tbuckley/cabot-search huggingface dataset:
GP contract settlement under threat
Authors: Caroline White
Journal: BMJ (2006)

Proposed revisions to the family doctors' national contract in the United Kingdom could be jeopardised if GPs and the government fail to reach an agreement on pensions.

The full costs of the current GP contract, which took effect in 2004, are not yet known. But interim figures indicate that the hike in GPs' income from the NHS—currently averaging £83,500 ($144,393; €121,490)—is likely to be substantially higher than the projected 30%, sparking alarm in the treasury about the knock-on effect on doctors' pension funds.

Details of the hard fought package of proposals for the revised contract were announced …
Diagnosing Obstructive Airways Disease From the Clinical Examination
Authors: Harold D. Cross
Journal: JAMA (1995)

<h3>To the Editor.</h3> —A long-term goal and practice of mine has been to avoid wasting time in data gathering. This means choosing the most efficient, accurate, and least expensive approaches available for obtaining accurate information. The article by Drs Holleman and Simel<sup>1</sup>shows that it is possible for three of four physicians to detect airflow obstruction when a cigarette smoking history of at least 70 pack-years is combined with a skillful chest examination. Their approach is time-consuming and results in an unacceptable high error rate, an important issue recently illustrated by Leape.<sup>2</sup>The time-consuming aspect and inaccuracy were demonstrated by Schneider and Anderson.<sup>3</sup>In their study, nine physicians were given 2 hours to examine 13 patients for evidence of chronic obstructive pulmonary disease. Some did not have enough time to complete the examination, and half the time their diagnosis was incorrect. Three peak flow measurements could have
Are Patents Impeding Medical Care and Innovation?
Authors: E. Richard Gold, Warren Kaplan, James Orbinski, Sarah Harland-Logan, Sevil N-Marandi
Journal: PLoS Medicine (2010)

Background to the debate: Pharmaceutical and medical device manufacturers argue that the current patent system is crucial for stimulating research and development (R&D), leading to new products that improve medical care. The financial return on their investments that is afforded by patent protection, they claim, is an incentive toward innovation and reinvestment into further R&D. But this view has been challenged in recent years. Many commentators argue that patents are stifling biomedical research, for example by preventing researchers from accessing patented materials or methods they need for their studies. Patents have also been blamed for impeding medical care by raising prices of essential medicines, such as antiretroviral drugs, in poor countries. This debate examines whether and how patents are impeding health care and innovation.
Is CPAP effective in reducing blood pressure in minimally symptomatic obstructive sleep apnoea?
Authors: Jean-Louis Pépin, Jean-François Timsit, Renaud Tamisier, Patrick Lévy
Journal: Thorax (2014)

Hypertension affects about 25% of the adult population worldwide.It ranks as the leading chronic risk factor for mortality, accounting for 13.5% of all deaths.Half of all strokes and ischaemic heart disease events are attributable to high blood pressure (BP). 1 2 Obstructive sleep apnoea (OSA) is now recognised as a risk factor for the development of hypertension in European and the US International Guidelines.OSA and hypertension are linked in a dose-response fashion.This is true even when the usual confounding factors such as age, alcohol, tobacco consumption and Body Mass Index are taken into account. 3In a large
Long-term Glucose Control in Patients with Pancreatic Transplants
Authors: Philippe Morel, Frederick C. Goetz, Kay Moudry-Munns, Esther Freier, David E. R. Sutherland
Journal: Annals of Internal Medicine (1991)

