tbuckley/cabot-search huggingface dataset:
Randomized Trial of an Oral Platelet Glycoprotein IIb/IIIa Antagonist, Sibrafiban, in Patients After an Acute Coronary Syndrome
Authors: Christopher P. Cannon, Carolyn H. McCabe, Steven Borzak, Timothy D. Henry, Marc D. Tischler, Hiltrud S. Mueller, Robert Feldman, Sebastian T. Palmeri, Kenneth Ault, Scott A. Hamilton, Joel M. Rothman, William F. Novotny, Eugene Braunwald
Journal: Circulation (1998)

Background —Inhibitors of the platelet glycoprotein IIb/IIIa receptor given intravenously have been shown to be effective in reducing ischemic complications after coronary angioplasty and in unstable angina, making this a promising new class of agents for the treatment and prevention of ischemic events in patients with acute coronary syndromes. Sibrafiban (Ro 48–3657) is an oral, peptidomimetic, selective antagonist of the glycoprotein IIb/IIIa receptor. Methods and Results —The Thrombolysis in Myocardial Infarction (TIMI) 12 trial was a phase II, double-blind, dose-ranging trial designed to evaluate the pharmacokinetics (PK), pharmacodynamics (PD), safety, and tolerability of sibrafiban in 329 patients after acute coronary syndromes. In the PK/PD cohort of TIMI 12, 106 patients were randomized to receive one of seven dosing regimens of sibrafiban, ranging from 5 mg daily to 10 mg twice daily for 28 days. In the safety cohort, 223 patients were randomized to one of four dose regimens of sibrafiban (ranging from 5 mg twice daily to 15 mg once daily) or aspirin for 28 days. High levels of platelet inhibition were achieved: mean peak values ranged from 47% to 97% inhibition of 20 μmol/L ADP-induced platelet aggregation on day 28 across the seven doses. Twice-daily dosing provided more sustained platelet inhibition (mean inhibition, 36% to 86% on day 28), whereas platelet inhibition returned to baseline levels by 24 hours with once-daily dosing. Major hemorrhage occurred in 1.5% of patients treated with sibrafiban and in 1.9% of patients treated with aspirin. Protocol-defined “minor” bleeding, usually mucocutaneous, occurred in 0% to 32% of patients in the various sibrafiban groups and in none of the patients treated with aspirin. Minor bleeding was related to total daily dose ( P =.002), once- versus twice-daily dosing ( P &lt;.0001), renal function ( P &lt;.0001), and presentation with unstable angina ( P &lt;.01). Conclusions —The oral glycoprotein IIb/IIIa antagonist sibrafiban achieved effective, long-term platelet inhibition with a clear dose-response but at the expense of a relatively high incidence of minor bleeding. Oral IIb/IIIa inhibition deserves further study as a new treatment strategy in patients after acute coronary syndromes.
Chest Physicians Recommend CT Screening for Lung Cancer Only for Older Smokers
Authors: Mike Mitka
Journal: JAMA (2013)

the risk factors for women,” Tsai said. Trauma in general may be a factor. Tsai and colleagues studied 581 homeless women veterans at 11 VA Homeless Women Veterans Program sites and found that women in the group had experienced a diverse array of trauma. For example, 82% said someone close to them had experienced a serious or lifethreatening illness, 67% reported having been raped, 61% had experienced a natural or manmade disaster, 53% had a friend or family member who was killed, 52% had been injured by a family member hitting or pushing them, and 27.7% had engaged in prostitution. Tsai said much of the trauma occurred before the women joined the military, and many remained at elevated risk of trauma after they returned home. He noted that some researchers theorize that people who have been traumatized may be at increased risk of further trauma in part because they may put themselves into potentially threatening situations. Homeless female veterans sometimes have a different set of needs than their male counterparts. Many have children and need to find housing that is suitable for children, explained Stephen Peck, MSW, of the nonprofit US Veterans Initiative. The majority of homeless female veterans have also experienced sexual trauma, which may make them less comfortable with participating in programs in which they are greatly outnumbered by men. Peck said his group found that many female homeless veterans declined to participate in their substance abuse program until the group developed a program specifically for women that allows women to attend day treatment as a cohort. Peck noted that his organization also offers on-site child care and a school with kindergarten through grade 8 to provide care and access to education for children whose mothers are seeking treatment. Tailoring interventions to the specific needs of subgroups of homeless vets may be crucial for both men and women, Tsai said. “Some individuals need more intensive services; some are able to do well on their own once they get housing,” he explained. Tsai recommended that physicians refer veterans at risk of homelessness to the VA, which he said is better equipped to handle issues surrounding homelessness and which is often free for veterans. The VA tries to make care as accessible as possible, not just at hospitals but also at outpatient clinics. The US Department of Housing and Urban Development–Veterans Affairs Supportive Housing (HUD-VASH) program provides vouchers to help homeless veterans find rental housing and also provides them with case management and clinical services (http://1.usa .gov/h52lnU).
Resident Forum
Authors: Angelo P. Giardino
Journal: JAMA (1990)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Natural history of aortoarteritis (Takayasu's disease).
Authors: R Subramanyan, J Joy, K G Balakrishnan
Journal: Circulation (1989)

