tbuckley/cabot-search huggingface dataset:
Epigenetic regulation of drug metabolism and transport
Authors: Lai Peng, Xiaobo Zhong
Journal: Acta Pharmaceutica Sinica B (2015)

The drug metabolism is a biochemical process on modification of pharmaceutical substances through specialized enzymatic systems. Changes in the expression of drug-metabolizing enzyme genes can affect drug metabolism. Recently, epigenetic regulation of drug-metabolizing enzyme genes has emerged as an important mechanism. Epigenetic regulation refers to heritable factors of genomic modifications that do not involve changes in DNA sequence. Examples of such modifications include DNA methylation, histone modifications, and non-coding RNAs. This review examines the widespread effect of epigenetic regulations on genes involved in drug metabolism, and also suggests a network perspective of epigenetic regulation. The epigenetic mechanisms have important clinical implications and may provide insights into effective drug development and improve safety of drug therapy.
Monitoring the medical education revolution
Authors: V. Wass
Journal: BMJ (2003)

The impact of new training programmes must be evaluated 

This is a time of great change in both undergraduate and postgraduate medical education. The General Medical Council's recommendations for Tomorrow's Doctors 1 have stimulated educational innovations and new curriculums in all British medical schools. Key changes include early patient contact from the beginning of the course; more emphasis on patient centred communication skills; an increased focus on ethics, culture, and ethnicity; and more training in the community. Different approaches to teaching are being introduced, such as special study modules to stimulate self directed learning,1 problem based …
Mitral Commissurotomy Performed During Anticoagulant Prophylaxis with Dicumarol
Authors: OLE STORM, ANDERS TYBJÆRG HANSEN
Journal: Circulation (1955)

Since it is possible to perform major surgical interventions on patients with lowered prothrombin-proconvertin concentration we have selected a group of patients suffering from mitral stenosis for further evaluation of this prophylactic measure. These patients are highly predisposed to thromboembolic complications. The controllable risk of hemorrhage might, therefore, be preferred to the heavy risk of thrombosis. The results of our investigations indicate a decrease in incidents of thromboembolism. No serious risk of bleeding is apparently introduced when an accurate and sensitive method of estimating the prothrombin level is used in the control of the treatment.
DISSOCIATION OF THE BIOLOGICAL PROPERTIES OF BACTERIAL ENDOTOXIN BY CHEMICAL MODIFICATION OF THE MOLECULE
Authors: Henry H. Freedman, Barnet M. Sultzer
Journal: The Journal of Experimental Medicine (1962)

The preparation and properties of three fractions isolated from the acetylation of endotoxin by acetic anhydride in the presence of anhydrous sodium acetate are described. One fraction is of primary interest for it allows the experimental dissociation of some of the myriad biological activities of the parent endotoxin. Pyrogenicity and acute toxicity are markedly reduced, and ability to confer tolerance to the lethality and pyrogenicity of homologous or heterologous endotoxins is equivalently diminished. In contrast, this acetylated derivative retains the ability to stimulate phagocytosis and, as shown in the following paper, to enhance non-specific host resistance to infection. Detoxification is reversible, the original toxicity and pyrogenicity being recovered following mild saponification. The implications of the findings are discussed, and it is suggested that the observed dissociation of biological properties is explained neither by deacetylation of the derivative in vivo nor by the observable alteration of physical state in the gross.
The differential diagnosis of acute pericarditis from the normal variant: new electrocardiographic criteria.
Authors: L E Ginzton, M M Laks
Journal: Circulation (1982)

