tbuckley/cabot-search huggingface dataset:
Noninferiority of Functional Outcome in Ambulatory Management of Obstructive Sleep Apnea
Authors: Samuel T. Kuna, Indira Gurubhagavatula, Greg Maislin, Sakhena Hin, Kathryn C. Hartwig, Sue McCloskey, Robert Hachadoorian, Sharon Hurley, Rajesh Gupta, Bethany Staley, Charles W. Atwood
Journal: American Journal of Respiratory and Critical Care Medicine (2011)

Rationale: Home portable monitor testing is increasingly being used to diagnose patients with obstructive sleep apnea (OSA) and to initiate them on continuous positive airway pressure (CPAP) treatment.Objectives: To compare functional outcome and treatment adherence in patients who receive ambulatory versus in-laboratory testing for OSA.Methods: Veterans with suspected OSA were randomized to either home testing or standard in-laboratory testing. Home testing consisted of a type 3 portable monitor recording followed by at least three nights using an automatically adjusting positive airway pressure apparatus. Participants diagnosed with OSA were treated with CPAP for 3 months.Measurements and Main Results: We measured the change in Functional Outcomes of Sleep Questionnaire score, with an a priori noninferiority delta of −1, and the mean daily hours of objectively measured CPAP adherence, with an a priori noninferiority delta of −0.75 hour/day. Of the 296 subjects enrolled, 260 (88%) were diagnosed with OSA, and 213 (75%) were initiated on CPAP. Mean ± SD functional outcome score improved 1.74 ± 2.81 in the home group (P < 0.001) and 1.85 ± 2.46 in the in-laboratory group (P < 0.0001). The lower bound of the one-sided 95% noninferiority confidence interval was −0.54. Mean ± SD hours of daily CPAP adherence were 3.5 ± 2.5 hours/day in the home group and 2.9 ± 2.3 hours/day in the in-laboratory group (P = 0.08). The lower bound of the one-sided 95% noninferiority confidence interval was 0.03.Conclusions: Functional outcome and treatment adherence in patients evaluated according to a home testing algorithm is not clinically inferior to that in patients receiving standard in-laboratory polysomnography.Clinical trial registered with www.clinicaltrials.gov (NCT00880165).
Preventing Hypothermia-Related Death
Authors: Dave Epstein
Journal: JAMA (1997)

<h3>To the Editor.</h3> —I disagree with a CDC Editorial Note in the<i>Morbidity and Mortality Weekly Report (MMWR)</i><sup>1</sup>that states, "Hypothermia-related morbidity and mortality can be prevented by early recognition and prompt medical care," followed by a list of some signs of hypothermia that practitioners should recognize. In the 3 patients excerpted from the<i>MMWR CDC Surveillance Summaries</i>(a polysubstance abuser, an alcoholic, and an individual with dementia who wandered), practitioners learned in the signs of hypothermia could not have saved their lives. Nobody was near these patients to recognize early symptoms and signs of hypothermia as they were beginning to die. In these patient populations, prevention of hypothermia-related mortality requires that human services are in place to keep persons at risk out of the cold. This correspondence is in no way intended to accuse human services efforts in Vermont—rather, it's just a reminder that we stay focused on
TREATMENT BY NEGLECT
Authors: THEODORE DILLER
Journal: JAMA (1923)

It seems to be the fundamental rule running through Nature that periods of rest or quiescence alternate with periods of activity, complete or incomplete. In this great world we know that light and darkness, summer and winter, rain and dryness alternate; and in our bodies respiration, heart beats and mental activity alternate with periods of rest. Joy and sorrow, hope and fear, exaltation and depression, love and hate alternate.  When we turn to the field of therapeutics, we can think of many conditions that require some active and immediate attention, such as injuries resulting from accidents; but in all cases—surgical or medical—there comes a period of rest. Following a gallbladder operation, removal of the tonsils or the appendix, the setting of a fracture, the removal of the prostate gland or of a cataract, a period of rest follows; so with therapeutics of medicine, such as drugs, baths and massage, administration
Membrane-Bound TNF Supports Secondary Lymphoid Organ Structure but Is Subservient to Secreted TNF in Driving Autoimmune Inflammation
Authors: Sigrid R Ruuls, Robert M Hoek, Vu N Ngo, Tom McNeil, Linda A Lucian, Mary J Janatpour, Heinrich Körner, Heleen Scheerens, Edith M Hessel, Jason G Cyster, Leslie M McEvoy, Jonathon D Sedgwick
Journal: Immunity (2001)
How To Learn from Patients: Fuller Albright's Exploration of Adrenal Function
Authors: Theodore B. Schwartz
Journal: Annals of Internal Medicine (1995)

