tbuckley/cabot-search huggingface dataset:
CD4+ CD7- CD28- T cells are expanded in rheumatoid arthritis and are characterized by autoreactivity.
Authors: D Schmidt, J J Goronzy, C M Weyand
Journal: Journal of Clinical Investigation (1996)

Clonal expansion of CD4+ T cells is a characteristic finding in patients with RA and is only infrequently found in patients with psoriatic arthritis and healthy controls. Expanded CD4+ clonotypes are present in the blood, infiltrate into the joint, and persist over years. We have not addressed the question of whether the expanded clonotypes have unique functional and phenotypic properties which may explain the preferential in vivo expansion in RA. In contrast to most CD4+ T cells, expanded clonotypes lacked the expression of the CD28 and CD7 cell surface molecules. Accordingly, the subsets of CD4+ CD28- (9.7 vs 1.7, P = 0.00002) and CD4+ CD7- T cells (21.5 vs 12.26, P = 0.018) were increased in RA patients compared with age-matched normal individuals. Despite the lack of CD28 expression, clonally expanded CD4+ T cells were not anergic but proliferated in response to immobilized anti-CD3 and could be maintained in tissue culture. In vivo expanded CD4+ T cells were autoreactive to ubiquitously distributed autoantigens. They responded in an autologous mixed lymphocyte reaction, and T cell clones isolated from selected patients proliferated to autologous peripheral blood adherent cells. These data suggest that in RA patients selected CD4+ T cells which share the CD7- CD28- phenotype escape from peripheral tolerance.
Making Breast Cancer Risk Assessment Personal
Authors: C. Vanchieri
Journal: JNCI Journal of the National Cancer Institute (2010)

Priscilla A. Furth, M.D., can imagine a day when breast cancer risk assessment is as simple and accurate as testing for heart disease risk. Like a blood test to check cholesterol levels, fi ne-needle aspiration could remove a few cells from the breast to look at genetic markers in young women. “You wouldn’t even need a piece of tissue, just some cells,” said the professor of oncology and medicine at Lombardi Comprehensive Cancer Center at Georgetown University Medical Center in Washington, D.C. “It’s a little dreamy, but it’s feasible.” Furth and many others are working hard to improve breast cancer risk assessment. But so far, the only well-tested way to gauge breast cancer risk is through models that use a few self-reported factors, including age, reproductive history (age at onset of menstruation, fi rst live birth), whether a mother or sister had breast cancer, and previous history of breast cancer. The Breast Cancer Risk Assessment Tool (BCRAT), also known as the Gail model, is one example. Unfortunately, existing models are more helpful in looking at populations than at specifi c women. “Our ability to assess risk at an individual level is somewhat lacking,” said Eitan Amir, M.D., who recently evaluated six assessment tools with his colleagues from the Division of Medical Oncology and Hematology at Princess Margaret Hospital in Toronto. “We need to improve those models.” Genomewide association studies linked several genetic variations, single-nucleotide polymorphisms (SNPs), to breast cancer. Adding those to the assessments makes sense. But the known genetic variations, except for the clearly infl uential BRCA1 and BRCA2 mutations, don’t yet give enough information to make them worth using, according to a National Cancer Institute study published in March in the New England Journal of Medicine. Meanwhile, the pressure is mounting; several companies are selling their versions of genetic tests to physicians or directly to the public ( see sidebar). The mammography debate (whether screening should begin at age 40 or 50 years) is moving this fi eld along as well. “Risk assessment is sexy again because of the issues related to the U.S. Preventive Services Task Force routine mammography recommendations,” said Susan M. Domchek, M.D. , associate professor of medicine at the Abramson Cancer Center
Relationship between cells obtained by bronchoalveolar lavage and survival in idiopathic pulmonary fibrosis.
Authors: K A Boomars, S S Wagenaar, P G Mulder, H van Velzen-Blad, J M van den Bosch
Journal: Thorax (1995)

The relationship between cell types in bronchoalveolar lavage (BAL) fluid and the clinical course of patients with idiopathic pulmonary fibrosis (IPF) has been the subject of several studies. However, the results of these studies are not conclusive. The aim of this study was to investigate the relationship between the absolute and relative cell numbers in BAL fluid from patients with IPF and their survival.Results obtained from the initial BAL fluid analyses of all histologically proven cases of IPF (n = 49) were selected retrospectively. Cox's proportional hazards survival analysis was used for estimating the relationship between absolute and relative cell numbers and survival.A negative relationship was found between both the absolute numbers and percentages of eosinophils in BAL fluid samples and survival. No such relationship was demonstrated for the absolute numbers or the percentages of any other cell type.Although this study has restrictions, these findings suggest a negative relationship between the absolute numbers and percentages of eosinophils in BAL fluid samples and survival in patients with IPF.
FACIAL HEMIATROPHY.STATISTICAL REVIEW OF ETIOLOGIC FACTORS AND PATHOGENESIS. REPORT OF A CASE WITH MORPHOLOGIC STIGMATA.
Authors: THEOPHIL KLINGMANN
Journal: JAMA (1907)