Objective: To evaluate the long-term effect on blood glucose levels of successful transplantation of part or all of an intact human pancreas in patients with insulin-dependent diabetes mellitus (IDDM). Design: Cohort study. Setting: Referral medical center. Patients: Thirty-seven patients with adequate data, representative of a group of 62 patients with functioning grafts (that is, insulin-independent) at 2 years after transplantation. The 62 patients came from a total of 178 patients in the University of Minnesota series as of July 1987, for a 2-year success rate of 35% (95% Cl, 27.8% to 41.8%). These patients were compared to two diabetic control groups (18 patients with IDDM under standard insulin treatment in a university diabetes clinic and 11 patients with IDDM whose pancreas grafts had failed) and to two nondiabetic groups (14 nondiabetic patients who received immunosuppressive drugs after kidney transplantation and 196 healthy control subjects). Measurements: Glycosylated hemoglobin was measured by the high-pressure liquid chromatography method, as total A1 (Hb A1) and the A1C subfraction (Hb A1C); results were expressed as a percentage of total hemoglobin. Main Results: Before pancreas transplantation, the 37 patients in the study group had a mean Hb A1 of 10.8%, consistent with moderate to marked hyperglycemia and not statistically different from the levels in the diabetic control groups. All 37 patients had values above the therapeutic target range of 5.4% to 7.4%. However, at 1 and 2 years after transplantation, the mean Hb A1 value had fallen sharply to 6.7% and 6.5%, respectively, well within target range (Cl of the difference, 3.4% to 4.8%; P < 0.001). These levels did not differ from the mean Hb A1 in the nondiabetic kidney transplant recipients but were slightly above the 6.2% value for the 196 healthy controls (Cl of the difference at 1 year, 0.2% to 0.8%). Serial values were available on 6 subjects for 5 years; these values were all well within target range. As expected, Hb A1C values were parallel to those of Hb A1. Conclusions: Pancreas transplantation, in our successful cases, lowered glycosylated hemoglobin to normal or near-normal levels that were sustained for as long as 5 years. These results compare favorably with those in our patients on standard treatment, and also with those in similar patients on intensive control reported by others. Further effort to improve transplant methods appears to be warranted.
Restricted usage of T cell receptor V alpha-V beta genes in infiltrating cells in the hearts of patients with acute myocarditis and dilated cardiomyopathy.
Authors: Y Seko, S Ishiyama, T Nishikawa, T Kasajima, M Hiroe, N Kagawa, K Osada, S Suzuki, H Yagita, K Okumura
Journal: Journal of Clinical Investigation (1995)

Prolonged myocardial cell damage initiated by acute myocarditis is thought to be one of the most important etiology of dilated cardiomyopathy. To investigate the immunological mechanisms involved in the pathogenesis of dilated cardiomyopathy, we analyzed the phenotypes of infiltrating cells and examined the expression of perforin in infiltrating cells in the hearts of patients with dilated cardiomyopathy as well as acute myocarditis. We also examined the expression of HLA and intercellular adhesion molecule-1 (ICAM-1) in myocardial tissue of these patients. Furthermore, to evaluate the antigen specificity of infiltrating T cells and persistence of viral genomes in the myocardial tissue, we analyzed the expression of T cell receptor (TCR) V alpha and V beta genes as well as enterovirus genomes by PCR. We found infiltration of perforin-expressing killer cells and enhanced expression of HLA class I and ICAM-1 in the myocardial tissue. We also found that the repertoires of TCR V alpha as well as V beta gene transcripts were restricted, indicating that a specific antigen in the hearts was targeted. Because no enterovirus genomes were detected in all patients, it is strongly suggested that a cell-mediated autoimmune mechanism triggered by virus infection may play a critical role in the pathogenesis of dilated cardiomyopathy. However, we could not exclude the possibility that viruses other than enteroviruses could be pathogenic in these patients.
New Studies Support Case for Bisphosphonates as Possible Chemopreventive Agent
Authors: C. Schmidt
Journal: JNCI Journal of the National Cancer Institute (2010)

in Haifa, both described evidence to suggest that bisphosphonate treatment for bone loss protects against breast cancer in postmenopausal women.Chlebowski reviewed case data from the Women's Health Initiative -an investigation into causes of death and disability in postmenopausal women administered by the National Institutes of Health -and found statistically signifi cantly fewer diagnoses of breast cancer among women who take bisphosphonates than in those who do not.A total of 5,092 invasive breast cancers were diagnosed after 1,163,344 personyears of follow-up in women not using bisphosphonate (for a rate of 4.38/1,000 person-years).In women using bisphosphonates, 64 invasive breast cancers were diagnosed after 19,466 person-years of
An Open-Label, Multicenter, Randomized, Phase II Study of Pazopanib in Combination with Pemetrexed in First-Line Treatment of Patients with Advanced-Stage Non–Small-Cell Lung Cancer
Authors: Giorgio V. Scagliotti, Enriqueta Felip, Benjamin Besse, Joachim von Pawel, Anders Mellemgaard, Martin Reck, Lionel Bosquee, Christos Chouaid, Pilar Lianes-Barragán, Elaine M. Paul, Rodrigo Ruiz-Soto, Entisar Sigal, Lone H. Ottesen, Thierry LeChevalier
Journal: Journal of Thoracic Oncology (2013)
Risk factors, clinical course and long‐term prognosis in hidradenitis suppurativa: a cross‐sectional study
Authors: C.B. Kromann, I.E. Deckers, S. Esmann, J. Boer, E.P. Prens, G.B.E. Jemec
Journal: British Journal of Dermatology (2014)

