tbuckley/cabot-search huggingface dataset:
EAACI position statement on asthma exacerbations and severe asthma
Authors: A. Custovic, S. L. Johnston, I. Pavord, M. Gaga, L. Fabbri, E. H. Bel, P. Le Souëf, J. Lötvall, P. Demoly, C. A. Akdis, D. Ryan, M. J. Mäkelä, F. Martinez, J. W. Holloway, S. Saglani, P. O'Byrne, A. Papi, S. Sergejeva, A. Magnan, S. Del Giacco, O. Kalayci, E. Hamelmann, N. G. Papadopoulos
Journal: Allergy (2013)

Asthma exacerbations and severe asthma are linked with high morbidity, significant mortality and high treatment costs. Recurrent asthma exacerbations cause a decline in lung function and, in childhood, are linked to development of persistent asthma. This position paper, from the European Academy of Allergy and Clinical Immunology, highlights the shortcomings of current treatment guidelines for patients suffering from frequent asthma exacerbations and those with difficult-to-treat asthma and severe treatment-resistant asthma. It reviews current evidence that supports a call for increased awareness of (i) the seriousness of asthma exacerbations and (ii) the need for novel treatment strategies in specific forms of severe treatment-resistant asthma. There is strong evidence linking asthma exacerbations with viral airway infection and underlying deficiencies in innate immunity and evidence of a synergism between viral infection and allergic mechanisms in increasing risk of exacerbations. Nonadherence to prescribed medication has been identified as a common clinical problem amongst adults and children with difficult-to-control asthma. Appropriate diagnosis, assessment of adherence and other potentially modifiable factors (such as passive or active smoking, ongoing allergen exposure, psychosocial factors) have to be a priority in clinical assessment of all patients with difficult-to-control asthma. Further studies with improved designs and new diagnostic tools are needed to properly characterize (i) the pathophysiology and risk of asthma exacerbations, and (ii) the clinical and pathophysiological heterogeneity of severe asthma.
Thymidylate Synthase Expression and Prognosis in Colorectal Cancer: A Systematic Review and Meta-Analysis
Authors: Sanjay Popat, Athena Matakidou, Richard S. Houlston
Journal: Journal of Clinical Oncology (2004)

A number of studies have investigated the relationship between thymidylate synthase (TS) expression and survival in colorectal cancer (CRC) patients. Although most have reported poorer overall and progression-free survival with high TS expression, estimates of the hazard ratio (HR) between studies differ wildly. To derive a more precise estimate of the prognostic significance of TS expression, we have reviewed published studies and carried out a meta-analysis.Twenty studies stratifying overall survival and/or progression-free survival in CRC patients by TS expression status were eligible for analysis. The principal outcome measure was the HR. Data from these studies were pooled using standard meta-analysis techniques.Thirteen studies investigated outcome in a total of 887 cases with advanced CRC, and seven studies investigated outcome in a total of 2,610 patients with localized CRC. A number of methods were used both to assess TS expression and to assign TS status. Sample sizes varied greatly, small sample sizes being a feature of the advanced disease studies. The combined HR estimate for overall survival (OS) was 1.74 (95% CI, 1.34 to 2.26) and 1.35 (95% CI, 1.07 to 1.80) in the advanced and adjuvant settings, respectively, but there was evidence of heterogeneity and possible publication bias.Tumors expressing high levels of TS appeared to have a poorer OS compared with tumors expressing low levels. Additional studies with consistent methodology are needed to define the precise prognostic value of TS.
Challenges to congenital genetic disorders with “RNA-targeting” chemical compounds
Authors: Yasushi Ogawa, Masatoshi Hagiwara
Journal: Pharmacology & Therapeutics (2012)

Patients of congenital diseases such as Down syndrome (DS) and Duchenne muscular dystrophy (DMD) have abnormalities in their chromosomes and/or genes. Therefore, it has been considered that drug treatments can serve to do little for these patients more than to patch over each symptom temporarily when it arises. Although we cannot normalize their chromosomes and genes with chemical drugs, we may be able to manipulate the amounts and patterns of mRNAs transcribed from patients' DNAs with small chemicals. Based on this simple idea, we have looked for chemical compounds which can be applicable for congenital diseases and found that protein kinase inhibitors such as INDY, TG003, and SRPIN340 are promising as clinical drugs for DS, DMD, and DDS, respectively.
Does Eating Garlic Lower Cholesterol?
Authors: Russell S. Kamer
Journal: Annals of Internal Medicine (1994)

