tbuckley/cabot-search huggingface dataset:
The Pharmacology of Anesthetic Drugs: A Syllabus for Students and Clinicians.
Journal: JAMA (1953)

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
Innate mechanism of pollen- and cat dander–induced oxidative stress and DNA damage in the airways
Authors: Koa Hosoki, David Redding, Toshiko Itazawa, Anirban Chakraborty, Nisha Tapryal, Sun Qian, Huibin Qi, Leopoldo Aguilera-Aguirre, Allan R. Brasier, Veeranki Sreenivas Phani, Tapas K. Hazra, Istvan Boldogh, Sanjiv Sur
Journal: Journal of Allergy and Clinical Immunology (2017)
Anti-CD27 Enhances Lymphoma Immunotherapy through Profound Myeloid Cell Recruitment
Authors: Anna H Turaj, Vikki L Field, Claude H.T. Chan, Christine A. Penfold, Jinny H. Kim, Sonya James, Kerry L Cox, Tibor Keler, Peter M Johnson, Aymen Al-Shamkhani, Stephen A Beers, Martin J. Glennie, Mark S Cragg, Sean H Lim
Journal: Blood (2016)
Long-Term Effects of AAV1/SERCA2a Gene Transfer in Patients With Severe Heart Failure
Authors: Krisztina Zsebo, Alex Yaroshinsky, Jeffrey J. Rudy, Kim Wagner, Barry Greenberg, Mariell Jessup, Roger J. Hajjar
Journal: Circulation Research (2013)

The Calcium Up-Regulation by Percutaneous Administration of Gene Therapy In Cardiac Disease (CUPID 1) study was a phase 1/phase 2 first-in-human clinical gene therapy trial using an adeno-associated virus serotype 1 (AAV1) vector carrying the sarcoplasmic reticulum calcium ATPase gene (AAV1/SERCA2a) in patients with advanced heart failure. The study explored potential benefits of the therapy at 12 months, and results were previously reported.To report long-term (3-year) clinical effects and transgene expression in the patients in CUPID 1.A total of 39 patients with advanced heart failure who were on stable, optimal heart failure therapy were randomized to receive intracoronary infusion of AAV1/SERCA2a in 1 of 3 doses (low-dose, 6×10(11) DNase-resistant particles; mid-dose, 3×10(12) DNase-resistant particles; and high-dose, 1×10(13) DNase-resistant particles) versus placebo. The following recurrent cardiovascular and terminal events were tracked for 3 years in all groups: myocardial infarction, worsening heart failure, heart failure-related hospitalization, ventricular assist device placement, cardiac transplantation, and death. The number of cardiovascular events, including death, was highest in the placebo group, high but delayed in the low- and mid-dose groups, and lowest in the high-dose group. Evidence of long-term transgene presence was also observed in high-dose patients. The risk of prespecified recurrent cardiovascular events was reduced by 82% in the high-dose versus placebo group (P=0.048). No safety concerns were noted during the 3-year follow-up.After a single intracoronary infusion of AAV1/SERCA2a in patients with advanced heart failure, positive signals of cardiovascular events persist for years.
Prognostic Impact of a 12-gene Progression Score in Non–muscle-invasive Bladder Cancer: A Prospective Multicentre Validation Study
Authors: Lars Dyrskjøt, Thomas Reinert, Ferran Algaba, Emil Christensen, Daan Nieboer, Gregers G. Hermann, Karin Mogensen, Willemien Beukers, Mirari Marquez, Ulrika Segersten, Søren Høyer, Benedicte P. Ulhøi, Arndt Hartmann, Robert Stöhr, Sven Wach, Roman Nawroth, Kristina Schwamborn, Cane Tulic, Tatjana Simic, Kerstin Junker, Niels Harving, Astrid C. Petersen, Jørgen B. Jensen, Bastian Keck, Marc-Oliver Grimm, Marcus Horstmann, Tobias Maurer, Ewout W. Steyerberg, Ellen C. Zwarthoff, Francisco X. Real, Núria Malats, Per-Uno Malmström, Torben F. Ørntoft
Journal: European Urology (2017)
Serum Matrix Metalloproteinase-7, Respiratory Symptoms, and Mortality in Community-Dwelling Adults. MESA (Multi-Ethnic Study of Atherosclerosis)
Authors: Hilary F. Armstrong, Anna J. Podolanczuk, R. Graham Barr, Elizabeth C. Oelsner, Steven M. Kawut, Eric A. Hoffman, Russell Tracy, Naftali Kaminski, Robyn L. McClelland, David J. Lederer
Journal: American Journal of Respiratory and Critical Care Medicine (2017)