The natural history of aortoarteritis was studied in 88 patients (54 women and 34 men). The average age was 24.0 +/- 8.8 years at onset of symptoms and 28.3 +/- 9.9 years at diagnosis. The follow-up period was 83.6 +/- 74.4 months from onset and 33.2 +/- 37.0 months from diagnosis. Ten patients (11.4%) died during follow-up (0.016 deaths/patient year), and 22 patients (25%) suffered major nonfatal events (0.042 events/patient year). The cumulative survival at 5 and 10 years after the onset was 91.0 +/- 3.3% and 84.0 +/- 5.6% (mean +/- SEM), respectively. The event-free survival rates at the same intervals after onset were 74.9 +/- 5.0% and 64.0 +/- 7.4%, respectively. The overall survival and event-free survival at 10 years after diagnosis was 80.3 +/- 6.5% and 61.6 +/- 7.5%, respectively. Patients with no complications or a mild single complication at diagnosis had a higher event-free survival rate than those with severe single complication or multiple complications at 5 years--97.0 +/- 2.9% and 59.7 +/- 7.3%, respectively (p less than 0.001). Severe hypertension (p less than 0.01), severe functional disability (p less than 0.01), and evidence of cardiac involvement (p less than 0.05) were good predictors of either death or major event on follow-up. These data are useful in making an objective assessment of the prognosis and in planning elective interventions.
Immunoaugmentative therapy. An unproven cancer treatment
Authors: S. Green
Journal: JAMA (1993)

THE BELIEF that the clinically normal human immune system maintains a continuous surveillance for cancer cells and can evoke an immunologic intervention to destroy them is so appealing and full of emotionally charged wishful thinking that it has become dogma in the lay literature. Because cancer is so prevalent, but so rarely detected in its earliest stages, it is easy for the entrepreneurs who sell unproven cancer treatments to explain that damage to the immune system caused the loss of its anticancer "surveillance" function and allowed the cancer to survive and flourish. They then claim that the "nontoxic" treatments they sell will "repair, replace, rejuvenate, or reactivate" the damaged immune system and allow the patient's own body to "cure itself of the cancer." Immunoaugmentative therapy (IAT), a treatment for cancer invented by zoologist Lawrence Burton, PhD, is based on these assertions.<sup>1</sup> Recently, the Office of Technology Assessment of the
Acute renal failure precipitated by radiographic contrast medium in a patient with rhabdomyolysis.
Authors: C G Winearls, J G Ledingham, A J Dixon
Journal: BMJ (1980)

Acute renal failure precipitated by radiographic contrast medium in a patient with rhabdomyolysis Myoglobinuria is an uncommon but important cause of acute tubular necrosis.'It was originally described in association with trauma but also occurs in cases of non-traumatic rhabdomyolysis, when diagnosis may be more difficult.2'Infusion intravenous urography is a standard investigation for acute renal impairment of obscure cause1; we report a case of acute renal failure precipitated by administration of radio- graphic contrast medium in a patient with undiagnosed rhabdomyolysis and renal impairment. Case reportA 57-year-old man presented with malaise and fever.His history was not helpful, but he mentioned that his urine was the colour of "oxtail soup."Biochemical data were: sodium 134 mmol(mEq)/l, potassium 4-3 mmol
Relationship between high-density lipoprotein paraoxonase gene M/L55 polymorphism and carotid atherosclerosis differs in smoking and nonsmoking men
Authors: Riikka Malin, Antti Loimaala, Arja Nenonen, Michele Mercuri, Ilkka Vuori, Matti Pasanen, Pekka Oja, Gene Bond, Timo Koivula, Terho Lehtim[auml ]ki
Journal: Metabolism (2001)
Risk factors for evolution of acquired aplastic anemia into myelodysplastic syndrome and acute myeloid leukemia after immunosuppressive therapy in children
Authors: Seiji Kojima, Akira Ohara, Masahiro Tsuchida, Toru Kudoh, Ryoji Hanada, Yuri Okimoto, Takashi Kaneko, Toshikuni Takano, Koichiro Ikuta, Ichiro Tsukimoto
Journal: Blood (2002)
Effect of Histamine and Its Methyl Derivatives on Cyclic AMP Metabolism in Gastric Mucosa and Its Blockade by an H2 Receptor Antagonist
Authors: Thomas P. Dousa, Charles F. Code
Journal: Journal of Clinical Investigation (1974)

