tbuckley/cabot-search huggingface dataset:
Placebo in Clinical Trials for Depression
Authors: David J. Kupfer, Ellen Frank
Journal: JAMA (2002)

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
Enhancement of human interferon production by neutral red and chloroquine: analysis of inhibition of protein degradation and macromolecular synthesis.
Authors: P B Sehgal, I Tamm, J Vilcek
Journal: The Journal of Experimental Medicine (1975)

Two lysosomotrophic drugs, neutral red and chloroquine, enhance polyinosinic:polycytidylic acid-induced interferon production by a strain of diploid human fibroblasts (FS-4). Treatment of cells with neutral red or chloroquine between 2.5 and 3.5 h after induction increases interferon yields 16- to 64- and 4- to 16-fold, respectively, in the subsequent 20.5 h. The two drugs inhibit the rates of protein degradation and of RNA and protein synthesis. In addition, neutral red is a very potent inhibitor of uridine transport into cells. Normalized dose-effect curves show that interferon superinduction is correlated with the inhibition of macromolecular synthesis, but not with that of protein degradation. Treatment of cells with chloroquine at low concentration (25 mug/ml) for a prolonged period of time (24 h) caused approximately 40% reduction in the rate of protein degradation. The usual rapid shutoff of interferon production and the effectiveness of effectiveness of actinomycin D superinduction are not altered by this treatment. This strongly suggests that inhibition of intralysosomal protein degradation does not significantly contribute to interferon superinduction. Degradation of the rapidly and the slowly turning over proteins was unaffected by actinomycin D under conditions of treatment known to enhance interferon production. Treatment with cycloheximide (5 or 50 mug/ml for 5 h) inhibited the rate of degradation of the rapidly turning over component by 10% and the slow component by 30-40%, which suggests that the two components turn over by distinct cellular mechanisms.
Industry sponsorship bias in research findings: a network meta-analysis of LDL cholesterol reduction in randomised trials of statins
Authors: H. Naci, S. Dias, A. E. Ades
Journal: BMJ (2014)

<h3>Background</h3> People increasingly communicate online, using visual communication mediums such as Skype and FaceTime. Growing demands on primary care services mean that new ways of providing patient care are being considered. Video consultation (VC) over the internet is one such mode. <h3>Aim</h3> To explore patients' and clinicians' experiences of VC. <h3>Design and setting</h3> Semi-structured interviews in UK primary care. <h3>Method</h3> Primary care clinicians were provided with VC equipment. They invited patients requiring a follow-up consultation to an online VC using the Attend Anywhere web-based platform. Participating patients required a smartphone, tablet, or video-enabled computer. Following VCs, semi-structured interviews were conducted with patients (<i>n</i> = 21) and primary care clinicians (<i>n</i> = 13), followed by a thematic analysis. <h3>Results</h3> Participants reported positive experiences of VC, and stated that VC was particularly helpful for them as working people and people with mobility or mental health problems. VCs were considered superior to telephone consultations in providing visual cues and reassurance, building rapport, and improving communication. Technical problems, however, were common. Clinicians felt, for routine use, VCs must be more reliable and seamlessly integrated with appointment systems, which would require upgrading of current NHS IT systems. <h3>Conclusion</h3> The visual component of VCs offers distinct advantages over telephone consultations. When integrated with current systems VCs can provide a time-saving alternative to face-to-face consultations when formal physical examination is not required, especially for people who work. Demand for VC services in primary care is likely to rise, but improved technical infrastructure is required to allow VC to become routine. However, for complex or sensitive problems face-to-face consultations remain preferable.
122 HCV BURDEN IN EUROPE: IMPACT OF NATIONAL TREATMENT PRACTICES ON FUTURE HCV-RELATED MORBIDITY AND MORTALITY THROUGH A MODELING APPROACH
Authors: S. Deuffic-Burban, P. Deltenre, M. Buti, T. Stroffolini, J. Parkes, N. Mühlberger, U. Siebert, C. Moreno, A. Hatzakis, W. Rosenberg, S. Zeuzem, P. Mathurin
Journal: Journal of Hepatology (2011)
Optimal Therapy for Relapsed Carcinoma of the Cervix After Primary Chemoradiation
Authors: Max Mano, Janet Kerr
Journal: Journal of Clinical Oncology (2004)

