tbuckley/cabot-search huggingface dataset:
Glucagonlike Peptide 1–Based Therapies and Risk of Hospitalization for Acute Pancreatitis in Type 2 Diabetes Mellitus
Authors: Sonal Singh, Hsien-Yen Chang, Thomas M. Richards, Jonathan P. Weiner, Jeanne M. Clark, Jodi B. Segal
Journal: JAMA Internal Medicine (2013)

Acute pancreatitis has significant morbidity and mortality. Previous studies have raised the possibility that glucagonlike peptide 1 (GLP-1)-based therapies, including a GLP-1 mimetic (exenatide) and a dipeptidyl peptidase 4 inhibitor (sitagliptin phosphate), may increase the risk of acute pancreatitis.To test whether GLP-1-based therapies such as exenatide and sitagliptin are associated with an increased risk of acute pancreatitis. We used conditional logistic regression to analyze the data.Population-based case-control study.A large administrative database in the United States from February 1, 2005, through December 31, 2008.Adults with type 2 diabetes mellitus aged 18 to 64 years. We identified 1269 hospitalized cases with acute pancreatitis using a validated algorithm and 1269 control subjects matched for age category, sex, enrollment pattern, and diabetes complications.Hospitalization for acute pancreatitis.The mean age of included individuals was 52 years, and 57.45% were male. Cases were significantly more likely than controls to have hypertriglyceridemia (12.92% vs 8.35%), alcohol use (3.23% vs 0.24%), gallstones (9.06% vs 1.34), tobacco abuse (16.39% vs 5.52%), obesity (19.62% vs 9.77%), biliary and pancreatic cancer (2.84% vs 0%), cystic fibrosis (0.79% vs 0%), and any neoplasm (29.94% vs 18.05%). After adjusting for available confounders and metformin hydrochloride use, current use of GLP-1-based therapies within 30 days (adjusted odds ratio, 2.24 [95% CI, 1.36-3.68]) and recent use past 30 days and less than 2 years (2.01 [1.37-3.18]) were associated with significantly increased odds of acute pancreatitis relative to the odds in nonusers.In this administrative database study of US adults with type 2 diabetes mellitus, treatment with the GLP-1-based therapies sitagliptin and exenatide was associated with increased odds of hospitalization for acute pancreatitis.
Current Concepts in Thrombotic Thrombocytopenic Purpura
Authors: Han-Mou Tsai
Journal: Annual Review of Medicine (2005)

Recent advances have demonstrated that thrombotic thrombocytopenic purpura (TTP), characterized by widespread thrombosis in the arterioles and capillaries, is caused by deficiency of a circulating zinc metalloprotease, ADAMTS13. Two types of TTP are recognized: autoimmune TTP, caused by inhibitory antibodies of ADAMTS13, and hereditary TTP, caused by genetic mutations of ADAMTS13. This article reviews the characteristics and function of ADAMTS13, the mechanism by which ADAMTS13 deficiency may lead to thrombosis, and the causes of ADAMTS13 deficiency. It also discusses how the new knowledge may improve the diagnosis and treatment of this previously mysterious disorder.
Controlled Trial of Intravenous Immune Globulin in Recent-Onset Dilated Cardiomyopathy
Authors: Dennis M. McNamara, Richard Holubkov, Randall C. Starling, G. William Dec, Evan Loh, Guillermo Torre-Amione, Alan Gass, Karen Janosko, Tammy Tokarczyk, Paul Kessler, Douglas L. Mann, Arthur M. Feldman
Journal: Circulation (2001)

