tbuckley/cabot-search huggingface dataset:
Ventricular fibrillation threshold in canine hearts with quinidine induced prolonged QT interval: effects of atrial pacing, isoproterenol, and lignocaine
Authors: H. INOUE, H. MATSUO, S. MASHIMA, T. SUGIMOTO, S. MURAO
Journal: Cardiovascular Research (1986)

Ventricular fibrillation threshold was determined using a train of pulses, 4 ms in duration, delivered at 10 ms intervals, in 20 anaesthetised dogs receiving toxic doses of quinidine sulphate (30 mg·kg−1) injected intravenously over 5 min to prolong the QT interval. The effects of atrial pacing, isoproterenol, and lignocaine on ventricular fibrillation threshold were investigated. Quinidine administration lowered the mean(SD) threshold from 14.7(5.1) to 8.8(3.6) mA (n=20, p<0.001). Atrial pacing shortened the mean(SD) basic cycle length from 652 to 400 ms and the QT interval (378(28) vs 334(19) ms, n=8, p<0.01) but did not alter the mean(SD) threshold (7.0(2.3) vs 7.5(1.5) mA). Isoproterenol infusion to maintain basic cycle length at 421 (23) ms shortened the mean(SD) QT interval to 291(14) ms (p<0.001) and increased the mean(SD) threshold to 13.6(5.9) mA (n=8, p<0.01). Lignocaine (plasma concentration 1.36 μg·ml−1) increased the mean(SD) threshold from 10.9(3.4) to 16.7(6.7) mA (n=7, p<0.02) without affecting basic cycle length and QT interval. Thus atrial pacing shortened the QT interval slightly but did not make the canine heart with a quinidine induced prolonged QT interval less vulnerable to electrically induced ventricular fibrillation, whereas both isoproterenol and lignocaine did, although they affected basic cycle length and QT interval differently.
Rituximab for refractory Evans syndrome and other immune‐mediated hematologic diseases
Authors: Elpis Mantadakis, Vassiliki Danilatou, Eftichia Stiakaki, Maria Kalmanti
Journal: American Journal of Hematology (2004)

Abstract The authors describe a 21‐year‐old man with long‐lasting Evans syndrome refractory to corticosteroids and immunosuppressive agents; the patient responded to four weekly infusions of rituximab. The patient relapsed with thrombocytopenia 7 months post‐therapy and was successfully re‐treated with two weekly doses of the same monoclonal antibody. He remains in remission for 7‐plus months after the second treatment. Therapy was well tolerated, and no infectious complications occurred, despite avoiding administration of prophylactic gammaglobulin. Rituximab appears safe and modestly effective in a variety of immune‐mediated hematologic diseases, including autoimmune hemolytic anemia, chronic immune thrombocytopenia, Evans syndrome, pure red cell aplasia, mixed type II cryoglobulinemia, cold agglutinin disease, and Waldenström's macroglobulinemia. However, as most of the published literature consists of case reports and small case series, international collaboration is essential in order to better define the efficacy and safety of this agent in children and adults with hematologic diseases. Am. J. Hematol. 77:303–310, 2004. © 2004 Wiley‐Liss, Inc.
Altered binding of 125I-labeled calmodulin to a 46.5-kilodalton protein in skin fibroblasts cultured from patients with cystic fibrosis.
Authors: E A Tallant, R W Wallace
Journal: Journal of Clinical Investigation (1987)

The levels of calmodulin and calmodulin-binding proteins have been determined in cultured skin fibroblasts from patients with cystic fibrosis (CF) and age- and sex-matched controls. Calmodulin ranged from 0.20 to 0.76 microgram/mg protein; there was no difference between calmodulin concentration in fibroblasts from CF patients and controls. Calmodulin-binding proteins of 230, 212, 204, 164, 139, 70, 59, 46.5, and 41 kD were identified. A protein with a mobility identical to the 59-kD calmodulin-binding protein was labeled by antiserum against calmodulin-dependent phosphatase. Although Ca2+/calmodulin-dependent phosphatase activity was detected, there was no different in activity between control and CF fibroblasts or in the level of phosphatase protein as determined by radioimmunoassay. Lower amounts of 125I-calmodulin were bound to the 46.5-kD calmodulin-binding protein in CF fibroblasts as compared with controls. The 46.5-kD calmodulin-binding protein may be reduced in CF fibroblasts or its structure may be altered resulting in a reduced binding capacity and/or affinity for calmodulin and perhaps reflecting, either directly or indirectly, the genetic defect responsible for cystic fibrosis.
THE HANDWRITING ON THE WALL: WHAT DOES IT PORTRAY?
Authors: A. E. BALDWIN
Journal: JAMA (1900)