Rationale: Matrix metalloproteinase-7 (MMP-7) has been implicated in interstitial lung disease pathobiology and proposed as a diagnostic and prognostic biomarker of idiopathic pulmonary fibrosis.Objectives: To test associations between serum MMP-7 and lung function, respiratory symptoms, interstitial lung abnormalities (ILA), and all-cause mortality in community-dwelling adults sampled without regard to respiratory symptoms or disease.Methods: We measured serum MMP-7 in 1,227 participants in MESA (Multi-Ethnic Study of Atherosclerosis) at baseline. The 5-year outcome data were available for spirometry (n = 697), cough (n = 722), and dyspnea (n = 1,050). The 10-year outcome data were available for ILA (n = 561) and mortality (n = 1,227). We used linear, logistic, and Cox regression to control for potential confounders.Measurements and Main Results: The mean (±SD) serum MMP-7 level was 4.3 (±2.5) ng/ml (range, 1.2–24.1 ng/ml). In adjusted models, each natural log unit increment in serum MMP-7 was associated with a 3.7% absolute decrement in FVC% (95% confidence interval [CI] = 0.9–6.6%), a 1.6-fold increased odds of exertional dyspnea (95% CI = 1.3–1.9), a 1.5-fold increased odds of ILAs (95% CI = 1.1–2.1), and a 2.2-fold increased all-cause mortality rate (95% CI = 1.9–2.5). The associations with ILA and mortality tended to be stronger among never-smokers (P values for interaction 0.06 and 0.01, respectively).Conclusions: Serum MMP-7 levels may be a quantitative biomarker of subclinical extracellular matrix remodeling in the lungs of community-dwelling adults, which may facilitate investigation of subclinical interstitial lung disease.
A phase 1A/1B, two-stage study of a PSA/IL-2/GM-CSF vaccine for the treatment of PSA-recurrent prostate cancer in hormone-naive and hormone-independent patients.
Authors: Gregory A. Daniels, Jessica Wang-Rodriguez, Kyoko Sakamoto, Weg Ongkeko, Michelle McKinney, Jonathan F. Head
Journal: Journal of Clinical Oncology (2014)

TPS3131 Background: Prostate cancer vaccines demonstrate clinical benefit in hormone refractory metastatic prostate cancer patients. The broader application to earlier disease stages remains both cost prohibitive and of unclear benefit. The aim of this trial evaluates the safety and tolerability of a simple recombinant PSA vaccine in men with either hormone naïve or hormone-independent prostate cancer without evidence of metastasis (“PSA-only”). Secondary aims include changes in PSA doubling time, time to measurable disease and vaccine-induced immunologic assessments. Methods: This is a Phase 1A/1B trial of PSA/IL-2/GM-CSF vaccine in recurrent prostate cancer in hormone-naïveand hormone-independent patients. Major inclusion criteria include adenocarcinoma of the prostate, rising serum PSA and no measurable disease. Phase 1A examines the rate of dose limiting adverse events (DLAEs) in an initial course of 6 vaccinations (“induction vaccination”). Phase 1B examines the rate of DLAEs with a continued coarse of an additional 6 vaccinations (“maintenance vaccine”) in another 28 patients. There will be an interim analysis after the first 20 patients accrue. All patients will receive intradermal injections of the PSA/IL-2/GM-CSF vaccine at weeks 1, 2, 3, 7,11, and 15. Secondary endpoints including serum PSA and prostatic acid phosphatase (PAP) level measurements along withimmunological evaluations. All patients will be evaluated for diseaseprogression at Week 19. If the Phase 1A portion of the trial demonstrates safety of the induction vaccination, 28 additional patients will be enrolled in the Phase 1B portion of the trial. Patients will receive maintenance vaccine alternating every 4 weeks between IL-2 and the complete vaccine (PSA/IL-2/GM-CSF) starting at week 23 and until week 43 (6 injections total). To date, eight of twenty patients have received at least one vaccine injection in the phase IA portion without DLAEs. Enrollment continues in phase IA.
Abstract P352: Associations Between Signs and Symptoms of Androgen Excess With Chronic Kidney Disease in Hispanic/Latina Women of Reproductive Age in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL)
Authors: Michelle L Meyer, Daniela Sotres-Alvarez, Anne Steiner, Larry Cousins, Gregory A Talavera, Jianwen Cai, Martha Daviglus, Laura R Loehr
Journal: Circulation (2017)