Letters1 June 1994Does Eating Garlic Lower Cholesterol?Russell S. Kamer, MD, Stephen Warshafsky, MD, and Steven L. Sivak, MDRussell S. Kamer, MDNew York Medical College; Valhalla, NY 10595Search for more papers by this author, Stephen Warshafsky, MDNew York Medical College; Valhalla, NY 10595Search for more papers by this author, and Steven L. Sivak, MDNew York Medical College; Valhalla, NY 10595Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-120-11-199406010-00012 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail IN RESPONSE:Drs. Lerner and Hulley mention only the null studies excluded, but most of the excluded studies favored garlic. Our objective was to study the effect of garlic on hypercholesterolemic patients, and we included trials in which most patients had cholesterol levels greater than 200 mg/dL. Most studies did not enroll patients based on cholesterol levels alone but rather on the presence of coronary artery disease, diabetes, hypertension, or hyperlipidemia of varying definitions. Thus, an arbitrary percentage cutoff was necessary. One study of 33 patients [1] showing no effect of garlic was excluded, but so was another randomized, placebo-controlled ...References1. Sitprija S, Plengvidhya C, Kangkaya V, Bhuvapanich S, Tunkayoon M. Garlic and diabetes mellitus phase II clinical trial. J Med Assoc Thai. 1987; 70(Suppl 2):223-7. Google Scholar2. Bordia A. Effect of garlic on blood lipids in patients with coronary heart disease. Am J Clin Nutr. 1981; 34:2100-3. Google Scholar3. Luley C, Lehmann-Leo W, Moller B, Martin T, Schwartzkopf W. Lack of efficacy of dried garlic in patients with hyperlipoproteinemia. Arzneimittelforschung. 1986; 36:766-8. Google Scholar4. Hulley SB, Feigal D, Martin M, Cummings SR. Designing a new study: IV. Experiments. In: Hulley SB, Cummings SR, eds. Designing Clinical Research. Baltimore: Williams & Wilkins; 1988:124. Google Scholar5. Kanziora J. Blutdruck and lipidsenkende wirkumg eines knoblauchpraparates in kombinatin mit einem diuretikum. Arztliche Forschung. 1988; 35:3-8. Google Scholar Author, Article, and Disclosure InformationAffiliations: New York Medical College; Valhalla, NY 10595 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byNutrients and trace elements as they affect blood pressure in the elderly 1 June 1994Volume 120, Issue 11Page: 969-970KeywordsCholesterolEatingHealth care quality assessmentHyperlipidemiaHypertensionStable coronary artery disease Issue Published: 1 June 1994 Copyright & PermissionsCopyright © 1994 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Complete heart block in a case of idiopathic hypertrophic subaortic stenosis: noninvasive correlates with the timing of atrial systole.
Authors: S Spilkin, A S Mitha, R E Matisonn, E Chesler
Journal: Circulation (1977)

A young man with IHSS who developed complete heart block was successfully treated with a permanent pacemaker. Echocardiography and other noninvasive techniques showed marked cycle-to-cycle variation in the evidence of subvalvular obstruction which decreased markedly when atrial systole preceded the ensuing paced complex by an appropriate interval. Because cycle length and therefore afterload were constant, it is concluded that diminished obstruction resulted from augmented ventricular end-diastolic volume produced by atrial contraction. The mitral valve echocardiogram showed unusual movements in diastole dependent upon the timing of atrial systole. Early reopening of the leaflets was a direct result of atrial contraction when the P waves were appropriately timed in presystole, whereas late reopening was passive and a result of ventricular filling in mid-diastole. Variations in intensity of the first heart sound correlated with the position of the mitral valve leaflets at the onset of ventricular systole.
The facts about franchising at Good Hope Hospital
Authors: D. Churchill
Journal: BMJ (2003)

EDITOR–The brief news item about Good Hope Hospital does not reflect what is happening here.1 We are disappointed that the BMJ should depart from its normal standards and mirror the tabloid press in making the story more important than the facts, which is inappropriate in a professional journal.