The founders of American dentistry had high professional ideals. The methods of practice at their command were the most crude and almost if not wholly mechanical. They deemed the specialty a part of the healing art and hence a department of the science of medicine. Such profound regard had early practitioners of dentistry for their calling that in almost every instance before or after they had begun practice they took up the study of general medicine. They were capable of practicing and did practice general medicine. The illustrious Haydon, Jeffries and many others were graduates of the best American and foreign medical colleges. Later, from 1810 to 1840—the latter date being that of the establishment of the Baltimore College of Dental Surgery—a long list of medically educated men gave honor and dignity to their special calling. These men were the peers of any in the practice of medicine. I doubt
Ameboma, the Forgotten Granuloma
Authors: Stephen M. Levine
Journal: JAMA (1971)

Amebomas or amebic granulomas are unusual sequelae of acute amebiasis. Because clinical diagnosis is often difficult and amebae may not be found in stool specimens, rectal biopsies, mucosal scrapings, and serological tests for amebae assume paramount importance in helping to establish a diagnosis of ameboma. The roentgenological appearance, in the correct clinical setting, may also suggest the diagnosis of ameboma. Treatment should include the tissue amebicide emetine hydrochloride, as well as antibiotics and luminal agents.
Cyclooxygenase inhibitors: Scope of their use and development in cancer chemotherapy
Authors: Mohammed Naseer A. Khan, Yong Sup Lee
Journal: Medicinal Research Reviews (2009)

The traditional nonsteroidal anti-inflammatory drugs (NSAIDs) exert their effect by inhibition of cyclooxygenase-1 (COX-1) as well as COX-2 enzymes. As COX-1 is responsible for maintaining normal biological functions, the nonselective inhibition of these enzymes caused side effects including gastrointestinal (GI) problems. Recently developed selective COX-2 inhibitors could reduce these adverse effects, but the evidence of cardiovascular side effects including an increased risk of myocardial infarction began to emerge, and some of the COX-2 inhibitors were eventually withdrawn from the market and this led to the downfall of this research. So, the discovery of novel COX-2 inhibitors with their safety profile became the biggest challenge in pharmaceutical research. However, recent mechanistic and clinical studies revolutionized this area by indicating the fact that COX-2 is involved in apoptosis resistance, angiogenesis, and tumor progression. Epidemiological data suggest that selective COX-2 inhibitors might prevent the development of cancers. Moreover, COX-2 is found to be overexpressed in many cancers thus making it an attractive therapeutic target for the prevention and treatment of a number of malignancies. The purpose of this review is to focus on the medicinal chemistry aspects of COX-2 inhibitors in cancer chemotherapy and recent reports on these inhibitors as anticancer agents. We attempted to cover only the COX inhibitors that showed anticancer activity, although a number of potent COX-2 inhibitors have been reported without their anticancer effects. Furthermore, structure-activity relationships (SAR) of different classes of compounds for COX-2 inhibition as well as anticancer activity, and their future applications are discussed.
Recombinant Probes for Visualizing Endogenous Synaptic Proteins in Living Neurons
Authors: Garrett G. Gross, Jason A. Junge, Rudy J. Mora, Hyung-Bae Kwon, C. Anders Olson, Terry T. Takahashi, Emily R. Liman, Graham C.R. Ellis-Davies, Aaron W. McGee, Bernardo L. Sabatini, Richard W. Roberts, Don B. Arnold
Journal: Neuron (2013)
Lymphopenia assessed during routine follow-up after immunochemotherapy (R-CHOP) is a risk factor for predicting relapse in patients with diffuse large B-cell lymphoma
Authors: L F Porrata, K Rsitow, D J Inwards, S M Ansell, I N Micallef, P B Johnston, T M Habermann, T E Witzig, J P Colgan, G S Nowakowski, C A Thompson, S N Markovic
Journal: Leukemia (2010)
Incidence of cancer in primary biliary cirrhosis: The mayo experience
Authors: Pardeep K. Nijhawan, Terry M. Therneau, Rolland E. Dickson, Jessica Boynton, Keith D. Lindor
Journal: Hepatology (1999)