Background —This prospective placebo-controlled trial was designed to determine whether intravenous immune globulin (IVIG) improves left ventricular ejection fraction (LVEF) in adults with recent onset of idiopathic dilated cardiomyopathy or myocarditis. Methods and Results —Sixty-two patients (37 men, 25 women; mean age ±SD 43.0±12.3 years) with recent onset (≤6 months of symptoms) of dilated cardiomyopathy and LVEF ≤0.40 were randomized to 2 g/kg IVIG or placebo. All underwent an endomyocardial biopsy before randomization, which revealed cellular inflammation in 16%. The primary outcome was change in LVEF at 6 and 12 months after randomiz. Overall, LVEF improved from 0.25±0.08 to 0.41±0.17 at 6 months ( P &lt;0.001) and 0.42±0.14 ( P &lt;0.001 versus baseline) at 12 months. The increase was virtually identical in patients receiving IVIG and those given placebo (6 months: IVIG 0.14±0.12, placebo 0.14±0.14; 12 months: IVIG 0.16±0.12, placebo 0.15±0.16). Overall, 31 (56%) of 55 patients at 1 year had an increase in LVEF ≥0.10 from study entry, and 20 (36%) of 56 normalized their ejection fraction (≥0.50). The transplant-free survival rate was 92% at 1 year and 88% at 2 years. Conclusions —These results suggest that for patients with recent-onset dilated cardiomyopathy, IVIG does not augment the improvement in LVEF. However, in this overall cohort, LVEF improved significantly during follow-up, and the short-term prognosis remains favorable.
Emerging mechanisms of T-tubule remodelling in heart failure
Authors: Ang Guo, Caimei Zhang, Sheng Wei, Biyi Chen, Long-Sheng Song
Journal: Cardiovascular Research (2013)

Cardiac excitation–contraction coupling occurs primarily at the sites of transverse (T)-tubule/sarcoplasmic reticulum junctions. The orderly T-tubule network guarantees the instantaneous excitation and synchronous activation of nearly all Ca2+ release sites throughout the large ventricular myocyte. Because of the critical roles played by T-tubules and the array of channels and transporters localized to the T-tubule membrane network, T-tubule architecture has recently become an area of considerable research interest in the cardiovascular field. This review will focus on the current knowledge regarding normal T-tubule structure and function in the heart, T-tubule remodelling in the transition from compensated hypertrophy to heart failure, and the impact of T-tubule remodelling on myocyte Ca2+ handling function. In the last section, we discuss the molecular mechanisms underlying T-tubule remodelling in heart disease.
Timing of peak bone mass in Caucasian females and its implication for the prevention of osteoporosis. Inference from a cross-sectional model.
Authors: V Matkovic, T Jelic, G M Wardlaw, J Z Ilich, P K Goel, J K Wright, M B Andon, K T Smith, R P Heaney
Journal: Journal of Clinical Investigation (1994)

To determine the timing of peak bone mass and density, we conducted a cross-sectional study of bone mass measurements in 265 premenopausal Caucasian females, aged 8-50 yr. Bone mass and bone mineral density were measured using dual X-ray absorptiometry and single-photon absorptiometry at the spine (anteroposterior, lateral), proximal femur, radius shaft, distal forearm, and the whole body. Bone mass parameters were analyzed using a quadratic regression model and segmented regression models with quadratic-quadratic or quadratic-linear form. The results show that most of the bone mass at multiple skeletal locations will be accumulated by late adolescence. This is particularly notable for bone mineral density of the proximal femur and the vertebral body. Bone mass of the other regions of interest is either no different in women between the age of 18 yr and the menopause or it is maximal in 50-yr-old women, indicating slow but permanent bone accumulation continuing at some sites up to the time of menopause. This gain in bone mass in premenopausal adult women is probably the result of continuous periosteal expansion with age. Since rapid skeletal mineral acquisition at all sites occurs relatively early in life, the exogenous factors which might optimize peak bone mass need to be more precisely identified and characterized.
Statins, Risk of Diabetes, and Implications on Outcomes in the General Population
Authors: Kang-Ling Wang, Chia-Jen Liu, Tze-Fan Chao, Chi-Ming Huang, Cheng-Hsueh Wu, Su-Jung Chen, Tzeng-Ji Chen, Shing-Jong Lin, Chern-En Chiang
Journal: Journal of the American College of Cardiology (2012)
Surely doctors should follow the spirit, rather than the letter, of the law
Authors: R H. James
Journal: BMJ (1999)

EDITOR—Am I the only one who thinks, after reading the article and comments on retrieving semen from a dead patient,1 that the world is going mad? We seem to be worshipping a goddess called Idealised Consent. The central theme seemed to be not the advisability of posthumous conception (which could well …
Editorial: Nonsurgical treatments for gastrointestinal hemorrhage
Authors: H. W. Boyce
Journal: JAMA (1975)

