tbuckley/cabot-search huggingface dataset:
Fortnightly Review: A rational approach to the management of hepatitis C infection
Authors: G M Dusheiko, S Khakoo, P Soni, L Grellier
Journal: BMJ (1996)

<h3>Key messages</h3> Summary points The natural course of chronic hepatitis C is not fully defined A range of disease exists—from mild asymptomatic infection with few consequences to serious disease with dire sequelae Pretreatment assessments of viral load and genotype or serotype may help in predicting response It is difficult to indicate the prognosis for younger patients with mild disease; they may need to be considered for treatment, so that the opportunity to avoid later disease is not forfeited It is not yet clear whether patients who are more responsive to interferon have a better prognosis
Abstract 18059: Long-Term Exposure to Increased Systolic Blood Pressure Has a Cumulative Effect on the Risk of Coronary Heart Disease but Not Stroke
Authors: Brian A Ference, Mohan Palla, Fayez Siddiqui, Faisal Majeed, Phillip D Levy, John M Flack, Robert D Brook
Journal: Circulation (2014)

Introduction: Numerous randomized trials (RCTs) have demonstrated that short-term exposure to lower systolic blood pressure (SBP) is causally associated with a lower risk of coronary heart disease (CHD) and ischemic stroke (IS).

Hypothesis: We tested the hypothesis that the duration of exposure to lower SBP influences the reduction in the risk of CHD and IS.

Methods: We estimated the effect of short-term exposure to lower SBP by conducting a meta-analysis of 70 RCTs involving 269,883 persons (13,393 CHD and 9,333 IS events); the effect of medium-term exposure to lower SBP using data from a meta-analysis of 61 prospective cohort studies involving 980,000 persons (34,000 CHD and 12,000 IS events); and the effect of long-term exposure to lower SBP by constructing a genetic SBP score composed of 26 polymorphisms associated with SBP and then conducting a meta-analysis of 52 studies involving up to 186,985 persons (64,434 CHD and 8,959 IS events) to evaluate the effect of genetically mediated lifelong exposure to lower SBP. We then compared the effect of short-term exposure to lower SBP in the RCTs with medium-term exposure to lower SBP in the cohort studies and long-term exposure to lower SBP in the genetic studies.

Results: The mean duration of exposure to lower SBP was 4.7 years in the RCTs, 12.7 years in the cohort studies, and 52.6 years in the genetic studies. Each 10 mmHg lower SBP was associated with 16.4% lower risk of CHD (95%CI: 9.7-22.6) in the RCTs, 27.2% lower risk of CHD (95%CI: 24.0-30.3) in the cohort studies, and 45.0% lower risk of CHD (95%CI: 34.9-55.2) in the genetic studies. The effect of duration of exposure to lower SBP on the risk of CHD was highly significant (p = 4.3x10-5). By contrast, each 10 mmHg lower SBP was associated with 31.9% (95%CI: 25.0-38.1) lower risk of IS in the RCTs, 34.1% (95%CI: 28.3-39.5) lower risk of IS in the cohort studies, and 44.9% (95%CI: 29.8-58.3) lower risk of IS in the genetic studies. The effect of duration of exposure to lower SBP on the risk of IS was not significant (p = 0.258).

Conclusions: Increasing duration of exposure to lower SBP is log-linearly associated with an increasing proportional reduction in the risk of CHD, but not IS. Therefore, SBP appears to have a cumulative effect on the risk of CHD but a threshold effect on the risk of IS.
Effects of Glucosamine and Chondroitin Supplementation on Knee Osteoarthritis: An Analysis With Marginal Structural Models
Authors: Shibing Yang, Charles B. Eaton, Timothy E. McAlindon, Kate L. Lapane
Journal: Arthritis & Rheumatology (2014)

