tbuckley/cabot-search huggingface dataset:
Contrasting effects of digitalis and dobutamine on baroreflex sympathetic control in normal humans.
Authors: H P Schobel, R M Oren, P J Roach, A L Mark, D W Ferguson
Journal: Circulation (1991)

BACKGROUND Digitalis glycosides augment cardiopulmonary baroreceptor mechanisms in animals. This could result from inotropic actions or from direct sensitization of cardiac mechanoreceptors. METHODS AND RESULTS To determine if digitalis has similar actions in humans and to evaluate the mechanisms involved, we measured muscle sympathetic nerve activity (MSNA; microneurography) during unloading of cardiopulmonary baroreceptors with incremental lower body negative pressure (LBNP; 0 to -15 mm Hg) and during the cold pressor test in 22 normal subjects (age 22 +/- 1 year, mean +/- SEM). Arterial and central venous pressures, heart rate, and MSNA were measured during LBNP before and after intravenous digitalis (Cedilanid 0.02 ng/kg, n = 8), dobutamine (2.8 +/- 0.5 micrograms/kg/min, n = 8), or placebo (n = 6). Digitalis and dobutamine produced similar increases in baseline mean arterial pressure and decreases in central venous pressure and MSNA. LBNP produced similar decreases in central venous pressure in all groups before and after drug administration. The MSNA responses to LBNP were markedly potentiated by digitalis but not by dobutamine or placebo. CONCLUSIONS Digitalis did not alter responses to the cold pressor test. Thus, digitalis selectively potentiated cardiopulmonary baroreflex regulation of sympathetic neural responses in normal humans, whereas dobutamine (another positive inotropic agent) did not produce this effect. We conclude that digitalis augments cardiopulmonary baroreflex control of sympathetic activity, probably by direct baroreceptor sensitization.
Therapy of hepatitis C: Other options
Authors: H L Bonkovsky
Journal: Hepatology (1997)

Because current standard therapy of chronic hepatitis C with α interferon is less than ideal, numerous other approaches have been studied. Iron in the liver, particularly that found in vascular endothelial cells of portal tracts, has been associated with decreased responsiveness to α interferon therapy. Iron reduction alone, generally achieved by therapeutic phlebotomy, regularly has been associated with biochemical improvement (decrease in serum alanine aminotransferase), but not with virological improvement. Iron reduction has been reported to increase the therapeutic response to α interferon. Most studies of this combination have been conducted in patients who had not responded to interferon alone; in these patients, improved responsiveness has been observed in some, but not all studies. In patients not previously treated, iron reduction was found in a recent trial to improve the sustained biochemical and virological response rate from 5% to 29%. Hepatic iron and chronic hepatitis C increase oxidative stress in the liver and are associated with decreases in hepatic glutathione levels. In one report, administration of N-acetyl cysteine, a sulfhydryl donor, led to improved response to interferon in chronic hepatitis C. Several cytokines and immunomodulators have undergone limited study; perhaps the most promising of these is thymosin α-1. In one small study, amantadine was found to produce some response in patients who previously had failed to respond to interferon. Ursodiol improves serum aminotransferase levels in chronic hepatitis C but has no antiviral effect, nor has it been found to improve histologic abnormalities. The future of therapy of chronic hepatitis C will likely include measures to decrease oxidative stress and injury and multidrug combinations, including inhibitors of the hepatitis C viral protease and RNA polymerase.
Identification and structural characterization of two incompletely processed forms of the fourth component of human complement.
Authors: A C Chan, J P Atkinson
Journal: Journal of Clinical Investigation (1983)

