tbuckley/cabot-search huggingface dataset:
An androgen receptor N-terminal domain antagonist for treating prostate cancer
Authors: Jae-Kyung Myung, Carmen A. Banuelos, Javier Garcia Fernandez, Nasrin R. Mawji, Jun Wang, Amy H. Tien, Yu Chi Yang, Iran Tavakoli, Simon Haile, Kate Watt, Iain J. McEwan, Stephen Plymate, Raymond J. Andersen, Marianne D. Sadar
Journal: Journal of Clinical Investigation (2013)

Hormone therapies for advanced prostate cancer target the androgen receptor (AR) ligand-binding domain (LBD), but these ultimately fail and the disease progresses to lethal castration-resistant prostate cancer (CRPC). The mechanisms that drive CRPC are incompletely understood, but may involve constitutively active AR splice variants that lack the LBD. The AR N-terminal domain (NTD) is essential for AR activity, but targeting this domain with small-molecule inhibitors is complicated by its intrinsic disorder. Here we investigated EPI-001, a small-molecule antagonist of AR NTD that inhibits protein-protein interactions necessary for AR transcriptional activity. We found that EPI analogs covalently bound the NTD to block transcriptional activity of AR and its splice variants and reduced the growth of CRPC xenografts. These findings suggest that the development of small-molecule inhibitors that bind covalently to intrinsically disordered proteins is a promising strategy for development of specific and effective anticancer agents.
Predictors of restenosis and long-term changes in mitral valve area after balloon mitral valvotomy with inoue balloon: a long-term (72–90 month) clinical and echocardiographic study
Authors: Kewal C. Goswami, Nitish Naik, Vinay K. Bahl, Kewal K. Talwar, Subhash C. Manchanda
Journal: Journal of the American College of Cardiology (2002)
The Late Prof. Harrison Allen.
Authors: Charles W. Burr
Journal: JAMA (1897)

Philadelphia, Nov. 30, 1897. <h3>To the Editor:</h3> —Will you kindly insert the following notice in your paper? At a meeting of the Philadelphia Neurological Society, held on November 22, the following action was taken: Whereas, The Philadelphia Neurological Society has heard with great regret of the death of Dr. Harrison Allen, it desires to offer its sympathy to his family and to give expression to its sense of the great loss which has been sustained by science and the medical profession. Dr. Allen was deeply interested in neurology, not only as a human and comparative anatomist, but also in various practical directions, as indicated by his valuable contributions to this Society and other medical bodies.
Letter: Laparoscopy explosion hazards with nitrous oxide.
Authors: I M Corall, J A Elias, L Strunin
Journal: BMJ (1976)

Hysteroscopy and laparoscopy differ in that in the former the uterine cavity is insufflated with gas or liquid to allow telescopic inspection whereas in the latter the peritoneal cavity is insufflated. Opening of the bowel by diathermy as performed by some physicians is not usually a part of laparoscopic sterilization although it may occur as a complication. In cases where diathermy of the bowel is part of an elect ive procedure nitrous oxide is generally used. For those performing tubal diathermy there is a choice of using carbon dioxide with a risk of cardiovascular collapse nitrous oxide with a theorectical risk of intraperitoneal explosion. Unfortunately, currently available data are insufficient to quantify these 2 risks.
Low-pressure-sensitive baroreceptor fibers recorded from rabbit carotid sinus nerves.
Authors: L Qu, S L Stuesse
Journal: Circulation Research (1991)

Activity was recorded from physiologically identified baroreceptor or chemoreceptor fibers in carotid sinus nerves of urethane-anesthetized spontaneously breathing rabbits. A carotid sinus area was vascularly isolated so that carotid sinus pressure and perfusion medium (Locke's solution or rabbit blood) could be controlled. The cervical sympathetic, vagus, and aortic depressor nerves were bilaterally cut to eliminate vagal and cardiopulmonary reflexes. Baroreceptor fibers could be divided into two groups: fibers with a mean firing threshold of 47.6 +/- 1.9 mm Hg and no activity below this threshold (37 fibers) and fibers that were active at low intrasinus pressures (18.1 +/- 2.2 impulses/sec at an intrasinus pressure of 0 mm Hg). The baroreceptor fibers that were spontaneously active at low pressures were also chemically sensitive: discharge rate was increased by 5-hydroxytryptamine (10 fibers, p less than 0.01), nicotine (10 fibers, p less than 0.01), or hypercapnia (13 fibers, p less than 0.001). The activity of baroreceptor fibers with a clear pressure threshold was usually decreased by hypercapnia (26 of 27 fibers, from 18.8 +/- 3.1 to 13.2 +/- 3.9 impulses/sec). Chemoreceptor fibers failed to respond to intrasinus pressure changes from 0 to 100 mm Hg (n = 25 fibers, p greater than 0.5) but were sensitive to chemical changes, as expected. Thus, there is a subset of baroreceptor fibers that, under certain conditions, is spontaneously active at very low intrasinus pressures and responds to changes in the chemical milieu.
Underdiagnosis of depression in primary care: by accident or design?
Authors: G. W. Berger
Journal: JAMA (1997)