Fuller Albright (1900-1969) was acknowledged as the preeminent clinical and investigative endocrinologist of his day by many of his contemporaries, but his many achievements are all but unknown to the present generation of physicians. This article describes how he used his clinical knowledge and a few tools—the measurement of urinary 17-ketosteroid excretion and the administration of methyltestosterone—to elucidate the major hormonal functions of the adrenal cortex and to clarify the pathophysiology of the Cushing syndrome. In addition, in a tour de force of clinical reasoning, he predicted, 5 years before the event, the discovery of a hormone that would reverse the endocrinologic abnormalities of congenital adrenal hyperplasia. Fittingly, he and pioneer pediatric endocrinologist Lawson Wilkins were the first to treat this disease successfully with cortisone.
Euthanasia: Should the Public Decide?-Reply
Authors: Robert J. Blendon
Journal: JAMA (1993)

<h3>In Reply.</h3> —Dr Shertz raises several important concerns about our article: (1) Is public opinion likely to influence future public policy on the controversial question of euthanasia? (2) In our society, is this appropriate? (3) Does the public understand the consequences of its preferences? (4) Did respondents understand the specific differences among the policy choices offered to them? Regarding the first issue, there exists a good deal of empirical research on this question. The results show that, under certain circumstances, public policy decisions are causally related to the direction of public opinion.<sup>1-3</sup>This occurs when (1) the issue is a highly salient one to Americans; (2) high levels of public support for particular policy are sustained over a number of years; and (3) there are no strong institutional barriers to a policy's implementation. The movement to legalize euthanasia meets all three of these criteria. As presented in our article,
Topical Chemotherapy in Human Urothelial Carcinoma Explants: A Novel Translational Tool for Preclinical Evaluation of Experimental Intravesical Therapies
Authors: Christian Bolenz, Eva-Maria Ikinger, Philipp Ströbel, Lutz Trojan, Annette Steidler, Mario I. Fernández, Patrick Honeck, Ute Gabriel, Christel Weiss, Rainer Grobholz, Peter Alken, Maurice Stephan Michel
Journal: European Urology (2008)
Abstract C52: Induction of homologous recombination by DNA nicks
Authors: Lianne E.M. Vriend, Przemek M. Krawczyk, Maria Jasin
Journal: Cancer Research (2013)

Abstract Homologous recombination (HR) is a major mechanism of DNA repair, such that mutations in HR genes are associated with tumor susceptibility. We have used a recently adapted system for genome engineering to study HR mechanisms in mammalian cells. Clustered regularly-interspaced short palindromic repeats (CRISPR) are prokaryotic adaptive immune systems that specifically cleave nucleic acids of invading pathogens. The effector phase of CRISPR system in Staphylococcus pyogenes consists of two main components, the endonuclease Cas9 and RNA strands that dictate the recognition sequence cleaved by Cas9. The activity of Cas9 resides in 2 nucleolytic domains, HNH-like and RuvC1-like, such that mutating the active site of either of these domains turns Cas9 into a DNA nicking enzyme. Here we applied the commonly used DR-GFP HR reporter to investigate the repair of both DNA double-strand breaks (DSBs) and nicks induced by Cas9 in human cells. We show that a DSB, introduced by wild-type (wt) Cas9 and a guide RNA (gRNA) directed to the I-SceI site of the DR-GFP reporter, induces HR at levels similar to the I-SceI endonuclease, demonstrating the robustness of the system and confirming the potential of the CRISPR system as a genome engineering tool. Cas9 with mutations in either of the nucleolytic domains also stimulates HR, albeit at much lower levels, suggesting that a nick can also be repaired by HR. Stimulation of HR by DNA nicks is not reduced by PARP inhibition and has the same genetic requirements as DSB-induced HR. Given that SSBs are induced by endogenous DNA metabolic processes as well as by many anti-cancer treatments, our results may advance the understanding of mechanisms responsible for repair of these abundant DNA lesions. Citation Format: Lianne E.M. Vriend, Przemek M. Krawczyk, Maria Jasin. Induction of homologous recombination by DNA nicks. [abstract]. In: Proceedings of the Third AACR International Conference on Frontiers in Basic Cancer Research; Sep 18-22, 2013; National Harbor, MD. Philadelphia (PA): AACR; Cancer Res 2013;73(19 Suppl):Abstract nr C52.
Treatment of Intractable Rheumatoid Arthritis With Combined Cyclophosphamide, Azathioprine, and Hydroxychloroquine
Authors: MaryEllen Csuka
Journal: JAMA (1986)