The purpose of this study was to estimate the effectiveness of the combination of glucosamine and chondroitin in relieving knee symptoms and slowing disease progression among patients with knee osteoarthritis (OA). The 4-year followup data from the Osteoarthritis Initiative data set were analyzed. We used a "new-user" design, for which only participants who were not using glucosamine/chondroitin at baseline were included in the analyses (n = 1,625). Cumulative exposure was calculated as the number of visits when participants reported use of glucosamine/chondroitin. Knee symptoms were measured with the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and structural progression was determined by measuring the joint space width (JSW). To control for the time-varying confounders that might be influenced by previous treatments, we used marginal structural models to estimate the effects on OA of using glucosamine/chondroitin for 3 years, 2 years, and 1 year. During the study period, 18% of the participants initiated treatment with glucosamine/chondroitin. After adjustment for potential confounders with marginal structural models, we found no clinically significant differences between users at all assessments and never-users of glucosamine/chondroitin in WOMAC pain (β = 0.68 [95% confidence interval (95% CI) -0.16 to 1.53]), WOMAC stiffness (β = 0.41 [95% CI 0 to 0.82]), and WOMAC function (β = 1.28 [95% CI -1.23 to 3.79]) or JSW (β = 0.11 [95% CI -0.21 to 0.44]). Use of glucosamine/chondroitin did not appear to relieve symptoms or modify disease progression among patients with radiographically confirmed OA. Our findings are consistent with the results of meta-analyses of clinical trials and extend those results to a more general population with knee OA.
Analysis of the human intestinal carboxylesterase and development of specific inhibitors to ameliorate the delayed diarrhea associated with CPT-ll administration.
Authors: Michael J. Hatfield, Lyudmila Tsurkan, Janice L. Hyatt, Carol C. Edwards, Monika Wierdl, Philip M. Potter
Journal: Cancer Research (2006)

5526   Carboxylesterases (CE) are members of the esterase class of enzymes and are involved in the metabolism of a broad range of xenobiotic substrates, including activation of the potent anticancer prodrug CPT-11. However, the high level expression of an intestinal CE in the gut appears to be partially responsible for the dose limiting toxicity (delayed diarrhea) for this drug. Therefore the development of specific inhibitors of this enzyme that prevent CPT-11 to SN-38 conversion in the intestine may serve to reduce the toxicity associated with CPT-11. The work reported here describes the purification, kinetic analysis, and biochemical characterization of a human intestinal CE (hiCE). This includes the analysis of the metabolism of clinically relevant substrates including CPT-11, heroin, and cocaine, as well as the development of specific hiCE inhibitors. Media containing secreted hiCE was obtained from baculovirus-infected Sf21 cells and the enzyme purified by ultrafiltration followed by ion-exchange and size exclusion chromatography. The resulting hiCE was determined to be greater than 98% pure by SDS-PAGE. We have determined the kinetic parameters for CPT-11 with the recombinant protein and they are in agreement with the enzyme purified from human liver. In addition, this CE converts cocaine to its inactive metabolite methylecgonine and heroin to 6-monoacetylmorphine. Selective inhibition of hiCE has also been achieved using a variety of dione-based inhibitors and we have demonstrated that these compounds can inhibit CEs intracellularly. Since we have hypothesized that the delayed diarrhea that occurs following CPT-11 administration results from activation of the drug in the gut epithelium, potentially these inhibitors may be utilized in the amelioration of this dose limiting toxicity. This work was supported in part by the American Lebanese Syrian Associated Charities.
Future Research Directions in Asthma. An NHLBI Working Group Report
Authors: Bruce D. Levy, Patricia J. Noel, Michelle M. Freemer, Michelle M. Cloutier, Steve N. Georas, Nizar N. Jarjour, Carole Ober, Prescott G. Woodruff, Kathleen C. Barnes, Bruce G. Bender, Carlos A. Camargo, Geoff L. Chupp, Loren C. Denlinger, John V. Fahy, Anne M. Fitzpatrick, Anne Fuhlbrigge, Ben M. Gaston, Tina V. Hartert, Jay K. Kolls, Susan V. Lynch, Wendy C. Moore, Wayne J. Morgan, Kari C. Nadeau, Dennis R. Ownby, Julian Solway, Stanley J. Szefler, Sally E. Wenzel, Rosalind J. Wright, Robert A. Smith, Serpil C. Erzurum
Journal: American Journal of Respiratory and Critical Care Medicine (2015)

