tbuckley/cabot-search huggingface dataset:
Stromal Deletion of the APC Tumor Suppressor in Mice Triggers Development of Endometrial Cancer
Authors: Pradeep S. Tanwar, LiHua Zhang, Drucilla J. Roberts, Jose M. Teixeira
Journal: Cancer Research (2011)

Abstract The contribution of the stromal microenvironment to the progression of endometrial cancer has not been well explored. We have conditionally expressed a mutant allele of adenomatous polyposis coli (APCcKO) in murine uterine stroma cells to study its effect on uterine development and function. In addition to metrorrhagia, the mice develop complex atypical endometrial gland hyperplasia that progresses to endometrial carcinoma in situ and endometrial adenocarcinoma as evidenced by myometrial invasion. Stromal cells subjacent to the carcinoma cells express alpha-smooth muscle actin (αSMA) with fewer cells expressing platelet-derived growth factor α compared with normal stromal cells, suggesting that the mutant stromal cells have acquired a more myofibroblastic phenotype, which have been described as cancer-associated fibroblasts and have been shown to induce carcinogenesis in other organ systems. Analyses of human endometrial cancer specimens showed substantial αSMA expression in the stroma compared with normal endometrial stroma cells. We also show that APCcKO mutant uteri and human endometrial cancer have decreased stromal levels of transforming growth factor β and bone morphogenetic protein activities and that the mutant uteri failed to respond to exogenous estradiol stimulation. The mutant stroma cells also had higher levels of vascular endothelial growth factor and stromal derived factor signaling components and diminished expression of estrogen receptor α and progesterone receptor, which is common in advanced stages of human endometrial cancer and is an indicator of poor prognosis. Our results indicate that de novo mutation or loss of heterozygosity in stromal APC is sufficient to induce endometrial hyperplasia and endometrial carcinogenesis by mechanisms that are consistent with unopposed estrogen signaling in the endometrial epithelium. Cancer Res; 71(5); 1584–96. ©2011 AACR.
The Biology of the Immune System
Authors: David P. Huston
Journal: JAMA (1997)

Intact immunity is fundamental for survival. The human immune system has evolved with the sophisticated biologic capacity to distinguish self from nonself and for memory through the process of clonal expansion. The ability to distinguish even subtle differences from self, and among myriad antigens, is possible by the rearrangement of genes that encode immunoglobulins and T-cell receptors, as well as by the requirement for T cells to recognize antigens in the context of presentation by HLA molecules encoded within the major histocompatibility complex. Modulation of immune function initiated by antigenic stimulation and cell-cell interactions is facilitated by a plethora of soluble mediators such as cytokines. This overview of the biology of the immune system provides a framework for understanding physiologic immune responses and how lacunar defects within the immune system explain the pathogenesis of immunologic disorders. Through such understanding, potential targets can be identified for therapeutic modulation of the immune system.
The Emergence of Priorities in Psychiatry
Authors: DAVID H. CLARK
Journal: American Journal of Psychiatry (1969)

The premises upon which the National Health Service was established have influenced the development of priorities in British psychiatry since 1948. Thus the egalitarian concept of a certain acceptable standard of service for everyone meant that initial postwar emphasis was largely upon raising the low standards of the poorest hospitals. In response to growing public and Parliamentary pressures, the emphasis has now shifted toward community services. Because the psychiatrist receives most of his income as a fixed salary from the NHS, he tends to allocate most of his time to those he feels are sickest rather than to those who can best afford his services.
Graves' Disease, Thymus Enlargement, and Hypercalcemia
Authors: Luca Giovanella, Sergio Suriano, Luca Ceriani
Journal: New England Journal of Medicine (2008)

To the Editor: A previously healthy 32-year-old man presented with dyspnea on exertion. Chest radiography showed mediastinal enlargement without pulmonary abnormalities. Magnetic resonance imaging ...
Who Is Responsible?
Authors: Bland W. Cannon
Journal: JAMA (1963)

