tbuckley/cabot-search huggingface dataset:
Letter by Cen Regarding Article, “Effect of Celecoxib on Cardiovascular Events and Blood Pressure in Two Trials for the Prevention of Colorectal Adenomas”
Authors: Ye-Ying Cen
Journal: Circulation (2007)

To the Editor:I read with interest the paper by Solomon et al 1 in which the authors have combined the analysis results of 2 independent trials, Adenoma Prevention With Celecoxib (APC) 2 and Prevention of Colorectal Sporadic Adenomatous Polyps (PreSAP), 3 in an attempt to estimate cardiovascular events (CVs) associated with celecoxib across 3 different dose regimens.I am concerned about the validity of their combined analysis and their conclusion that celecoxib at 200 or 400 mg twice daily (APC) or at 400 mg once daily (PreSAP) showed a nearly 2-fold increase in CV risk.First, patients in APC differed significantly from patients in PreSAP regarding some very important baseline clinical characteristics-including prevalence of hypertension, smoking, lowdose aspirin use, and lipid-lowering drug use-that are known to be possible predictors of CV events.For example, 414 patients (31%) in APC were on low-dose aspirin compared with 159 patients (17%) in PreSAP.Five hundred sixteen patients (38%) in APC were on lipid-lowering drugs compared with 159 patients (17%) in PreSAP.We do not know whether increased CV events in APC were caused by drug interactions with celecoxib.We do know that CV risk was the greatest for patients with a history of CVs at baseline.To justify a combined hazard ratio, the authors ran 2 Cox models to compare the 2 dose arms in APC and to compare APC with PreSAP.The large differences among the hazard ratios (3.4,2.6, and 1.3) made it unconvincing that one could combine those results, even though the heterogeneity tests were insignificant.The relatively small probability value (0.13) suggests some difference.It may not be appropriate to apply the conclusion drawn from the combined estimate to both patient populations.My other concerns involve modeling issues.The authors do not report the interactions between low-dose aspirin use with celecoxib or between lipid-lowering drugs with celecoxib.Furthermore, we do not know how their stratified model was derived and which covariates were included.We also do not know which covariates were used for the 2 Cox models to generate the 2 hazard ratios that they combined.With access to complete data from both trials, the authors could have performed a much more rigorous and comprehensive statistical analysis by fitting a Cox regression model to the entire data from both trials.In this model, with complete data, the authors could have formally tested the validity of combining the 3 dose regimens and derived a more statistically sound combined hazard ratio for the entire dataset.Furthermore, the authors could have potentially investigated the dose effect, and this might have provided a better summary of the drug safety.The authors have made an important contribution to our understanding of the adverse effects of celecoxib at 400-and 800-mg doses.I look forward to additional results from their collaboration.
A piece of my mind. Her daughter, her doctor
Authors: M. Khankhoje
Journal: JAMA (1991)

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 Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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) 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
Left ventricular pressure-dimension relationships in the conscious dog
Authors: L. D. HORWITZ, V. S. BISHOP
Journal: Cardiovascular Research (1972)

The dynamic function of the left ventricle was described in terms of internal diameter, pressure, and flow in conscious sedated dogs at rest and during isoproterenol and metaraminol infusions. The diastolic pressure-diameter curve was sigmoidal in shape, negative in pressure in early diastole, and affected by viscous, and probably inertial, forces.
Trends in anti‐D immune globulin for childhood immune thrombocytopenia: Usage, response rates, and adverse effects
Authors: Michelle Long, Leslie A. Kalish, Ellis J. Neufeld, Rachael F. Grace
Journal: American Journal of Hematology (2011)