Hidradenitis suppurativa (HS) causes considerable morbidity. The long-term prognosis is of obvious interest to both patients and physicians. We conducted this study to determine the prognosis and risk factors in patients diagnosed with HS.To describe the long-term prognosis and the clinical course of HS and its association to known risk factors.A postal follow-up survey with uncomplicated factual questions was conducted. As all of the patients were well acquainted with their long-standing disease, this was thought to be sufficient for meaningful results. All cases were diagnosed by a dermatologist. Overall, 212 patients diagnosed with HS between 1981 and 2001 were studied after a median follow-up period of 22 years (range 12-32).The overall response rate was 71.2%, with 60.8% (129/212) valid (fully completed) questionnaires. Remission was reported by 39.4% (50/127) and improvement by 31.5% (40/127). Unchanged severity was reported by 20.5% (26/127), and 8.7% (11/127) experienced worsening disease. Tobacco smoking was reported by 92.2% (119/129). Among nonsmokers, 40% (35/88) reported remission vs. 29% (17/59) of active smokers. A higher proportion of nonobese patients (45%) reported remission than obese patients (23%).We found that 39.4% of the sample reported remission of HS. Suspected risk factors appeared to influence the prognosis. Smoking and obesity were significantly linked to a lower rate of self-reported remission. The notion that lifestyle factors play a role in HS appears to be supported by this survey.
Left Upper Quadrant Mass
Authors: Harold Simon
Journal: JAMA (1961)

Dr. Stanley P. Bohrer: A 43-year-old man entered the hospital for the first time with a 6-month history of anorexia and a 25-lb. weight loss. His appetite was fine, but after a few mouthfuls of food he felt full. He had slight discomfort in his left flank, and he noticed he belched more than usual. Two weeks prior to his admission he had a gastrointestinal series which was interpreted: Barium passed through the esophagus, which appeared normal. The stomach was markedly displaced anteriorly and to the right by a mass in the left upper quadrant. No intrinsic abnormality of the stomach or duodenum was noted. I do not believe that this mass arises from the spleen, because the outline of the spleen appears to be visible separately on at least one of the films. I would favor a renal origin, but another retroperitoneal or suprarenal origin could be considered as
Noncytopathic Clearance of Lymphocytic Choriomeningitis Virus from the Hepatocyte
Authors: Luca G. Guidotti, Persephone Borrow, Amy Brown, Heike McClary, Rick Koch, Francis  V. Chisari
Journal: The Journal of Experimental Medicine (1999)

We have previously shown that interferon and tumor necrosis factor noncytopathically abolish hepatitis B virus (HBV) replication from the hepatocyte and kidney tubular epithelial cells in vivo. Here we show that a persistent lymphocytic choriomeningitis virus (LCMV) infection is cleared from the hepatocyte noncytopathically when the same cytokines are induced in the liver by antigen-nonspecific stimuli. These results indicate that, like HBV, LCMV is also susceptible to intracellular inactivation by cytokine-induced antiviral mechanisms that are operative in the hepatocyte. In contrast, LCMV is not cleared from intrahepatic nonparenchymal cells or splenocytes, indicating that, unlike the hepatocyte, these cells do not produce the factors required to inactivate LCMV. Antiviral mechanisms like these may have evolved to maintain the functional integrity of vital organs in the face of massive infection.
Fixed Hyponatremia with Normal Responses to Varying Salt and Water Intakes
Authors: Arnold I. Miles, Mark A. Needle
Journal: New England Journal of Medicine (1971)

THERE are many well documented cases of cerebral disease causing hyponatremia due to the inappropriate secretion of antidiuretic hormone.1 A cerebral salt-wasting syndrome with clinical dehydration has also been described.2 The present report concerns a patient with cerebrovascular disease who had a fixed serum sodium concentration of 120 mEq per liter and responded appropriately to variations in his salt and water intake.Case ReportJ.W. (M.H. 46–58–11), a 48-year-old black man, was admitted in a comatose state from another hospital on March 27, 1970, after a fall. On carotid arteriography an occlusion of the left internal carotid artery at its . . .
Thyroid Hormone Treatment: New Insights Into an Old Therapy
Authors: David S. Cooper
Journal: JAMA (1989)