It has been suggested that facial hemiatrophy is primarily caused by arrest of development during the growing period or toward the end of it. As far as I have been able to find, there are no typical cases recorded that support this view, and as a prominent feature in the case that is the object of this paper which I offer as an apology for introducing a subject that has been thoroughly and repeatedly discussed and is perhaps not of special interest. Since Parry<sup>1</sup>first described facial hemiatrophy, particularly since the investigations of Romberg,<sup>2</sup>Lande<sup>3</sup>and Eulenburg,<sup>4</sup>the number of reported cases has been slowly increasing; nevertheless the disease is still comparatively infrequent; for this reason, and from the fact that our knowledge of nerve influence on nutritive processes is incomplete with but one satisfactory postmortem examination,<sup>5</sup>the etiology and pathology of the disorder can
Letrozole Therapy Alone or in Sequence with Tamoxifen in Women with Breast Cancer
Authors: Henning Mouridsen, Anita Giobbie-Hurder, Aron Goldhirsch, Beat Thürlimann, Robert Paridaens, Ian Smith, Louis Mauriac, John F. Forbes, Karen N. Price, Meredith M. Regan, Richard D. Gelber, Alan S. Coates
Journal: New England Journal of Medicine (2009)

The aromatase inhibitor letrozole, as compared with tamoxifen, improves disease-free survival among postmenopausal women with receptor-positive early breast cancer. It is unknown whether sequential treatment with tamoxifen and letrozole is superior to letrozole therapy alone.In this randomized, phase 3, double-blind trial of the treatment of hormone-receptor-positive breast cancer in postmenopausal women, we randomly assigned women to receive 5 years of tamoxifen monotherapy, 5 years of letrozole monotherapy, or 2 years of treatment with one agent followed by 3 years of treatment with the other. We compared the sequential treatments with letrozole monotherapy among 6182 women and also report a protocol-specified updated analysis of letrozole versus tamoxifen monotherapy in 4922 women.At a median follow-up of 71 months after randomization, disease-free survival was not significantly improved with either sequential treatment as compared with letrozole alone (hazard ratio for tamoxifen followed by letrozole, 1.05; 99% confidence interval [CI], 0.84 to 1.32; hazard ratio for letrozole followed by tamoxifen, 0.96; 99% CI, 0.76 to 1.21). There were more early relapses among women who were assigned to tamoxifen followed by letrozole than among those who were assigned to letrozole alone. The updated analysis of monotherapy showed that there was a nonsignificant difference in overall survival between women assigned to treatment with letrozole and those assigned to treatment with tamoxifen (hazard ratio for letrozole, 0.87; 95% CI, 0.75 to 1.02; P=0.08). The rate of adverse events was as expected on the basis of previous reports of letrozole and tamoxifen therapy.Among postmenopausal women with endocrine-responsive breast cancer, sequential treatment with letrozole and tamoxifen, as compared with letrozole monotherapy, did not improve disease-free survival. The difference in overall survival with letrozole monotherapy and tamoxifen monotherapy was not statistically significant. (ClinicalTrials.gov number, NCT00004205.)
Long-term Domiciliary Oxygen in Chronic Bronchitis with Pulmonary Hypertension
Authors: R. D. Stark, P. Finnegan, J. M. Bishop
Journal: BMJ (1973)

Five patients with chronic bronchitis and pulmonary hypertension were treated with oxygen in their homes for periods of between 6 and 24 months. Oxygen was supplied for 15 hours daily from cylinders or from an oxygen concentrator and few practical difficulties arose. After 23 to 59 weeks of treatment there were significant decreases in pulmonary arterial pressure and vascular resistance, and four of the five patients no longer had pulmonary hypertension at rest. Two of these patients had shown little response after three weeks of treatment. There was a reduction in the number of episodes of congestive cardiac failure compared with the corresponding period before treatment. Two of the patients improved enough to return to work. These results are encouraging enough to justify a controlled trial of the treatment in a large number of patients.
TCT-748 Double The Dose Of Clopidogrel Or Switch To Prasugrel To Antagonize Proton Pump Inhibitor Interaction
Authors: jean-philippe collet, Jean-Sebastien Hulot, Jeremie Abtan, Ghalia Anzaha, Johanne Silvain, Matheieu Kerneis, Guillaume Cayla, Sophie Galier, Olivier Barthelemy, Farzin Beygui, Vanessa Gallois, Delphine Brugier, Gilles Montalescot
Journal: Journal of the American College of Cardiology (2012)
Preventing Diabetes
Authors: Steven Teutsch
Journal: Diabetes Care (2006)

Readers of Diabetes Care know that the prevalence and cost of diabetes is increasing rapidly. Without a suitable population health response, the epidemic of obesity coupled with an aging population will relentlessly increase that burden. Breakthroughs in management of diabetes and systematic delivery of effective clinical services may ameliorate the enormous cost of the disease, but that is not the solution. The real answer lies in preventing the disease in the first place.