Good Hope Hospital has not been taken over by Secta. The franchising process has involved …
STUDIES ON X-RAY EFFECTS
Authors: Elsa Hill, John J. Morton, William D. Witherbee
Journal: The Journal of Experimental Medicine (1919)

These experiments indicate that the direct action of x-rays in more powerful doses than can be applied therapeutically is somewhat injurious to tumor cells, but by no means destroys them. Experiment 1 also indicates that the cancer cells establish a resistance to the x-rays after repeated doses. This harmonizes with the experience of clinicians who have succeeded in checking cancerous growths for some time but reach a point where no response can be effected by repeated doses. The rays of low penetration used in Experiment 2 are apparently more harmful to tumor cells than the penetrating rays used in Experiment 1.
Burkitt's lymphoma: The Rosetta Stone deciphering Epstein-Barr virus biology
Authors: Martin Rowe, Gemma L. Kelly, Andrew I. Bell, Alan B. Rickinson
Journal: Seminars in Cancer Biology (2009)

Epstein-Barr virus was originally identified in the tumour cells of a Burkitt's lymphoma, and was the first virus to be associated with the pathogenesis of a human cancer. Studies on the relationship of EBV with Burkitt's lymphoma have revealed important general principles that are relevant to other virus-associated cancers. In addition, the impact of such studies on the knowledge of EBV biology has been enormous. Here, we review some of the key historical observations arising from studies on Burkitt's lymphoma that have informed our understanding of EBV, and we summarise the current hypotheses regarding the role of EBV in the pathogenesis of Burkitt's lymphoma.
THE SCHOOL TRAINING OF YOUTH.
Authors: CHARLES E. WINSLOW
Journal: JAMA (1898)

The two essential parts of a human being are mind and body, and so constituted are they that each is of the utmost importance to the other. They are bound together by ties that render them inseparable through life. A suffering body depresses the mind; a harassed mind wearies the body. That which strengthens the human organism, stimulates the intellect to action. Raptures of the mind thrill the body. This being true, how important that from the first days of life, the intellectual and physical should grow and develop side by side. That laws of health obeyed increase and add pleasure to life, should be known by every man, woman and child in our land. Health with a fair mind is worth more than a brilliant intellect in a feeble constitution. The broadening light of knowledge reveals truths in cause and effect of hygienic principles before unknown. These bear added
Precursor loss triggers AIDS
Authors: Hema Bashyam
Journal: The Journal of Experimental Medicine (2007)

HIV and its simian counterpart, SIV, replicate rapidly after infection but often take many years to subdue the immune system and cause AIDS. Okoye et al. (page 2171) now find that these slow burner viruses only cause disease after they deplete the precursor cells that give rise to pathogen-fighting effector cells.






Figure 1

Loss of TCM cells during chronic SIV infection (bottom) depletes pathogen-fighting TEM cells and triggers AIDS.




The effector memory T (TEM) cells that battle these viruses at infection sites develop from a pool of CD4+ central memory (TCM) cells that are stored in secondary lymphoid organs. Although the virus infects both types of cells simultaneously, TEM cells are the first casualties. This early depletion of TEM cells is not completely devastating; the TCM population quickly cranks out more TEM cells. But this defensive strategy is obviously not foolproof: infected individuals eventually develop AIDS.

Okoye et al. now identify the glitch in the strategy by tracking disease progression in SIV-infected rhesus macaques. Newly generated TEM cells were short lived, they found, as persistent activation by the virus induced their death. And unlike in earlier stages of infection, TCM cells no longer came to the rescue, as they were also crippled by viral infection. The virus thus tamed the immune system by stimulating one population to death and destroying its back-up.

Based on these results, stabilizing the TCM pool may be a more effective way to prevent the onset of AIDS than controlling viral load—the goal of current vaccination strategies. Rising viral loads might not be the trigger for AIDS, as viral loads remained constant while CD4+ T cell levels declined during the later stages of disease.

Recent studies from other groups show that survival of patients with AIDS correlates with more circulating TCM cells, supporting the idea that protecting the TCM niche might keep AIDS at bay. The team is now trying to identify the factors that bolster TCM cell levels and how HIV/SIV dismantles them.
Paternalism and medical ethics.
Authors: R Gillon
Journal: BMJ (1985)

In one of a series of articles on philosophical medical ethics, Gillon considers various moral arguments in support of medical paternalism. He maintains that the utilitarian principle of maximizing happiness by improving health, minimizing suffering, and prolonging life is not promoted by granting physicians the authority to deceive patients or to make decisions for them in areas of moral and subjective choice. If one wants to do good for a patient, one generally needs to find out what the patient wants one to do. Gillon concludes that many utilitarians agree with deontologists that respect for autonomy is required if human welfare really is to be maximized.
THE EFFECT OF INSULIN HYPOGLYCEMIA ON THE CIRCULATION 1
Authors: A. Carlton Ernstene, Mark D. Altschule
Journal: Journal of Clinical Investigation (1931)