To the Editor.  —As a busy family practitioner, I think one of the reasons seems obvious why many patients are being seriously undertreated for depression. 1 Most patients do not have an easy time accepting a diagnosis that implies to them a weakness in their character, which psychiatric diagnoses are apt to do. When a physician takes the time to explain the chemical nature of the illness and the fact that it is a medical disease, it is usually possible to convince the patient to start medication. Once the results of therapy are seen, it is seldom a problem to have the patient continue. Thus, one of the basic problems may reside in having the physician find the necessary time to educate and convince the patient of the medical nature of the disease.  As a rule, we do not have this problem of convincing the patient of a diagnosis with other medical diseases
Association of poly(ADP-ribose) polymerase 1 and a novel candidate locus, LOC127086, with systemic lupus erythematosus
Authors: H. A Martens, I. M Nolte, G. van der Steege, M. Schipper, C. G M Kallenberg, G. J te Meerman, M. Bijl
Journal: Annals of the Rheumatic Diseases (2007)

The frequency of reversible and irreversible visual impairment was determined in children with severe and profound sensorineural deafness, as subnormal vision can adversely affect their educational and social development. Eighty three of 87 such children attending an audiology service were examined to assess the incidence and severity of visual impairment. Each child underwent a detailed ophthalmic assessment. The criteria for visual impairment were visual acuity &lt; 6/9 Snellen or equivalent and/or abnormal binocular vision. Forty five had a normal ophthalmic examination (54.2%). Twenty nine had visual impairment (34.9%) and nine had ophthalmological abnormalities that did not interfere with vision (10.9%). A higher proportion of children with risk factors for visual pathology demonstrated visual impairment than those in whom there were no risk factors. None the less, 44% of visual impairment was among patients without risk factors. The results underline the need to examine all children with severe and profound sensorineural deafness soon after diagnosis and indicate that children with multiple handicaps have a greater likelihood of visual impairment (11 of 14 cases).
Postoperative Changes in the Electrocardiogram in Congenital Heart Disease
Authors: BERNHARD LANDTMAN
Journal: Circulation (1954)

Electrocardiograms of forty-six cases of pure pulmonary stenosis were analyzed before and after valvulotomy. The electrocardiograms taken at the last postoperative examinations (three months or longer after the operation) revealed significant changes as compared with the preoperative tracings. It is suggested that these changes may be due to the diminished load on the right ventricle and right auricle after the operation. Evidence is presented that electrocardiography offers a simple and valuable means for the evaluation of the result of valvulotomy in pure pulmonary stenosis.
Effect of Periodontal Treatment on Glycemic Control of Diabetic Patients
Authors: Wijnand J. Teeuw, Victor E.A. Gerdes, Bruno G. Loos
Journal: Diabetes Care (2010)

Dr. Friedlander (1) makes an interesting supporting remark to our recently published systematic review and meta-analysis (2). We agree with his argument that, besides periodontal treatment, treatment of other oral inflammatory processes (i.e., endodontic therapy for teeth with root-canal infections) may also positively affect the glycemic control …
The future of medicine lies in truly shared decision making
Authors: R. Moynihan
Journal: BMJ (2013)

Could the public play a greater role in helping reform the healing profession?



One of the welcome shifts under way in medicine is the move towards “shared decision making,” where hubris and hierarchy give way to humility and equality.1 Part of a wider reshaping of the roles and responsibilities of patients and professionals,2 the shift is challenging the long held belief that doctors know best. Rather than experts who persuade, in the new model the professionals support people in making more informed decisions about their health. But what if we take this notion of a meeting of equals seriously? Could people help professionals to make more informed decisions? Not by offering tips to the surgeon from the operating table but rather by citizens playing a more active role in some of the big and pressing debates about the future health of medicine.

