tbuckley/cabot-search huggingface dataset:
Ipilimumab Plus Sargramostim vs Ipilimumab Alone for Treatment of Metastatic Melanoma
Authors: F. Stephen Hodi, Sandra Lee, David F. McDermott, Uma N. Rao, Lisa H. Butterfield, Ahmad A. Tarhini, Philip Leming, Igor Puzanov, Donghoon Shin, John M. Kirkwood
Journal: JAMA (2014)

Cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) blockade with ipilimumab prolongs survival in patients with metastatic melanoma. CTLA-4 blockade and granulocyte-macrophage colony-stimulating factor (GM-CSF)-secreting tumor vaccine combinations demonstrate therapeutic synergy in preclinical models. A key unanswered question is whether systemic GM-CSF (sargramostim) enhances CTLA-4 blockade.To compare the effect of ipilimumab plus sargramostim vs ipilimumab alone on overall survival (OS) in patients with metastatic melanoma.The Eastern Cooperative Oncology Group (ECOG) conducted a US-based phase 2 randomized clinical trial from December 28, 2010, until July 28, 2011, of patients (N = 245) with unresectable stage III or IV melanoma, at least 1 prior therapy, no central nervous system metastases, and ECOG performance status of 0 or 1.Patients were randomized to receive ipilimumab, 10 mg/kg, intravenously on day 1 plus sargramostim, 250 μg subcutaneously, on days 1 to 14 of a 21-day cycle (n = 123) vs ipilimumab alone (n = 122). Ipilimumab treatment included induction for 4 cycles followed by maintenance every fourth cycle.Primary end point: comparison of length of OS. Secondary end point: progression-free survival (PFS), response rate, safety, and tolerability.Median follow-up was 13.3 months (range, 0.03-19.9). Median OS as of December 2012 for ipilimumab plus sargramostim was 17.5 months (95% CI, 14.9-not reached) vs 12.7 months (95% CI, 10.0-not reached) for ipilimumab. The 1-year survival rate for ipilimumab plus sargramostim was 68.9% (95% CI, 60.6%-85.5%) compared to 52.9% (95% CI, 43.6%-62.2%) for ipilimumab alone (stratified log-rank 1-sided P = .01; mortality hazard ratio 0.64 [1-sided 90% repeated CI, not applicable-0.90]). A planned interim analysis was conducted at 69.8% of expected events (104 observed with 149 expected deaths). Planned interim analysis using the O'Brien-Fleming boundary was crossed for improvement in OS. There was no difference in PFS. Median PFS for ipilimumab plus sargramostim was 3.1 months (95% CI, 2.9-4.6) vs 3.1 months (95% CI, 2.9-4.0) for ipilimumab alone. Grade 3 to 5 adverse events occurred in 44.9% (95% CI; 35.8%-54.4%) of patients in the ipilimumab plus sargramostim group vs 58.3% (95% CI, 49.0%-67.2%) of patients in the ipilimumab-alone group (2-sided P = .04).Among patients with unresectable stage III or IV melanoma, treatment with ipilimumab plus sargramostim vs ipilimumab alone resulted in longer OS and lower toxicity, but no difference in PFS. These findings require confirmation in larger studies with longer follow-up.clinicaltrials.gov Identifier: NCT01134614.
Nitric Oxide in Cirrhosis
Authors: Jaye P.F. Chin-Dusting
Journal: Annals of Internal Medicine (1998)