non-small-cell lung cancer (NSCLC) is performance status (PS).Patients with an Eastern Cooperative Oncology Group-Zubrod PS of 2 (ambulatory and capable of all selfcare but unable to carry out any work activities; up and about more than 50% of waking hours) or a Karnofsky PS of 60% or 70% (unable to work, able to live at home and care for most personal needs; a varying amount of assistance is needed; KPS 70%: cares for self, unable to carry on normal activity or do active work; KPS 60%: requires occasional assistance but is able to care for most of own needs) are less likely to benefit.There are sufficient data to support the use of single-agent chemotherapy over supportive care only in patients with good PS. [1]2][3] Furthermore, there are sufficient data to conclude that combination chemotherapy is more toxic than single-agent chemotherapy, even when nonplatinum combinations are used. 4 The available data fail to clearly prove that combination chemotherapy is superior to single-agent chemotherapy with regard to survival for patients with PS 2.The American Society of Clinical Oncology Expert Panel concluded that the available data in 2003 supported the use of single-agent chemotherapy in patients with metastatic NSCLC and PS 2. The data presented here by Perrone et al from a subgroup analysis of the Multicenter Italian Lung Cancer in the Elderly Study are consistent with this conclusion.However, another subgroup analysis and a recent small trial dedicated to patients with PS 2 have concluded that selected twodrug combinations may be superior to single agents. 5,6 As such, the role of combination chemotherapy in the management of PS 2 patients generates debate.We agree with Perrone et al that, in a randomized clinical trial dedicated to PS 2 patients, single-agent chemotherapy is at present an appropriate control arm.This implies that, at the time of enrollment, the oncologist has already decided to treat the patient with chemotherapy.Although there are insufficient data to support the routine use of combination chemotherapy in patients with PS 2, there are clinical trials underway for PS 2 patients who use combination chemotherapy as a control arm, which was inspired by the aforementioned subgroup analysis. 6,7 Deciding on the best chemotherapy for PS 2 patients remains an active area of research.The rapid advances in chemotherapy for NSCLC, including continued development of less toxic, targeted chemotherapy agents, and clinical trials dedicated to important subgroups of patients (eg, patients with PS 2 or bronchioloalveolar histology) may soon merit another update.
The Primacy of Insulin-Reply
Authors: Samuel Vaisrub
Journal: JAMA (1977)

In Reply.—  Our readers will be grateful to Dr Unger for clarifying the bihormonal abnormality hypothesis. Much of the bias would have been eliminated from my editorial had primacy and primary been replaced by more appropriate terms. This, in effect, was done in the first paragraph:  Unger's group and others have marshalled experimental evidence to ascribe anessentialrole to glucagon excess in these homeostatic disturbances.... As a corollary to these experimental findings emerged the concept of diabetes as abihormonal disorder dependent not only on insulin deficiency but also on glucagon excess.
Long-term Dietary Cadmium Intake and Postmenopausal Endometrial Cancer Incidence: A Population-Based Prospective Cohort Study
Authors: Agneta Åkesson, Bettina Julin, Alicja Wolk
Journal: Cancer Research (2008)