In 2010, the Food and Drug Administration (FDA) added a black box warning to anti-D immune globulin (Rho(D) immune globulin, anti-D) for immune thrombocytopenia (ITP) to warn of the complications related to severe hemolysis. The objective of this retrospective medical record review was to examine recent trends in anti-D use to treat ITP and rates of adverse events in a single large pediatric hematology program. Over a 7-year period, 176 (35%) of 502 ITP patients at our center received anti-D. Anti-D was the second most commonly prescribed drug for ITP from 2003 to 2010 overall and was given first most frequently (41%). Sixty-four percent of patients responded to anti-D, but 36% had adverse effects, including five patients requiring hospitalization. From 2003 to 2010, the use of anti-D as an initial therapy for ITP significantly decreased (P < 0.001). This trend preceded the 2010 FDA black box warning. In our experience, anti-D was associated with a significant number of adverse effects when used as a treatment for ITP, although none were life-threatening. Despite recent guidelines suggesting anti-D therapy for initial treatment for ITP, anti-D therapy for ITP has significantly decreased over the past 7 years.
Neurocysticercosis — Is the Elimination of Parasites Beneficial?
Authors: Julio Sotelo
Journal: New England Journal of Medicine (2004)

Taenia solium causes two different diseases. When the adult cestode infests the human intestine, taeniasis develops; it is generally asymptomatic, but the host becomes a continuous source of taenia eggs, which are expelled every day in the feces, which may then contaminate vegetables and food in areas with poor sanitary conditions. Cysticercosis develops when humans or pigs ingest food contaminated with taenia eggs, which cross the digestive tract, enter the circulation, and lodge in the tissues (usually the brain or muscles). Humans are the only hosts for the cestode, whereas both humans and pigs are hosts for the embryo. The . . .
Effect of Artificial Pacing of the Heart on Cardiac and Renal Function
Authors: J. O. HUMPHRIES, E. J. HINMAN, L. BERNSTEIN, W. G. WALKER
Journal: Circulation (1967)

Six patients with complete heart block provided an opportunity to study renal hemodynamic responses to increases in heart rate produced by an artificial pacemaker. Observations were made at rest and following exercise during idioventricular rhythm and slow rates and were repeated after increasing the rate to 70/min by means of an artificial pacemaker. Ability to excrete a water load was impaired at the slow idioventricular rate; this was associated with a reduced glomerular filtration rate. No acute improvement in renal function occurred with pacemaker-induced increase in heart rate except in the presence of congestive heart failure. With long-term pacing (7 to 8 months), the glomerular filtration rate and the ability to excrete solute-free water increased in all patients studied. The acute increase in free water clearance which occurred with increased heart rate in the presence of congestive heart failure suggests that decreased renal perfusion may be responsible for the inability to excrete excess water. The dilutional hyponatremia in congestive heart failure may be explained on this basis. Changes in indices of cardiac function in these patients were similar to those reported by others. No change in resting cardiac output occurred at heart rates between 40 and 70/min in the absence of congestive heart failure. The response to exercise, however, was greater at the higher rates.
Antibody-Mediated Delivery of Anti–<i>KRAS</i>-siRNA <i>In Vivo</i> Overcomes Therapy Resistance in Colon Cancer
Authors: Sebastian Bäumer, Nicole Bäumer, Neele Appel, Lisa Terheyden, Julia Fremerey, Sonja Schelhaas, Eva Wardelmann, Frank Buchholz, Wolfgang E. Berdel, Carsten Müller-Tidow
Journal: Clinical Cancer Research (2015)