Thyroid hormone preparations are among the most commonly prescribed medications in this country: in 1986, an estimated 20 million prescriptions were written for various forms of thyroid supplementation. Thyroid hormone formulations and the indications for thyroid hormone therapy have changed dramatically over the years, reflecting refinements in the understanding of thyroid physiology and thyroid hormone pharmacology. These changes have contributed to the bewildering array of thyroid hormone preparations that are available to the practitioner, as well as uncertainty about the proper therapeutic use of thyroid hormone. Thyroid hormone preparations can be classified into two broad categories: synthetic and biologic. Synthetic thyroxine (T<sub>4</sub>) is the preferred form of thyroid hormone for almost all therapeutic indications. Because of its 1-week half-life, thyroxine yields relatively stable blood levels, with only minimal daily fluctuations in serum T<sub>4</sub>concentrations. Furthermore, since peripheral tissues generate triiodothyronine (T<sub>3</sub>) from circulating T<sub>4</sub>, a preparation
Abstract 4538: Small ubiquitin-related modifier-1 (SUMO-1) modification of retinoic acid receptor α (RARα) regulates its nuclear localization and metabolic stability
Authors: Yanfen Fang, Lei Zhang, Yan Yan, Bo Yang, Qiaojun He
Journal: Cancer Research (2011)

Abstract Retinoic acid receptor α (RARα) has been demonstrated to be one of the most important retinoic acid receptors through which all-trans retinoic acid (ATRA) exerts its biologic effects on differentiation of leukemic cells. Previous studies have demonstrated that RARα is subject to several post-translational modifications that regulate its functions, including phosphorylation and ubiquitination. Here we are the first to show a small ubiquitin-related modifier-1 (SUMO-1) modification of RARα, and this modification might play an essential role in ATRA-induced differentiation of acute myeloid leukemia cells (HL60 and NB4) and osteosarcoma cells (U2OS). We found that SUMO-1 covalently modified RARα both in vivo and in vitro, and lysine 399 is the modification site as mutation of lysine 399 to arginine in RARα completely abolished the conjugation of SUMO-1 to RARα. We then observed that covalent modification by SUMO-1 led to the nuclear localization of RARα after ATRA treatment. Either mutation of RARα at lysine 399 or silencing of SUMO-1 could significantly block ATRA-induced RARα nuclear localization. We further found that SUMO-1 also regulated the functions of RARα by controlling RARα metabolic stability. The conjugation of ubiquitin to RARα was markedly enhanced when the lysine 399 site of RARα was mutated into arginine. Moreover, the half-life of the wild type RARα was much longer (approximate 3-fold) than the lysine 399 mutant form. These two lines of evidence indicated that SUMO-1 modification protected RARα from ubiquitin-dependent degradation. Furthermore, we observed that RARα with the deficient of SUMO-1 modification could not exert its function to regulate ATRA-induced differentiation of leukemia cells and osteosarcoma cells, which was evidenced by the decreased expression of the differentiation markers. Taken together, our data presented for the first time that sumoylation of RARα proteins at lysine 399 by SUMO-1 contributed to the nuclear localization and stability of the nuclear receptor, which might facilitate the ATRA signal transduction. Our study reveals a novel molecular mechanism for the regulation of RARα in ATRA-induced differentiation of tumor cells. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4538. doi:10.1158/1538-7445.AM2011-4538
Perforation of the Heart by Flexible Transvenous Pacemaker
Authors: Monoj Goswami
Journal: JAMA (1971)

Two patients sustained myocardial perforation following transvenous flexible pacemaker insertion. In both cases the electrodes became attached to the tricuspid valve, and this probably led to the complication. It had been believed that myocardial perforation could not occur with the new flexible pacemaker catheters. However, on the basis of these two cases we must now recognize that myocardial perforation is a potential hazard with all types of transvenous pacemaker electrodes.
Drug resistant tuberculosis can be controlled, says WHO
Authors: P. Brown
Journal: BMJ (2000)

