tbuckley/cabot-search huggingface dataset:
First Chronic Platelet Glycoprotein IIb/IIIa Integrin Blockade
Authors: Conrad Simpfendorfer, Kandice Kottke-Marchant, Marsha Lowrie, Robert J. Anders, Daniel M. Burns, Dave P. Miller, Christopher S. Cove, Anthony C. DeFranco, Stephen G. Ellis, David J. Moliterno, Russell E. Raymond, Joseph M. Sutton, Eric J. Topol
Journal: Circulation (1997)

Background Clinical studies have demonstrated the efficacy of intravenous administration of agents that block platelet glycoprotein IIb/IIIa receptors in the setting of percutaneous coronary revascularization. Although the optimal duration of treatment has not been determined, more prolonged receptor blockade has been associated with increased efficacy. Orally active glycoprotein IIb/IIIa receptor antagonists may be advantageous and required for chronic therapy. Methods and Results Thirty patients with unstable angina who were undergoing percutaneous coronary interventions were randomized to placebo or Xemilofiban 35 mg orally before and 20 to 25 mg TID for 30 days after angioplasty. Bleeding events, platelet aggregation, and pharmacokinetic and hematologic parameters were assessed during hospitalization and at 2 and 4 weeks after drug initiation. Xemilofiban produced a rapid, sustained, marked inhibition of platelet aggregation. ADP-induced platelet aggregation at 2 hours after the initial dose at 2 and 4 weeks was 15%, 8%, and 11% in the Xemilofiban group compared with 80%, 68%, and 69% in the placebo group. Among 20 patients randomized to Xemilofiban there was 1 death after emergency coronary bypass surgery complicated by severe bleeding diathesis, and 3 patients had major bleeding events. Patients on Xemilofiban for 30 days reported episodes of mild mucocutaneous bleeding. Conclusions Xemilofiban, an orally active glycoprotein IIb/IIIa receptor inhibitor, produced rapid, sustained, extensive inhibition of platelet aggregation for a period of up to 30 days. At the dose initially tested, however, acute major bleeding and mucocutaneous bleeding during chronic administration were encountered.
Health secretary sparks controversy by his support for a 12 week limit for abortion
Authors: C. Dyer
Journal: BMJ (2012)

We conducted a prospective study of patient9s understanding of the Patient9s Charter. Every patient attending the Accident and Emergency (A&amp;E) Department of St Bartholomew9s Hospital over a 7-day period was questioned by an interviewer. Those not interviewed by this process were sent a postal questionnaire. A total of 584 patients attended during the study period, from whom 451 data sets were collected, a response rate of 77%. Only 51 patients were aware of The Patient9s Charter guarantee of 9immediate assessment9. When asked what they understood by 9immediate9, 67% of respondents considered this to mean 15 min or longer. Fifty-four per cent of respondents felt that this assessment should be performed by a nurse. A follow-up study conducted over a 48-h period in January 1994 showed no significant difference in the responses to the same questions. We conclude that the vast majority of patients in this study exhibited a very low level of awareness regarding the guarantees of The Patient9s Charter. We also note that their interpretation of the term 9initial assessment9 is at variance with that expressed by the NHS Chief Executive in a widely circulated document.
The Nicolal Case: A Biography
Authors: Frederick Butzen
Journal: JAMA (1983)

The First World War began with the assassination of the heir to the throne of the Austro-Hungarian Empire by Serbian nationalists. Four and one-half years later, more than 13 million men had died under arms and 26 million were wounded; nations lay shattered or were bled white and bankrupt. In terms of its effects on Western civilization, it was the most disastrous war since the Fourth Crusade—and easily the stupidest. Each nation claimed the special prerogatives of history, justice, and divine favor (some with less reason than others) and summoned its scientists and men of letters to write in defense of the cause. However, a few did speak out against the war; among them was a professor of medicine at the University of Berlin named Georg Friedrich Nicolai. Dr Nicolai is the subject of a new biography by Wolf Zuelzer, MD, emeritus professor in pediatric research at Wayne State University,
Patterns of Hormonal Signals and Hormone Action
Authors: Ernst Knobil
Journal: New England Journal of Medicine (1981)