Several observers have directed attention to the fact that insulin hypoglycemia may precipitate symptoms and signs of serious disturb- ance in the cardiovascular system.Gigon (1), in 1923, reported that a patient with diabetes mellitus had died from myocardial failure after the third dose of insulin.Reinwein (2) observed two patients with diabetes mellitus and circulatory insufficiency in whom the administra- tion of insulin caused a decided increase in the degree of congestive failure.Joslin (3) and Blotner (4) reported cases in which cardiac infarction developed shortly after the administration of insulin, and von Noorden and Isaac (5) observed several patients with coronary artery disease in whom insulin hypoglycemia apparently was the cause of death.Several instances have been recorded in which insulin hypoglycemia precipitated typical attacks of angina pectoris (6, 7, 8).Further evidence of altered cardiac physiology during insulin hypoglycemia is afforded by the electrocardiographic studies of Middleton and Oatway (9) and others.The changes observed consisted of diminished amplitude or inversion of the T-wave.Although the effect of insulin shock on the pulse rate and arterial blood pressure of man has been studied by several investigators (10, 11, 12, 13), but little attention has been paid to the effect of the hypoglycemic state on the minute volume output of the heart.In the only reported measurements, Lauter and Baumann (13), using the ethyl iodide method of Henderson and Haggard ( 14), recorded an increased circulatory minute volume during hypoglycemia in five
Hemophilus influenzae Type b Disease
Authors: Stephen R. Redmond
Journal: JAMA (1984)

Day-care centers are a relatively new phenomena of American society that bring together large numbers of young children susceptible to contagious disease. This study examines the incidence and risk factors of endemic<i>Hemophilus influenzae</i>type b disease both in the general population and in day-care attendees in Monroe County, New York, for 1982 and 1983. The attack rate in the general population (excluding day-care attendees) was highest in children younger than 1 year (131.9 cases per 100,000 per year) and in those 1 to 2 years old (75.7 cases per 100,000 per year) compared with older children. The relative risk for day-care attendees was much greater than that of the general population. It was 12.3 times greater for children younger than 1 year, 7.2 times greater for those 1 to 2 years old, and 3.8 times greater for those 2 to 3 years old. We conclude that children attending day-care facilities face a substantial increased risk of contracting invasive<i>H influenzae</i>type b disease. Efforts to prevent susceptibility and contagious spread of this disease in this population seem necessary. (<i>JAMA</i>1984;252:2581-2584)
Mitochondrial dysfunction and cytoskeletal disruption during chemical hypoxia to cultured rat hepatic sinusoidal endothelial cells: The pH paradox and cytoprotection by glucose, acidotic pH, and glycine
Authors: Yoshiya Nishimura, Lewis H. Romer, John J. Lemasters
Journal: Hepatology (1998)

We investigated mechanisms underlying death of cultured rat liver sinusoidal endothelial cells exposed to chemical hypoxia with KCN (2.5 mmol/L) to simulate the adenosine triphosphate (ATP) depletion and reductive stress of anoxia. During chemical hypoxia, acidotic pH prevented cell death. Glucose (0.3-10 mmol/L) also prevented cell killing. Cytoprotection by glucose but not acidosis was associated with prevention of ATP depletion. After 4 hours of chemical hypoxia at pH 6.2 (simulated ischemia), rapid cell death occurred when pH was restored to pH 7.4 with or without washout of KCN (simulated reperfusion). This pH-dependent reperfusion injury (pH paradox) was prevented after KCN washout at pH 6.2. Glycine (0.3-3 mmol/L) also prevented the pH paradox, but glucose did not. The initial protection by acidotic pH and glycine during simulated reperfusion was lost when pH was later restored to 7.4 or glycine was subsequently removed. Mitochondria depolarized during chemical hypoxia. After washout of cyanide, mitochondrial membrane potential (△Ψ) did not recover in cells that subsequently lost viability. Conversely, those cells that repolarized after cyanide washout did not subsequently lose viability. The actin cytoskeleton and focal adhesions became severely disrupted during chemical hypoxia at both pH 6.2 and 7.4 and did not recover after cyanide washout under any condition. Glucose during chemical hypoxia prevented cytoskeletal disruption. In conclusion, endothelial cell damage during simulated ischemia/reperfusion involves mitochondrial dysfunction, ATP depletion, and ATP-dependent cytoskeletal disruption. Glycine and acidotic pH prevented cell killing after reperfusion but did not reverse mitochondrial injury or the profound disruption to the cytoskeleton.
Public awareness on cystic fibrosis: results from a national pragmatic survey
Authors: Fulvio Braido, Ilaria Baiardini, Massimo Sumberesi, Giorgio Walter Canonica, Francesco Blasi, Carlo Castellani
Journal: European Respiratory Journal (2015)