For years physicians have attempted to develop nonsurgical methods to slow or stop upper gastrointestinal bleeding. There is obvious need for a safe and effective nonoperative method for producing gastrointestinal hemostasis, especially for patients who are poor surgical risks. Gastric hypothermia by lavage of the stomach with iced water or saline is believed by many to be the safest and simplest way to reduce bleeding from the stomach.<sup>1,2</sup>Palmer<sup>1</sup>has reported that about two thirds of acute upper gastrointestinal hemorrhages either are slowed or stopped by iced water in his experience with more than 1,400 patients. Some argue that lavage is unproved, but until a better method is devised, gastric cleansing and cooling likely will remain the first step in diagnostic preparation and therapy of upper gastrointestinal bleeding. In the early 1960s, hypothermia machines were placed on the market to produce gastric freezing as treatment for peptic ulcer
Novel Neurotransmitters and Their Neuropsychiatric Relevance
Authors: Solomon H. Snyder, Christopher D. Ferris
Journal: American Journal of Psychiatry (2000)

The purpose of this review is to integrate insights regarding novel neurotransmitters or neuromodulators of neuropsychiatric significance.Evolving concepts of neurotransmitter criteria are reviewed in light of the unexpected properties displayed by recently identified transmitters.Classic criteria for transmitters were based on the properties of acetylcholine but were markedly revised with the recognition of the catecholamines, serotonin, gamma-aminobutyric acid (GABA), and other amino acid transmitters and neuropeptides. Nitric oxide and carbon monoxide are notably atypical, as they are not stored in synaptic vesicles, are not released by exocytosis, and do not act at postsynaptic membrane receptor proteins. D-Serine, recently appreciated as the endogenous ligand for the glycine site of the glutamate N-methyl-D-aspartate (NMDA) receptor, overturns fundamental axioms of biology as well as those of neuroscience. It is a D-amino acid, and it is synthesized and stored in glia rather than neurons. Released glutamate acts on receptors on the protoplasmic astrocytes closely apposed to the synapse to release D-serine, which coactivates postsynaptic NMDA receptors together with glutamate. D-Serine is formed by serine racemase, which directly converts L-serine to D-serine. Inhibitors of this enzyme should reduce NMDA neurotransmission and might be therapeutic in stroke and other conditions associated with glutamate excitotoxicity.The diversity of novel neurotransmitters and venues of their activity afford multiple opportunities for therapeutic intervention.
Presence of<i>Epidermal Growth Factor Receptor</i>Gene T790M Mutation as a Minor Clone in Non–Small Cell Lung Cancer
Authors: Michio Inukai, Shinichi Toyooka, Sachio Ito, Hiroaki Asano, Shuji Ichihara, Junichi Soh, Hiroshi Suehisa, Mamoru Ouchida, Keisuke Aoe, Motoi Aoe, Katsuyuki Kiura, Nobuyoshi Shimizu, Hiroshi Date
Journal: Cancer Research (2006)

Abstract The threonine-to-methionine substitution at amino acid position 790 (T790M) of the epidermal growth factor receptor (EGFR) gene has been reported in progressing lesions after gefitinib treatment in non–small cell lung cancer (NSCLC) that causes sensitive tumors to become resistant to gefitinib. Alternatively, the EGFR T790M mutation might be present in small fractions of tumor cells before drug treatment, and the tumor cells harboring the T790M mutation might be enriched during the proliferation after drug treatment. We developed a mutant-enriched PCR assay to detect small fractions of cells with T790M mutation and used this technique to detect mutations in 280 NSCLCs, including gefitinib-treated 95 cases. Although the direct sequencing detected only 1 T790M mutant case, the mutant-enriched PCR (confirmed to enrich one mutant out of 1 × 103 wild-type alleles) detected 9 additional cases among 280 cases. As linkage to clinicopathologic factors, the T790M mutation showed no bias for sex, smoking status, or histology but was significantly more frequent in advanced tumors (9 of 111 cases) than in early-stage tumors (1 of 169 cases; P = 0.0013). Among gefitinib-treated cases, gefitinib-sensitive mutations were found in 30 cases. The T790M mutation was present in 3 of 7 no-responders with the gefitinib-sensitive mutation and was not present in 19 responders (P = 0.014). Our results indicate that the T790M mutation is sometimes present in a minor population of tumor cells during the development of NSCLC and suggest that the detection of small fractions of T790M mutant alleles may be useful for predicting gefitinib resistance of NSCLCs with sensitive EGFR mutations. (Cancer Res 2006; 66(16): 7854-8)
Chemotactic activity generated from the fifth component of complement by plasma kallikrein of the rabbit.
Authors: R C Wiggins, P C Giclas, P M Henson
Journal: The Journal of Experimental Medicine (1981)