One of the many new insights afforded by the advent of radioimmunoassays has been the recognition that the pattern of adenohypophyseal hormone secretion is episodic rather than continuous, as had been previously supposed. This pattern is particularly striking in the case of the gonadotropic hormones, which are delivered to the circulation as discrete, rhythmic pulses in all mammals studied to date.1 From the time they were first described, these pulsatile discharges of gonadotropin were thought to be due to intermittent stimulation by the hypothalamic gonadotropin-releasing hormone (GnRH), which reaches the gonadotropes of the anterior pituitary gland by way of the . . .
Failure of captopril to reverse the renal crisis of scleroderma
Authors: E. A. Brown, G. A. Macgregor, R. N. Maini
Journal: Annals of the Rheumatic Diseases (1983)

Captopril, an oral inhibitor of angiotensin converting enzyme, has recently been described as causing a dramatic reversal of the renal crisis in scleroderma in 2 patients<sup>1</sup>. We report here 2 patients with scleroderma, hypertension, and rapidly deteriorating renal function who were given captopril. Despite good blood pressure control, captopril had no effect on renal function, both patients requiring long-term haemodialysis.
Loss of p53 in Enterocytes Generates an Inflammatory Microenvironment Enabling Invasion and Lymph Node Metastasis of Carcinogen-Induced Colorectal Tumors
Authors: Sarah Schwitalla, Paul K. Ziegler, David Horst, Valentin Becker, Irina Kerle, Yvonne Begus-Nahrmann, André Lechel, K. Lenhard Rudolph, Rupert Langer, Julia Slotta-Huspenina, Franz G. Bader, Olivia Prazeres da Costa, Markus F. Neurath, Alexander Meining, Thomas Kirchner, Florian R. Greten
Journal: Cancer Cell (2012)
The Making of a Smoke-free Medical Center
Authors: Richard D. Hurt, Kenneth G. Berge, Kenneth P. Offord, David A. Leonard, Doreen K. Gerlach, Chris Larson Renquist, Michael R. O'Hara
Journal: JAMA (1989)

The concept of smoke-free medical facilities is in its formative stages, and such policies have received broad support. Although smoking has been restricted at Mayo Medical Center for many years, in 1986 it was decided that the medical center should become smoke free. This report summarizes the methods used in developing and implementing a smoke-free policy. This experience suggests that with proper planning, the implementation can be smooth. The message being given to patients and staff concerning the health risk of smoking is now more consistent, and there has been wide acceptance of the policy by staff and patients. It is concluded that such a policy can be effectively implemented, if it is well planned and supported.
The myth of an AIDS free world
Authors: D. Kamerow
Journal: BMJ (2012)

Control isn’t the same as eradication



Two events here in Washington, DC, have got me thinking about HIV and AIDS. The first was a revival of Larry Kramer’s searing 1985 AIDS play The Normal Heart , which I saw recently. The second was the widely publicised 19th International AIDS Conference, held here at the end of July.1

Watching The Normal Heart I was reminded how grim things were in the early 1980s. Set in New York City, the play follows its hero, the gay activist Ned Weeks (a thinly disguised alter ego of the author), as he rants and raves about the unknown plague that is killing dozens and then hundreds of gay men every month. No one will listen, even fellow members of his activist organisation. Another major character is a physician who is caring for the dying men, basically serving as a palliative care doctor because she can isolate no pathogen and has no effective treatments. The city health department won’t pay attention, and the government won’t sponsor enough research to find the cause and its cure. It is a …
Effects of the oral endothelin-receptorantagonist bosentan on echocardiographicand doppler measures in patients with pulmonary arterial hypertension
Authors: Nazzareno Galiè, Alan L. Hinderliter, Adam Torbicki, Thierry Fourme, Gerald Simonneau, Tomas Pulido, Nilda Espinola-Zavaleta, Guido Rocchi, Alessandra Manes, Robert Frantz, Marcin Kurzyna, Sherif F. Nagueh, Robyn Barst, Richard Channick, Karl Dujardin, Andrew Kronenberg, Isabelle Leconte, Maurizio Rainisio, Lewis Rubin
Journal: Journal of the American College of Cardiology (2003)
Changing End Points in Breast-Cancer Drug Approval — The Avastin Story
Authors: Ralph B. D'Agostino
Journal: New England Journal of Medicine (2011)