Cyclophosphamide, azathioprine, and hydroxychloroquine sulfate were prescribed for 31 patients (26 women and five men) with rheumatoid arthritis refractory to conventional therapy. Maintenance drug dosages (mean +/- SD) were as follows: cyclophosphamide, 30 +/- 24 mg/day; azathioprine, 74 +/- 44 mg/day; and hydroxychloroquine sulfate, 210 +/- 92 mg/day. Disease suppression began in 30 patients within three to 24 months (mean, nine months). Results after 43 months (range, 12 to 102 months) were as follows: 16, complete remission; seven, near remission; seven, partial disease suppression; one, no response. None remained in prolonged remission without some form of therapy. Treatment was discontinued in three patients because of pulmonary infection (two) or thrombocytopenia (one). Four patients had five malignant neoplasms (surgical cures) before therapy (two breast, one colon, one melanoma, one endometrial); four patients developed a malignant neoplasm during combined drug therapy (one colon, one endometrial, one lung, one erythroleukemia); and three died. The absolute risk of malignancy from combined drug therapy is still unclear. We concluded that combined use of remittive agents may have promise in treatment of severe rheumatoid arthritis; cyclophosphamide should be replaced with a nonalkylating agent; and the place of combined drug therapy remains uncertain in the absence of controlled trials.
Targeting ROR1 Inhibits Epithelial–Mesenchymal Transition and Metastasis
Authors: Bing Cui, Suping Zhang, Liguang Chen, Jianqiang Yu, George F. Widhopf, Jessie-F. Fecteau, Laura Z. Rassenti, Thomas J. Kipps
Journal: Cancer Research (2013)

Abstract Metastasis is responsible for 90% of cancer-related deaths. Strategies are needed that can inhibit the capacity of cancer cells to migrate across the anatomic barriers and colonize distant organs. Here, we show an association between metastasis and expression of a type I receptor tyrosine kinase–like orphan receptor, ROR1, which is expressed during embryogenesis and by various cancers, but not by normal postpartum tissues. We found that expression of ROR1 associates with the epithelial–mesenchymal transition (EMT), which occurs during embryogenesis and cancer metastasis. Breast adenocarcinomas expressing high levels of ROR1 were more likely to have gene expression signatures associated with EMT and had higher rates of relapse and metastasis than breast adenocarcinomas expressing low levels of ROR1. Suppressing expression of ROR1 in metastasis-prone breast cancer cell lines, MDA-MB-231, HS-578T, or BT549, attenuated expression of proteins associated with EMT (e.g., vimentin, SNAIL-1/2, and ZEB1), enhanced expression of E-cadherin, epithelial cytokeratins (e.g., CK-19), and tight junction proteins (e.g., ZO-1), and impaired their migration/invasion capacity in vitro and the metastatic potential of MDA-MB-231 cells in immunodeficient mice. Conversely, transfection of MCF-7 cells to express ROR1 reduced expression of E-cadherin and CK-19, but enhanced the expression of SNAIL-1/2 and vimentin. Treatment of MDA-MB-231 with a monoclonal antibody specific for ROR1 induced downmodulation of vimentin and inhibited cancer cell migration and invasion in vitro and tumor metastasis in vivo. Collectively, this study indicates that ROR1 may regulate EMT and metastasis and that antibodies targeting ROR1 can inhibit cancer progression and metastasis. Cancer Res; 73(12); 3649–60. ©2013 AACR.
Not Sold on Performance Measures
Authors: Michael E. Miller
Journal: Annals of Internal Medicine (2008)