Immunoprecipitates of human C4 from EDTA-plasma were incubated with [14C]methylamine and analyzed by sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis and fluorography. In addition to finding label in the alpha-chains of the secreted (C4s) and predominant plasma (C4p) forms of C4, two additional molecules with apparent molecular weights of approximately 168,000 (p168) and approximately 125,000 (p125) covalently incorporated methylamine, indicating the presence of an internal thioester bond. These two molecules were present at a concentration of approximately 5% of total plasma C4 and were not immunoprecipitated by antisera to C3 or alpha 2-macroglobulin. A human hepatoma-derived cell line (HepG2), in addition to synthesizing C4s and small quantities of the polypeptide precursor of C4 (pro-C4), was found to secrete p168 and p125 at concentrations of 14 +/- 4.8 and 21 +/- 9.2% (mean +/- SD), respectively, of total secreted C4. These molecules were not found intracellularly. Both molecules were present on reduced, but not nonreduced, SDS-polyacrylamide gels. Chido (C4B) and Rodgers' (C4A) alloantisera precipitated the C4A and C4B variants of pro-C4, p168, p125, and C4s. Both tryptic and Staphylococcus aureus V8 protease peptide analyses showed homology between p168 and the beta- and alpha-chains and between p125 and the alpha- and gamma-chains. Partial NH2-terminal sequencing revealed that the beta-chain was NH2-terminal in p168 and that the alpha-chain was NH2-terminal in p125. Taken together, these data indicate that p168 and p125 represent uncleaved beta-alpha- and alpha-gamma-fragments of pro-C4, respectively. Thus, in most individuals, plasma C4 consists of five structurally distinct molecules, the single polypeptide precursor (pro-C4), the three-subunit secreted (C4s) and predominant plasma (C4p) forms of C4, and two incompletely processed two-subunit molecules with uncleaved beta-alpha- (p168) or uncleaved alpha-gamma (p125)-subunits. In addition, all five molecules are observed for both C4A (Rodgers) and C4B (Chido) structural genes.
Health Service or Sickness Service?
Authors: A. S. Simpson
Journal: BMJ (1972)

SIR,-In your leading article on "Clofibrate in Ischaemic Heart Disease" (25 December, p. 765) mention is made of the numbers and percentages of patients in the clofibrate and placebo groups who "died suddenly from myocardial infarction."This statement embraces both sudden deaths and fatal myocardial infarction.In the analysis of the results we deliberately distinguished sudden deaths from fatal myocardial infarcts and believe that this distinction may be important in such clinical trials.-Weare, etc.,
Digoxin: Mythology or Evidence?
Authors: Rodney H. Falk
Journal: Annals of Internal Medicine (1991)

Letters15 August 1991Digoxin: Mythology or Evidence?Rodney H. Falk, MDRodney H. Falk, MDSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-115-4-329_1 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the Editors:I thank Dr. Zatuchni for his comments on our recent article on digoxin for atrial fibrillation (1, 2). I believe, however, that he has both missed the point and failed to take its message to heart. Contrary to his statement, we do understand why digoxin has been popular for 200 years. Its effects on resting heart rate in atrial fibrillation—the most obvious property of the drug—can be dramatic. We stress, however, that the natural human state is not one of perpetual rest and therefore that observations in the office do not necessarily reflect the behavior of the...References1. Zatuchni J. Requiem for Digoxin? [Letter]. Ann Intern Med. 1991;114:993. LinkGoogle Scholar2. FalkLeavitt RJ. Digoxin for atrial fibrillation: a drug whose time has gone? Ann Intern Med. 1991;114:573-5. LinkGoogle Scholar3. Jull-MollerEdvardssonRehnqvist-Alzberg SNN. Sotalol versus quinidine for the maintenance of sinus rhythm after direct current cardioversion of atrial fibrillation. Circulation. 1990;82:1932-9. CrossrefMedlineGoogle Scholar4. PritchettMcCarthyWilkinson EEW. Propafenone treatment of symptomatic paroxysmal supraventricular arrhythmias. Ann Intern Med. 1991;114:539-44. LinkGoogle Scholar5. PietersenHelleman AH. Usefulness of flecainide for prevention of paroxysmal atrial fibrillation and flutter. Am J Cardiol. 1991;67:713-7. CrossrefMedlineGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Boston University School of Medicine Boston, MA 02118 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 15 August 1991Volume 115, Issue 4Page: 329-329KeywordsAtrial fibrillationBehaviorDrugsHeartHeart rate Issue Published: 15 August 1991 PDF DownloadLoading ...
Pharmacokinetics of peginterferon ALFA-2A (40KD, PEGASYS) compared to peginterferon ALFA-2B (12KD, PEGINTRON) in naive patients with chronic hepatitis C (CHC)
Authors: R. Bruno, P. Sacchi, V. Ciappina, E. Maffezzini, S.F.A. Patruno, C. Zocchetti, G. Filice
Journal: Journal of Hepatology (2003)
Abstract 2995: Metronomic albumin-bound paclitaxel and topotecan has potent antitumor activity in ovarian cancer
Authors: Ashley N. Davis, Yvonne G. Lin-Liu, Rebecca A. Previs, Heather J. Dalton, Behrouz Zand, Justin Bottsford-Miller, Robert Coleman, Anil K. Sood
Journal: Cancer Research (2014)