In a cell-free system prepared from guinea pig gastric mucosa, histamine and Nalpha-methyl-histamine produced dose-dependent stimulation of cyclic AMP formation and 1,4-methylhistamine had a minimal stimulatory effect. N-methyl-N'-(2-[5-methylimidazole-4-yl-methylthio]-ethyl) -thiourea (metiamide), a new H2 receptor inhibitor, selectively blocked the stimulation of adenylate cyclase by histamine and its active methyl derivative but had no substantial effect on the basal adenylate cyclase activity or adenylate cyclase stimulated by sodium fluoride. Metiamide inhibited the histamine stimulation of adenylate cyclase at 1/100 the concentration of the histamine. Histamine, its methyl derivatives, and metiamide did not influence the activity of cyclic AMP phosphodiesterase from gastric mucosa. Therefore, histamine stimulates gastric mucosal adenylate cyclase via interaction with the H2 receptor without influencing cyclic AMP breakdown, and N-methylation of histamine on the side chain preserves or even increases its stimulating ability. On the other hand, N-methylation in the ring nearly abolishes the ability of histamine to interact with the H2 receptor.
Leukemia as a Problem in Preventive Medicine
Authors: Macfarlane Burnet
Journal: New England Journal of Medicine (1958)

MY first choice of a subject for the Cutter Lecture on Preventive Medicine was naturally something from my own primary field of interest, viral disease. There was a disadvantage, however, that work on the public-health side of viral disease has become of rather minor interest in my own laboratory and not much that is new can be reported on our main topic of Murray Valley encephalitis.For the last two years, however, I have had to undertake the responsibility of acting as chairman to the Australian Government's National Radiation Advisory Committee, which is concerned with advising on the medical hazards . . .
Waits for emergency care are worst for 10 years, figures show
Authors: G. Iacobucci
Journal: BMJ (2015)

Performance on waiting time targets by hospital emergency departments in England has fallen to its worst level for a decade, official figures have shown.

Figures published by NHS England show that only 92.6% of patients in emergency departments were seen within four hours in the quarter from October to December 2014, below the target of 95%.1 The performance is the worst quarterly result against the target since it was introduced in 2004. This is the second time that the target has been missed since the coalition government came to power: the previous lowest performance was 94.1%, recorded in the first three months of 2013.

The other three UK countries are also missing the target at present.

The news came as six hospitals in England were forced to declare “major incidents” owing to patient demand reaching a level …
Environmental Inequality in Exposures to Airborne Particulate Matter Components in the United States
Authors: Michelle L. Bell, Keita Ebisu
Journal: Environmental Health Perspectives (2012)