Section:ChooseTop of pageAbstract <<Asthma Origins and Primar...Asthma Heterogeneity: Phe...Disease ModificationPersonalized Asthma Contr...Implementation ResearchCross-Cutting Themes to D...ConclusionsReferencesCITING ARTICLES
Abstract 15421: Acute Intravenous Infusion of Human Stresscopin (JNJ-39588146) Improves Left Ventricular Systolic Performance in Dogs with Advanced Heart Failure
Authors: Peter J Gengo, Mengjun Wang, Kefei Zhang, Itamar Ilsar, Ramesh C Gupta, Sharad Rastogi, David Uhlinger, Katherine Figueroa, Nigel P Shankley, Hani N Sabbah
Journal: Circulation (2012)

Background: JNJ-39588146/human Stresscopin (STC) is a newly identified peptide member of the corticotropin-releasing factor (CRF) family that binds selectively and with high affinity to the CRF typ...
Differential Gene Up-Regulation by Hypoxia-Inducible Factor-1α and Hypoxia-Inducible Factor-2α in HEK293T Cells
Authors: Victoria Wang, David A. Davis, Muzammel Haque, L. Eric Huang, Robert Yarchoan
Journal: Cancer Research (2005)

Abstract Cells exposed to hypoxia respond by increasing the level of hypoxia-inducible factor-1 (HIF-1). This factor then activates a number of genes by binding to hypoxia response elements in their promoter regions. A second hypoxia-responsive factor, HIF-2, can activate many of the same genes as HIF-1. Overexpression of HIFs accompanies the pathogenesis of many tumors. It is unclear, however, as to the respective role of these factors in responsiveness to hypoxia and other stresses. To address this issue, we used microarray technology to study the genes activated in HEK293T cells by hypoxia or transfection with the α chain of HIF-1 (or mutant HIF-1 resistant to degradation) or HIF-2. Fifty-six genes were found to be up-regulated at least 3-fold by either hypoxia or transfection. Of these, 21 were elevated both by transfection with HIF-1α and with HIF-2α, and 14 were preferentially activated by HIF-1α including several involved in glycolysis. Ten genes were preferentially activated by HIF-2α, including two (CACNA1A and PTPRZ1) implicated in neurologic diseases. Interestingly, most HIF-2α–responsive genes were not substantially activated by hypoxia. An additional 10 genes were up-regulated by hypoxia but minimally activated by HIF-1α or HIF-2α transfection. Ten of the genes were studied by quantitative real-time PCR and/or by Northern blot and the results paralleled those found with microarray technology. Although confirmation in other systems will be necessary, these results indicate that whereas some genes are robustly activated by both HIF-1 and HIF-2, others can be preferentially activated by one or the other factor.
Correspondence Re: J. R. Mackey et al., ImmunohistochemicalVariation of Human Equilibrative Nucleoside Transporter 1 Protein inPrimary Breast Cancers. Clin. Cancer Res., 8: 110ndash;116, 2002.
Authors: Laith Dabbagh, Robert W. Coupland, Carol E. Cass, John R. Mackey
Journal: Clinical Cancer Research (2003)

We write to update our previous report [(1)][1] of immunohistochemical analysis of frozen breast cancer samples for the hENT1[1][2] protein. In this paper, we analyzed 33 samples of frozen breast cancers and identified marked variability in the staining intensities for hENT1 protein, normalized to
WITHDRAWN: Tumor-targeting, pH-sensitive nanoparticles for docetaxel delivery to drug-resistant cancer cells
Authors: Jin Wook Tak, Tran Thuan Hiep, Pham Thanh Tung, Bijay Kumar Poudel, Kyu bong Woo, Dong Shik Kim, Han-Gon Choi, In Koo Chun, Jee-Heon Jeong, Chul Soon Yong, Jong Oh Kim
Journal: Asian Journal of Pharmaceutical Sciences (2015)

This article has been withdrawn at the request of the author(s) and/or editor. The Publisher apologizes for any inconvenience this may cause. The full Elsevier Policy on Article Withdrawal can be found at http://www.elsevier.com/locate/withdrawalpolicy.
Isolated Lingual Dyskinesia in Multiple Sclerosis
Authors: Jung E. Park, Katharine Alter, Mark Hallett
Journal: JAMA Neurology (2015)