Abstract Environmental pollutants mimicking the effects of estrogen are suggested to contribute to the high incidence of hormone-related cancers, but supporting data are sparse. A potent estrogen-like activity of the pollutant cadmium, mediated via the estrogen receptor-α, has been shown in vivo. We prospectively examined the association between cadmium exposure and incidence of postmenopausal endometrial cancer. The Swedish Mammography Cohort is a population-based prospective cohort of 30,210 postmenopausal women free of cancer diagnose at baseline (1987) and who completed a food frequency questionnaire at baseline and in 1997. We estimated the dietary cadmium intake based on the questionnaire data and the cadmium content in all foods. During 16.0 years (484,274 person-years) of follow-up between the baseline and mid-2006, we ascertained 378 incident cases of endometrioid adenocarcinoma. The average estimated dietary cadmium intake was 15 μg/day (80% from cereals and vegetables). Cadmium intake was statistically significantly associated with increased risk of endometrial cancer in all women; the multivariate relative risk (RR) was 1.39 [95% confidence interval (CI), 1.04–1.86; Ptrend = 0.019], comparing highest tertile versus lowest. Among never-smoking women with body mass index (BMI) of &amp;lt;27 kg/m2, the RR was 1.86 (95% CI, 1.13–3.08; Ptrend = 0.009). We observed a 2.9-fold increased risk (95% CI, 1.05–7.79) associated with long-term cadmium intake consistently above the median at both baseline 1987 and in 1997 in never-smoking women with low bioavailable estrogen (BMI of &amp;lt;27 kg/m2 and nonusers of postmenopausal hormones). Our results support the hypothesis that cadmium may exert estrogenic effects and thereby increase the risk of hormone-related cancers. [Cancer Res 2008;68(15):6435–41]
PREVALENCE AND MORPHOLOGY OF CORONARY ARTERY PLAQUE ACROSS VARIOUS METABOLIC DISORDERS: EVALUATION USING CARDIAC COMPUTED TOMOGRAPHY ANGIOGRAPHY
Authors: Adekunle Shittu, Naser Ahmadi, Ferdinand Flores, Vahid Nabavi, Faraz Khan, Farhaad Khan, Fereshteh Hajsadeghi, Matthew J. Budoff
Journal: Journal of the American College of Cardiology (2011)
<scp><i>KIT</i></scp><scp><i>D</i></scp><i>816</i><scp><i>V</i></scp> and <scp><i>JAK</i></scp><i>2</i><scp><i>V</i></scp><i>617</i><scp><i>F</i></scp> mutations are seen recurrently in hypereosinophilia of unknown significance
Authors: Juliana Schwaab, Roland Umbach, Georgia Metzgeroth, Nicole Naumann, Mohamad Jawhar, Karl Sotlar, Hans‐Peter Horny, Timo Gaiser, Wolf‐Karsten Hofmann, Susanne Schnittger, Nicholas C.P. Cross, Alice Fabarius, Andreas Reiter
Journal: American Journal of Hematology (2015)

Myeloproliferative neoplasms with eosinophilia are commonly characterized by a normal karyotype and remain poorly defined at the molecular level. We therefore investigated 426 samples from patients with hypereosinophilia of unknown significance initially referred for screening of the FIP1L1-PDGFRA (FP) fusion gene also for KIT D816V and JAK2 V617F mutations. Overall, 86 (20%) patients tested positive: FP+ in 55 (12%), KIT D816V+ in 14 (3%), and JAK2 V617F+ in 17 (4%) patients, respectively. To gain better insight into clinical characteristics, we compared these cases with 31 additional and well-characterized KIT D816V+ eosinophilia-associated systemic mastocytosis (SM-eo) patients enrolled within the "German Registry on Disorders of Eosinophils and Mast cells." Significant differences included younger age, male predominance, and higher eosinophil counts for FP+ cases while abdominal lymphadenopathy, ascites, and serum tryptase levels >100 μg/l were characteristic for those with KIT D816V. Leukocytes, hemoglobin, and splenomegaly did not differ significantly. A median of three additional mutations, most frequently TET2 and SRSF2, were identified in 12/13 KIT D816V+ SM-eo patients with available material indicating a more complex molecular pathogenesis. Median survival was not reached for FP+ cases but was only 26 and 41 months for KIT D816V+ SM and JAK2 V617F+ MPN-eo, respectively. Eosinophilia of ≥2 × 10(9) /l was identified as discriminator for inferior survival in KIT D816V+ and/or JAK2 V617F+ patients (median survival 20 months vs. not reached, P = 0.002). Thus, there is a clear prognostic and therapeutic rationale for detection of KIT D816V and JAK2 V617F in the diagnostic work up of eosinophilia.
Digitalis Delirium
Authors: GERARD CHURCH, HENRY J. L. MARRIOTT
Journal: Circulation (1959)

The use and suitability of the term digitalis delirium are briefly discussed. Attention is drawn to the paucity of detailed reports on this important manifestation of digitalis poisoning. Three cases of digitalis delirium resulting from toxicity with 3 different preparations—gitalin, digoxin, and digitoxin—are presented. The first case demonstrates how the signs of early intoxication in a single patient may vary with different preparations and indeed with the same glycoside on separate occasions. The second case provides an alarming example of delirium which, although provoked by a short-acting glycoside, nevertheless lasted longer than 2 weeks. The third illustrates how easily the diagnosis of digitalis intoxication can go unrecognized when superimposed on a complex clinical picture. The clinical features of these cases are discussed in the light of previous reports.
Characterization of hemoglobin bassett (α94Asp→Ala), a variant with very low oxygen affinity
Authors: Osheiza Abdulmalik, Martin K. Safo, Norma B. Lerner, Josiree Ochotorena, Evgueni Daikhin, Vinaysagar Lakka, Rosa Santacroce, Donald J. Abraham, Toshio Asakura
Journal: American Journal of Hematology (2004)