Growing evidence indicates that toxicity of fine particulate matter ≤ 2.5 μm in diameter (PM2.5) differs by chemical component. Exposure to components may differ by population.We investigated whether exposures to PM2.5 components differ by race/ethnicity, age, and socioeconomic status (SES).Long-term exposures (2000 through 2006) were estimated for 215 U.S. census tracts for PM2.5 and for 14 PM2.5 components. Population-weighted exposures were combined to generate overall estimated exposures by race/ethnicity, education, poverty status, employment, age, and earnings. We compared population characteristics for tracts with and without PM2.5 component monitors.Larger disparities in estimated exposures were observed for components than for PM2.5 total mass. For race/ethnicity, whites generally had the lowest exposures. Non-Hispanic blacks had higher exposures than did whites for 13 of the 14 components. Hispanics generally had the highest exposures (e.g., 152% higher than whites for chlorine, 94% higher for aluminum). Young persons (0-19 years of age) had levels as high as or higher than other ages for all exposures except sulfate. Persons with lower SES had higher estimated exposures, with some exceptions. For example, a 10% increase in the proportion unemployed was associated with a 20.0% increase in vanadium and an 18.3% increase in elemental carbon. Census tracts with monitors had more non-Hispanic blacks, lower education and earnings, and higher unemployment and poverty than did tracts without monitors.Exposures to PM2.5 components differed by race/ethnicity, age, and SES. If some components are more toxic than others, certain populations are likely to suffer higher health burdens. Demographics differed between populations covered and not covered by monitors.
Cholinergic Modification of Glucose-Induced Biphasic Insulin Release in Vitro
Authors: R. Sharp, S. Culbert, J. Cook, A. Jennings, I. M. Burr
Journal: Journal of Clinical Investigation (1974)

An in vitro system for perifusion of rat pancreatic islets has been utilized to define the effects of cholinergic agents on the dynamics of insulin release. In the absence of glucose the effects of either acetylcholine or acetyl-β-methylcholine were minimal at concentrations up to 10−5 mM. In the presence of low glucose concentration (2.4 mM), both of the muscarinic agents produced dose-dependent biphasic insulin release. Under these conditions significant insulin release was observed over both phases at concentrations of the muscarinic agents as low as 10−8 mM. Further, the dose response curves relating muscarinic concentration to the total amount of insulin released in each of the two phases showed lack of parallelism between the curves. Nicotinic acid in concentrations up to 10−5 mM had no effect on insulin release in the presence of 2.4 mM glucose. When the glucose concentration was increased to 16.4 mM, the effects of the muscarinic agents were significantly less than those observed in the presence of 2.4 mM glucose. This held true whether the effect was defined as absolute increment due to the muscarinic agent or as percentage of enhancement. Atropine inhibited insulin release induced by both acetylcholine and by 16.4 mM glucose. These data indicate that cholinergic stimulation can play a significant role in modifying insulin release patterns.
Acceleration of wound healing in gastric ulcers by local injection of neutralising antibody to transforming growth factor beta 1.
Authors: H Ernst, P Konturek, E G Hahn, T Brzozowski, S J Konturek
Journal: Gut (1996)

BACKGROUND: Application of neutralising antibodies (NAs) to transforming growth factor beta 1 (TGF beta 1) improves wound healing in experimental glomerulonephritis and dermal incision wounds. TGF beta 1 has been detected in the stomach, but despite the fact that this cytokine plays a central part in wound healing no information is available to determine if modulation of the TGF beta 1 profile influences the healing of gastric ulcers. This study examines gastric ulcer healing in the rat after local injection of NAs to TGF beta 1. METHOD: Chronic gastric ulcers were induced in Wistar rats by the application of 100% acetic acid to the serosal surface of the stomach. Immediately after ulcer induction and on day 2, NAs to TGF beta 1 (50 micrograms), TGF beta 1 (50 ng), saline or control antibodies (IgG; 50 micrograms) were locally injected into the subserosa. Controls received no subserosal injections. Animals were killed on day 5 or 11, the ulcer area was measured planimetrically, sections were embedded in paraffin wax, and stained with trichrome or haematoxylin and eosin. Depth of residual ulcer was assessed on day 11 by a scale of 0-3, the percentage of connective tissue was determined by a semiquantitative matrix score and granulocytes and macrophages in the ulcer bed were also assessed. RESULTS: The application of NAs to TGF beta 1 led to a significant acceleration of gastric ulcer healing on day 11 (0.6 (SD 0.8) v 3.7 (SD 2.6) mm2), a reduction in macrophages (23.7 (SD 22.6) v 38 (26) per 40 x power field) and granulocytes (8.5 (SD 5.6) v 20 (10) per 40 x power field), fewer histological residual ulcers (mean 1 (SD 0.9) v 2 (1.1)), a reduced matrix score, and a regenerative healing pattern. Excessive scarring was seen in the TGF beta 1 treated group. CONCLUSION: Further treatment of gastric ulcers may induce a new treatment modality by local injection of NA to TGF beta 1 in an attempt to accelerate and improve ulcer healing.
Sulpiride improves inadequate lactation.
Authors: O Ylikorkala, A Kauppila, S Kivinen, L Viinikka
Journal: BMJ (1982)