Cystic Fibrosis (CF) is a life threatening disorder that primarily affects the lungs and digestive system that represents an important cause of morbidity and mortality. Research has provided effective tools for disease prevention and treatment [1]. Defective gene and its protein product were discovered in 1989 [2–4] and screening systems are available for carrier identification [5] Moreover, new-borns screening for CF facilitates early diagnosis and genetic counselling. Thanks to more effective drugs availability [6, 7], life expectancy has significantly grown in the last decades [8], with more than 45% of the CF patients aged >18 years and with a satisfying quality of life [9]. The results of a national pragmatic survey show that public awareness on cystic fibrosis is poor <http://ow.ly/JztjM> The authors thank Lega Italiana Fibrosi Cistica – Lombardia (Milan, Italy).
Changes in Renal Function Following Nephroureterectomy May Affect the Use of Perioperative Chemotherapy
Authors: Matthew G. Kaag, Rebecca L. O'Malley, Padraic O'Malley, Guilherme Godoy, Mang Chen, Marc C. Smaldone, Ronald L. Hrebinko, Jay D. Raman, Bernard Bochner, Guido Dalbagni, Michael D. Stifelman, Samir S. Taneja, William C. Huang
Journal: European Urology (2010)
SIMPLE APPLIANCE FOR TRAINING INFANTS TO STOOL
Authors: Cary Eggleston
Journal: JAMA (1918)

It is the common practice for physicians and the "baby books" to recommend the training of infants to have regular movements of the bowels by the insertion into the anus of the end of an ordinary clinical thermometer, or by the use of small glycerin or soap suppositories. The use of suppositories is objectionable, owing to their expense and the possibility of irritating the delicate mucous membrane through their hygroscopic properties, when they have to be employed very frequently. The soap suppository is liable also to prove irritating if used often, and unless a fresh suppository is made for each occasion, the practice is unclean and not hygienic. The clinical thermometer is expensive; it is delicate and very likely to be broken, possibly within the anus; and, being straight, it is clumsy when the infant ismade to sit up on a chair or chamber. These disadvantages of the usual methods
MicroRNAs in Disease and Potential Therapeutic Applications
Authors: Harris S Soifer, John J Rossi, Pål Sætrom
Journal: Molecular Therapy (2007)

MicroRNAs (miRNAs) are 21-24 nucleotide (nt) duplex RNAs that are created from precursor transcripts by subsequent processing steps mediated by members of the RNAseIII family, Drosha and Dicer. One of the two strands is incorporated into the active sites of the Argonaute family of proteins, where it serves as a guide for Watson-Crick base pairing with complementary sequences in target messenger RNAs (mRNAs). In mammals, the majority of miRNAs guide the RNA-induced silencing complex (RISC) to the 3' untranslated regions (UTRs) of mRNA targets, with the consequence that translation of the target mRNAs is inhibited. The importance of miRNAs in normal cellular development and metabolism is only now being realized. miRNA deficiencies or excesses have been correlated with a number of clinically important diseases ranging from myocardial infarction to cancers. The loss or gain of miRNA function can be caused by a single point mutation in either the miRNA or its target or by epigenetic silencing of primary miRNA transcription units. This review summarizes miRNA biogenesis and biology, explores the potential roles miRNAs can play in a variety of diseases, and suggests some therapeutic applications for restoring or inhibiting miRNA function.
Erratum: Corrigendum: Frequent somatic mutations of the transcription factor ATBF1 in human prostate cancer
Authors: X Sun, H F Frierson, C Chen, C Li, Q Ran, K B Otto, B L Cantarel, R L Vessella, A C Gao, J Petros, Y Miura, J W Simons, J-T Dong
Journal: Nature Genetics (2005)