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 Neurology HomeNew OnlineCurrent IssueFor Authors Podcast 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 Neurology journal
How well does physician selection of microbiologic tests identify Clostridium difficile and other pathogens in paediatric diarrhoea? Insights using multiplex PCR-based detection
Authors: C. Stockmann, M. Rogatcheva, B. Harrel, M. Vaughn, R. Crisp, M. Poritz, S. Thatcher, E.K. Korgenski, T. Barney, J. Daly, A.T. Pavia
Journal: Clinical Microbiology and Infection (2014)
Abstract 2839: Differences in Incidence and Outcome of Out-of-Hospital Cardiac Arrest Among Communities in Osaka: The Utstein Osaka Project
Authors: Tatsuya Nishiuchi, Yasuaki Hayashino, Shunichi Fukuhara, Taku Iwami, Yasuyuki Hayashi, Kentaro Kajino, Tetsuhisa Kitamura, Atsushi Hiraide, Hidekazu Yukioka, Tetsuya Matsuoka
Journal: Circulation (2009)

Introduction Awareness that survival of out-of-hospital cardiac arrest (OHCA) differs substantially among regions is growing. Differences in OHCA incidence and outcome across communities in Osaka remain to be clarified. We assessed whether OHCA incidence and outcome differ across medical districts in Osaka.

Methods This population-based prospective observational study included all adult OHCA patients resuscitated by emergency medical services (EMS) personnel in Osaka from January 1, 2005 to December 31, 2007. Osaka (8.8 million residents/1,898 square kilometers) has eight medical districts (470,000 –2,630,000 residents, median 950,000), each with a local medical control (MC) advisory board. Each board develops its own cardiopulmonary resuscitation (CPR) protocols, provides on-line medical directions to ambulance personnel, and evaluates the provision of prehospital emergency care to improve the quality of care in its medical district. All the data were prospectively collected according to the Utstein criteria in cooperation with the EMS personnel and physicians in receiving hospitals.

Results During the three years, a total of 15,942 EMS-resuscitated OHCA were reported in Osaka. Average annual incidence was 74.7 per 100,000 population for adults older than 20 years, ranging from 57.4 to 84.8 per 100,000 across the eight medical districts ( P <0.001). A total of 923 (6%) were bystander-witnessed OHCA with initial rhythm of ventricular fibrillation (VF) or pulseless ventricular tachycardia (VT); the average annual incidence was 4.3 per 100,000 adults older than 20 years, ranging from 2.8 to 5.6 per 100,000 across the medical districts ( P <0.001). Survival was 289/923 (31%), ranging from 13% to 47% ( P <0.001). Patients with a favorable neurological outcome accounted for 185/923 (20%), ranging from 5% to 27% ( P =0.01).

Conclusions Significant differences in OHCA incidence and outcome were observed among medical districts in Osaka. MC advisory boards should make efforts to identify modifiable factors (e.g. time factors related to “the chain of survival”, CPR protocols, and postresuscitation care provided by receiving hospitals) that would contribute to improving outcomes in their community.
Mucosal inflammation in bronchial biopsies of morbidly obese asthma subjects
Authors: Astrid van Huisstede, Vera van Rijn, Arjan Rudolphus, Manuel Castro Cabezas, Guido Mannaerts, Christian Taube, Pieter Hiemstra, Gert-Jan Braunstahl
Journal: European Respiratory Journal (2013)

Background: Asthma in obese subjects is poorly understood and is described as a specific phenotype. Literature suggests neutrophilic airway inflammation in these patients in contrast to the classic eosinophilic inflammation.  Aim: To investigate the nature of bronchial inflammation in obese asthma patients.  Methods: This is a cross-sectional study in obese patients with confirmed diagnosis of asthma (GINA guidelines) and non asthmatic patients undergoing bariatric surgery. In central bronchial biopsies taken during bariatric surgery, eosinophils, neutrophils and mast cells in submucosa were analysed.  Results: 29 obese asthmatics and 47 obese non-asthmatics were included. The groups did not differ in gender, age, BMI, abdominal circumference or smoking history. Asthma subjects had a significant lower FEV 1 , ACQ and methacholine PD20 than controls (87 vs 98%pred, p  Conclusions: This is the first study were bronchial biopsies are performed in morbidly obese asthma patients, showing that asthma is not characterized by increased number of either eosinophils, neutrophils or mast cells in bronchial mucosa. These findings suggest that airway inflammation is not a major contributor to the development of asthma in the morbidly obese.
An Introduction to Hospitals and Inpatient Care
Authors: W. F. Whitcomb
Journal: JAMA (2003)