Abstract Hemoglobin (Hb) Bassett, an abnormal Hb variant with a markedly reduced oxygen affinity, was discovered in a Caucasian (Anglo‐Saxon) male child who experienced episodes of cyanosis. Cation‐exchange and reversed‐phase (RP) high‐performance liquid chromatography (HPLC) showed that the patient has an abnormal Hb, with a mutation in the α‐globin. Tryptic peptide digest of the abnormal α‐globin with subsequent HPLC analysis revealed abnormal elution of the α‐T11 peptide. Further studies with Edman sequencing and electrospray mass spectrometry of tryptic peptide α‐T11, as well as structural analysis by X‐ray crystallography revealed an Asp→Ala substitution at the α94 (G1) position, a match for Hb Bassett. Detailed functional studies showed that this Hb variant had a markedly reduced oxygen affinity ( P 50 at pH 7.0 = 22 mmHg; Hb A P 50 = 10.5 mmHg), reduced Bohr effect (−0.26 compared to − 0.54 in Hb A), and low subunit cooperativity ( n = 1.4, compared to 2.6 in Hb A). X‐ray crystallography results explain the probable effects of the structural modification on the oxygen‐binding properties of this Hb variant. Am. J. Hematol. 77:268–276, 2004. © 2004 Wiley‐Liss, Inc.
TCT-709 Hemodynamic Outcomes of Post-dilatation in Transcatheter Aortic Valve Replacement
Authors: Molly Forster, Omar K. Khalique, Susheel Kodali, Mathew Williams, Isaac George, Tamim Nazif, Jean-Michel Paradis, Kendra J. Grubb, Martin Leon, Rebecca Hahn
Journal: Journal of the American College of Cardiology (2013)
The Long-Term Follow-Up of Patients Undergoing Saphenous Vein Bypass Surgery
Authors: DAVID S. CANNOM, D. CRAIG MILLER, NORMAN E. SHUMWAY, THOMAS J. FOGARTY, PAT O. DAILY, MARIE HU, BYRON BROWN, DONALD C. HARRISON
Journal: Circulation (1974)

The results of the first 400 consecutive patients (335 males, 65 females; mean age 52 years) having saphenous vein-coronary artery graft surgery at Stanford between October 1968 and January 1972 were reviewed. Through patient or physician contact, 100% follow-up period was achieved in the 375 patients surviving surgery. The mean follow-up period was 9.9 months, with the range 2 to 40 months. The operative mortality was 6.5%; patients having this surgery electively had a 0.8% mortality. The major cause of operative mortality was myocardial infarction (9 patients) and congestive heart failure and cardiogenic shock (10 patients). Predominant postoperative morbidity was due to pulmonary emboli (17 patients) and intrathoracic hemorrhage requiring thoracotomy (11 patients). The use of anticoagulants in the early postoperative period has reduced the incidence of pulmonary emboli. Angina was completely relieved in 79% (295 patients), 237 of whom had returned to full time employment. However, another 12% either were unchanged from their preoperative symptomatic state or incurred major late complications. This group includes 15 patients (3.9%) who had late deaths from cardiovascular causes. Another 23 patients had late, nonfatal myocardial infarctions. Using as a data base the degree of preoperative congestive heart failure, the extent of electrocardiographic changes and the presence of mitral regurgitation, a prognostic preoperative clinical risk-benefit guideline has been developed for use in any patient undergoing saphenous vein coronary artery graft surgery.
Air Pollution–Related Prothrombotic Changes in Persons with Diabetes
Authors: Lotte Jacobs, Jan Emmerechts, Chantal Mathieu, Marc F. Hoylaerts, Frans Fierens, Peter H. Hoet, Benoit Nemery, Tim S. Nawrot
Journal: Environmental Health Perspectives (2009)