ORIGINALITY in the discussion of the goals of medical schools is at best fantasy because any one who has a continued interest in medical education has been exposed to numerous treatises on this subject. Any hope of success in this assigned task resides in the technique of analysis which offers me the opportunity of stimulating constructive thoughts for those of you concerned with the future of medical education. Before entering into a critique on our educational system, it seems reasonable that we particularize first its end product, our present day physician. Many have referred to him as an LMD, the usual abbreviation for Local Medical Doctor, yet its designation for our purpose is Lost Medical Disciple—lost from the disciplines of scholarship in the adaptation to the demands of our way of life. Perhaps many physicians rightly deserve this label. If so, what deficiencies in the individual, or in his education,
Improving Health Care
Authors: Vincent D. Taylor
Journal: New England Journal of Medicine (1969)

THE new administration in Washington has now sounded the tocsin over the "overwhelming crisis" in health care, thus joining a long list of predecessors who have decried the shortcomings of American medicine and urged action to remedy them. The deficiencies have persisted in spite of the many years of effort and large sums of money that have been devoted to identifying and demonstrating improved models of health-care delivery. The crisis in health care persists because, although we have learned a great deal about what constitutes improved medical care, we have almost no knowledge of how to get improved practices widely . . .
Determinants of normal coronary artery dimensions in humans.
Authors: W H Leung, M L Stadius, E L Alderman
Journal: Circulation (1991)

Studies of normal human coronary dimensions have been performed primarily in postmortem hearts. We evaluated the influence of age, body habitus, and regional myocardial mass on coronary dimensions in living patients with normal coronary vessels.Arteriographically normal coronary angiograms were analyzed from the following groups of subjects: group 1 (age, 15-34 years) consisted of 30 post-cardiac transplant patients with donor hearts from male subjects aged 15-34 years, group 2 (age, 35-54 years) consisted of 12 post-cardiac transplant patients with donor hearts from male subjects aged 35-54 years and 26 male subjects investigated for atypical chest pain, and group 3 (age, 55-74 years) consisted of 26 male subjects investigated for atypical chest pain. All angiograms were performed after sublingual nitroglycerin. Measurements of the dimensions of the left main, proximal left anterior descending, proximal left circumflex, and proximal right coronary arteries were made using a computer-assisted edge-detection algorithm. The regional myocardial mass supplied by each vessel was derived from echocardiographically derived total left ventricular mass and a semiquantitative angiographic territory scoring system based primarily on the number and length of its terminal nutrient branches.Linear regression analysis showed that coronary vessel cross-sectional area and total coronary cross-sectional area increase with regional myocardial mass and decrease linearly with age. Multivariate regression analysis revealed that regional myocardial mass and age were independent predictors of cross-sectional area for each vessel and for the total coronary cross-sectional area. We speculate that age-related decline in physical activity, in part, may be responsible.
Renal Hypoprostaglandism, Hypertension, and Type IV Renal Tubular Acidosis Reversed by Furosemide
Authors: SAMI A. SANJAD
Journal: Annals of Internal Medicine (1983)

A 13-year-old white girl with severe hypertension and type IV renal tubular acidosis had decreased renal chloride clearance and exaggerated sodium chloride reabsorption by the ascending limb of Henle during hypotonic saline diuresis. Urinary prostaglandin E2 excretion was markedly diminished and often undetectable (0 to 37 ng/24 h). Treatment with oral furosemide completely reversed the hypertension and hyperkalemic acidosis, and effected a 20-fold rise in urinary prostaglandin E2. Sodium chloride reabsorption by the thick ascending limb of Henle decreased from 93.5% to 79.3%. Renal hypoprostaglandism may have a pathogenic role in this syndrome by enhancing chloride reabsorption in the ascending limb of Henle leading to extracellular fluid volume expansion, hypertension, and suppression of the renin-angiotensin-aldosterone axis. The therapeutic effects of furosemide may be partially mediated by enhancing the biosynthesis of renal prostaglandins or inhibiting their breakdown.
Regional and Systemic Hemodynamic Patterns in Rabbits with Neurogenic Hypertension
Authors: NATALIE ALEXANDER, VINCENT DeQUATTRO
Journal: Circulation Research (1974)