Patients with primary biliary cirrhosis (PBC) may be at increased risk for malignancies. Several studies have addressed the risk of specific malignancies; however, there is little information about overall incidences of malignancies in these patients. We hypothesize that these patients may be at an increased risk for cancer. We performed a retrospective chart review evaluating patients with the diagnosis of PBC and malignancies. We reviewed records of patients with PBC presenting to the Mayo Clinic between 1976 and 1985. The diagnosis of PBC was made using evidence of cholestasis, positive antimitochondrial antibody titers and liver biopsy findings consistent with PBC. The incidence of malignancies were then compared with published data by the Surveillance, Epidemiology and End Results (SEER) program of the National Cancer Institute. Of the 1,692 patients with PBC in the Mayo Clinic data base, 114 patients were identified with primary cancer. The number of malignancies was higher than would be anticipated by chance alone; with 93 observed versus 62.4 expected events (P <.001). Hepatobiliary malignancies had a relative risk of 46 (P <.0001) for women and 55 (P <.0001) in men. There was a dramatic increased risk for development of hepatobiliary malignancies. PBC patients might benefit from more aggressive surveillance for hepatobiliary malignancies during their lifetime.
Expression of basic fibroblast growth factor and its receptor by smooth muscle cells and endothelium in injured rat arteries. An en face study.
Authors: V Lindner, M A Reidy
Journal: Circulation Research (1993)

Release of endogenous basic fibroblast growth factor (bFGF) has been shown to initiate smooth muscle cell (SMC) proliferation following balloon catheter denudation in rat arteries. The mechanisms that contribute to the continued replication of the cells that subsequently form the neointima are not well understood. We have examined expression of bFGF and fibroblast growth factor receptor 1 (FGFR-1) in luminal SMCs as well as endothelium at various times after injury, which allowed us to study both replicating as well as quiescent cells. Using in situ hybridization on en face preparations, we were able to detect mRNA in luminal cells that was not observed by analysis of artery cross sections. We demonstrate that mRNA for bFGF was found in replicating SMCs and endothelial cells. bFGF mRNA was not detectable in either cell type at quiescence despite nuclear staining for bFGF. Expression of FGFR-1 mRNA was observed in replicating endothelial and SMCs at similar times after injury. These data provide evidence that in injured arteries the ligand/receptor system of bFGF and FGFR-1 may be involved in the continued proliferative response of SMCs leading to neointima formation. Furthermore, our results suggest a role for bFGF in reestablishing the endothelial lining in denuded vessels.
Time-Dependent and Tissue-Specific Accumulation of mtDNA and Respiratory Chain Defects in Chronic Doxorubicin Cardiomyopathy
Authors: Dirk Lebrecht, Bernhard Setzer, Uwe-Peter Ketelsen, Jörg Haberstroh, Ulrich A. Walker
Journal: Circulation (2003)

Doxorubicin causes a chronic cardiomyopathy of unknown pathogenesis. We investigated whether acquired defects in mitochondrial DNA (mtDNA) and interconnected respiratory chain dysfunction may represent a molecular mechanism for its late onset.Rats were treated weekly with intravenous doxorubicin (1 mg/kg) for 7 weeks, starting at 11 weeks of age (group B). Controls received saline. Group C received doxorubicin identically to group B, but the course was started at 41 weeks of age. All rats were killed at week 48. Doxorubicin was also injected once, either 6 days (group D) or 2 hours (group E) before euthanasia. Heart and skeletal muscle were examined. Only group B rats developed a significant clinical, macroscopic, histological, and ultrastructural cardiomyopathy. Group B hearts had the lowest cytochrome c oxidase (COX) activity (24% of controls; P=0.003), the highest citrate synthase activity (135% of controls; P=0.005), and the highest production of superoxide. In group B, the respiratory subunit COXI, which is encoded by mtDNA, was reduced (P<0.001), as was mtDNA (49% of controls, P<0.001). Group C hearts differed from group B in their lower cardiomyopathy score (P=0.006), higher COX activity (P=0.02), and higher mtDNA content (P=0.04). Group B and to a lesser extent group C hearts contained deleted mtDNA. There was no detectable mitochondrial toxicity in group D and E hearts or in skeletal muscle.In doxorubicin cardiomyopathy, mtDNA alterations, superoxide, and respiratory chain dysfunction accumulate long-term in the absence of the drug and are associated with a late onset.
<i>TCF7L2</i>Polymorphisms and Progression to Diabetes in the Diabetes Prevention Program
Authors: Jose C. Florez, Kathleen A. Jablonski, Nick Bayley, Toni I. Pollin, Paul I.W. de Bakker, Alan R. Shuldiner, William C. Knowler, David M. Nathan, David Altshuler
Journal: New England Journal of Medicine (2006)