Background: Androgen excess among women is characterized by high levels of testosterone and is a feature of polycystic ovary syndrome (PCOS), a common reproductive endocrine disorder in women. Evidence from animal and human studies show that androgens may promote renal dysfunction. The association between signs and symptoms of androgen excess and chronic kidney disease (CKD), however, has been relatively unexplored. Methods: HCHS/SOL is a community-based cohort study of 16,415 self-identified Hispanic/Latino adults from diverse backgrounds in the US, including 3,801 women age 18-44 years at visit 1 (2008-2011). This preliminary cross-sectional analysis describes results from 994 reproductive-aged women who attended the ongoing visit 2 (2014-2017) by Sept. 2016. Signs and symptoms of androgen excess included menstrual cycle length (&gt;35 days or too irregular), self-reported PCOS, and oral contraceptive use to regulate menstrual cycles or acne. We also evaluated each component separately. CKD was defined as either a low estimated glomerular filtration rate (eGFR; &lt;60 ml/min/1.73 m 2 ) or albuminuria based on a urine albumin/creatinine ratio ≥30 mg/g. Estimates are adjusted for sampling design, site, age, Hispanic/Latina background, education, smoking status, and body mass index. Results: Among women reporting any sign or symptom of androgen excess (unweighted N=278), 9% reported cycles &gt;35 days, 51% reported cycles too irregular, 49% reported oral contraceptive use to regulate cycles or acne, and 19% self-reported PCOS. Compared to women without any sign or symptom of androgen excess, women reporting a sign or symptom of androgen excess had a higher mean body mass index, waist circumference, albumin/creatinine ratio, and prevalence of hypertension and the metabolic syndrome. The prevalence of CKD (7%, 95% confidence interval (CI): 4-13%) was the same with or without signs and symptoms of androgen excess, and the association was not significant after adjusting for covariates (odds ratio (OR): 1.0; 95% CI: 0.4-2.1). When individual components were analyzed, women reporting cycles too irregular had higher odds of CKD (OR: 1.5; 95% CI: 0.6-3.7) compared to women reporting cycles of 24-35 days, although not statistically significant. Conclusion: Over a fourth of Hispanic/Latina women reported signs and symptoms of androgen excess. Overall, there were no statistically significant associations with CKD among women reporting signs and symptoms of androgen excess. Completion of visit 2 would allow us to draw a more robust conclusion and to further characterize these relationships.
Overall Survival Results of a Trial Assessing Patient-Reported Outcomes for Symptom Monitoring During Routine Cancer Treatment
Authors: Ethan Basch, Allison M. Deal, Amylou C. Dueck, Howard I. Scher, Mark G. Kris, Clifford Hudis, Deborah Schrag
Journal: JAMA (2017)

This study assesses overall survival associated with electronic patient-reported symptom monitoring vs usual care during routine cancer treatment.
Prognostic impact of the number of examined lymph nodes (LNs) in resected node negative (pNo) non-small cell lung cancer (NSCLC).
Authors: Obiageli Uchenna Ogbata, Xinhua Yu, Raymond U Osarogiagbon
Journal: Journal of Clinical Oncology (2012)