Twenty-eight newly delivered mothers with inadequate lactation volunteered for a placebo-controlled double-blind trial of sulpiride 50 mg thrice daily for four weeks. Treatment was allocated at random, and serum prolactin concentrations and breast-milk yields were measured before and serially during the trial. Of the 26 women who completed the trial, 14 had taken sulpiride and 12 the placebo. In the sulpiride-treatment group the mean maternal serum prolactin concentration rose from 49.0 +/- SE 3.6 micrograms/l to a maximum of 402.1 +/0 43.2 micrograms/l at two weeks; in the placebo-treated group, however, the concentration fell during the trial (from 84.7 +/- 24.0 micrograms/l to 47.8 +/- 8.6 micrograms/l). Mean breast-milk yields also increased in the sulpiride-treatment group (by an average of 212-265 ml) and fell in the women given placebo. Of the 14 infants in the sulpiride-treatment group, four did not need supplementary feeds during the trial; in the control group, however, all infants continued to require such feeds. Infants in the sulpiride-treatment group gained significantly more weight than did the controls (p less than 0.05). Three women taking sulpiride complained of mild side effects, but none occurred in the infants. These findings suggest that sulpiride is an effective treatment for inadequate lactation in the puerperium.
Combined epigenetic therapy with the histone methyltransferase EZH2 inhibitor 3-deazaneplanocin A and the histone deacetylase inhibitor panobinostat against human AML cells
Authors: Warren Fiskus, Yongchao Wang, Arun Sreekumar, Kathleen M. Buckley, Huidong Shi, Anand Jillella, Celalettin Ustun, Rekha Rao, Pravina Fernandez, Jianguang Chen, Ramesh Balusu, Sanjay Koul, Peter Atadja, Victor E. Marquez, Kapil N. Bhalla
Journal: Blood (2009)
759. In Search of an Effective Target: In Vivo Approach Using HIV-1 Specific siRNA and Ribozyme Libraries
Authors: Hoshang J. Unwalla, Atilla A. Seyhan, Brian H. Johnston, John J. Rossi
Journal: Molecular Therapy (2006)

Short interfering RNA (siRNA) and ribozymes have been shown to silence HIV-1 gene expression by site-specific cleavage of viral mRNA. A major factor determining whether ribozymes or siRNAs will be effective for post-transcriptional gene silencing is the choice of an appropriate target site on the mRNA. Conventional approaches for target site selection often do not work due to structural motifs in the mRNA that preclude accessibility of these RNA-based antivirals. An effective screening strategy for potential targets on the viral genome is use of HIV specific siRNA or ribozyme libraries in cell culture coupled with HIV challenge assays and selective survival. For siRNA site selection, an HIV specific siRNA library spanning all possible HIV-specific siRNA sequences of 21-mer length were created and inserted between convergent human U6 and H1 promoters, cloned in a lentiviral vector and transduced into HIV susceptible CEM cells. On Day 15 post infection, extensive cell death was observed followed by a repopulation of infected cells that were presumably protected from HIV on day 30. Viable cells were then analyzed for the siRNA sequence they harbored. These results will be presented. HIV RNA is known to traffic through the nucleolus. An HIV-specific ribozyme library was created by inserting Ribozymes with fully randomized arms into the body of the U16 small nucleolar RNA and expressed from the U6 promoter to co-localize the ribozyme molecules with its target. The library was then co-transfected with pNL-TK that renders the infected cells susceptible to gancyclovir. Ribozyme RNA was amplified by RT-PCR from surviving cells and recloned into pTZ-U6+1 for the next round of selection. After three rounds of selection, the ribozyme molecules were sequenced and it was determined that two sequences were repeatedly enriched from different clones. Sequence C36 and C10 were then tested against HIV-1 in individual antiviral assays. Sequence C36 showed a 60% inhibition of HIV-1 p24 levels in culture supernatant of infected cells. Alignment of the putative target sequence on the HIV-1 genome showed that C36 could actually target two sites on the viral genome. One of which is close to a conserved site in the U5 region of HIV-1 LTR and another region is in the Pol gene. C10 gave approximately a 45% inhibition over three individual experiments. These data will be presented. The potential impact of these studies on HIV-1 gene therapy will be discussed.