Common polymorphisms of the transcription factor 7-like 2 gene (TCF7L2) have recently been associated with type 2 diabetes. We examined whether the two most strongly associated variants (rs12255372 and rs7903146) predict the progression to diabetes in persons with impaired glucose tolerance who were enrolled in the Diabetes Prevention Program, in which lifestyle intervention or treatment with metformin was compared with placebo.We genotyped these variants in 3548 participants and performed Cox regression analysis using genotype, intervention, and their interactions as predictors. We assessed the effect of genotype on measures of insulin secretion and insulin sensitivity at baseline and at one year.Over an average period of three years, participants with the risk-conferring TT genotype at rs7903146 were more likely to have progression from impaired glucose tolerance to diabetes than were CC homozygotes (hazard ratio, 1.55; 95 percent confidence interval, 1.20 to 2.01; P<0.001). The effect of genotype was stronger in the placebo group (hazard ratio, 1.81; 95 percent confidence interval, 1.21 to 2.70; P=0.004) than in the metformin and lifestyle-intervention groups (hazard ratios, 1.62 and 1.15, respectively; P for the interaction between genotype and intervention not significant). The TT genotype was associated with decreased insulin secretion but not increased insulin resistance at baseline. Similar results were obtained for rs12255372.Common variants in TCF7L2 seem to be associated with an increased risk of diabetes among persons with impaired glucose tolerance. The risk-conferring genotypes in TCF7L2 are associated with impaired beta-cell function but not with insulin resistance. (ClinicalTrials.gov number, NCT00004992. [ClinicalTrials.gov]).
EFFECT OF EICOSAPENTAENOIC ACID ON THE PREVENTION OF PERIPROCEDURAL (TYPE IVA) MYOCARDIAL INFARCTION FOLLOWING PERCUTANEOUS CORONARY INTERVENTION
Authors: Akiyoshi Kurita, Hiroaki Takashima, Katsuhisa Waseda, Shinichiro Sakurai, Hirohiko Ando, Soichiro Kumagai, Daiki Kato, Akihiro Suzuki, Masanobu Fujimoto, Tetsuya Amano
Journal: Journal of the American College of Cardiology (2014)
Changes in the Use and Costs of Diagnostic Imaging Among Medicare Beneficiaries With Cancer, 1999-2006
Authors: Michaela A. Dinan
Journal: JAMA (2010)

Context Emerging technologies, changing diagnostic and treatment patterns, and changes in Medicare reimbursement are contributing to increasing use of imaging in cancer.Imaging is the fastest growing expense for Medicare but has not been examined among beneficiaries with cancer.Objective To examine changes in the use of imaging and how those changes contribute to the overall cost of cancer care.Design, Setting, and Patients Analysis of a nationally representative 5% sample of claims from the US Centers for Medicare & Medicaid Services from 1999 through 2008.Patients were Medicare beneficiaries with incident breast cancer, colorectal cancer, leukemia, lung cancer, non-Hodgkin lymphoma, or prostate cancer. Main Outcome Measures Use and cost of imaging by modality, year, and cancer type.Results There were 100 954 incident cases of breast cancer, colorectal cancer, leukemia, lung cancer, non-Hodgkin lymphoma, and prostate cancer from 1999 through 2006.Significant mean annual increases in imaging use occurred among all cancer types for positron emission tomography (35.9%-53.6%),bone density studies (6.3%-20.0%),echocardiograms (5.0%-7.8%),magnetic resonance imaging (4.4%-11.5%),and ultrasound (0.7%-7.4%).Conventional radiograph rates decreased or stayed the same.As of 2006, beneficiaries with lung cancer and beneficiaries with lymphoma incurred the largest overall imaging costs, exceeding a mean of $3000 per beneficiary within 2 years of diagnosis.By 2005, one-third of beneficiaries with breast cancer underwent bone scans and half of beneficiaries with lung cancer or lymphoma underwent positron emission tomography scans.Mean 2-year imaging costs per beneficiary increased at a rate greater than the increase in mean total costs per beneficiary for all cancer types. ConclusionImaging costs among Medicare beneficiaries with cancer increased from 1999 through 2006, outpacing the rate of increase in total costs among Medicare beneficiaries with cancer.
Mouse Bone Marrow Derived Mesenchymal Stem Cells Supress Airway Inflammation In Both Chronic and Acute Murine Asthma Model
Authors: Tunc Akkoc, Ismail Ogulur, Gulben Gurhan, Ayca Aksoy, Gokhan Duruksu, Deniz Filinte, Erdem Kombak, Isil B. Barlan, Erdal Karaoz
Journal: Journal of Allergy and Clinical Immunology (2014)
The Cardiac Arrhythmia Suppression Trial (CAST)
Authors: Jeremy N. Ruskin
Journal: New England Journal of Medicine (1989)