We examined the quantitative electrocardiographic differentiation of acute pericarditis from normal variant ST-T changes. The ECGs of 19 patients with acute pericarditis were compared with those of 20 subjects with typical normal variant changes. Patients were excluded if their ECGs demonstrated conditions that markedly altered repolarization. The positive predictive values (PPV) and negative predictive values (NPV) of previously reported criteria were not high (PPV = 0.54-0.83, NPV = 0.56-0.58). In contrast, in the present study, a T-wave amplitude in lead V6 of less than or equal to 0.3 mV diagnosed acute pericarditis (p less than 0.005, PPV = 0.85, NPV = 0.85), but there was overlap of patients between the groups. The ratio of the amplitude of the onset of the ST segment to the amplitude of the T wave in that lead (ST/T ratio in V6) proved to be the most reliable discriminator. An ST/T ratio greater than or equal to 0.25 diagnosed all patients with acute pericarditis (p less than or equal to 0.005, PPV = 1.0, NPV = 1.0). The ST/T ratio greater than 0.25 in V4, V5 (both p less than 0.005, PPV = 0.87, NPV = 1.0) and I (p less than or equal to 0.005, PPV = 0.80, NPV = 0.81) were also significant discriminators. Thus, if V6 is unavailable, an ST/T ratio greater than or equal to 0.24 in V5, V4 or I is highly suggestive of acute pericarditis. An ST/T ratio greater than or equal to 0.25 in V6 discriminated the ECGs of all patients with acute pericarditis from normal variants in this study.
Tension development and sarcomere length in rat cardiac trabeculae. Evidence of length-dependent activation.
Authors: H E ter Keurs, W H Rijnsburger, R van Heuningen, M J Nagelsmit
Journal: Circulation Research (1980)

We studied the influence of inotropic factors on the shape of the relation between tension and sarcomere length.Tension measurements were performed on thin trabeculae dissected from the right ventricle of the rat heart.Sarcomere length was measured by laser diffraction techniques and controlled by a servomotor system.The relations between tension and sarcomere length were derived from contractions at various extracellular calcium concentrations [Ca 2+ ] o .The time course of tension development was dependent on both sarcomere length and [Ca 2+ ] o .At all [Ca 2+ ] o , the tension attained during contraction was zero at sarcomere lengths of 1.55-1.60pm and maximal at a sarcomere length of 2.35 /im.Neither a summit nor a descending limb was found in the sarcomere length-tension relation.At [Ca 2+ ] o = 0.5 mM, tension increased linearly with sarcomere length, whereas at [Ca 2+ ] o = 2.5 mM, it approached maximal tension exponentially with sarcomere length.The relations between tension and sarcomere length derived from isometric contractions of the muscle and of sarcomeres were identical, and this suggests that shortening of sarcomeres does not contribute significantly to the effect of [Ca 2+ ] o .The relations between tension and sarcomere length obtained at [Ca 2+ ] o = 0.5 mM from contractions 30 seconds after a potentiating burst of stimuli (4 seconds at 4 Hz) were identical to the relation between tension and sarcomere length at [Ca 2+ ] o = 2.5 mm.Our results are consistent with the hypothesis that cardiac muscle length affects contractile performance by its influence on excitation contraction coupling.CircRes 46: [703][704][705][706][707][708][709][710][711][712][713][714] 1980 THE shape of the relation between tension and sarcomere length in cardiac papillary muscle suggests length-dependent activation of the contractile system (Jewell, 1977).However, there are no data on the effect of inotropic interventions on this curve.Only muscle length-tension curves are available, and these give conflicting results (Jewell, 1977;Huntsman and Stewart, 1977;Sonnenblick, 1962;Bodem et al., 1976).It is known that during isometric contractions there is considerable shortening of sarcomeres in the central region of papillary muscle.This happens at the expense of stretch of damaged regions near the clamps holding the ends of the specimen (Krueger and Pollack, 1975;Pollack and Krueger, 1976;Julian et al., 1976;Julian and Sollins, 1975).The damaged regions as well as the normal region may be influenced by inotropic factors.The interpretation of results of isometric contractions of the muscle is therefore ambiguous.The purpose of the present study was to examine the effect of different calcium concentrations on the relations
Intestinal Protozoa in Mentally Deficient Children
Authors: G. D. Belios, W. Cooper
Journal: BMJ (1953)

ANAL FISSURE MBPUH 805 nation to develop into infection.The antibiotic therapy con- sists of penicillin " distaquaine " fortified, 300,000 units, and streptomycin 0.5 g. both three times a day for four days, The graft is inspected on the fourth or fifth post-operative day and the mould removed.Any excess skin is removed and a piece of cotton-wool is placed over the grafted area to keep it dry.The patient is discharged on the fifth or sixth day post-operatively with the wound healed.Goodsall (1892) practised sphincterotomy with good results.He did not excise the ulcer but simply cut through the subcutaneous sphincter.The wound healed by secondary intention.In patients with chronic fissures who are unwilling to undergo operation this process has more to commend it than digital dilatation. DiscussionAn anal fissure is a non-malignant pondition of the anus,
"TUBERCULOSIS AMONG SCANDINAVIANS"
Authors: D. A. Stewart
Journal: JAMA (1925)