Until recently, we had few effective strategies for attacking the root of the problem over the longer term. Those now exist. We need to promote primary prevention strategies to improve nutrition and reduce sedentary behavior, but to do so will require a major societal commitment to safe, walkable communities; good recreational facilities; changes in agricultural subsidies and marketing of poor food choices; school nutrition education and physical activity programs; social supports; financial incentives for fitness; and much more. The Guide to Community Preventive Services has begun to assess the effectiveness of those interventions (1).

While we await the implementation and impact of primary prevention strategies, there are concrete actions that clinicians could take now if the necessary financial and delivery systems were in place. The Diabetes Prevention Program (DPP) unequivocally demonstrated the potential for slowing the progression of glucose impairment to diabetes. Metformin was effective, but the behavioral interventions were almost twice as effective (2), and …
Hyperbaric oxygen breathing and radiation therapy
Authors: H. A. van den Brenk
Journal: JAMA (1971)

One of several factors which affect the response of primary and secondary cancers to x-rays is the state of tissue oxygenation. All normal or neoplastic cells which are rendered anoxic or severely hypoxic when they are being irradiated become radioresistant, and two to three times the dose is required to produce the same degree of damage as would be required if relatively low concentrations (oxygen pressure [Po<sub>2</sub>&lt; 5 mm Hg) of molecular oxygen in solution were present. Most normal tissues of the body are adequately oxygenated in this respect. Macroscopic and microscopic appearances of growing solid tumors in humans, and direct measurements of tumor tissue Po<sub>2</sub>strongly suggest that zones of radiobiologically anoxic tumor tissue develop, particularly those zones more distant from existing blood vessels which border on necrotic regions. The degree of anoxia developing during cancerous growth is closely related to the facility with which a
Transmissible Spongiform Encephalopathies
Authors: Anne M. Haywood
Journal: New England Journal of Medicine (1997)

The transmissible spongiform encephalopathies are caused by infectious agents but usually present as genetic or sporadic disorders. The nature of the infectious agents is not known. In 1986 a new transmissible spongiform encephalopathy, which was called bovine spongiform encephalopathy or "mad cow disease," was described in Britain.1 In 1996 the British noted cases of Creutzfeldt–Jakob disease that differed from other cases of the same disease and named this entity new variant Creutzfeldt–Jakob disease.2 The possible association of new variant Creutzfeldt–Jakob disease with bovine spongiform encephalopathy brought these rare diseases to public and political attention. This review summarizes the background information . . .
P3-143: Disease control with a second Epidermal Growth Factor Receptor (EGFR) tyrosine kinase inhibitor (TKI) after failure of a first TKI in Asian patients with non-small cell lung cancer (NSCLC)
Authors: Ross Soo, Alvin Wong, Siew-Woon Lim, Tan-Min Chin, Richie Soong
Journal: Journal of Thoracic Oncology (2007)
The Influence of Pericardiectomy on the Hemodynamics of Chronic Constrictive Pericarditis
Authors: ANGEL R. VIOLA
Journal: Circulation (1973)

Preoperative and postoperative right heart catheterizations were performed on six patients with chronic constrictive pericarditis. Before surgery the patients characteristically showed distinct elevation of right ventricular end-diastolic, pulmonary arterial and wedge pressures. During the operation, right and left ventricular pressure curves were recorded both before and after pericardial resection. Before decortication, the average values of end-diastolic pressures for the right and left ventricles were 17 and 20 mm Hg respectively. No significant changes were observed after pericardiectomy was completed. However, all patients showed excellent clinical recoveries. Postoperative catheterizations performed two to five months after operation disclosed normal intracardiac pressures. Persistent impairment of ventricular performance in the early period after pericardiectomy must be attributed to a reversible myocardial failure.
Reduced Heart Rate Response to Dipyridamole as a Marker of Left Ventricular Dysfunction in Diabetic Patients Undergoing Myocardial Perfusion Scintigraphy
Authors: Andrea De Lorenzo, Ronaldo S. L. Lima
Journal: Clinical Nuclear Medicine (2009)