KRAS mutations are frequent driver mutations in multiple cancers. KRAS mutations also induce anti-EGFR antibody resistance in adenocarcinoma such as colon cancer. The aim of this study was to overcome anti-EGFR antibody resistance by coupling the antibody to KRAS-specific siRNA.The anti-EGFR antibody was chemically coupled to siRNA. The resulting complex was tested for antibody binding efficiency, serum stability and ability to deliver siRNA to EGFR-expressing cells. Western blotting, viability, apoptosis, and colony formation assays were performed for efficacy evaluation in vitro. Furthermore, therapeutic activity of the antibody-KRAS-siRNA complexes was examined in in vivo xenograft mouse tumor models.Antibody-siRNA complexes were targeted and internalized via the EGFR receptor. Upon internalization, target gene expression was strongly and specifically repressed, followed by a reduced proliferation and viability, and induced apoptosis of the cells in vitro. Clonogenic growth of mutant KRAS-bearing cells was suppressed by KRAS-siRNA-anti-EGFR antibody complexes. In xenograft mouse models, anti-EGFR antibody-KRAS-siRNA complexes significantly slowed tumor growth in anti-EGFR-resistant cells.The coupling of siRNA against KRAS to anti-EGFR antibodies provides a novel therapy approach for KRAS-mutated EGFR-positive cancer cells in vitro and in vivo. These findings provide an innovative approach for cancer-specific siRNA application and for enhanced therapeutic potential of monoclonal antibody therapy and personalized treatment of cancer entities.
TISSUE DOPPLAR-DERIVED E/E' RATIO AT STENT IMPLANTATION IS A POWERFUL PREDICTOR OF IN-STENT RESTENOSIS IN PATIENTS WITH CORONARY ARTERY DISEASE
Authors: Naohiro Komura, Kenichi Tsujita, Kenshi Yamanaga, Kenji Sakamoto, Sunao Kojima, Shinji Tayama, Koichi Kaikita, Seiji Hokimoto, Kiyoshi Hibi, Kazuo Kimura, Satoshi Umemura, Hisao Ogawa
Journal: Journal of the American College of Cardiology (2014)
LENGTH OF HOSPITALIZATION WITH VARIOUS TREATMENTS FOR DEPRESSION
Authors: DONALD C. LANGSLEY, HELLE SIIRDMA
Journal: American Journal of Psychiatry (1965)

The findings show that treatment of neurotic or psychotic depression with tranylcypromine or imipramine results in a shorter hospitalization than treatment with EST. Because we found that the length of hospitalization was approximately equal with either group, our original hypothesis that the hospitalization would be shorter with tranylcypromine than with imipramine was negated. It should be repeated that degress of improvement or efficacy of treatment were not tested other than by assuming that sending the patient home from the hospital meant that a reasonable degree of improvement or recovery from the depression had been attained.
Chondrogenesis of periodontal ligament stem cells by transforming growth factor-β3 and bone morphogenetic protein-6 in a normal healthy impacted third molar
Authors: Sunyoung Choi, Tae-Jun Cho, Soon-Keun Kwon, Gene Lee, Jaejin Cho
Journal: International Journal of Oral Science (2013)

The periodontal ligament-derived mesenchymal stem cell is regarded as a source of adult stem cells due to its multipotency. However, the proof of chondrogenic potential of the cells is scarce. Therefore, we investigated the chondrogenic differentiation capacity of periodontal ligament derived mesenchymal stem cells induced by transforming growth factor (TGF)-β3 and bone morphogenetic protein (BMP)-6. After isolation of periodontal ligament stem cells (PDLSCs) from human periodontal ligament, the cells were cultured in Dulbecco's modified Eagle's medium (DMEM) with 20% fetal bovine serum (FBS). A mechanical force initiated chondrogenic differentiation of the cells. For chondrogenic differentiation, 10 µg⋅L−1 TGF-β3 or 100 µg⋅L−1 BMP-6 and the combination treating group for synergistic effect of the growth factors. We analyzed the PDLSCs by fluorescence-activated cell sorting and chondrogenesis were evaluated by glycosaminoglycans assay, histology, immunohistochemistry and genetic analysis. PDLSCs showed mesenchymal stem cell properties proved by FACS analysis. Glycosaminoglycans contents were increased 217% by TGF-β3 and 220% by BMP-6. The synergetic effect of TGF-β3 and BMP-6 were shown up to 281% compared to control. The combination treatment increased Sox9, aggrecan and collagen II expression compared with not only controls, but also TGF-β3 or BMP-6 single treatment dramatically. The histological analysis also indicated the chondrogenic differentiation of PDLSCs in our conditions. The results of the present study demonstrate the potential of the dental stem cell as a valuable cell source for chondrogenesis, which may be applicable for regeneration of cartilage and bone fracture in the field of cell therapy. Human stem cells taken from the connective tissue that attaches teeth to the underlying bone can give rise to new cartilage. Because such tissue can be obtained fairly easily during dental surgery, the findings—reported by Jaejin Cho and his co-workers at the Seoul National University, Korea—suggest that patient-specific dental stem cells could provide a personalized way to treat a number of cartilage and bone disorders. Cho's team isolated dental stem cells from the connective tissue, or periodontal fibers, attached to an impacted third molar taken from an otherwise healthy donor. They added growth factors to induce a process called 'chondrogenesis' and ran a battery of genetic, chemical and histological tests to demonstrate that the cells had taken the first steps toward cartilage formation.
Patients with learning disability in the community
Authors: T. J Aspray, R. M Francis, S. P Tyrer, S. J Quilliam
Journal: BMJ (1999)