Hard evidence on the prevention of drug resistant tuberculosis by using properly controlled treatment programs was gathered by the WHO. However, the WHO warned that a window of opportunity to prevent the spread of drug resistant strains will be missed if urgent action is not taken to persuade more health authorities to use its recommended treatment strategy. Reports from 58 countries have shown a disturbingly high prevalence of drug-resistant strains of Mycobacterium tuberculosis in Eastern Europe and Asia, while countries that have used the recommended treatment strategy tend to have low rates of resistance. The WHO has been arguing for directly observed treatment, short course for years on the basis of small-scale studies that show it helps to prevent the emergence of resistance. In countries like India, China, Indonesia, Bangladesh, and Pakistan, the scale of drug resistance is still unknown with high incidence of tuberculosis. Prevalence of tuberculosis is still high in Estonia, as well as in some provinces of India and China although the scale of the problem is small.
Needle Biopsy in the Diagnosis of Thyroid Nodules Appearing after Radiation
Authors: George Crile, Caldwell B. Esselstyn, William A. Hawk
Journal: New England Journal of Medicine (1979)

Ever since the 1930's a high proportion of all cancers of the thyroid have been induced by radiation.1 It has also been known for many years that the type of cancer that is induced by radiation is papillary, tends to appear in young people and carries little risk of causing death.2 In fact, in the Cleveland Clinic's five to 34-year follow-up of 307 patients with papillary carcinoma less than 1 per cent of the patients who gave a history of exposure to radiation died of thyroid cancer.3 A similar experience, with a mortality rate of only 0.6 per cent in . . .
Breast cancer, dermatofibromas and arsenic.
Authors: P Dantzig
Journal: Cancer Research (2009)

Abstract Abstract #4160 Background: Dermatofibromas are common benign tumors in women and breast cancer is the most common malignancy in women and an environmental etiology has been suspected in both conditions. The aim of this study is to determine if there is any relationship between the two conditions.&amp;#x2028; Materials and Methods: 5 patients with dermatofibromas and 10 control patients(2 groups) had blood arsenic levels and their skin biopsies measured for arsenic by inductively coupled mass spectometry. Fifty randomly selected patients with breast cancer and 50 control patients were examined for the presence of dermatofibromas.&amp;#x2028; Results: The patients with dermatofibromas had no detectable blood arsenic but the dermatofibromas were found to have an arsenic concentration of .171 micrograms/gram. One control group(5 patients) with no detectable blood arsenic had a skin concentration of .07 micrograms/gram and the other control group (5 patients) with an average blood concentration of 6 micrograms/liter had a concentration in their skin of .06 micrograms/gram. 43/50 patients with breast cancer had dermatofibromas and 32/50 had multiple dermatofibromas, compared with 10/50 control patients with dermatofibromas and only 1/50 with multiple dermatofibromas. In all breast cancer patients, the dermatofibromas preceded the breast cancer by many years though none of the patients could give an exact answer to that question.&amp;#x2028; Conclusions: Dermatofibromas may represent a reservoir for arsenic and may interfere with the rapid excretion of arsenic resulting in prolonged exposure. Arsenic may be important to the development of dermatofibromas as shown by the proliferation of endothelial cells, the main target of arsenic toxicity, and the increased melanin and hemosiderin, the classic causes of hyperpigmentation in chronic arsenic toxicity.Dermatofibromas represent a sign of chronic arsenic exposure, a powerful environmental carcinogen, 5-20 years prior to the clinical signs of breast cancer, when the changes in the cells would first be developing. This is the first time that any link to an environmental carcinogen has been shown in breast cancer and may represent an important venue to dramatically decrease the number of cases in the future. The dermatofibroma, especially multiple dermatofibromas, represent an important cutaneous sign of women at risk for breast cancer. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 4160.
Type 2 Herpes Simplex Virus and Vulvar Carcinoma in Situ
Authors: Peter E. Schwartz, Frederick Naftolin
Journal: New England Journal of Medicine (1981)

Squamous-cell carcinoma in situ (CIS) of the vulva is now being reported at an increasing frequency. Its association with cervical CIS and invasive cancer has been recognized, and a "field effect" has been proposed to explain cases of CIS of the vulva, vagina, and cervix as responses to a common stimulus.1 , 2 Furthermore, genital CIS lesions are often multicentric. These disorders are especially alarming to patients, since CIS of the cervix can progress to invasive cancer. One topical and especially noteworthy candidate for the role of a common carcinogenic stimulus is herpes simplex virus Type 2 (HSV2), which has been associated . . .