Letters15 July 2008Not Sold on Performance MeasuresMichael E. Miller, MDMichael E. Miller, MDFrom Medical Care Affiliates, Boston, MA 02199.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-149-2-200807150-00019 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:I've practiced internal medicine with 3 colleagues for 28 years and have no desire to impede the improvement of patient safety and care quality. However, in their recent article, Landon and Normand (1) evoke more questions than answers, leaving me unconvinced of the value of performance measurements and unenthusiastic about embracing them.Where is the evidence that public reporting of performance measures and pay-for-performance programs improve (rather than worsen) outcomes and reduce (rather than increase) health care costs?Are these programs the best place to invest limited resources in repairing today's pressing health care problems, such as ...Reference1. Landon BE, Normand SL. Performance measurement in the small office practice: challenges and potential solutions. Ann Intern Med. 2008;148:353-7. [PMID: 18316754] LinkGoogle Scholar Author, Article, and Disclosure InformationAuthors: Michael E. Miller, MDAffiliations: From Medical Care Affiliates, Boston, MA 02199.Disclosures: None disclosed. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoPerformance Measurement in the Small Office Practice: Challenges and Potential Solutions Bruce E. Landon and Sharon-Lise T. Normand Not Sold on Performance Measures Bruce E. Landon and Sharon-Lise T. Normand Metrics 15 July 2008Volume 149, Issue 2Page: 146KeywordsChartsConflicts of interestDrugsElectronic medical recordsHealth careHealth care qualityPatientsPerformance measuresPrimary care physiciansSafety ePublished: 15 July 2008 Issue Published: 15 July 2008 Copyright & PermissionsCopyright © 2008 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Environmental chemical exposures and disturbances of heme synthesis.
Authors: W E Daniell, H L Stockbridge, R F Labbe, J S Woods, K E Anderson, D M Bissell, J R Bloomer, R D Ellefson, M R Moore, C A Pierach, W E Schreiber, A Tefferi, G M Franklin
Journal: Environmental Health Perspectives (1997)

Porphyrias are relatively uncommon inherited or acquired disorders in which clinical manifestations are attributable to a disturbance of heme synthesis (porphyrin metabolism), usually in association with endogenous or exogenous stressors. Porphyrias are characterized by elevations of heme precursors in blood, urine, and/or stool. A number of chemicals, particularly metals and halogenated hydrocarbons, induce disturbances of heme synthesis in experimental animals. Certain chemicals have also been linked to porphyria or porphyrinuria in humans, generally involving chronic industrial exposures or environmental exposures much higher than those usually encountered. A noteworthy example is the Turkish epidemic of porphyria cutanea tarda produced by accidental ingestion of wheat treated with the fungicide hexachlorobenzene. Measurements of excreted heme precursors have the potential to serve as biological markers for harmful but preclinical effects of certain chemical exposures; this potential warrants further research and applied field studies. It has been hypothesized that several otherwise unexplained chemical-associated illnesses, such as multiple chemical sensitivity syndrome, may represent mild chronic cases of porphyria or other acquired abnormalities in heme synthesis. This review concludes that, although it is reasonable to consider such hypotheses, there is currently no convincing evidence that these illnesses are mediated by a disturbance of heme synthesis; it is premature or unfounded to base clinical management on such explanations unless laboratory data are diagnostic for porphyria. This review discusses the limitations of laboratory measures of heme synthesis, and diagnostic guidelines are provided to assist in evaluating the symptomatic individual suspected of having a porphyria.
Eradication of systemic B-cell tumors by genetically targeted human T lymphocytes co-stimulated by CD80 and interleukin-15
Authors: Renier J. Brentjens, Jean-Baptiste Latouche, Elmer Santos, Francesc Marti, Michael C. Gong, Clay Lyddane, Philip D. King, Steven Larson, Mark Weiss, Isabelle Rivière, Michel Sadelain
Journal: Nature Medicine (2003)
Thyrotropin-Secreting Pituitary Adenomas: Clinical and Biochemical Heterogeneity
Authors: Neil Gesundheit
Journal: Annals of Internal Medicine (1989)

Study Objective: To evaluate the clinical and biochemical features of patients with TSH (thyroid-stimulating hormone, thyrotropin)-secreting pituitary tumors; to measure the biologic activity in vitro of circulating TSH from selected patients before and after pituitary surgery. Design: Case series. Setting: Patients in an endocrinology unit. Patients: Nine patients with TSH-secreting pituitary tumors. Measurements and Main Results: All patients had hyperthyroidism, elevated free thyroxine and triiodothyronine levels, and detected levels of TSH. The free alpha subunit, a tumor marker for neoplasms of gonadotropic or thyrotropic cell origin, was elevated in all nine patients. Seven of the nine patients had been treated with thionamides, radioactive iodine, or thyroidectomy for presumed primary hyperthyroidism. The delay from the initial treatment of hyperthyroidism to the correct diagnosis of a pituitary neoplasm was 6.2 ± 4.8 (mean ± SD) years. Two of the seven patients with macroadenomas died in the perioperative period (one at NIH, one at a referring hospital). Of the remaining five patients with macroadenomas, four have residual tumor and inappropriate TSH secretion, despite surgery and radiation therapy, at follow-up from 3.5 to 6 years. In contrast, the two patients with microadenomas are clinically cured 2.5 and 4 years after transsphenoidal adenomectomy. The biologic to immunologic (B/I) ratio of serum TSH, determined preoperatively in five patients with TSH-secreting tumors, was elevated compared with euthyroid subjects. In three patients the B/I ratio of serum TSH was also measured after pituitary surgery; in two the elevated B/I ratio returned to normal after successful pituitary adenomectomy, while in the third this ratio remained elevated after incomplete adenoma resection. Conclusions: With the routine availability of ultrasensitive TSH assays and their increasing use to confirm thyrotoxicosis from all causes, we expect that TSH-secreting pituitary tumors will be diagnosed earlier, before inappropriate antithyroid therapy, permitting an improved outcome.
Generalized eruptive histiocytoma
Authors: G.I. STABLES, RONA M. MACKIE
Journal: British Journal of Dermatology (1992)