Letters pp 536

Over the past 20 years we have witnessed the closure of large residential hospitals for adults with mental handicap and an exodus from these institutions into community care. This move wasmotivated by a desire to give people with handicaps the opportunity to live as normal a life as possible.1 However, concerns have been expressed by the Department of Health,2 some psychiatrists,3 and patients themselves4 about the change.

Adults with learning disability are more prone than the rest of the population to chronic health problems, including epilepsy, dementia, hepatitis, peptic ulcer, dysphagia, and problems relatedto sensory impairment.5 Age related diseases such as stroke, cardiovascular disease, and malignancy will also be of growing concern as life expectancy increases. Many may be surprised to learn that in the Netherlands mental retardation is the greatest single source of …
Atrial fibrillation in heart failure patients: Prevalence in daily practice and effect on the severity of symptoms. Data from the ALPHA study registry
Authors: Gaetano M. De Ferrari, Catherine Klersy, Paolo Ferrero, Cecilia Fantoni, Diego Salerno‐Uriarte, Lorenzo Manca, Paolo Devecchi, Giulio Molon, Miriam Revera, Antonio Curnis, Simona Sarzi Braga, Francesco Accardi, Jorge A. Salerno‐Uriarte
Journal: European Journal of Heart Failure (2006)
Telomere length predicts cardiovascular disease
Authors: I. Spyridopoulos, T. von Zglinicki
Journal: BMJ (2014)

Measurement in humans is unlikely to be useful until we find out how and why

Atherosclerosis is an age related disease characterised by systemic oxidative stress and low grade chronic inflammation. Telomeres consist of DNA repeats at the ends of chromosomes, which shorten with every cell division. They can reach a critically short length, precipitating a form of cellular decline and ageing called cell senescence.

Evidence that oxidative stress drives telomere shortening in human cells led to the suggestion that telomere length in peripheral blood cells might be a marker for age related risk of mortality and morbidity and, specifically, for cardiovascular diseases.1 In their paper, Haycock and coauthors (doi:10.1136/bmj.g4227) present the first meta-analysis that integrates data from 24 individual studies on the link between telomere length and cardiovascular risk.2 As expected, the authors found an inverse relationship between telomere length within leucocytes and risk of coronary heart disease. Importantly, this association remained significant in analyses confined to prospective studies and was independent of conventional vascular risk factors. However, short telomeres did not predict risk of cerebrovascular disease.

The harmonisation of data from …
Genotoxicants Target Distinct Molecular Networks in Neonatal Neurons
Authors: Glen E. Kisby, Antoinette Olivas, Melissa Standley, Xinfang Lu, Patrick Pattee, Jean O’Malley, Xiaorong Li, Juan Muniz, Srinavasa R. Nagalla
Journal: Environmental Health Perspectives (2006)

Exposure of the brain to environmental agents during critical periods of neuronal development is considered a key factor underlying many neurologic disorders.In this study we examined the influence of genotoxicants on cerebellar function during early development by measuring global gene expression changes.We measured global gene expression in immature cerebellar neurons (i.e., granule cells) after treatment with two distinct alkylating agents, methylazoxymethanol (MAM) and nitrogen mustard (HN2). Granule cell cultures were treated for 24 hr with MAM (10-1,000 microM) or HN2 (0.1-20 microM) and examined for cell viability, DNA damage, and markers of apoptosis.Neuronal viability was significantly reduced (p < 0.01) at concentrations > 500 microM for MAM and > 1.0 microM for HN2; this correlated with an increase in both DNA damage and markers of apoptosis. Neuronal cultures treated with sublethal concentrations of MAM (100 microM) or HN2 (1.0 microM) were then examined for gene expression using large-scale mouse cDNA microarrays (27,648). Gene expression results revealed that a) global gene expression was predominantly up-regulated by both genotoxicants; b) the number of down-regulated genes was approximately 3-fold greater for HN2 than for MAM; and c) distinct classes of molecules were influenced by MAM (i.e, neuronal differentiation, the stress and immune response, and signal transduction) and HN2 (i.e, protein synthesis and apoptosis).These studies demonstrate that individual genotoxicants induce distinct gene expression signatures. Further study of these molecular networks may explain the variable response of the developing brain to different types of environmental genotoxicants.
ACTINOMYCOSIS OF THE ABDOMINAL WALL
Authors: HENRY ALBERT
Journal: JAMA (1923)