Letters15 June 1998Nitric Oxide in CirrhosisJaye P.F. Chin-Dusting, PhD and Brindi Rasaratnam, MBBSJaye P.F. Chin-Dusting, PhDBaker Medical Research Institute; Victoria, AustraliaAlfred Hospital; Victoria, AustraliaSearch for more papers by this author and Brindi Rasaratnam, MBBSBaker Medical Research Institute; Victoria, AustraliaAlfred Hospital; Victoria, AustraliaSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-128-12_Part_1-199806150-00022 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail IN RESPONSE:We agree that endotoxin (and NO) may be only partly responsible for the findings we observed. It is also likely that the cardiovascular abnormalities stem from many mechanisms and that they depend on disease severity. In a previous study of cirrhotic patients with normal basal forearm blood flow, responses to acetylcholine were significantly attenuated [1]. This finding occurred concurrently with evidence that smooth muscle-derived NO concentrations were elevated. Responses to the NO synthase inhibitor NG -monomethyl-L-arginine (L-NMMA) were unaffected. In our study, the patients exhibited increased peripheral vasodilation, enhanced responses to L-NMMA and acetylcholine, and increased plasma nitrite ...References1. Ryan J, Jennings G, Dudley F, Chin-Dusting J. Smooth muscle derived nitric oxide is elevated in isolated forearm veins in human alcoholic cirrhosis. Clin Sci. 1996; 91:23-8. Google Scholar2. Kessler P, Baucrsaxhs J, Busse R, Schini-Kerth VB. Inhibition of inducible nitric oxide synthase restores endothelium-dependent relaxations in proinflammatory mediator-induced blood vessels. Arterioscler Thromb Vasc Biol. 1997; 17:1746-55. Google Scholar3. Farinati F, De Maria N, Marafin C, Fagiuoli S, Della Libera G, Naccarato R. Hepatocellular carcinoma in alcoholic cirrhosis: is sex hormone imbalance a pathogenetic factor? Eur J Gastroenterol Hepatol. 1995; 7:145-50. Google Scholar4. Taddei S, Virdis A, Ghiadoni L, Mattei P, Sudano I, Berminin G, et al. Menopause is associated with endothelial dysfunction in women. Hypertension. 1996; 28:576-82. Google Scholar Author, Article, and Disclosure InformationAuthors: Jaye P.F. Chin-Dusting, PhD; Brindi Rasaratnam, MBBSAffiliations: Baker Medical Research Institute; Victoria, AustraliaAlfred Hospital; Victoria, Australia PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 15 June 1998Volume 128, Issue 12_Part_1Page: 1046-1047KeywordsAcetylcholineBlood flowBlood plasmaEndotoxemiaEndotoxinsEstradiolNitratesNitric oxideRenal failureVasodilation ePublished: 15 August 2000 Issue Published: 15 June 1998 Copyright & PermissionsCopyright © 1998 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Dangerous to Your Health
Authors: R. C. Derbyshire
Journal: JAMA (1978)

To the Editor.—  Because of several articles that have recently been published emphasizing the negative aspects of continuing medical education (CME), one might conclude that a paraphrase of the warning in cigarette advertisements should appear in each program. It might read as follows:  faculty has determined that continuing education is dangerous to your mental health.  The article by Stross and Harlan entitled  Impact of Mandatory Continuing Medical Education (239:2663, 1978) is no exception. The authors have joined the chorus of people who claim that no one has proved that CME causes changes in the habits of practice of physicians or that they even learn anything from their efforts. I dispute these claims. Habits of practice tend to change gradually rather than overnight. Furthermore, individuals learn in various ways. Regardless of methods, however, all improvements in practice are due to some form of continuing education so that with present
Venous pressure changes during orthostasis
Authors: P. AVASTHEY
Journal: Cardiovascular Research (1972)

Pressure measurements were made in the right atrium, vena cavae, and internal jugular vein in supine and erect positions in eight normal subjects and two patients with massive pericardial effusion. The pressures were identical at the above sites in supine position. On assumption of the erect posture, pressure decreased in veins superior to the heart and became negative (— 7 to —18 cm, average — 11 cm H2O) in the superior vena cava in subjects with essentially normal cardiovascular systems. A marked increase in pressure (9 to 21 cm, average 15 cm H2O) was observed in the internal jugular vein in these subjects just superior to the thoracic inlet above which pressure either remained close to atmospheric level or decreased by 1 cm H2O/cm vertical height. This venous pressure gradient across the thoracic inlet is due to potential collapse of the internal jugular vein which results from decrease in the transmural pressure of the vein in the neck in erect posture. No such gradient was observed in the two subjects with massive pericardial effusion when erect as the elevated venous pressure maintained positive transmural pressure throughout the venous system in all body positions.
The Safety of Roundup Pesticide-Reply
Authors: Marion Moses
Journal: JAMA (1989)