The hemodynamic basis of neurogenic hypertension was studied in unanesthetized rabbits 10 minutes to 30 days after sinoaortic denervation (SAD). The fractional distribution of 86 Rb to body tissues was determined and used to calculate regional blood flow from the value of cardiac output obtained from an arterial dilution curve of the indicator. Sham-operated rabbits served as controls. Increased cardiac output was a major hemodynamic component of SAD hypertension in 69% of the rabbits studied 1-40 hours postoperatively (acutely) but in only 25% of those studied 3-30 days after surgery (chronically). In the majority of the chronic SAD rabbits, increased total peripheral resistance (TPR) was the basis of the hypertension. All SAD rabbits had increased heart rates. Acutely, most high-cardiac output hypertensive rabbits had increased splanchnic resistance with normal blood flow, whereas all of them had low or normal renal resistance with high blood flow. Flows were increased in other major regions. Acutely, in the few high-TPR hypertensive rabbits, resistance was significantly increased in splanchnic tissue, liver, and carcass but not in the kidneys. Chronically, renal resistance was elevated in both types of hypertension. Chronic high-TPR rabbits had increased resistance in all major regions, but, unlike the acute high-TPR group, increased carcass resistance was located in bone rather than skeletal muscle. In the few chronic high-cardiac output hypertensive rabbits, TPR was reduced and regional blood flows were high with the exception of that to the kidneys and liver. Skin received a larger percent of cardiac output in chronic hypertensive rabbits than it did in acute hypertensive rabbits regardless of the hemodynamic basis of the hypertension.
A3.8 Association between clinical, histopathological and molecular features in primary Sjögren’s Syndrome: a retrospective study
Authors: Francesco Carubbi, Alessia Alunno, Paola Cipriani, Paola Di Benedetto, Piero Ruscitti, Onorina Berardicurti, Onelia Bistoni, Sara Caterbi, Elena Bartoloni, Roberto Gerli, Roberto Giacomelli
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background and Objectives</h3> Although minor salivary gland (MSG) biopsy is the diagnostic gold standard to identify focal lymphocytic sialoadenitis (FLS) in primary Sjögren's syndrome (pSS), the association between MSG histopathology and clinical picture is still unknown. Histological studies are based on hematoxilin and eosin (H&amp;E) staining, however new approaches such as immunofluorescence or molecular biology assays, allow to stratify pSS patients according to other variables including germinal center (GC)-like structure presence and cytokine expression. Such evaluation may represent a powerful tool to be employed in clinical practice in order to predict pSS clinical picture and eventually disease prognosis. We aimed to investigate the relationship between the characteristic of the immune infiltrate, GCs presence, molecular expression of cytokines involved in inflammation and lymphoneogenesis, laboratory and clinical features in a large cohort of pSS patients. <h3>Materials and Methods</h3> 104 pSS patients were retrospectively evaluated and 40 subjects with sicca symptoms (20 with normal MSGs and 20 with non-specific chronic sialoadenitis (NSCS)) acted as controls. H&amp;E stained sections were assessed for histological pattern (normal, NSCS, FLS), Chisholm and Mason grading system, Tarpley score, a grading for the severity of inflammatory infiltrate and the focus score. Immunofluorescence staining for CD3, CD20 and CD21 was performed to identify the grade of lymphoid organization and the presence of GCs. Part of MSGs were processed for real time PCR testing LTa, LTb, BAFF, CXCR4, CXCL12, CXCR5, CXCL13, CCR7, CCL19 and CCL21. <h3>Results</h3> pSS patients displayed higher levels of all cytokines compared to normal MSGs and non- specific glandular inflammation according to the different histological scores (all p&lt;0.0001). pSS patients also displayed a peculiar inflammatory scenario characterised by B/T cell segregation and GC presence. All cytokines were more expressed in pSS samples displaying GCs compared to pSS without GCs (all p&lt;0.0001). Univariate analysis revealed that GC presence was associated with autoantibodies, hypergammaglobulinemia, salivary gland swelling, Tarpley score, focus score, and extraglandular involvement. At multivariate analysis the only clinical variable independently associated with GCs was extraglandular involvement. <h3>Conclusions</h3> In pSS histopathologic features, mainly GC presence, are associated with a peculiar cytokine expression pattern and a severe clinical subset of the disease.
Health secretary suspends reconfiguration of children's heart surgery in England
Authors: C. Dyer
Journal: BMJ (2013)

Plans to concentrate children’s heart surgery in seven of 10 units in England and to close the other three have been suspended after an independent panel commissioned by the health secretary, Jeremy Hunt, concluded they were based on “a flawed analysis.”

The decision to concentrate services, taken last July as part of the “Safe and Sustainable” review of paediatric congenital heart surgery, sparked controversy, and two of the units earmarked to stop providing the surgery challenged the move in the High Court. 