Reports of cases of actinomycosis of the abdominal wall are so rare, and the features are so significant, that the recording of two new cases and a brief discussion of the subject seems to us to be worth while. Actinomycosis of the abdominal wall is probably always secondary to the involvement of the gastro-intestinal tract, chiefly in the region of the appendix or cecum. Nevertheless, there are cases in which the first symptoms, at least those of a focal or localizing type, are referred to the abdominal wall rather than to some organ within that cavity. In other cases, the involvement of the wall is so extensive, as compared to that within the cavity, as entirely to overshadow the latter. <h3>REPORTS OF CASES</h3><h3>Case 1 (by J. W. H.).</h3> —K. S., a girl, aged 11, had initial symptoms of acute appendicitis. Jan. 29, 1917, the third day of illness, a
Troubles in Medical Academe
Authors: Alfred Coodley
Journal: JAMA (1976)

To the Editor.—  I would take issue, in part as Dr Hussey has, with what Dr Davis said in his original comments (236:388, 1976). There is no question that many of the leading medical schools, in addition to Harvard, have taken the position that it is their obligation to allow students of minority groups to enter despite lower than usual grade point averages and performances on medical aptitude tests.  Such schools feel that every American, despite his or her racial background, should be fully entitled to receive a medical education. Obviously, they realize that tutoring facilities for such students throughout medical school may be necessary, since these students may not have had the opportunity or motivation to acquire the modus operandi to apply themselves consistently. This often stems from the low socioeconomic, cultural, and scientific milieu in which many have lived for long years, coupled with their own minimal expectation
Long-term protection of ischaemic myocardium by nitroglycerin ointment
Authors: M. CHIARIELLO, G. BREVETTI, G. AMBROSIO, A. CATAFFO, U. POLLICE, M. CONDORELLI
Journal: Cardiovascular Research (1984)

To assess whether the reduction in ischaemic injury during acute myocardial infarction induced by nitroglycerin (NTG) results in a decrease in tissue necrosis, 96 rats were assigned to two groups. The first group (n=34) was sham-operated. The second group of 62 rats was randomised in a ratio of 2:1 into control (n=43) and treated (n=19) subgroups following coronary artery occlusion. Treated animals received an application of 2% NTG ointment every 8 h immediately post-occlusion. All rats were killed 48 h after coronary artery occlusion and total creatine kinase activity (CK) of the left ventricle (LV) was measured. Infarct size calculated by CK depletion was 65.2±14.3% (mean±SD) of LV in control rats, and 51.6±14.0% of LV in NTG-treated (p<0.02). In a further series of 46 rats with coronary occlusion, the area of infarcted myocardium 21 days post-occlusion was assessed by planimetry on histological sections. In rats with control occlusion (n=22), the extent of infarction was 30.6±4.8% of LV, and in NTG-treated rats (n=24) it was 16.2±5.8% of LV (p<0.001). The amount of scar tissue in the infarcted myocardium 21 days post-occlusion was also determined by measuring LV hydroxyproline and collagen content in an additional 32 rats randomly assigned to a control (n=11), a NTG-treated (n=9) and a sham-operated group (n=12). By this method, infarct size 21 days post-coronary occlusion was 37.4±2.6% of LV in control animals and 22.3±2.6% of LV in NTG-treated animals (p<0.001). In conclusion, this study shows that NTG given as 2% ointment to rats with coronary occlusion may protect myocardium from ischaemic necrosis, and that this effect is sustained, resulting in the formation of smaller scars.