Abstract Objective: There is growing recognition of the important role of metronomic chemotherapy for cancer treatment. Based on their unique anti-angiogenic effects, we tested the efficacy of dual albumin-bound paclitaxel (ABP), which stimulates Thrombospondin-1, and topotecan, which inhibits Hypoxia-inducible factor 1-α, chemotherapy at metronomic dosing in ovarian carcinoma. Methods: We examined the effects of ABP and topotecan in vitro (MTT) and in vivo using SKOV3ip1, HeyA8 and HeyA8-MDR orthotopic mouse models of ovarian cancer. We also examined effects on proliferation (Ki67), apoptosis (TUNEL), and angiogenesis (MVD) in tumor samples obtained at necropsy. Results: In vitro cytotoxicity assays revealed similar effects (IC50=20-60 nM) of maximum tolerated dosing (MTD) and metronomic dosing of ABP on HeyA8 tumor cells (p&amp;lt;0.05). In vivo therapy experiments using the SKOV3ip1 and HeyA8 tumor models demonstrated that treatment with metronomic ABP alone and in combination with metronomic topotecan resulted in significant reductions in tumor weight, 62% and 96% respectively as compared to controls (p&amp;lt;0.01). Combination treatment with metronomically dosed ABP and topotecan further reduced tumor growth by 82% compared to topotecan alone (p&amp;lt;0.01). In the chemoresistant tumor model, HeyA8-MDR, metronomically dosed monotherapy with either cytotoxic agent had a modest effect on tumor growth however, combination therapy decreased tumor burden by 74% when compared to controls (p&amp;lt;0.01). Metronomic ABP monotherapy resulted in reduced cell proliferation (p&amp;lt;0.001), reduced tumor angiogenesis (p≤0.01), and increased apoptosis (p&amp;lt;0.01). Conclusions: Metronomically-dosed albumin-bound paclitaxel and topotecan offer a highly effective and novel therapeutic approach in ovarian carcinoma that merits further clinical development. Citation Format: Ashley N. Davis, Yvonne G. Lin-Liu, Rebecca A. Previs, Heather J. Dalton, Behrouz Zand, Justin Bottsford-Miller, Robert Coleman, Anil K. Sood. Metronomic albumin-bound paclitaxel and topotecan has potent antitumor activity in ovarian cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2995. doi:10.1158/1538-7445.AM2014-2995
Pulmonary Resection for Localized Aspergillosis
Authors: David V. Pecora, M. Wilson Toll
Journal: New England Journal of Medicine (1960)

ASPERGILLUS, most commonly Aspergillus fumigatus, is ubiquitous. Human infection with this organism, although uncommon, is being recognized with increasing frequency. The disease has been described in grain and hay handlers, but may affect persons in other occupations. Virchow, in 1856, described bronchopulmonary aspergillosis, but it was not until 1950 that Gerstl and his associates1 first reported pulmonary resection for the disease. Few patients have been benefited by medical regimens. It appears that surgery is the treatment of choice for the localized form. It is the purpose of this communication to review the surgical experiences reported to date2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 in addition to . . .
Control of salicylate intolerance with fish oils
Authors: E. Healy, L. Newell, P. Howarth, P.S. Friedmann
Journal: British Journal of Dermatology (2008)

We report three patients with disabling salicylate-induced intolerance who experienced abrogation of symptoms following dietary supplementation with omega-3 polyunsaturated fatty acids (PUFAs). All three patients experienced severe urticaria, asthma requiring systemic steroid therapy and anaphylactic reactions. After dietary supplementation with 10 g daily of fish oils rich in omega-3 PUFAs for 6-8 weeks all three experienced complete or virtually complete resolution of symptoms allowing discontinuation of systemic corticosteroid therapy. Symptoms relapsed after dose reduction. Fish oil appears a safe and effective treatment for this difficult and often serious condition.
Clinical Investigators and the Pharmaceutical Industry
Authors: CALVIN M. KUNIN
Journal: Annals of Internal Medicine (1978)