Population studies suggest that persons with diabetes are more sensitive to the effects of particulate matter (PM) air pollution. However, the biological mechanisms of a possible prothrombotic effect underlying this enhanced susceptibility remain largely unknown.We hypothesized that exposure to PM causes prothrombotic changes in persons with diabetes, possibly via systemic inflammation.Our study included 137 nonsmoking adults with diabetes who were outpatients at the University Hospital Leuven. Recent exposure (2 hr before examination) to ambient PM was measured at the entrance of the hospital. Individual chronic exposure to PM was assessed by measuring the area occupied by carbon in airway macrophages obtained by sputum induction. Platelet function was measured ex vivo with the PFA-100 platelet function analyzer, which simulates a damaged blood vessel; we analyzed the function of platelets in primary hemostasis under high shear conditions. Total and differential blood leukocytes were counted.Independent of antiplatelet medication, an interquartile range (IQR) increase of 39.2 microg/m3 in PM10 (PM with aerodynamic diameter <or= 10 microm) concentration measured 2 hr before the clinical examination (recent exposure) was associated with a decrease of 21.1 sec [95% confidence interval (CI), 35.3 to 6.8] in the PFA-100 closure time (i.e., increased platelet activation) and an increase in blood leukocytes of 512 per microliter of blood (95% CI, 45.2979). Each area increase of 0.25 microm2 (IQR) in carbon load of airway macrophages (chronic exposure) was associated with an increase of 687 leukocytes per microliter of blood (95% CI, 2241,150).A relevant increase in recent PM exposure was associated with a change in platelet function toward a greater prothrombotic tendency. The magnitude of the change was about two-thirds (in the opposite direction) of the average effect of antiplatelet medication. Diabetic patients showed evidence of proinflammatory response to both recent and chronic exposure to PM air pollution.
Long-Term Space Flight Simulation Reveals Infradian Rhythmicity in Human Na+ Balance
Authors: Natalia Rakova, Kathrin Jüttner, Anke Dahlmann, Agnes Schröder, Peter Linz, Christoph Kopp, Manfred Rauh, Ulrike Goller, Luis Beck, Alexander Agureev, Galina Vassilieva, Liubov Lenkova, Bernd Johannes, Peter Wabel, Ulrich Moissl, Jörg Vienken, Rupert Gerzer, Kai-Uwe Eckardt, Dominik N. Müller, Karl Kirsch, Boris Morukov, Friedrich C. Luft, Jens Titze
Journal: Cell Metabolism (2013)
Method-dependent increase in lipoprotein(a) in insulin-dependent diabetes mellitus during pregnancy
Authors: Hadewijch L.M. Pekelharing, Netty L. Aalders, Gerard H.A. Visser, Jaap J. van Doormaal, Bonno N. Bouma, Henne A. Kleinveld, Herman J.M. van Rijn
Journal: Metabolism (1995)
Abstract A51: The HoxD locus: Its contribution to osteogenic phenotype and malignancy of Ewing sarcoma
Authors: Guenther HS Richter, Kristina von Heyking, Laura Roth, Miriam Ertl, Stefan Burdach
Journal: Cancer Research (2014)

Abstract Ewing sarcoma (ES), an osteogenic malignancy that mainly affects children and young adults, is characterized by early metastasis to lung and bone. Microarray analysis revealed genes of the HoxD locus to be clearly over-expressed in primary ES. Especially, genes such as HOXD10, HOXD11 and HOXD13 normally involved in bone formation and ossification pattern of bones are significantly over-expressed in ES. The expression of HOXD10, HOXD11 or HOXD13 seems not to be influenced via ES pathognomonic ews/ets translocations, since RNA interference of EWS-FLI1 or its over-expression in mesenchymal stem cells did not influence HOXD expression. However, RNA knock down of DKK2, a canonical WNT/β-catenin agonist and critical mediator of osteolytic tumor growth in ES resulted in a significant suppression of HOXD11 and HOXD13 expression. Subsequently, RNA interference of individual HoxD genes demonstrated HOXD11 and HOXD13 to be critical for in vitro proliferation and contact independent growth of ES. Similarly, in vitro invasiveness of ES lines was dependent on HOXD10, HOXD11 as well as HOXD13 and seemed mediated via MMP1, since down-regulation of individual HoxD genes similarly resulted in a suppression of MMP1 expression. But, HoxD genes only marginally influenced the expression of osteogenic genes in ES nor did they promote its chondrogenic or osteogenic differentiation. Whether HOXD10, HOXD11 or HOXD13 expression further metastasis or contribute to osteolytic tumor growth is currently investigated in a xenograft model using Rag2-/-gammaC-/- mice and data will be presented. Citation Format: Guenther HS Richter, Kristina von Heyking, Laura Roth, Miriam Ertl, Stefan Burdach. The HoxD locus: Its contribution to osteogenic phenotype and malignancy of Ewing sarcoma. [abstract]. In: Proceedings of the AACR Special Conference on Pediatric Cancer at the Crossroads: Translating Discovery into Improved Outcomes; Nov 3-6, 2013; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2013;74(20 Suppl):Abstract nr A51.