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
Abstract 12127: Integrated Flow-Mediated Vasodilation Response Predicts Cardiovascular Events in Elderly Patients at Cardiovascular Risk Factor
Authors: Tomoyuki Kabutoya, Satoshi Hoshide, Yukiyo Ogata, Kazuo Eguchi, Kazuomi Kario
Journal: Circulation (2014)

Introduction: The integrated flow-mediated vasodilation (FMD) response was shown to be associated with cardiovascular risk factors, but the association between the integrated FMD response and consequent cardiovascular events has been unclear. Hypothesis: We assessed the hypothesis that the integrated FMD response predicts consequent cardiovascular events. Methods: We enrolled 575 patients who had at least one cardiovascular risk factor (hypertension, dyslipidemia, diabetes, or smoking). We measured the FMD magnitude of the percentage change in peak diameter (ΔFMD), and we measured the integrated FMD response calculated as the area under the dilation curve during a 120-sec dilation period (FMD-AUC 120 ) using a semiautomatic edge-detection algorithm. The primary outcome was defined as any cardiovascular event (a composite of cardiovascular death, and hospitalization for myocardial infarction, stroke, or heart failure). Results: The mean duration of follow-up was 35±22 months (range: 1-74 months). During the follow-up period, 34 cardiovascular events were recorded. Among the elderly patients (age[[Unable to Display Character: &amp;#8201;]]≥[[Unable to Display Character: &amp;#8201;]]65 yrs, n[[Unable to Display Character: &amp;#8201;]]=[[Unable to Display Character: &amp;#8201;]]281), the patients with the lowest tertile of FMD-AUC 120 (FMD-AUC 120 &lt;[[Unable to Display Character: &amp;#8201;]]5.6) suffered a higher incidence of cardiovascular events compared with the patients with the higher two tertiles (FMD-AUC 120 ≥[[Unable to Display Character: &amp;#8201;]]5.6) (log rank 4.16, p=0.041). The association remained significant after adjusting for age, gender and office systolic blood pressure (hazard ratio 1.25, p=0.039). In the younger patients (age[[Unable to Display Character: &amp;#8201;]]&lt;[[Unable to Display Character: &amp;#8201;]]65 yrs, n[[Unable to Display Character: &amp;#8201;]]=[[Unable to Display Character: &amp;#8201;]]294), cardiovascular events were similar among the patients with the lowest tertile and those with the higher two tertiles of FMD-AUC 120 . Cardiovascular events were also similar in the patients with the lowest tertile and the higher two tertiles of ΔFMD in both the elderly and younger patients. Conclusions: The integrated FMD response, but not ΔFMD, predicted cardiovascular events in elderly patients with a cardiovascular risk factor.
A DNA Vaccine Targeting Fos-Related Antigen 1 Enhanced by IL-18 Induces Long-lived T-Cell Memory against Tumor Recurrence
Authors: Yunping Luo, He Zhou, Masato Mizutani, Noriko Mizutani, Cheng Liu, Rong Xiang, Ralph A. Reisfeld
Journal: Cancer Research (2005)

Abstract A novel vaccination strategy induced specific CD8+ T cell–mediated immunity that eradicated spontaneous and experimental pulmonary cancer metastases in syngeneic mice and was also effective in a therapeutic setting of established breast cancer metastases. This was achieved by targeting transcription factor Fos-related antigen 1(Fra-1), overexpressed by many tumor cells, with an ubiquitinated DNA vaccine against Fra-1, coexpressing secretory IL-18. Insight into the immunologic mechanisms involved was provided by adoptive transfer of T lymphocytes from successfully immunized BALB/c mice to syngeneic severe combined immunodeficient (SCID) mice. Specifically, long-lived T memory cells were maintained dormant in nonlymphoid tissues by IL-18 in the absence of tumor antigen. Importantly, a second tumor cell challenge of these SCID mice restored both, robust tumor-specific cytotoxicity and long-lived T-cell memory, capable of eradicating established pulmonary cancer metastases, suggesting that this vaccine could be effective against tumor recurrence.