Rabbit plasma kallikrein incubated with rabbit C5 resulted in the generation of chemotactic and secretagogue activity for rabbit neutrophils. This effect on C5 appeared to be due to kallikrein itself and not to a contaminating enzyme, because it could be inhibited by anti-kallikrein IgG or by soybean trypsin inhibitor to the same extent the kinin generation by the same kallikrein preparation was inhibited by these agents. The chemotactic response was consistent with the generation of a C5a-like peptide from C5 because the effect could be partially inhibited by carboxypeptidase N and was related to the generation of a small (approximately 14,000 mol wt) fragment of C5. No direct chemotactic response was detectable for kallikrein, activated Hageman factor, high-molecular weight kininogen, or intact C5. Incubation of Kallikrein, high-molecular weight kininogen, and Hageman factor together, so that activation of all three proteins occurred, did not results in the generation of detectable chemotactic activity.
National Research Council adds its voice to campaign for a more healthy US diet
Authors: B. Larsen
Journal: JAMA (1989)

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
Efficacy and safety of gemcitabine, oxaliplatin, and bevacizumab in advanced biliary-tract cancers and correlation of changes in 18-fluorodeoxyglucose PET with clinical outcome: a phase 2 study
Authors: Andrew X Zhu, Jeffrey A Meyerhardt, Lawrence S Blaszkowsky, Avinash R Kambadakone, Alona Muzikansky, Hui Zheng, Jeffrey W Clark, Thomas A Abrams, Jennifer A Chan, Peter C Enzinger, Pankaj Bhargava, Eunice L Kwak, Jill N Allen, Sanjay R Jain, Keith Stuart, Kerry Horgan, Susan Sheehan, Charles S Fuchs, David P Ryan, Dushyant V Sahani
Journal: The Lancet Oncology (2009)
MicroRNA-324-3p Promotes Renal Fibrosis and Is a Target of ACE Inhibition
Authors: Daniela Macconi, Susanna Tomasoni, Paola Romagnani, Piera Trionfini, Fabio Sangalli, Benedetta Mazzinghi, Paola Rizzo, Elena Lazzeri, Mauro Abbate, Giuseppe Remuzzi, Ariela Benigni
Journal: Journal of the American Society of Nephrology (2012)

The contribution of microRNA (miRNA) to the pathogenesis of renal fibrosis is not well understood. Here, we investigated whether miRNA modulates the fibrotic process in Munich Wistar Fromter (MWF) rats, which develop spontaneous progressive nephropathy. We analyzed the expression profile of miRNA in microdissected glomeruli and found that miR-324-3p was the most upregulated. In situ hybridization localized miR-324-3p to glomerular podocytes, parietal cells of Bowman's capsule, and most abundantly, cortical tubules. A predicted target of miR-324-3p is prolyl endopeptidase (Prep), a serine peptidase involved in the metabolism of angiotensins and the synthesis of the antifibrotic peptide N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP). In cultured tubular cells, transient transfection with a miR-324-3p mimic reduced Prep protein and activity, validating Prep as a target of this miRNA. In MWF rats, upregulation of miR-324-3p associated with markedly reduced expression of Prep in both glomeruli and tubules, low urine Ac-SDKP, and increased deposition of collagen. ACE inhibition downregulated glomerular and tubular miR-324-3p, promoted renal Prep expression, increased plasma and urine Ac-SDKP, and attenuated renal fibrosis. In summary, these results suggest that dysregulation of the miR-324-3p/Prep pathway contributes to the development of fibrosis in progressive nephropathy. The renoprotective effects of ACE inhibitors may result, in part, from modulation of this pathway, suggesting that it may hold other potential therapeutic targets.
Risk-Adapted Management for Patients With Clinical Stage I Seminoma: The Second Spanish Germ Cell Cancer Cooperative Group Study
Authors: Jorge Aparicio, José R. Germà, Xavier García del Muro, Pablo Maroto, José A. Arranz, Alberto Sáenz, Agustín Barnadas, Joan Dorca, Josep Gumà, David Olmos, Romá Bastús, Joan Carles, Daniel Almenar, Miguel Sánchez, Luis Paz-Ares, Juan J. Satrústegui, Begoña Mellado, Ana Balil, Marta López-Brea, Alfredo Sánchez
Journal: Journal of Clinical Oncology (2005)