As more and more voices inside the medical establishment identify the problem of too much medicine (bmj.com/too-much-medicine), a broader conversation with a wider …
Generation of HIV-1–specific CD8+ cell responses following allogeneic hematopoietic cell transplantation
Authors: Ann E. Woolfrey, Uma Malhotra, Robert D. Harrington, John McNevin, Thomas J. Manley, Stanley R. Riddell, Robert W. Coombs, Frederick R. Appelbaum, Larry Corey, Rainer Storb
Journal: Blood (2008)
An Inherent Role of Integrin-Linked Kinase-Estrogen Receptor α Interaction in Cell Migration
Authors: Filippo Acconcia, Bramanandam Manavathi, Joseph Mascarenhas, Amjad H. Talukder, Gordon Mills, Rakesh Kumar
Journal: Cancer Research (2006)

Abstract Integrin-linked kinase (ILK) and estrogen receptor (ER)-α modulate cell migration. However, the crosstalk between ERα and ILK and the role of ILK in ERα-mediated cell migration remain unexplored. Here, we report that ILK participates in ERα signaling in breast cancer cells. We found that ILK binds ERα in vitro and in vivo through a LXXLL motif in ILK. Estrogen prevented ERα-ILK binding, resulting in phosphatidylinositol 3-kinase (PI3K)–dependent increase in ILK kinase activity. Furthermore, the regulation of ERα-ILK interaction was dependent on the PI3K pathway. Unexpectedly, transient knockdown or inhibition of ILK caused hyperphosphorylation of ERα Ser118 in an extracellular signal–regulated kinase/mitogen-activated protein kinase pathway–dependent manner and an enhanced ERα recruitment to the target chromatin and gene expression, a process reversed by overexpression of ILK. Compatible with these interactions, estrogen regulated cell migration via the PI3K/ILK/AKT pathway with stable ILK overexpression hyperactivating cell migration. Thus, status of ILK signaling may be an important modifier of ER signaling in breast cancer cells and this pathway could be exploited for therapeutic intervention in breast cancer cells. (Cancer Res 2006; 66(22): 11030-8)
ABC of 1 to 7: services for children: outpatient clinics and day care.
Authors: H B Valman
Journal: BMJ (1982)

If children are to receive appropriate health care they need a spectrum of connected services: primary care from general practice and the school health service and secondary care mainly through the hospital.The hospital provides accident and emergency, outpatient, day, and inpatient services.To use resources most efficiently the district services for acutely ill children should be centralised in one department in the main hospital; ideally facilities for inpatient, outpatient, and day care should be close together. Outpatient consultationAn average-sized unit cannot manage more than about 1000 new outpatients and 5000 return visits a year.Ideally all children should be seen within a week of referral, but in many units urgent cases are seen within a week and others in two or three weeks.The referral letter should describe the doctor's worries, current medication, investigations performed, and the family or social background.Referral letters are read by the consultant, who determines the date of the appointment according to the probable diagnosis.If the letter is illegible or vital information is missing a dangerous delay may occur before the child is seen.Packing the clinic with spuriously urgent cases may prevent any child from having an adequate consultation.New patients are usually seen by a consultant or by a registrar who discusses the children with the consultant.Parents need to know that not every child can see the consultant, or fewer patients would be seen.Most parents prefer to see the same doctor each time.Considerable paediatric experience is needed before outpatient care can be provided competently and ideally a doctor with less than a year's experience in paediatrics should not do this work alone.
"The Glory That Was Greece"
Authors: L. D. Anagnostopoulos
Journal: JAMA (1969)