<h3>To the Editor:</h3> —I scarcely think that your answer to an inquiry on this subject (The Journal, January 17, p. 223) was quite as full as it might have been. There are definite differences between people of one nationality and another as to their resistance to tuberculosis. Environment does count, of course, so that one of a resistant race may have this good resistance counterbalanced by bad environment, and one of poor racial resistance may get along splendidly in good environment. Yet differences in races are marked. I might refer to a paper by Dr. Louis B. Dublin of the Metropolitan Life Association published in the<i>Transactions of the American Tuberculosis Association</i>, 1923. In the city of New York and the state of Pennsylvania, the death rates from tuberculosis among Italian born and among Jews are considerably lower than the death rates among native Americans; and from these, the scale
Thyroiditis and Alkaline Phosphatase
Authors: R. TUR KASPA
Journal: Annals of Internal Medicine (1978)

Letters and Corrections1 October 1978Thyroiditis and Alkaline PhosphataseR. TUR KASPA, M.D., Y. NAPARSTEK, M.D.R. TUR KASPA, M.D.Search for more papers by this author, Y. NAPARSTEK, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-89-4-578_3 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: Dalovisio, Blonde, Cortez, and Pankey (Ann Intern Med88:505-507, 1978) have reported elevated alkaline phosphatase levels in three patients with subacute thyroiditis. They noted that they could find no previous reports of this enzyme abnormality. During the past year, three patients with subacute thyroiditis were admitted to our department. Results of their thyroid and liver function tests are given in Table 1. It may be seen that two of the patients had elevated alkaline phosphatase levels without other evidence of liver disfunction. One of them received aspirin while the second was treated with azathioprine for a period... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Hadassah University Hospital Jerusalem Israel PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited ByPersistent vocal cord paralysis in subacute thyroiditis.Thyroid Disease and Alkaline PhosphataseDAVID V. HAMILTON, M.B., B. CHIR. 1 October 1978Volume 89, Issue 4Page: 578-578KeywordsAspirinEnzymesLiverLiver function testsPhosphatasesThyroid Issue Published: 1 October 1978 PDF DownloadLoading ...
Contribution of Plastoelasticity to the Tone of the Cat Portal Vein
Authors: ROBERT S. ALEXANDER
Journal: Circulation Research (1971)

Isolated helical strips of cat portal vein were subjected to sudden stresses to produce immediate elastic extension followed by a slow plastoelastic extension or "creep". Recovery from this creep was evaluated by restretching with varying intervals between stretches. In appropriately stimulated vessels, significant creep recovery continues for periods in excess of 20 minutes. Both the rate and the ultimate magnitude of the creep recovery were substantially increased by contractile activity produced by norepinephrine or electrical stimulation. The rate and ultimate magnitude of creep recovery were decreased by dilator drugs, although some recovery persisted. The only factors found capable of blocking creep recovery were complete inactivation of the contractile machinery by removal of calcium from the system or maintainence of tension on the tissue during the recovery period. This behavior is explained by a model in which contracted elements are capable of slowly converting into a stable shortened configuration capable of passively maintaining venous tone until mechanical stress causes a plastoelastic extension to the longer configuration.
Old age psychiatry in Swansea
Authors: DD Williams
Journal: BMJ (1999)

This new specialty has many advantages. It is particularly rewarding to those interested in local history, social and industrial change, and the history of the twentieth century. Our patients are survivors, people who have had long, often interesting, and sometimes distinguished lives, people who span the whole of the social spectrum. My only contact with an air vice marshall and a Bluebell girl has been as patients. I have also met the last rat catcher who worked at the local flour mill.

It is a specialty that bridges the divide between hospital and community. A large part of my time is devoted to the latter and there are many benefits. The key to good practice is unhurried assessment of patients in their homes. This approach, although time consuming, is clinically rewarding, and there are several hidden gains which are not obvious until you have worked in the specialty.

