tbuckley/cabot-search huggingface dataset:
Peginterferon alpha-2a is associated with higher sustained virological response than peginterferon alfa-2b in chronic hepatitis C: Systematic review of randomized trials
Authors: Tahany Awad, Kristian Thorlund, Goran Hauser, Davor Stimac, Mahasen Mabrouk, Christian Gluud
Journal: Hepatology (2009)

A combination of weekly pegylated interferon (peginterferon) alpha and daily ribavirin represents the standard of care for the treatment of chronic hepatitis C according to current guidelines. It is not established which of the two licensed products (peginterferon alpha-2a or peginterferon alfa-2b) is most effective. We performed a systematic review of head-to-head randomized trials to assess the benefits and harms of the two treatments. We searched the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, and LILACS through July 2009. Using standardized forms, two reviewers independently extracted data from each eligible trial report. We statistically combined data using a random effects meta-analysis according to the intention-to-treat principle. We identified 12 randomized clinical trials, including 5,008 patients, that compared peginterferon alpha-2a plus ribavirin versus peginterferon alfa-2b plus ribavirin. Overall, peginterferon alpha-2a significantly increased the number of patients who achieved a sustained virological response (SVR) versus peginterferon alfa-2b (47% versus 41%; risk ratio 1.11, 95% confidence interval 1.04–1.19; P = 0.004 [eight trials]). Subgroup analyses of risk of bias, viral genotype, and treatment history yielded similar results. The meta-analysis of adverse events leading to treatment discontinuation included 11 trials and revealed no significant differences between the two peginterferons. Conclusion: Current evidence suggests that peginterferon alpha-2a is associated with higher SVR than peginterferon alfa-2b. However, the paucity of evidence on adverse events curbs the decision to definitively recommend one peginterferon over the other, because any potential benefit must outweigh the risk of harm. (HEPATOLOGY 2010.)
Long-term follow-up of cytogenetically normal CEBPA-mutated AML
Authors: Friederike Pastore, Daniela Kling, Eva Hoster, Annika Dufour, Nikola P Konstandin, Stephanie Schneider, Maria C Sauerland, Wolfgang E Berdel, Thomas Buechner, Bernhard Woermann, Jan Braess, Wolfgang Hiddemann, Karsten Spiekermann
Journal: Journal of Hematology & Oncology (2014)

The aim of this study was to analyze the long-term survival of AML patients with CEBPA mutations. We investigated 88 AML patients with a median age of 61 years and (1) cytogenetically normal AML (CN-AML), (2) monoallelic (moCEBPA) or biallelic (biCEBPA) CEBPA mutation, and (3) intensive induction treatment. 60/88 patients have been described previously with a shorter follow-up. Median follow-up time was 9.8 years (95% CI: 9.4-10.1 years) compared to 3.2 and 5.2 years in our former analyses. Patients with biCEBPA mutations survived significantly longer compared to those with moCEBPA (median overall survival (OS) 9.6 years vs. 1.7 years, p = 0.008). Patients ≤60 years and biCEBPA mutations showed a favorable prognosis with a 10-year OS rate of 81%. Both, bi- and moCEBPA- mutated groups had a low early death (d60) rate of 7% and 9%, respectively. Complete remission (CR) rates for biCEBPA- and moCEBPA- mutated patients were 82% vs. 70% (p = 0.17). biCEBPA- mutated patients showed a longer relapse free survival (RFS) (median RFS 9.4 years vs. 1.5 years, p = 0.021) and a lower cumulative incidence of relapse (CIR) compared to moCEBPA- mutated patients. These differences in OS and RFS were confirmed after adjustment for known clinical and molecular prognostic factors. In this long-term observation we confirmed the favorable prognostic outcome of patients with biCEBPA mutations compared to moCEBPA- mutated CN-AML. The high probability of OS (81%) in younger patients is helpful to guide intensity of postremission therapy.
Subarachnoid Hemorrhage and Loss of Consciousness
Authors: R. Loch Macdonald
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
Role of Endothelial Dysfunction in Atherosclerosis
Authors: Jean Davignon, Peter Ganz
Journal: Circulation (2004)