7025 Background: In the US, 29% of patients undergo curative-intent surgery for NSCLC. Absence of LN metastasis and the extent of LN examination influence survival. 44% of patients with pathological node negative (pN0) disease die within 5 years. There is no consensus on the optimal number of LNs to be examined to determine pN0 stage. We hypothesized that patients with few examined nodes may have missed nodal metastasis and increasing the number of LNs examined would improve survival. Methods: Retrospective SEER database analysis of NSCLC resections from 1998 to 2002, with survival updated to 2008. Patients with first primary, pN0 NSCLC, with one or more LNs examined, met our study criteria. Cox regression and competing risk models were used for survival analysis. A p value &lt;0.05 was considered statistically significant. Results: 8,137 patients met inclusion criteria and were evaluated. A median of 6 LNs were examined in this cohort. Patients who underwent pneumonectomy and lobectomy had more LNs examined than those who had sub-lobar resections. Higher number of LNs examined was associated with better overall survival (OS) and lung cancer specific survival (LCSS), at a plateau of 8 LNs for both outcomes (Table). Having mediastinal LNs examined also resulted in increased OS and LCSS (p&lt;0.05). Conclusions: The pathologic assessment of LNs in surgical specimens is often suboptimal. Examining more LNs may have increased the likelihood of correct staging. Lower numbers of LNs examined probably result in understaging. Examining 8 or more total LNs and mediastinal LNs examined improved both OS and LCSS. [Table: see text]
Desmosomes in Human Disease
Authors: Nicole A. Najor
Journal: Annual Review of Pathology Mechanisms of Disease (2018)

Tissue integrity is crucial for maintaining the homeostasis of living organisms. Abnormalities that affect sites of cell-cell contact can cause a variety of debilitating disorders. The desmosome is an essential cell-cell junctional protein complex in tissues that undergo stress, and it orchestrates intracellular signal transduction. Desmosome assembly and junctional integrity are required to maintain the overall homeostasis of a tissue, organ, and organism. This review discusses the desmosome and the human diseases associated with its disruption.
Nature and Nurture: What Determines Tumor Metabolic Phenotypes?
Authors: Jared R. Mayers, Matthew G. Vander Heiden
Journal: Cancer Research (2017)

Abstract Understanding the genetic basis of cancer has led to therapies that target driver mutations and has helped match patients with more personalized drugs. Oncogenic mutations influence tumor metabolism, but other tumor characteristics can also contribute to their metabolic phenotypes. Comparison of isogenic lung and pancreas tumor models suggests that use of some metabolic pathways is defined by lineage rather than by driver mutation. Lung tumors catabolize circulating branched chain amino acids (BCAA) to extract nitrogen for nonessential amino acid and nucleotide synthesis, whereas pancreatic cancer obtains amino acids from catabolism of extracellular protein. These differences in amino acid metabolism translate into distinct pathway dependencies, as genetic disruption of the enzymes responsible for utilization of BCAA nitrogen limits the growth of lung tumors, but not pancreatic tumors. These data argue that some cancer metabolic phenotypes are defined by cancer tissue-of-origin and environment and that these features constrain the influence of genetic mutations on metabolism. A better understanding of the factors defining tumor nutrient utilization could be exploited to help improve cancer therapy. Cancer Res; 77(12); 3131–4. ©2017 AACR.
What happens when targets for waiting times change?
Authors: John Appleby
Journal: BMJ (2017)

In Soviet era Russia Pyotr Petrov, manager of the state run ball bearing factory on the outskirts of Magnitogorsk studied the new production target. The target came from the chief department for ball bearing production, part of the Ministry of Automobile and Tractor Industries. From now on the Magnitogorsk factory was to produce 200 tons of ball bearings a month. “200 tons! That’s a huge increase in the number of ball bearings,” Petrov thought, “... or is it?” At the end of the month the factory had managed to meet its target: one, 3.7 m diameter, 200 ton, ball bearing.

Poorly designed or badly policed targets can create perverse incentives (a giant ball bearing), but they can also provide the right motivation to improve performance. So what has been the real life experience of the NHS and its use of targets, particularly to improve waiting times?