Virtually all new drugs are introduced, evaluated, and marketed under the control of the pharmaceutical industry and general supervision of the Food and Drug Administration (FDA). The clinical investigator must look to the pharmaceutical industry for support of studies of drugs, and the industry, in turn, needs the investigator to evaluate agents before FDA approval and to present findings in the medical media. A survey of members of the Infectious Disease Society of America has shown heavy dependence on the pharmaceutical industry for support of applied studies of antibacterial and other chemotherapeutic agents. More than half the respondents believed that industry support was essential, about one third felt it was useful, and about one quarter would prefer other sources of support. Several proposals are presented to clarify the relations between investigators and the pharmaceutical industry and to provide for a broad-based clinical infectious disease consortium to provide research funds and plan educational programs in the field of infectious disease.
Physiological and Pathological Ageing
Authors: N. W. Shock
Journal: JAMA (1962)

This volume stands as a monument to Dr. Vladimir Korenchevsky, one of the pioneers in gerontological research. Published posthumously under the able editorship of Dr. Geoffrey H. Bourne, it carries the stamp of the beliefs of Dr. Korenchevsky. Born in Russia in 1880, Dr. Korenchevsky emigrated to Great Britain, in 1920, where he became a senior research worker at the Lister Institute for Preventive Medicine. In 1945 he established the Oxford Gerontological Unit through the support of the Nuffield Foundation, so that he has had a direct role in the development of experimental gerontology. This volume reflects his wide background of experience. Korenchevsky believed that "old age is an abnormal, pathological syndrome, in which physiological processes of ageing are complicated and aggravated by various so-called degenerative diseases of old age." As a student of aging, Korenchevsky was impressed by what he called "the many vicious circles of regressive changes which
180-W XPS GreenLight Laser Therapy for Benign Prostate Hyperplasia: Early Safety, Efficacy, and Perioperative Outcome After 201 Procedures
Authors: Alexander Bachmann, Gordon H. Muir, Edward J. Collins, Benjamin B. Choi, Shahin Tabatabaei, Oliver M. Reich, Fernando Gómez-Sancha, Henry H. Woo
Journal: European Urology (2011)
Elastic Stockings in the Prevention of Pulmonary Embolism
Authors: Robert W. Wilkins, Joseph R. Stanton
Journal: New England Journal of Medicine (1953)

IN a recent study it was found that the incidence of pulmonary embolism was reduced in hospital patients who wore elastic stockings as compared with those who wore nonelastic stockinette throughout their hospital stay.§ The explanation offered was that there was an increase in linear velocity (not in volume) of blood flow in the leg veins of those who wore elastic stockings. The acceleration of flow was assumed to result from a reduction in the caliber of the veins when they were compressed by the elastic stockings. This acceleration of venous flow supposedly lessened the tendency to phlebothrombosis in the . . .
Importance of basal nitric oxide synthesis in regulation of myocardial blood flow
Authors: Z. Benyo, G. Kiss, C. Szabo, C. Csaki, A. G B Kovach
Journal: Cardiovascular Research (1991)

Journal Article Importance of basal nitric oxide synthesis in regulation of myocardial blood flow Get access Zoltán Benyó, Zoltán Benyó Correspondence to: Dr Kovách Search for other works by this author on: Oxford Academic PubMed Google Scholar Gergely Kiss, Gergely Kiss Search for other works by this author on: Oxford Academic PubMed Google Scholar Csaba Szabó, Csaba Szabó Search for other works by this author on: Oxford Academic PubMed Google Scholar Csilla Csáki, Csilla Csáki Search for other works by this author on: Oxford Academic PubMed Google Scholar Arisztid G B Kovách Arisztid G B Kovách Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 25, Issue 8, August 1991, Pages 700–703, https://doi.org/10.1093/cvr/25.8.700 Published: 01 August 1991 Article history Accepted: 17 June 1991 Published: 01 August 1991
Severe Hypertension due to Autonomic Dysreflexia-Reply
Authors: H. Haydon Hill
Journal: JAMA (1986)

<h3>In Reply.—</h3> We thank Dr Pelligra for his letter and agree with him that the entity autonomic dysreflexia in quadriplegic patients could in some situations constitute a hypertensive emergency. As he points out, in most patients this condition is set off by bladder distention and usually is relieved by catheterization. In one recent patient of ours, it was elicited by the suprapubic catheter itself acting as a noxious stimulus. Simple relocation of the catheter reduced the elevation in blood pressure. In those cases in which such remedies are ineffective, treatment with an antihypertensive agent such as oral clonidine loading or intravenous labetalol should prevent complications.
Dependence of proteoglycan induced arthritis in BALB/c mice on the development of autoantibodies to high density proteoglycans.
Authors: P H Wooley, S W Siegner, J D Whalen, R L Karvonen, F Fernandez-Madrid
Journal: Annals of the Rheumatic Diseases (1992)