The Royal Brompton Infirmary in London was unsuccessful, but Hunt referred the issue to the Independent Reconfiguration Panel (IRP) after campaigners for Leeds General Infirmary launched the legal action that led to a victory in …
Case 9-1988
Authors: Richard C. Cabot, Robert E. Scully, Eugene J. Mark, William F. McNeely, Betty U. McNeely, Edward R. Wolpow, Edward P. Richardson
Journal: New England Journal of Medicine (1988)

Presentation of Case First admission. A 57-year-old right-handed woman was admitted to the hospital because of dizziness, nausea, and "things jumping around" in her visual fields. She was well until six years earlier, when she experienced the abrupt onset of vertigo with vomiting. She was seen elsewhere; a diagnosis of labyrinthitis was made, and meclizine was prescribed, with improvement in two days. She was then well until three weeks before admission, when she awoke with a vague bifrontal headache and nausea. During the next two days progressively severe vertigo recurred. Meclizine was again administered and was continued during the next . . .
Texas Eliminates Dumping
Authors: Arnold S. Relman
Journal: New England Journal of Medicine (1986)

The transfer of uninsured patients from private to public hospitals for purely economic reasons, a practice known as "dumping," has attracted much unfavorable publicity of late, particularly when it has involved patients requiring emergency care. As I noted last year,1 medical judgment should always prevail over economic and administrative considerations in decisions about the movement of acutely ill or injured patients from one hospital to another; otherwise, much harm can be done. There is always risk and discomfort when such patients are transferred, even when they are thought to be "stabilized." That is why transfer can be justified only when . . .
Is Self-Monitoring of Blood Glucose Appropriate for All Type 2 Diabetic Patients? The Fremantle Diabetes Study
Authors: Hubert Kolb, Berthold Schneider, Lutz Heinemann, Volker Lodwig, Stephan Martin
Journal: Diabetes Care (2006)

The analysis of self-monitoring of blood glucose (SMBG) in the community-based observational Fremantle Diabetes Study (1) becomes even more interesting when combined with three other studies of SMBG in type 2 diabetes: the Italian Qualita ed Esito in Diabetologia (QuED) Project (2), analyses of the Kaiser Permanente Northern California Medical Care Program (3), and the German …
FIRST: Fractional Flow Reserve and Intravascular Ultrasound Relationship Study
Authors: Ron Waksman, Jacek Legutko, Jasvindar Singh, Quentin Orlando, Steven Marso, Timothy Schloss, John Tugaoen, James DeVries, Nicholas Palmer, Michael Haude, Stacy Swymelar, Rebecca Torguson
Journal: Journal of the American College of Cardiology (2013)
The Coronary-Care Unit: Necessity or Luxury?
Authors: Charles A. Sanders
Journal: New England Journal of Medicine (1973)

Since the introduction of the coronary-care unit by Dr. Hughes Day a decade ago, there has been an enormous proliferation of such units throughout the United States. The widespread acceptance of the unit as the standard of treatment for patients with suspected or proved acute myocardial infarction has been based primarily on data, usually collected retrospectively, showing that such a facility leads to marked reduction of in-hospital mortality in such patients through early detection and treatment of life-threatening arrhythmias or sudden cardiac arrest. In view of these findings, possible factors contributing to establishment of coronary-care units may be fear on . . .
Doctors reluctant to work on child protection committees, survey shows
Authors: Owen Dyer
Journal: BMJ (2004)

Paediatricians in England and Wales are being frightened away from child protection work by fears of complaints from parents, says the Royal College of Paediatrics and Child Health.

Each primary care trust is supposed to appoint a paediatrician as a “designated doctor” to serve on the area child protection team. But the college has discovered that 30% of these posts are unfilled. Similar problems affect the “named doctor” programme in hospital trusts. Both roles are unpaid.

