predefined greater number of treatment cycles), switch-maintenance (administration of an active agent immediately after completion of the initial course of chemotherapy), and continuation-maintenance (ongoing administration of a lower intensity version of the first-line chemotherapy regimen). These approaches differ from traditional second line, which is defined as treatment administered after documented clinical progression subsequent to first-line therapy.There are no data to support continuation chemotherapy in advanced NSCLC. Switch-maintenance trials with erlotinib and pemetrexed have demonstrated an improvement in overall survival. Thus far, continuation-maintenance has shown an improvement in progression-free survival, without an overall survival advantage.