BALB/c mice were immunised with high or low density native human cartilage proteoglycans, or the respective core proteins obtained from chondroitin ABC lyase digestion. Mice injected with high density native proteoglycans developed arthritis whereas mice injected with low density proteoglycans or with core proteins did not. Analysis of the immune response by enzyme linked immunosorbent assay (ELISA) and western blot showed a stronger and more polyspecific response in animals injected with low density proteoglycans compared with mice with arthritis which had been injected with high density proteoglycans. Autoantibodies to mouse high density proteoglycans were only present in mice injected with native human high density proteoglycans, however. The data suggest that an arthritogenic epitope lies within the glycosaminoglycan rich region of the native proteoglycan molecule, which may induce an autoantibody response and subsequently arthritis in BALB/c mice.
Medical ethics conference hears about professional responsibility, patient autonomy, and corporate power
Authors: C. Dyer
Journal: BMJ (2012)

Should a woman in a minimally conscious state have artificial nutrition and hydration withdrawn and be allowed to die? That was the stark question facing delegates at the BMA’s “Morals and Medicine” conference on 22 February.

Tom was convinced that his wife Sarah, injured in an accident and left in a near vegetative state, would not have wanted to be kept alive. Her family agreed. After her uncle had a stroke Sarah had said that she would not want to be absolutely dependent on others. Watching a television programme about Tony Bland, the Hillsborough football ground disaster survivor who was in a permanent vegetative state, she had remarked that it was “cruel to keep him alive like that.”

Sarah’s doctor pointed out that she seemed to relax when massaged and to enjoy the sun on her face and seeing the ducks in the park. Tom and her family were looking at her from …
Termination of paroxysmal supraventricular tachycardia with a single oral dose of diltiazem and propranolol.
Authors: S J Yeh, F C Lin, Y Y Chou, J S Hung, D Wu
Journal: Circulation (1985)

The efficacy of a single oral dose combination of 120 mg diltiazem and 160 mg propranolol in terminating paroxysmal supraventricular tachycardia (PSVT) was evaluated in 15 patients. All 15 patients underwent electrical induction of PSVT that lasted longer than 15 min, and all underwent randomized crossover placebo and diltiazem and propranolol studies on 2 consecutive days. On each day PSVT was induced and placebo or diltiazem and propranolol was administered 15 min later. Electrical conversion of PSVT was performed when severe symptoms occurred or at the end of 240 min. With placebo PSVT lasted 164 +/- 89 (mean +/- SD) min; four patients had spontaneous conversion. With diltiazem and propranolol PSVT lasted 39 +/- 49 min (p less than .001); 14 patients had spontaneous conversion in an average of 27 +/- 15 min. None of the 14 patients had electrical reinduction of sustained PSVT after conversion. The sinus nodal recovery time during spontaneous or electrical conversion of PSVT was 911 +/- 459 msec with placebo and 1076 +/- 270 msec with diltiazem and propranolol (NS). Two patients developed transient second-degree atrioventricular block and junctional rhythm while on diltiazem and propranolol. Serum diltiazem and propranolol levels (ng/ml) after diltiazem and propranolol in five patients were, respectively, 49 +/- 26 and 108 +/- 101 at 15 min, 232 +/- 147 and 228 +/- 148 at 30 min, 254 +/- 169 and 370 +/- 393 at 45 min, 280 +/- 115 and 209 +/- 189 at 60 min, 188 +/- 72 and 268 +/- 264 at 120 min, and 118 +/- 57 and 265 +/- 148 at 240 min.(ABSTRACT TRUNCATED AT 250 WORDS)
402 IMPACT OF HEPATITIS C VIRUS INFECTION ON LIVER- RELATED MORTALITY IN A LARGE COMMUNITY-BASED COHORT OF INNER CITY RESIDENTS
Authors: J. Grebely, J. Raffa, C. Lai, M. Krajden, B. Fischer, T. Kerr, G. Dore, M. Tyndall
Journal: Journal of Hepatology (2009)
[708] PREVALENCE OF AUTOANTIBODIES IN A PORTUGUESE POPULATION WITH NONALCOHOLIC STEATOHEPATITIS
Authors: S.S. Fernandes, J. Carvalho, R. Pinho, A.P. Silva, S. Leite, A. Furtado, R. Nogueira, J.C. Fraga
Journal: Journal of Hepatology (2007)