As the major regulator of vascular homeostasis, the endothelium exerts a number of vasoprotective effects, such as vasodilation, suppression of smooth muscle cell growth, and inhibition of inflammatory responses. Many of these effects are largely mediated by nitric oxide, the most potent endogenous vasodilator. Nitric oxide opposes the effects of endothelium-derived vasoconstrictors and inhibits oxidation of low-density lipoprotein. A defect in the production or activity of nitric oxide leads to endothelial dysfunction, signaled by impaired endothelium-dependent vasodilation. Accumulating evidence suggests that endothelial dysfunction is an early marker for atherosclerosis and can be detected before structural changes to the vessel wall are apparent on angiography or ultrasound. Many of the risk factors that predispose to atherosclerosis can also cause endothelial dysfunction, and the presence of multiple risk factors has been found to predict endothelial dysfunction. A number of clinical trials have shown that 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) improve endothelial dysfunction in patients with coronary risk factors beyond what could be attributed to their impact on plasma lipids. Studies have elucidated several possible mechanisms by which statin therapy may improve endothelial dysfunction, including upregulation of nitric oxide production or activity and reduction of oxidative stress.
Association of Provider–Patient Visit Frequency and Patient Outcomes on Hemodialysis
Authors: Yelena Slinin, Haifeng Guo, Suying Li, Jiannong Liu, Kristine Ensrud, David T. Gilbertson, Allan J. Collins, Areef Ishani
Journal: Journal of the American Society of Nephrology (2012)

In January of 2004, the Centers for Medicare & Medicaid Services tied provider reimbursement for outpatient hemodialysis services to the number of provider-patient visits per month. We aimed to determine whether greater visit frequency associated with lower mortality and hospitalization rates among incident hemodialysis patients in a large, nationally representative contemporary cohort. Using US Renal Data System data for 130,892 patients who initiated in-center hemodialysis between October 1, 2003 and September 30, 2006, we determined associations between the frequency of provider visits and mortality, first hospitalization, multiple hospitalizations, and cause-specific hospitalizations. Our primary analysis used Cox proportional hazards models, but we also performed time-varying Cox proportional hazards and instrumental variable analyses. In the primary analysis, we did not detect a significance difference in mortality among patients with four provider visits per month compared with those patients with fewer provider visits (adjusted HR=0.98; 95% CI=0.96-1.01), but the risk for first hospitalization was 4% lower among those patients with more frequent visits (adjusted HR=0.96; 95% CI=0.95-0.97). The time-varying Cox analysis produced similar results. The fully adjusted instrumental variable analysis showed a 0.07% higher risk for death that was not statistically significant (P=0.88) but a significant 2.3% lower risk for first hospitalization (P=0.001) for patients with four provider visits per month. In summary, greater frequency of provider visits to hemodialysis patients associates with a small but significant reduction in hospitalizations, but it does not consistently associate with lower risk for death.
Pendrin Regulation in Mouse Kidney Primarily Is Chloride-Dependent
Authors: Marion Vallet, Nicolas Picard, Dominique Loffing-Cueni, Marinos Fysekidis, May Bloch-Faure, Georges Desche[Combining Circumflex Accent]nes, Sylvie Breton, Pierre Meneton, Johannes Loffing, Peter S. Aronson, Re[Combining Acute Accent]gine Chambrey, Dominique Eladari
Journal: Journal of the American Society of Nephrology (2006)