Professor Alan Craft, president of the college, said that paediatricians have never felt more isolated than they do now. The paediatrician Professor Sir Roy …
Age-related changes in skin wrinkles assessed by a novel three-dimensional morphometric analysis
Authors: S. Akazaki, H. Nakagawa, H. Kazama, O. Osanai, M. Kawai, Y. Takema, G. Imokawa
Journal: British Journal of Dermatology (2002)

A system has been developed whereby the morphology of the skin surface can be evaluated directly in three dimensions. This system employs a non-invasive device that utilizes white light of halogen origin, and which allows the computation of wrinkle depth and width, and other parameters of skin surface morphology. Using innovative engineering, an optical system has been devised so that light is transmitted via a slit and can be used to measure not only replicas of the skin but also the skin surface directly. The measurement area is 6.4 x 6.4 mm, and the theoretical resolution with a x 50 magnification lens is within 12.5 micro m.To use this system to study age-related changes in the morphology of wrinkles at the eye corner areas of women of varying ages.One hundred and one healthy women (age range 20-80 years) residing in the Tokyo area were the subjects used in this study.Wrinkles demonstrated a rapid increase in depth in women aged 40 years or older, and plateaued at the age of 60 years. Surface morphology parameters yielded results similar to those of age-related changes in wrinkles.This new analytical system provides a rapid and convenient non-invasive method to evaluate skin surface morphology in three dimensions, especially with respect to wrinkle formation. The results obtained using this system provide a deeper insight into the mechanistic relationship between wrinkles and skin elasticity.
Index Case of Fatal Inhalational Anthrax Due to Bioterrorism in the United States
Authors: Larry M. Bush, Barry H. Abrams, Anne Beall, Caroline C. Johnson
Journal: New England Journal of Medicine (2001)

This case report provides a description of the first case of fatal inhalational anthrax in the United States in 25 years. This 63-year-old newspaper photo editor had a rapidly progressive febrile illness, and lumbar puncture showed cloudy cerebrospinal fluid with numerous polymorphonuclear leukocytes and many large gram-positive bacilli, singly and in chains. A diagnosis of inhalational anthrax was made, and despite aggressive treatment the patient died soon thereafter. The infection appeared to have been transmitted through mail contaminated with anthrax spores as a result of biologic terrorism.
ON TEACHING AND LEARNING
Authors: Ward Darley
Journal: JAMA (1961)

The phenomenal advances in medical science during the last generation might suggest to the unwary that contemporary medical education is an unqualified success. Medical educators, however, have not been disposed to accept this view. In the last decade they have swept aside a host of curricular practices and educational procedures honored by tradition and comfortably familiar. One currently being challenged is the widespread belief that teachers are born, not made, and its corollary that the process of teaching and learning cannot be subjected to scientific scrutiny and analysis. A small group at the University of Buffalo, a strange alliance of medical teachers and educationists, undertook to examine this question five years ago. An annual Summer Seminar on Medical Teaching is one outcome of their effort. The Association of American Medical Colleges was an early co-sponsor of this event, and latterly has continued the venture independently with the assistance of the
Allergy to bumblebee venom. II IgE cross‐reactivity between bumblebee and honeybee venom
Authors: S. O. Stapel, J. Waanders‐Lijster de Raadt, A. W. van Toorenenbergen, H. de Groot
Journal: Allergy (1998)

To obtain more information on IgE cross‐reactivity between bumblebee venom and honeybee venom, we tested sera from venom‐sensitized patients for specific IgE against venoms from the European bumblebee (Bombus terrestris), the North American bumblebee (Megabombm pennsylvanicus), and the honeybee (Apis mellifera). RAST, RAST‐inhibition, and immunoblotting experiments indicate that bumblebee venom and honeybee venom contain venom‐specific IgE‐binding epitopes. These results suggest that immunotherapy using honeybee venom may not be effective in all bumblebee venom‐allergic patients. Our experiments also revealed differences in IgE binding for venom from European and American bumblebees.
Blood Tranfusion Outfit
Authors: J. M. Vaughan
Journal: BMJ (1939)

Shortly before the outbreak of war the Medical Research Council, acting for the Ministry of Health, established four depots in the Home Counties to collect, store, and distribute blood for civilian air raid casualties in London and the surrounding districts.These depots and the London sector hospitals were provided with special apparatus for the withdrawal and administration of blood.The apparatus as originally issued inverted position when it is required to administer blood by gravity.(In Fig. 1 the screw cap has been removed and replaced by a rubber bung.)The bottle is marked at 180 c.cm. and 540 c.cm. for measuring the anticoagulant solution and blood.Anticoagulant.-The anticoagulant solution used at present is 1.05 per cent.sodium citrate in 0.85 per cent.sodium chloride.Both salts must be of a high grade of