In December 2007, the Oncologic Drugs Advisory Committee (ODAC) of the Food and Drug Administration (FDA) met to discuss the risks and benefits of Genentech's Avastin (bevacizumab) for use in combination with paclitaxel for first-line treatment of locally recurrent or metastatic HER2-negative breast cancer. In an unusual move, Genentech and the FDA proposed that the committee (on which I serve as a voting consultant) consider progression-free survival rather than overall survival as the primary end point. In the key study submitted, bevacizumab plus paclitaxel was statistically superior to paclitaxel alone in terms of progression-free survival but not overall survival. Surprisingly, . . .
Superoxide dismutase restores contractile and metabolic dysfunction through augmentation of adenosine release in coronary microembolization.
Authors: S Takashima, M Hori, M Kitakaze, H Sato, M Inoue, T Kamada
Journal: Circulation (1993)

This study was undertaken to test the hypothesis that administration of superoxide dismutase (SOD) restores the contractile and metabolic dysfunction in coronary microembolization and that these beneficial effects of SOD are attributable to the restoration of 5'-nucleotidase activity and subsequent augmentation of adenosine release.In 78 dogs before and after an injection of microspheres (15 microns in diameter) into the left anterior descending coronary artery, regional coronary blood flow (CBF), fractional shortening (FS), and lactate extraction ratio (LER) were measured with and without administration of recombinant human SOD (50 micrograms/kg/min i.c.). In the untreated dogs (n = 6), both FS and LER decreased after coronary microembolization (2.0 x 10(5) microspheres per ml CBF [mL/min]). FS and LER decreased from 24.2 +/- 1.3% to 5.1 +/- 1.2% and from 23.0 +/- 1.1% to -10.5 +/- 2.9%, respectively. These ischemic changes were associated with coronary hyperemic flow (141 +/- 8 versus 92 +/- 1 mL/100 g/min) and adenosine release (5.8 +/- 0.5 versus 0.4 +/- 0.1 nmol/100 g/min). Pretreatment with SOD augmented the hyperemic flow to 164 +/- 4 mL/100 g/min and enhanced the release of adenosine (9.6 +/- 0.6 nmol/100 g/min) associated with improvement of functional and metabolic dysfunction (FS, 14.8 +/- 2.3%; LER, 15.1 +/- 3.1%). Administration of SOD at 10 minutes (n = 5) and 30 minutes (n = 5) after coronary embolization restored the contractile function and lactate metabolism (at 10 minutes: FS, 16.7 +/- 2.2% and LER, 16.7 +/- 3.9%; at 30 minutes: FS, 11.1 +/- 1.3% and LER, 7.2 +/- 3.1%). However, administration of SOD 60 minutes after coronary embolization (n = 6) did not restore the contractile and metabolic dysfunction. The restoration of the contractile and metabolic dysfunction by SOD treatment was blunted by adenosine receptor blockade with 8-phenyltheophylline (n = 5). Myocardial 5'-nucleotidase activity at 2 hours after embolization was restored with SOD treatment at 10 minutes (n = 5) and 30 minutes (n = 5) after embolization. However, SOD treatment at 60 minutes after embolization (n = 6) did not restore 5'-nucleotidase activity compared with the SOD pretreatment group. Furthermore, coronary submaximal vasodilation induced by papaverine (n = 5) and adenosine (n = 5) abolished the beneficial effects of SOD.We conclude that 1) in sustained myocardial ischemia, SOD treatment attenuates ischemic injury caused by coronary microembolization by restoration of 5'-nucleotidase activity and augmentation of adenosine release; 2) this beneficial effect of SOD is observed even after coronary microembolization; and 3) the beneficial effects of SOD are attributable to coronary vasodilation produced by augmented adenosine release.
Entrainment of ventricular tachycardia: explanation for surface electrocardiographic phenomena by analysis of electrograms recorded within the tachycardia circuit.
Authors: J M Almendral, C D Gottlieb, M E Rosenthal, N J Stamato, A E Buxton, F E Marchlinski, J M Miller, M E Josephson
Journal: Circulation (1988)