<h3>To the Editor:—</h3> Dr. Strange's comments (<b>206</b>:377, 1968) in response to Dr. Richards' article contain historical inaccuracies. To state that "feticide and infanticide are peculiarly Greek" suggests that he has unjustifiably generalized and exaggerated from the laws of Lycurgus of Sparta that the grossly deformed infants be exposed to die (these laws were not imposed on other Greek cities); it also suggests that Dr. Strange is unfamiliar with the greatest part of the Bible which refers repeatedly to mass murders of infants and children. These murders were aiming at genocide (Egypt), propitiating deities like Moloch (a semitic God) with the sacrifices of hecatombs of unblemished infants, or securing a throne (Herod). How do these compare with the laws of Lycurgus? And was Pythagoras, to whose ethics Dr. Strange gives a little credit, not Greek? He lived after Lycurgus and before Thales, and his followers were almost exclusively Greek for
The Christian Burial Society--Letter from Dr. Eager
Authors: J. Eager
Journal: BMJ (1843)

severe, the sulphate of copper solution and the red precipitate ointment; if very active, the sulphate of copper in substance, or the nitrate of silver, either in solution, ointment, or substance."-p.75But although so warm an advocate for the iitrate of silver, Mr. Walker very properly cautions his readers against using it too often, so as to cause ulceration of the conjunctiva, or permanent disco- loration.To avoid these evils, he recommends the sulphate of copper to be substituted for it when the symptoms improve.We have carefully looked through the whole of Mr.Walker's work, and can conscientiously pronounce it to be no less valuable as a record of his experience than as a guide to the practitioner.We are particularly pleasedwith the chapters on Iritis and Amaurosis, which are described fully and clearly, and without those subtle minutihe and infinitesimal subdivisions that are to be found inmany ophthalmological treatises.We can only express our hope, in conclusion, that it will meet with the success which it amply deserves.
Chhattisgarh's proposal to outsource diagnostic services draws criticism
Authors: M. Kay
Journal: BMJ (2013)

Jan Swasthya Abhiyan (JSA), the Indian arm of the global People’s Health Movement, which works to establish equitable healthcare and development, has criticised the Chhattisgarh government for outsourcing diagnostic services in public health facilities.

“Healthcare is a fundamental right. Allowing the involvement of the for-profit private sector into an area considered a fundamental human right will only increase inequity,” said Rakhal Gaitonde of JSA.

In …
Lung-volume reduction improves dyspnea, dynamic hyperinflation, and respiratory muscle function.
Authors: F J Martinez, M M de Oca, R I Whyte, J Stetz, S E Gay, B R Celli
Journal: American Journal of Respiratory and Critical Care Medicine (1997)

Lung-volume reduction surgery (LVRS) improves static lung elastic recoil in selected patients with severe chronic obstructive pulmonary disease (COPD). This explains the increase in FEV1 in many COPD patients who undergo LVRS, but fails to explain clinical improvement in those without changes in FEV1. We prospectively evaluated 17 patients after pulmonary rehabilitation but prior to and again at least 3 mo after bilateral LVRS done via median sternotomy. In addition to pulmonary function, lung elastic recoil, walking distance, and exercise capacity, we evaluated static and dynamic respiratory muscle (RM) function, and dyspnea. In 12 patients we also quantified dynamic hyperinflation (end-expiratory and end-inspiratory lung volume [EELV and EILV, respectively]). After LVRS, FEV1 rose from 26.7 +/- 1.8 to 39.0 +/- 3.7% predicted (p < 0.004), whereas TLC dropped from 134.7 +/- 4.8 to 118.3 +/- 4.4% predicted (p < 0.0002), and RV from 239.6 +/- 14.8 to 180.3 +/- 8.7% predicted (p < 0.0002). Isowork dyspnea decreased as assessed with a visual analogue scale (VAS) (79.6 +/- 5.2 versus 49.3 +/- 7.5 mm, p < 0.005) and the Borg scale (7.1 +/- 0.6 versus 3.5 +/- 0.6, p = 0.002). Walking distance improved significantly and, in the 12 patients in whom they were measured, EELV and EILV decreased at rest and at isowork. Maximal transdiaphragmatic pressure rose from 67.1 +/- 8.3 to 92.0 +/- 7.5 cm H2O (p < 0.03). Resting RM function changed little, but at isowork improved significantly after LVRS. Excluding one outlier, there was a strong linear correlation between the change in Borg-scale score at equivalent work loads before and after LVRS and the change in EELV (% predicted TLC, r = 0.75, p < 0.001), as well as between the change in Borg-scale score and the absolute decrease in end-expiratory pleural pressure (Ppl(e)) (r = 0.78, p = 0.004). Successful LVRS improves not only lung recoil, but also respiratory muscle function, and reduces dynamic hyperinflation. These changes help explain the decreased dyspnea and improved exercise capacity seen after LVRS, and add to current understanding of the mechanisms by which this procedure may help selected patients with severe emphysema.
European centre plays down threat from avian influenza
Authors: Rory Watson
Journal: BMJ (2005)

The new centre responsible for assessing the risk from communicable diseases in the European Union tried this week to play down the fears sparked by the recent arrival of H5N1 avian influenza in Turkey and Romania.