The case is reported of a 56-year-old female who over 18 months developed a symmetrical eruption of hundreds of bluish-red papules, a small number of which have spontaneously resolved. The clinical and histopathological findings were compatible with the diagnosis of generalized eruptive histiocytoma. The ultrastructural findings in this case suggest that this condition which is in the non-X group of histiocytic disorders is closely related to histiocytosis X.
Ebstein's Anomaly Associated with Cardiomyopathy and Pulmonary Hypertension
Authors: ROBERT G. SUMNER, WILLIAM J. JACOBY, DONALD H. TUCKER
Journal: Circulation (1964)

A patient is described with cardiomyopathy and intracavitary electrocardiographic findings typical of Ebstein's anomaly of the tricuspid valve. The cardiomyopathy was characterized by extreme thickness of the left ventricular wall on angiocardiography, elevated end-diastolic pressures of the ventricles, and prominent "a" waves in the atrial pressure pulses. Moderately severe pulmonary hypertension, which has not previously been described in Ebstein's anomaly, was also attributed to the cardiomyopathy. This case illustrates the increasing number of associations with which Ebstein's anomaly has been reported and emphasizes the importance of considering this diagnosis in planning the cardiac catheterization of patients with congenital heart disease. The necessity of demonstrating coexisting Ebstein's anomaly in patients with congenital heart disease is indicated by the formidable mortality of such patients at surgery.
Neonatal hepatitis in Taiwan
Authors: A P Mowat
Journal: Hepatology (1988)

Fifty-six patients with moderate to severe neonatal hepatitis were followed for 12 to 78 months. Two died from causes other than hepatitis itself and were free from liver disease at the time of death. Of the remaining 54 patients, seven died of hepatitis, two are living with chronic liver disease and psychomotor retardation, and 45 are living without liver disease. High peak bilirubin levels and liver histologic findings of periportal fibrosis, moderate to severe portal inflammation, and/or diffuse giant cell transformation appear to be major factors predictive for poor outcome. Cytomegalovirus (CMV) infection was a common associated infection. Evidence of CMV infection was found in 22 (49%) of the 45 patients studied. Three of them died, and one is still living with cirrhosis of the liver. Metabolic disorders such as alpha-1-anti-trypsin deficiency, galactosemia, and aminoaciduria and/or aminoacidemia were carefully screened but were not found in these cases. A fatal case had a sibling who had died of a similar disease course. Chinese infants may have metabolic and familial cholestasis diseases requiring further investigation.
Atrial Fibrillation and Epidural Hematoma Associated with Lightning Stroke
Authors: Z. V. Morgan, R. N. Headley, Eben A. Alexander, C. Glenn Sawyer
Journal: New England Journal of Medicine (1958)

CUDDEN death from lightning is not common; the ^ nation's reported deaths from lightning average approximately 300 per year, with a national average mortality of 1.9 deaths per 1,000,000 population per year. The death rate in North Carolina from lightning is between 1.0 and 2.4 deaths per 1,000,000 population per year.1 The opportunity to observe persons who survive a stroke of lightning is rare, and there are no published figures regarding the number of such survivals. We recently had an opportunity to observe a patient who presented some unusual features, which prompt the following case report.Case ReportA 52-year-old . . .
Zoledronic Acid Produces Antitumor Effects on Mesothelioma Through Apoptosis and S-Phase Arrest in p53-Independent and Ras prenylation-Independent Manners
Authors: Shinya Okamoto, Kiyoko Kawamura, Quanhai Li, Makako Yamanaka, Shan Yang, Toshihiko Fukamachi, Yuji Tada, Koichiro Tatsumi, Hideaki Shimada, Kenzo Hiroshima, Hiroshi Kobayashi, Masatoshi Tagawa
Journal: Journal of Thoracic Oncology (2012)