> My only contact with an air vice marshall and a Bluebell girl has been as patients 

The Easter weekend was wet and cold. Many areas had …
Dry Mouth and Dysglycemia
Authors: Emanuel Cheraskin
Journal: JAMA (1974)

<h3>To the Editor.—</h3> Occasional published reference has been made concerning the relationship between diabetes mellitus and xerostomia (dry mouth). Conner et al<sup>1</sup>have studied this relationship in a more quantitative fashion. They reported recently that parotid salivary flow in an age- and sexmatched sample of 30 diabetics and 30nondiabetics is significantly different. The mean parotid flow in the diabetics was only one-fourth that of the controls, and the statistical significance of the mean difference in flow rate was less than the 1% confidence level (<i>P</i>&lt;.01). Scant attention, however, has been given to the possible association of xerostomia and overall carbohydrate metabolism (hyperglycemia, normoglycemia, and hypoglycemia).<sup>2</sup>Considering these three aspects of glycemia, there appears to be a distinct correlation between xerostomia and dysglycemia, both hyperglycemia and hypoglycemia (<i>J Am Geriatr Soc</i>12:337, 1964). In an age- and sex-paired analysis of 38 subjects, a classic three-hour glucose tolerance
Depression, Psychotropic Medication, and Risk of Myocardial Infarction
Authors: Laura A. Pratt, Daniel E. Ford, Rosa M. Crum, Haroutune K. Armenian, Joseph J. Gallo, William W. Eaton
Journal: Circulation (1996)

Background There is suggestive evidence that depression increases risk of myocardial infarction (MI), but there are no prospective studies in which the measure of depression corresponds to clinical criteria. This study examines prospectively whether a major depressive episode increases the risk of incident MI and evaluates the role of psychotropic medication use in this relationship. Methods and Results The study is based on a follow-up of the Baltimore cohort of the Epidemiologic Catchment Area Study, a survey of psychiatric disorders in the general population. A history of major depressive episode, dysphoria (2 weeks of sadness), and psychotropic medication use were assessed in 1981, and self-reported MI was assessed in 1994. Sixty-four MIs were reported among 1551 respondents free of heart trouble in 1981. Compared with respondents with no history of dysphoria, the odds ratio for MI associated with a history of dysphoria was 2.07 (95% CI, 1.16 to 3.71), and the odds ratio associated with a history of major depressive episode was 4.54 (95% CI, 1.65 to 12.44), independent of coronary risk factors. In multivariate models, use of barbiturates, meprobamates, phenothiazines, and lithium was associated with an increased risk of MI, whereas use of tricyclic antidepressants and benzodiazepines was not. Among individuals with no history of dysphoria, only lithium use was significantly associated with MI. Conclusions These data suggest that a history of dysphoria and a major depressive episode increase the risk of MI. The association between psychotropic medication use and MI is probably a reflection of the primary relationship between depression and MI.
Interleukin 2 Therapy for Disseminated Cancer
Authors: Richard Kradin
Journal: JAMA (1987)

<h3>To the Editor.—</h3> We read with interest the article by Lotze et al<sup>1</sup>and the accompanying editorial by Dr Moertel.<sup>2</sup>We share Dr Moertel's concerns about how scientific information is distributed to the public. However, his criticisms have now contributed to an overzealous news media campaign. Dr Moertel's editorial was widely publicized and we fear has succeeded in damaging the reputation of all interleukin 2 (IL-2)-related scientific programs. This is unfortunate, since trials of IL-2 and adoptive cell transfers are under way that are designed to diminish the toxicity of lymphokine-activated killer cell and IL-2 regimens. A phase II immunotherapy trial is under way at the Massachusetts General Hospital in which cultured tumor-infiltrating lymphocytes and relatively low dosages of IL-2 (3×10<sup>6</sup>U/d) are being administered. Seven patients have been treated in medical beds outside of the intensive care unit and have not experienced hypotension, respiratory distress, or
The Cancer Cell: Dynamic Aspects and Modifications in Cell-Surface Organization
Authors: Garth L. Nicolson, George Poste
Journal: New England Journal of Medicine (1976)