In Reply.—  Because of inadequate studies submitted to the Environmental Protection Agency for the registration of glyphosate in 1972, its oncogenicity status is not fully known. The class D listing, which also means not classifiable as to human carcinogenicity, is interim, and repeated studies are in progress. Glyphosate is contaminated with N -nitroso-glyphosate, but the Environmental Protection Agency decided not to require separate testing of this nitrosamine contaminant. In regard to the World Health Organization's conclusion, a substance can be an oncogen and not a carcinogen.  California has its own pesticide registration division. The California Department of Food and Agriculture classifies glyphosate as a mouse oncogen, and considers unacceptable a chronic effects study accepted by the Environmental Protection Agency. 1   In regard to the effects of Roundup on the skin, a letter (dated July 26, 1988) from Edwin Tinsworth of the Environmental Protection Agency to Dr Timothy Long of Monsanto,
Point: Diabetic Patients and Coronary Calcium
Authors: Matthew J. Budoff
Journal: Diabetes Care (2003)

The use of electron beam tomography (EBT) is becoming increasingly accepted for risk stratification in the asymptomatic patient (1). Coronary artery calcium (CAC), as measured by EBT, has been shown to be a marker of increased risk in every prognostic study published to date, in both symptomatic and asymptomatic cohorts (2). The relationship of CAC to angiographic disease holds the same tight correlation in persons with diabetes as in nondiabetic patients (3), suggesting that the risk stratification with EBT will be as robust in individuals with diabetes as in others. The only prognostic study of EBT and diabetes published to date demonstrates that diabetic subjects with CAC were four times more likely to suffer a cardiac event than nondiabetic subjects with low calcium scores ( P < 0.001) (4).

The new National Cholesterol Education Panel (NCEP) guidelines (5) support the conclusions of the Prevention Conference V and the American College of Cardiology (ACC)/American Heart Association (AHA) report that high coronary calcium scores signify and confirm increased risk for future cardiac events. “Therefore, measurement of coronary calcium is an option for advanced risk assessment in appropriately selected persons. In persons with multiple risk factors, high …
(5) Delayed cold urticaria
Authors: C.N.A. Matthews, R.P. Warin
Journal: British Journal of Dermatology (1977)

Journal Article (5) Delayed cold urticaria Get access C.N.A. Matthews, C.N.A. Matthews Bristol Royal Infirmary Search for other works by this author on: Oxford Academic Google Scholar R.P. Warin R.P. Warin Bristol Royal Infirmary Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 97, Issue s15, 1 December 1977, Pages 32–33, https://doi.org/10.1111/j.1365-2133.1977.tb14313.x Published: 01 December 1977
Elastase contributes to antigen-induced mucociliary dysfunction in ovine airways.
Authors: T G O'Riordan, R Otero, Y Mao, I Lauredo, W M Abraham
Journal: American Journal of Respiratory and Critical Care Medicine (1997)

Antigen-induced bronchoconstriction is associated with impairment of mucociliary clearance with a time course that is consistent with the initial influx of neutrophils into the airway. In this study we tested the hypothesis that elastase released from activated neutrophils contributes to the acute (0 to 6-hr) antigen-induced mucociliary dysfunction. Tracheal mucous velocity CTMV), an index of mucociliary function, was measured with a roentgenographic technique before and serially after airway challenge with Ascaris suum antigen alone, or after pretreatment with aerosolized alpha1-protease inhibitor (alpha1-PI, 10 mg) or the specific neutrophil elastase inhibitor ICI 200,355 (10 mg). Antigen alone significantly decreased TMV. Treatment with either alpha1-PI or ICI 200,355, given either at 30 min before antigen challenge or 1 h after challenge, significantly attenuated the antigen-induced reduction in TMV at 6 h after challenge, whereas sheep treated with inactivated alpha1-PI were not protected from this antigen-induced event. Inhalation of ovine elastase (obtained from stimulated neutrophils) significantly decreased TMV, and this effect was also blocked by pretreatment with alpha1-PI. Both alpha1-PI and ICI 200,355 inhibited the activity of elastase obtained from stimulated ovine neutrophils. To verify that the neutrophil numbers and elastase activity increased in sheep airways after antigen challenge, nine animals underwent bronchoalveolar lavage (BAL) at 2 h and 4 h after instillation of A. summ antigen. Four hours after challenge, the number of neutrophils had increased by 50-fold, and free elastase activity in lavage fluid had increased. These data indicate that the antigen-induced impairment of mucociliary clearance is partly dependent on increased elastase activity, and that elastase inhibitors may be useful in protecting against mucociliary dysfunction.
Abstract 473: Elevated cAMP decreases migratory potential in pancreatic cancer cells
Authors: Noah Zimmerman, Ishan Roy, Jessica Wilson, Michael Dwinell
Journal: Cancer Research (2012)