Zsuzsanna Jakab, the director of the Stockholm based European Centre for Disease Prevention and Control (ECDC), said, “Our opinion is [that] the risk to public health is very small, very limited, at present, except for those dealing directly …
Abscess formation in a giant gastrointestinal stromal tumor of the stomach following endoscopic biopsy
Authors: S. Nozawa, T. Bando, T. Nagata, K. Tsukada
Journal: Endoscopy (2006)

The development of transient bacteremia during or after gastrointestinal endoscopy is a well-known phenomenon but one which usually has no clinical significance. Antibiotic prophylaxis is not recommended, except for patients at high risk [1]. However, we had a patient with a gastric gastrointestinal stromal tumor who developed an abscess after undergoing endoscopic biopsy.
The Thyroid and Its Diseases
Authors: J. H. M Means
Journal: Annals of Internal Medicine (1964)

The Phylogeny, Ontogeny, Anatomy and Metabolic Regulation of the Thyroid. Thyroid Hormone Synthesis and Secretion. Thyroid Hormone Transport, Cellular Uptake, Metabolism and Molecular Action. Normal Physiology of the Hypothalamic-Pituitary-Thyroidal System, And Its Relation to the Neural System and Other Endocrine Glands. Effects of Drugs, Disease and Other Agents on Thyroid Function, The Nonthyroidal Illness Syndrome. Evaluation of Thyroid Function in Health and Disease. Autoimmunity to the Thyroid  Hashimoto's Thyroiditis. Adult Hypothyroidism. Graves' Disease and the Manifestations of Thyrotoxicosis. Diagnosis and Treatment of Graves' Disease. Complications of Graves' Disease. Thyrotoxicosis of Other Etiologies. Thyroid Dysfunnction in the Pregnant Patient. Ontogenesis of Thyroid Function, Thyroid Hormone, And Brain Development, Diagnosis and Treatment of Congenital Hypothyroidism. Genetic Defects of Thyroid Hormone Supply, Transport and Action. Multinodular Goiter. Thyroid Neoplasia. Acute and Subacute Thyroiditis. Iodine Deficiency Disorders. Surgery of the Thyroid Gland.
GROWTH CHARACTERISTICS OF TUBERCLE BACILLI AND CERTAIN OTHER MYCOBACTERIA IN H<scp>E</scp>L<scp>A</scp> CELLS
Authors: Charles C. Shepard
Journal: The Journal of Experimental Medicine (1957)

By making use of the increased phagocytosis which follows the exposure of HeLa cells to tissue culture media containing selected horse sera, it was possible to introduce all of the mycobacterial species studied into the cells, where many of them proceeded to grow. Fully virulent strains of tubercle bacilli filled much of the cytoplasm in a few days and formed characteristic cords not seen with other strains. The strains said to be less virulent, R1Rv, BCG, H37Ra, and R1Ra, grew less rapidly and in characteristic patterns. Their rates of multiplication in HeLa cells were in the order named and correlated well with their reported pathogenicity for mice and guinea pigs. Six INH-resistant strains grew at rates characteristic of fully virulent strains. Among the "rapidly growing" species, M. phlei and M. smegmatis did not show evidence of growth in the cells, although M. fortuitum did. Some strains with optimal temperatures on bacteriological media below 37°C, M. balnei, M. marinum, and M. platypoecilus, grew rapidly in HeLa cells, especially at temperatures of 31 to 35°C. The growth patterns of the bacilli in HeLa cells appear sufficiently specific to be useful in differentiation among the mycobacteria.
The Surgical Significance of Aberrant Renal Arteries in Relation to Systemic Hypertension
Authors: JOHN R. DERRICK, KENNETH R. T. TYSON
Journal: Circulation (1961)

Three cases of hypertension associated with vascular insufficiency of aberrant renal arteries are presented. Two patients were subjected to revascularization procedures. The types of pathologic processes associated with aberrant renal arteries in production of segmental renal ischemia are discussed. Considerations of diagnosis and therapy of such lesions are reviewed.