Two targets become somewhat iconic: one arising from the Labour Party’s 2007 manifesto pledge that “by the end of 2008, no NHS patient will have to wait longer than a maximum of 18 weeks …
Adverse Cerebral Outcomes after Coronary Bypass Surgery
Authors: M D Hariawala
Journal: New England Journal of Medicine (1997)

Background Acute changes in cerebral function after elective coronary bypass surgery are a difficult clinical problem.We carried out a multicenter study to determine the incidence and predictors of -and the use of resources associated with -perioperative adverse neurologic events, including cerebral injury. MethodsIn a prospective study, we evaluated 2108 patients from 24 U.S. institutions for two general categories of neurologic outcome: type I (focal injury, or stupor or coma at discharge) and type II (deterioration in intellectual function, memory deficit, or seizures). ResultsAdverse cerebral outcomes occurred in 129 patients (6.1 percent).A total of 3.1 percent had type I neurologic outcomes (8 died of cerebral injury, 55 had nonfatal strokes, 2 had transient ischemic attacks, and 1 had stupor), and 3.0 percent had type II outcomes (55 had deterioration of intellectual function and 8 had seizures).Patients with adverse cerebral outcomes had higher in-hospital mortality (21 percent of patients with type I outcomes died, vs. 10 percent of those with type II and 2 percent of those with no adverse cerebral outcome; P Ͻ 0.001 for all comparisons), longer hospitalization (25 days with type I outcomes, 21 days with type II, and 10 days with no adverse outcome; P Ͻ 0.001), and a higher rate of discharge to facilities for intermediate-or long-term care (47 percent, 30 percent, and 8 percent; P Ͻ 0.001).Predictors of type I outcomes were proximal aortic atherosclerosis, a history of neurologic disease, and older age; predictors of type II outcomes were older age, systolic hypertension on admission, pulmonary disease, and excessive consumption of alcohol. ConclusionsAdverse cerebral outcomes after cor- onary bypass surgery are relatively common and serious; they are associated with substantial increases in mortality, length of hospitalization, and use of intermediate-or long-term care facilities.New diagnostic and therapeutic strategies must be developed to lessen such injury.
Burden of illness in second-line colorectal cancer: A systematic literature review.
Authors: Eugenia Priedane, Yingxin Xu, David Wilson, Juan Guillermo Jasso Mosqueda, Sheikh Usman Iqbal, Sarah Naoshy
Journal: Journal of Clinical Oncology (2012)

e14061 Background: Colorectal cancer (CRC) is the third and second most common cancer in males and females, respectively, worldwide. Based on cases diagnosed in 2008, the age-adjusted incidence rate of CRC was 47.2/100,000/year in the US. Approximately 15-25% of all new cases are diagnosed with metastases and half of all cases result in metastases, representing an increased health and economic burden. The objective of this study was to gain a more in-depth understanding of the epidemiology, clinical and economic burden of second-line CRC in the US, Europe big 5, BRIC-M countries, and Japan. Methods: A Cochrane standard systematic literature review was performed using EMBASE, PubMed, NHSEED databases, and data from key congresses. Searches were conducted using specifically tailored search algorithms for years 2006-2011. Results: Of the 1,377 citations reviewed, 10 studies were identified (6 were epidemiology studies). No information on the number of patients treated for second-line mCRC was found. Estimates of median overall survival were short and varied from 7-18.7 months. New chemotherapy regimens, younger patients, and patients without KRAS mutations are associated with longer overall survival. Information on clinical burden of disease was also limited. The majority of patients presented with liver metastases (73%) and cardiovascular disease (63%). Three clinical trials evaluated quality of life (QoL) with significant heterogeneities in study design, population, treatment regimens and assessment instruments used. No statistically significant results favored targeted therapy. Only 1 study conducted in the US assessed economic burden in patients treated with either bevacizumab or cetuximab. At 6 months the total health care cost was $73,712 and $81,781 respectively, with main cost drivers being outpatient and targeted therapy costs. Conclusions: A substantial evidence gap regarding knowledge of burden of illness in second-line mCRC limits informed clinical and economic decision making. Further research is required to evaluate country-specific epidemiologic and survival data, QoL, resource utilization and cost variation associated with active treatment and end of life care. Research funded by Sanofi/Regeneron.
Patient and Public Safety Maximized by Rapid Opioid Taper
Authors: Aaron S. Geller
Journal: JAMA Internal Medicine (2017)

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