Abstract Pancreatic ductal adenocarcinoma (PDAC) remains one of the most lethal cancers, primarily resulting from inherent, aggressive dissemination. As elevated concentrations of cAMP are known to inhibit cell movement in multiple tissues, we investigated the role of cAMP in regulating migration of model pancreatic cancer cells. Increased cAMP concentrations were induced either through forskolin, an activator of adenylyl cyclase, the cAMP analog 6-bnz-cAMP, or by two phosphodiesterase cyclic nucleotide inhibitors, cilostamide or IBMX. Transwell migration assays demonstrated cAMP elevating agents significantly decreased migration of Panc1, MiaPaCa2, and HPAFII pancreatic cancer cell lines. In Panc1 cells, inhibition was dose-dependent and not significantly different between forskolin, cilostamide, or IBMX treatment. Importantly, a significant decrease in cell migration was also observed in cells treated with 6-bnz-cAMP, a specific activator of protein kinase A. The decrease in migration did not reflect alterations in cell proliferation as cell cycle analysis demonstrated little to no change in proliferation in treated compared to control cells. Similarly, the decrease in cell migration was not a function of programmed cell death as apoptosis was not elevated in cells treated with cAMP elevating agents. Consistent with its known role in F-actin rearrangement, elevated levels of cAMP increased phosphorylated RhoA and the resultant decrease in active RhoA-GTP. As expected, fluorescence microscopy indicated a significant increase in cortical actin formation along the perimeter of forskolin or cilostamide-treated cells. Taken together these data suggest that the novel use of existing anti-inflammatory drugs that target the cAMP signaling networks have the potential to block pancreatic cancer dissemination. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 473. doi:1538-7445.AM2012-473
Normal ranges of angiogenesis regulatory proteins in human platelets
Authors: Jon E. Peterson, David Zurakowski, Joseph E. Italiano, Lea V. Michel, Lucius Fox, Giannoula L. Klement, Judah Folkman
Journal: American Journal of Hematology (2010)

Platelets sequester angiogenesis regulatory proteins early in tumor growth, which suggests a new avenue for monitoring disease. To date, there are no clinically relevant reference ranges for markers of early angiogenesis. We introduce a new ELISA-based method for accurate and reproducible measurement of vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF), platelet factor 4 (PF4), thrombospondin-1 (TSP-1), fibroblast growth factor, basic (bFGF), and endostatin in platelets. To facilitate clinical applicability, the platelet levels in isolated samples were determined utilizing a new actin ELISA method. Platelets from healthy donors at single and repetitive time points were used for the assessment of normal ranges of these proteins. The physiological levels in platelets were: VEGF (0.74 +/- 0.37 pg/10(6) platelets); PDGF (23 +/- 6 pg/10(6)); PF4 (12 +/- 5 ng/10(6)); TSP-1 (31 +/- 12 ng/10(6)); bFGF (0.44 +/- 0.15 pg/10(6)); and endostatin (5.6 +/- 3.0 pg/10(6)). There was an excellent correlation (R(2) = 0.7) between the platelet levels calculated with the actin ELISA and complete blood count. The levels of the platelets were higher than those in platelet-poor plasma by factors of: VEGF (215-fold); PDGF (914-fold); PF-4 (516-fold); TSP-1 (813-fold); and bFGF (17-fold). The endostatin levels were nearly equivalent. The biovariability of the platelet proteins in eight healthy subjects over a 5-week period was found to be minimal. We describe accurate and direct measurements of the concentrations of VEGF, bFGF, PDGF, TSP-1, endostatin, and PF4 in platelets of healthy human subjects. In contrast to the highly variable levels in plasma and serum, the platelet-derived measurements were accurate and reproducible with minimal biovariability.
Lysosomes in Biology and Pathology
Authors: David Lagunoff
Journal: JAMA (1974)