To assess the efficacy of a risk-adapted treatment policy for patients with stage I seminoma by using universally accepted risk criteria.Between 1999 and 2003, 314 patients with clinical stage I seminoma after orchiectomy were prospectively included. One hundred patients (31.8%) presented no risk factors and were managed with surveillance. In contrast, 131 patients (41.7%) had tumors larger than 4 cm, 33 patients (10.5%) had rete testis involvement, and 50 patients (15.9%) had both risk factors. All the latter received two courses of adjuvant carboplatin.Chemotherapy was well tolerated, as only 17 patients (7.9%) presented grade 3 to 4 toxicity. Relapses were observed in six patients (6.0%) on surveillance and in seven patients (3.3%) treated with carboplatin (0.8% of tumors larger than 4 cm, 9.1% of those involving the rete testis, and 6.0% of patients with both risk criteria). All were located at the retroperitoneum, except for one at the spermatic cord. Median tumor size was 25 mm (range, 11 to 70 mm), and median time to relapse was 9 months (range, 4 to 28 months). All patients were rendered disease-free with chemotherapy (etoposide plus cisplatin). Median follow-up was 34 months (range, 12 to 72 months). The actuarial 5-year disease-free survival rate was 93.4% for patients on surveillance and 96.2% for patients treated with adjuvant chemotherapy. Overall 5-year survival was 100%.Adjuvant carboplatin is effective in reducing the relapse rate in patients with stage I seminoma and risk factors. A risk-adapted strategy is safe and feasible and should be considered an alternative to systematic approaches, such as irradiation, chemotherapy, or surveillance.
Improvement in Survival after Paraquat Ingestion Following Introduction of a New Formulation in Sri Lanka
Authors: Martin F Wilks, Ravindra Fernando, P. L Ariyananda, Michael Eddleston, David J Berry, John A Tomenson, Nicholas A Buckley, Shaluka Jayamanne, David Gunnell, Andrew Dawson
Journal: PLoS Medicine (2008)

Background Pesticide ingestion is a common method of self-harm in the rural developing world. In an attempt to reduce the high case fatality seen with the herbicide paraquat, a novel formulation (INTEON) has been developed containing an increased emetic concentration, a purgative, and an alginate that forms a gel under the acid conditions of the stomach, potentially slowing the absorption of paraquat and giving the emetic more time to be effective. We compared the outcome of paraquat self-poisoning with the standard formulation against the new INTEON formulation following its introduction into Sri Lanka. Methods and Findings Clinical data were prospectively collected on 586 patients with paraquat ingestion presenting to nine large hospitals across Sri Lanka with survival to 3 mo as the primary outcome. The identity of the formulation ingested after October 2004 was confirmed by assay of blood or urine samples for a marker compound present in INTEON. The proportion of known survivors increased from 76/297 with the standard formulation to 103/289 with INTEON ingestion, and estimated 3-mo survival improved from 27.1% to 36.7% (difference 9.5%; 95% confidence interval [CI] 2.0%–17.1%; p = 0.002, log rank test). Cox proportional hazards regression analyses showed an approximately 2-fold reduction in toxicity for INTEON compared to standard formulation. A higher proportion of patients ingesting INTEON vomited within 15 min (38% with the original formulation to 55% with INTEON, p < 0.001). Median survival time increased from 2.3 d (95% CI 1.2–3.4 d) with the standard formulation to 6.9 d (95% CI 3.3–10.7 d) with INTEON ingestion (p = 0.002, log rank test); however, in patients who did not survive there was a comparatively smaller increase in median time to death from 0.9 d (interquartile range [IQR] 0.5–3.4) to 1.5 d (IQR 0.5–5.5); p = 0.02. Conclusions The survey has shown that INTEON technology significantly reduces the mortality of patients following paraquat ingestion and increases survival time, most likely by reducing absorption.