This study sought to find among clinical, hemodynamic and left ventricular perfusion and function data obtained from myocardial perfusion scintigraphy (MPS), those associated with a reduced heart rate (HR) response to dipyridamole in diabetic patients. This phenomenon, although previously described as a marker of autonomic dysfunction in patients with diabetes, has not been fully elucidated.One hundred two consecutive diabetic patients undergoing dual-isotope (rest Tl-201/dipyridamole stress Tc-99m tetrofosmin) MPS were prospectively enrolled. A reduced HR response to dipyridamole was considered present if the ratio between maximal HR after dipyridamole infusion and rest HR was <or=1.20. MPS images were interpreted semiquantitatively, and perfusion scores were calculated. Left ventricular ejection fraction (LVEF) was automatically obtained. A logistic regression analysis was used to find variables independently associated with a reduced HR response to dipyridamole.A reduced HR response to dipyridamole was found in 46.1% of the patients and was associated with the presence of chronic renal failure (chi2 = 6.4), with high baseline HR (chi2 = 4.7) and low poststress LVEF (chi2 = 10.6).Attenuation of the HR response to dipyridamole was frequent and was strongly associated with reduced LVEF. Autonomic dysfunction may be reflected in the higher baseline HR but should not be considered the sole mechanism accounting for the reduction in HR response to dipyridamole in patients with diabetes.
Kidney transplantation and seat belt legislation.
Authors: J F Thompson, R F Wood, A P Cahill, P M Franklin, P J Morris
Journal: BMJ (1983)

The results are given of a study to identify the causes of death in a group of donors whose kidneys were transplanted in the period immediately before the introduction of the new seat belt legislation in the United Kingdom (U.K.), and to assess the likely impact of the new laws on the supply of cadaveric kidneys in the U.K. It is noted that although the wearing of seat belts will undoubtedly cause a shift in the pattern of injury resulting from car accidents and reduce the number of deaths, there will still be a number of seriously injured patients who may be potential organ donors. About 8000 cadaver kidneys from 4000 brain dead patients are potentially available each year in the U.K., but only 1000 are used. Thus even if a small reduction in the number of donors does occur as a result of the new seat belt laws it could easily be offset by promoting a modest increase in the rate of retrieval of organs from all the other potential donors.
Will the revolution in genetics improve healthcare?
Authors: L. Smeeth, T. v. Staa
Journal: BMJ (2012)

We need randomised trials to tell us 

The new millennium has brought with it an explosion in genetic knowledge. Future generations are likely to look back at this time as the beginning of a new era in human genetics and health. The major challenge facing researchers is how to translate this new knowledge into improved health and healthcare, and progress has been slower than predicted.1 2 Simply knowing that a genetic variant is associated with an increased risk of a disease or that it influences a response to drug treatment is only half the picture. The new research frontiers are how this knowledge should be used and assessing the clinical and cost effectiveness of such use. A linked research study by Hollands and colleagues (doi:10.1136/bmj.e4708) is a pioneering attempt to use a genetic discovery to improve healthcare.3

Increased knowledge of the underlying genetic causes of disease has already made major contributions. For example, the finding that genetic variants of components of the complement pathway were associated with age related macular degeneration stimulated a whole new area of research and suggested …
Concerns About Concussion Rates in Female Youth Soccer
Authors: Anthony P. Kontos, R. J. Elbin, Tracey Covassin
Journal: JAMA Pediatrics (2014)

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Ventilation/Perfusion Mismatch of One Lung in a Patient with Takayasu??s Arteritis
Authors: YUTAKA SUZUKI
Journal: Clinical Nuclear Medicine (1986)

A case of Takayasu's arteritis with pulmonary artery involvement was reported. Pulmonary artery involvement was first detected by ventilation/perfusion imaging, which showed ventilation/perfusion mismatch of the right lung, and was confirmed by pulmonary arteriography. Pulmonary artery involvement of Takayasu's arteritis is one of the disease processes causing ventilation/perfusion mismatch.
CD4(+) T cells tolerized ex vivo to host alloantigen by anti-CD40 ligand (CD40L:CD154) antibody lose their graft-versus-host disease lethality capacity but retain nominal antigen responses.
Authors: B R Blazar, P A Taylor, R J Noelle, D A Vallera
Journal: Journal of Clinical Investigation (1998)

A major goal of the transplant field is to tolerize donor T cells to prevent graft-versus-host disease (GVHD) (1). We describe an ex vivo approach in which the blockade of CD40 ligand (CD40L:CD154):CD40 interactions, a pathway required for optimal T cell expansion, induces donor CD4(+) T cells to become tolerant to host alloantigens (2). High doses of tolerized cells did not cause GVHD lethality in vivo. T cells had intact responses to antigens not present during tolerization. Tolerance was long lived and not readily reversible in vivo. These data have significant implications for the use of tolerization approaches to prevent human GVHD.