In an elegant introductory essay to the first volume of<i>Lysosomes in Biology and Pathology</i>published in 1969, Christian de Duve wrote of the lysosome: It is a concept, the result of an interaction mediated by a specific assortment of techniques between an observer and an object.... Other investigators looking at the same object with other methods, or even other biochemists exploring it with the same methods, could have arrived at different views. This disclaimer cannot diminish the immense importance to biology of de Duve's discovery of the lysosome or, as he might put it, the discovery of de Duve's concept of the lysosome. Consider for a moment the difficulties that would be encountered in the study of man if the function, no less the existence, of the digestive tract remained unknown. That was essentially the state of knowledge with respect to the cell at the time de Duve set
A 45-Year-Old Woman With Obsessive-Compulsive Disorder
Authors: Michael A. Jenike
Journal: JAMA (2001)

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
Insights into coronary artery disease gained from metabolic imaging.
Authors: H R Schelbert, D Buxton
Journal: Circulation (1988)

Positron emission tomography offers the possibility of evaluating and quantifying regional myocardial blood flow and metabolism. Used in patients with coronary artery disease, positron emission tomography has demonstrated sustained metabolic activity in regions with reduced blood flow and impaired contractile function, and it thereby enables differentiation between viable myocardium and myocardium that has succumbed to necrosis and scar formation. Viable myocardial regions identified by metabolic rather than functional or blood-flow criteria are frequently observed in patients after an acute coronary event and in patients with stable coronary artery disease. Positron emission tomography reflects either acute myocardial ischemia, "hibernation," as well as "myocardial stunning." Findings from metabolic imaging have proved useful in characterizing more accurately coronary artery disease and its functional consequences. These findings have been found equally useful for clinical management.
Myeloma cells block RUNX2/CBFA1 activity in human bone marrow osteoblast progenitors and inhibit osteoblast formation and differentiation
Authors: Nicola Giuliani, Simona Colla, Francesca Morandi, Mirca Lazzaretti, Roberto Sala, Sabrina Bonomini, Maria Grano, Silvia Colucci, Mirija Svaldi, Vittorio Rizzoli
Journal: Blood (2005)
Abstract 4418: The histopathological characteristics of mucin-depleted foci in patients with sporadic colorectal cancer
Authors: Eiji Sakai, Hirokazu Takahashi, Eiji Yamada, Takuma Higurashi, Hidenori Ohkubo, Kunihiro Hosono, Hiroki Endo, Shingo Kato, Atsushi Nakajima, Changxu Cui, Reika Takamatsu, Naoki Yoshimi
Journal: Cancer Research (2012)

Abstract Introduction: In experimental models, Mucin-depleted foci (MDF), formed by dysplastic crypts devoid of mucin production have been recognized to be correlated with colorectal carcinogenesis and to serve as preneoplastic lesions of colorectal cancer (CRC). In humans, there is only one report of identification of MDF mainly in patients with familial adenomatous polyposis, however the histological characteristics of human MDF was not discussed sufficiently in this report. Therefore, we conducted this study to identify MDF in sporadic CRC patients and to evaluate the histological characteristics of human MDF. Materials and Methods: Colonic samples from 53 patients of sporadic CRC were stained with Alcian blue and examined for the presence of MDF. Subsequently, the samples were also examined for the presence of aberrant crypt foci (ACF) by methylene blue staining. We classified MDF into two categories, namely, flat-MDF and protruded-MDF (having the characteristics of both ACF and MDF), and analyzed their histological characteristics. Results: We found a total of 354, 41 and 19 colonic mucosal lesions with a mean multiplicity of 44, 38.9 and 66.9 crypts (ACF, flat-MDF and protruded-MDF, respectively). The density of MDF was 0.0082 lesions/cm2. ACF identified in sporadic CRC patients corresponded to hyperplastic or non-dysplasic lesions. On the other hand, MDF (both of flat-MDF and protruded-MDF) identified in these patients corresponded to low-grade dysplasia. In addition, we found that Paneth cell metaplasia and inflammatory cell infiltration were specific histological features of MDF. These histopathological characteristics have been reported to be associated with the development of CRC. Conclusions: This is the first report of a study conducted to investigate the density and histopathological characteristics of MDF in a large sample of sporadic CRC patients. Our results indicate that MDF might represent preneoplastic lesions in human colorectal carcinogenesis. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4418. doi:1538-7445.AM2012-4418