The Cardiac Arrhythmia Suppression Trial (CAST) was designed to examine the hypothesis that suppressing asymptomatic or mildly symptomatic ventricular ectopic activity after myocardial infarction would reduce the rate of sudden death. CAST, which was preceded by a well-designed feasibility study, the Cardiac Arrhythmia Pilot Study,1 is the first long-term, multicenter, multidrug, placebo-controlled trial of the safety and efficacy of antiarrhythmic drug therapy in reducing the risk of sudden death.2 The preliminary results, as presented in the media and in expanded form in this issue of the Journal,2 have astounded most observers and challenge much of the conventional wisdom about . . .
The Coronary Drug Project
Authors: E. Scheiffele
Journal: JAMA (1972)

<h3>To the Editor.—</h3> The Coronary Drug Project's report (220:996, 1972) of long-term therapy with dextrothyroxine sodium refers to calorigenic effects due to levothyroxine sodium contamination as possible explanation for the adverse effects. This observation has led to the discontinuation of the drug regimen in the project. We have assayed several samples of the dextrothyroxine commercially available in the United States by a modification of a very sensitive method<sup>1</sup>that allows detection of levothyroxine contamination as low as 0.1%. The dextrothyroxine preparations we tested were found to contain 0.8% to 1.0% of levothyroxine. Daily doses of 6 mg of dextrothyroxine sodium thus contain up to 60μg levothyroxine sodium, an amount that may very well exert calorigenic effects significant in regard to aggravation of coronary heart disease.
Palliative options of last resort: a comparison of voluntarily stopping eating and drinking, terminal sedation, physician-assisted suicide, and voluntary active euthanasia
Authors: T. E. Quill
Journal: JAMA (1997)

Palliative care is generally agreed to be the standard of care for the dying, but there remain some patients for whom intolerable suffering persists. In the face of ethical and legal controversy about the acceptability of physician-assisted suicide and voluntary active euthanasia, voluntarily stopping eating and drinking and terminal sedation have been proposed as ethically superior responses of last resort that do not require changes in professional standards or the law. The clinical and ethical differences and similarities between these 4 practices are critically compared in light of the doctrine of double effect, the active/passive distinction, patient voluntariness, proportionality between risks and benefits, and the physician's potential conflict of duties. Terminal sedation and voluntarily stopping eating and drinking would allow clinicians to remain responsive to a wide range of patient suffering, but they are ethically and clinically more complex and closer to physician-assisted suicide and voluntary active euthanasia than is ordinarily acknowledged. Safeguards are presented for any medical action that may hasten death, including determining that palliative care is ineffective, obtaining informed consent, ensuring diagnostic and prognostic clarity, obtaining an independent second opinion, and implementing reporting and monitoring processes. Explicit public policy about which of these practices are permissible would reassure the many patients who fear a bad death in their future and allow for a predictable response for the few whose suffering becomes intolerable in spite of optimal palliative care.
Parents claiming a link between MMR vaccine and autism lose final appeal for legal aid
Authors: Clare Dyer
Journal: BMJ (2004)

Families who blame the measles, mumps, and rubella triple vaccine (MMR vaccine) for their children's autism lost their final appeal for legal aid funding last week.

But 11 families who claim the vaccine caused other conditions—such as epilepsy, encephalitis, and deafness—or who allege that their children were injured by earlier versions of the MMR vaccine which are now withdrawn, won funding to investigate the prospects of a claim against the vaccine's manufacturers.

The Funding Review Committee, which hears appeals against decisions by the Legal Services Commission (LSC) to …
Anabolic Steroid Use Among Male High School Seniors
Authors: Michael P Eriksen
Journal: JAMA (1989)

<h3>To the Editor. —</h3> Documenting the prevalence of substance abuse is the first step in developing effective prevention strategies. In this regard, the article by Buckley et al<sup>1</sup>made a positive contribution to the control and prevention of steroid use among male high school seniors. This article received considerable publicity for its findings, largely from the authors' suggestion that extrapolation of its survey results indicated that 250 000 to 500 000 male adolescents in this country are presently using anabolic steroids. Of course, both the broadcast and print media chose to emphasize the higher estimate. In reviewing this article, we feel that the ability to generalize their results and the corresponding national prevalence estimates must be questioned because of the manner in which the sample was selected. The sample of high schools selected for study was restricted to those that employ a certified athletic trainer. Further, it was noted