The essential features of tumor cells that distinguish them from their normal counterparts are their ability to proliferate in an uncontrolled fashion, invade normal tissues and metastasize to distant sites, though these behavioral alterations are not always coupled. It is now recognized that changes in the surface properties of tumor cells may be important in determining aspects of each of these major behavioral characteristics.Within the primary tumor, alterations in the surface properties of tumor cells contribute to their escape from many of the controls and social restraints to which normal cells are subject. The proliferation . . .
Multiple Crystal Cross-Sectional Echocardiography in the Diagnosis of Cyanotic Congenital Heart Disease
Authors: DAVID J. SAHN, RICHARD TERRY, ROBERT O'ROURKE, GEORGE LEOPOLD, WILLIAM F. FRIEDMAN
Journal: Circulation (1974)

A new multiple crystal echocardiographic system was used to assess cross-sectional cardiac anatomy in real time in fifty infants and children with cyanotic heart disease, and the findings were compared to normals. Four standard transducer positions were employed to evaluate sagittal and transverse cardiac cross-sections. Studies in patients with tetralogy of Fallot demonstrated an enlarged aorta overriding the septum with preservation of mitral-aortic continuity. In the absence of pulmonary atresia the main pulmonary artery could be identified in all of these patients. The diagnosis of d -transposition of the great vessels was established by viewing great vessel orientation in transverse section at the second intercostal space and observing a rightward and anteriorly placed great artery. In sagittal projections a retrosternal aorta and mitral-pulmonic continuity was observed. In one patient with d -transposition, apposition in systole of the ventricular septum and anterior leaflet of the mitral valve was identified as the cause of left ventricular outflow tract obstruction. Descriptions are provided of the findings in patients with l -transposition, double outlet right ventricle, and truncus arteriosus. The new multiscan method allows a substantially more precise determination of intra- and extra-cardiac spatial relationships than single crystal techniques. Multiscan echocardiography is safe, widely applicable, and provides clinically important information to assist in the diagnosis and management of infants and children with cyanotic heart disease.
PDGF-BB induces intratumoral lymphangiogenesis and promotes lymphatic metastasis
Authors: Renhai Cao, Meit A. Björndahl, Piotr Religa, Steve Clasper, Stina Garvin, Dagmar Galter, Björn Meister, Fumitaka Ikomi, Katerina Tritsaris, Steen Dissing, Toshio Ohhashi, David G. Jackson, Yihai Cao
Journal: Cancer Cell (2004)
HIGHER EDUCATION FOR PHARMACISTS.
Authors: JOSEPH P. REMINGTON
Journal: JAMA (1896)

TheAmerican Medical Associationhas a deep interest in the education of the pharmacist; with improved methods and extended courses in the great medical schools, with the practices of medicine and pharmacy ever widening and developing, it must follow that better education for the pharmacist and more of it is imperatively demanded. The first organized effort in America to instruct those who had entered the drug business resulted in the establishment of the Philadelphia College of Pharmacy in 1821; since then colleges have been established in New York, Baltimore, Boston, Brooklyn, Buffalo, San Francisco, Chicago, Cincinnati, Cleveland, Kansas City, Louisville, Toronto, Montreal, Washington, Pittsburg, St. Louis, Iowa City, St. Paul, Lawrence (Kan.), Ann Arbor (Mich.), Madison (Wis.), Atlanta, Albany, Newark, Columbus, Ada (Ohio), Lebanon (Ohio), Lafayette (Ind.), Richmond, Scio (Ohio), New Orleans, Nashville and Detroit. The first years of all of these institutions were struggles for existence; the difficulties which were
Cystic fibrosis patients now live 20 years longer than in the 1990s, Canadian study shows
Authors: S. Mayor
Journal: BMJ (2014)

People with cystic fibrosis are living for 20 years longer than they did in the 1990s, figures from a Canadian study have shown.

Researchers analysed data from the Canadian Cystic Fibrosis Registry,1 a population based cohort that collects demographic and yearly clinical information on patients who receive care at the 43 accredited cystic fibrosis centres in Canada. The registry …
Who Are Less Likely to Receive Subsequent Chemotherapy Beyond First-Line Therapy for Advanced Non-small Cell Lung Cancer?: Implications for Selection of Patients for Maintenance Therapy
Authors: Jong-Mu Sun, Joon Oh Park, Young-Woong Won, Jung-Hoon Kim, Jina Yun, Jeeyun Lee, Yeon Hee Park, Jin Seok Ahn, Myung-Ju Ahn, Keunchil Park
Journal: Journal of Thoracic Oncology (2010)