Transient entrainment was demonstrated during 59 pacing events in 18 episodes of sustained uniform ventricular tachycardia (VT) while recording electrograms from the site of origin of tachycardia (LE-SOO). During entrainment, the morphology of the initial component of the LE-SOO was identical to the morphology observed during the tachycardia in 13 VTs (group I), but in five VTs (group II), the initial component changed at a "critical" paced cycle length. The presence of the proposed surface electrocardiographic criteria for entrainment--fixed fusion and a first postpacing complex without fusion but occurring at the paced cycle length--were integrally dependent on the morphologic changes in the local presystolic electrogram. Fixed fusion of the surface electrocardiogram at one or more paced cycle lengths was detected during entrainment at 35 of 59 paced cycle lengths in 12 of 18 tachycardias, 10 of which were group I and two of which were group II VTs. Fixed fusion demonstrated by analysis of the LE-SOO was observed at one or more pacing cycle lengths in 17 of 18 VTs. In five tachycardias in which surface electrocardiographic fusion was not observed, fixed fusion was evident on analysis of the left ventricular LE-SOO during right ventricular pacing. The first postpacing interval, as measured at the surface electrocardiogram, was consistently equal to the paced cycle length in only one of 18 tachycardias and was greater than the VT cycle length in eight of 17 tachycardias. A pathway with a long conduction time was demonstrated during entrainment. However, in those 12 VTs in patients in whom pacing was performed at more than one cycle length and there was preservation of the LE-SOO morphology, the conduction time between the stimulus and presystolic electrogram remained constant. Thus, no evidence for "atrioventricular nodal-like" decremental conduction was observed over a wide range of pacing cycle lengths. We conclude that: (1) two of the previously proposed criteria for diagnosis of entrainment (fixed fusion on the surface electrocardiogram and a first postpacing interval equal to the paced cycle length) are overly restrictive criteria for definition of "entrainment" of VT, (2) analysis of endocardial recordings from the site of origin of tachycardia during attempted entrainment of VT is useful for documenting the presence of entrainment, and (3) such analysis provides a basis for the understanding of surface electrocardiographic phenomenon associated with entrainment.
Prevention of Gonococcal Ophthalmia Neonatorum
Authors: Hugh C. Dillon
Journal: New England Journal of Medicine (1986)

Investigators from Kenya, Canada, and Belgium have collaborated on several studies of ophthalmia neonatorum in Nairobi, Kenya.1 2 3 In this issue of the Journal, they report on the efficacy of ceftriaxone, a third-generation cephalosporin, for the treatment of gonococcal ophthalmia neonatorum.3 The authors touch on several interesting points in discussing the rationale for this study. These include the high incidence of maternal gonococcal infection in developing countries; the lack of systematic prophylaxis of ophthalmia neonatorum; a dramatic increase in the prevalence in Kenya of penicillin-resistant gonococci, which now account for 60 percent of the strains; a high incidence of gonococcal . . .
Response to Single Dose of Aspartame or Saccharin by NIDDM Patients
Authors: David L Horwitz, Michael McLane, Peter Kobe
Journal: Diabetes Care (1988)

Twelve normal subjects and 10 subjects with non-insulin-dependent diabetes mellitus were given, in random order at intervals of greater than or equal to 1 wk, three drinks of the same beverage: one unsweetened, one sweetened with 400 mg aspartame, and one sweetened with 135 mg saccharin. The amount of sweetener approximated that in 1 L of sugar-free soft drink. Plasma glucose, insulin, and glucagon were measured for 3 h after ingestion of the test beverage. Plasma glucose declined slightly throughout the test period, probably due to fasting, with no differences between the three treatments. Neither sweetener affected peak insulin levels in subjects with or without diabetes. Analysis of area under the curve showed that mean insulin levels were statistically significantly higher after aspartame than after saccharin or unsweetened beverage in normal subjects only, but the magnitude of the difference was small and unlikely to be of physiological importance in the absence of differences in glucose levels. Furthermore, the differences could largely be accounted for by a decrease in insulin values after both unsweetened beverage and saccharin, with no change from baseline after aspartame. Glucagon levels showed time-to-time variation but no overall differences. We conclude that ingestion of aspartame- or saccharin-sweetened beverages by fasting subjects, with or without diabetes, did not affect blood glucose homeostasis.
Effect of Potassium Administration on (1) Peripheral Vascular Reactivity and (2) Blood Pressure of the Potassium-Deficient Rat
Authors: MEYER FRIEDMAN, S. CHARLES FREED, RAY H. ROSENMAN
Journal: Circulation (1952)

One hour after administration of potassium chloride to potassium-deficient rats, the depressed peripheral vascular response to pressor substances was significantly elevated. Administration of potassium chloride to potassium-deficient rats also returned to higher levels the lowered blood pressure of previously normotensive, as well as hypertensive rats. It appears that the depressor effect of potassium deprivation is due to the loss of peripheral vascular reactivity, both of which are rapidly restored by potassium administration specifically.
Plasma fucosyltransferase as an indicator of imminent blastic crisis
Authors: Ila Shah‐Reddy, David H. Kessel, Ta‐Hsu Chou, Ila Mirchandani, Urmilla Khilanani
Journal: American Journal of Hematology (1982)

Abstract Plasma fucosyltransferase activity was evaluated as an indicator of an impending blastic transformation in 25 patients with chronic granulocytic leukemia (CGL). Fifteen age‐and sex‐matched controls were also studied. The level of enzyme activity was significantly higher in the plasma of patients with blastic transformation (1,630 ± 570 units) compared with steady state chronic granulocytic leukemia (509 ± 110 units) and normal controls (354 ± 57 units). In three patients with CGL, a rise in fucosyltransferase activity preceded any other clinical or laboratory parameter of blastic transformation by 16–20 weeks.
Senescence in pancreatic carcinogenesis: from signalling to chromatin remodelling and epigenetics
Authors: Shiv K Singh, Volker Ellenrieder
Journal: Gut (2013)

Mutational activation of K-Ras is a key genetic event involved in the initiation of pancreatic carcinogenesis. However, K-Ras generally fails to transform precursor lesions into invasive cancers due to activation of powerful fail-safe programmes that counteract transformation and growth. The importance of cellular senescence, a permanent cell growth arrest, is increasingly being recognised as a critical fail-safe programme in pancreatic carcinogenesis. Emerging evidence suggests that oncogene-induced senescence requires transcriptional induction of the <i>CDKN2A</i> gene locus as well as comprehensive chromatin modifications involved in epigenetic silencing of pro-proliferative genes. Moreover, recent work in pancreatic cancer mouse models proposes that inactivation of the <i>CDKN2A</i> tumour suppressor locus is the molecular switch required for senescence evasion and unleashed K-Ras driven malignant transformation in the pancreas.
Untoward Effects of Anticonvulsants
Authors: Henn Kutt, Sydney Louis
Journal: New England Journal of Medicine (1972)

All effective anticonvulsants produce unwanted phenomena. These can be divided into three categories. In the first, the signs and symptoms of intoxication occur predictably in all patients with high drug concentrations and doses. Secondly, true side effects occur in patients on the usual therapeutic doses of a drug. These are undesirable by-products of the pharmacologic action of the drug and manifest in a relatively large proportion of patients using it. They appear to be partially dose related. Thirdly, there are idiosyncratic reactions, which appear to be the result of unusual organismal reactions to a drug. They are quite rare, are . . .
Multifactorial Interventions Before Laser Photocoagulation Improve Outcome of Diabetic Macular Edema
Authors: Ramandeep Singh, Vishali Gupta, Amod Gupta, Nishant Sachdev, Mangat R. Dogra, Anil Bhansali
Journal: Diabetes Care (2006)

Diabetic macular edema is often associated with multiple comorbid systemic conditions (1). In a pilot study (2), multifactorial interventions in clinically significant macular edema (CSME) led to a decrease in retinal thickness. However, the effect of these interventions, before laser photocoagulation, on the outcome of diabetic macular edema has not been studied.

In a prospective study, 125 patients (180 eyes; 72 men and 53 women; median age 55 years [range 38–72]) completed a minimum follow-up of 1 year (median 1.8 years [range 1.0–2.7]). All underwent multifactorial interventions, including initiation of insulin therapy ( n = 47), newer oral hypoglycemic agents ( n = …
Vasculitis in association with atherosclerosis
Authors: C.C. HARLAND, P. E. KILBY
Journal: British Journal of Dermatology (1992)

Journal Article Vasculitis in association with atherosclerosis Get access C.C. HARLAND, C.C. HARLAND Department of Dermatology University Hospital, Queen's Medical Centre, Nottingham NG7 2UH, U.K. Search for other works by this author on: Oxford Academic Google Scholar P. E. KILBY P. E. KILBY Department of Dermatology University Hospital, Queen's Medical Centre, Nottingham NG7 2UH, U.K. Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 126, Issue 1, 1 January 1992, Pages 90–91, https://doi.org/10.1111/j.1365-2133.1992.tb08413.x Published: 01 January 1992
The enzymatic activities of CD38 enhance CLL growth and trafficking: implications for therapeutic targeting
Authors: T Vaisitti, V Audrito, S Serra, R Buonincontri, G Sociali, E Mannino, A Pagnani, A Zucchetto, E Tissino, C Vitale, M Coscia, C Usai, C Pepper, V Gattei, S Bruzzone, S Deaglio
Journal: Leukemia (2014)