Recent studies indicate that pendrin, an apical Cl−/HCO3− exchanger, mediates chloride reabsorption in the connecting tubule and the cortical collecting duct and therefore is involved in extracellular fluid volume regulation. The purpose of this study was to test whether pendrin is regulated in vivo primarily by factors that are associated with changes in renal chloride transport, by aldosterone, or by the combination of both determinants. For achievement of this goal, pendrin protein abundance was studied by semiquantitative immunoblotting in different mouse models with altered aldosterone secretion or tubular chloride transport, including NaCl loading, hydrochlorothiazide administration, NaCl co-transporter knockout mice, and mice with Liddle's mutation. The parallel regulation of the aldosterone-regulated epithelial sodium channel (ENaC) was examined as a control for biologic effects of aldosterone. Major changes in pendrin protein expression were found in experimental models that are associated with altered renal chloride transport, whereas no significant changes were detected in pendrin protein abundance in models with altered aldosterone secretion. Moreover, in response to hydrochlorothiazide administration, pendrin was downregulated despite a marked secondary hyperaldosteronism. In contrast, α-ENaC was markedly upregulated, and the molecular weight of a large fraction of γ-ENaC subunits was shifted from 85 to 70 kD, consistent with previous results from rat models with elevated plasma aldosterone levels. These results suggest that factors that are associated with changes in distal chloride delivery govern pendrin expression in the connecting tubule and cortical collecting duct.
Antiangiogenic Agents, Chemotherapy, and the Treatment of Metastatic Transitional Cell Carcinoma
Authors: Nicholas J. Vogelzang
Journal: Journal of Clinical Oncology (2013)

A 69-year-old man with a 100 pack-year history of smoking developed gross hematuria. His medical history included hypertension, a silent myocardial infarction, and a cerebrovascular accident complicated by seizures. Cystoscopy and biopsy showed a 4-cm mass at the right ureteral orifice positive for a high-grade papillary transitional cell carcinoma (TCC) with muscularis propria invasion (Fig 1). The computed tomography (CT)/positron emission tomography (PET) scan of the chest, abdomen, and pelvis showed hydronephrosis and hydroureter with marked cortical thinning and multiple bilateral PET-avid pulmonary nodules, with the largest in the left upper lung measuring 3.0 × 2.5 cm (Figs 2A, 3A), biopsy of which showed invasive high-grade urothelial carcinoma. The patient consented to join a clinical trial for metastatic TCC (USON [US Oncology Network study] 06040) involving treatment with gemcitabine, cisplatin, and sunitinib (GCS) 37.5 mg per day. Four days later, he experienced a 10-day hospitalization for acute pancreatitis and neutropenia. Sunitinib was discontinued, and he completed four additional cycles of GC. CT/PET showed that the right ureteral mass and all lung nodules had regressed or disappeared (Figs 2B, 3B). The largest remaining lung nodule at 1.4 cm showed no metabolic activity. He underwent a radical cystoprostatectomy and right nephroureterectomy, disclosing residual high-grade urothelial carcinoma infiltrating the full thickness of the ureteral wall. There was carcinoma in situ of the bladder, and 42 nodes were negative for cancer. The surgery was followed by a small, uncomplicated myocardial infarction. A scheduled left thoracotomy to remove the remaining nodule was cancelled. No additional chemotherapy was administered, and the patient remains free of recurrence 2 years from initiation of chemotherapy. The 1.4-cm nodule has calcified and remains stable and metabolically inactive. He has no sequelae of chemotherapy or surgery, with a creatinine level of 1.35 mg/dL.
Abstract 3116: Serine protease inhibitor Kazal type 1 plays a role of colon carcinogenesis through the epidermal growth factor receptor
Authors: Satoshi Ida, Masaki Ohmuraya, Hiroshi Tanaka, Masayuki Watanabe, Hiroshi Takamori, Tooru Beppu, Hideo Baba
Journal: Cancer Research (2010)

Abstract Serine protease inhibitor Kazal type 1 (SPINK1: mouse homolog Spink3), which is also known as tumor associated trypsin inhibitor (TATI), is mainly produced in the acinar cells. The role of SPINK1 has been postulated to be the prevention of inadvertent proteolysis in the pancreas caused by intra-acinar premature activation of trypsinogen. SPINK1 is expressed not only in normal human pancreatic acinar cells, but also in a various cancers, including colon cancer. In the colon cancer, previous reports said high expression of SPINK1 correlates with metastasis and poor prognosis. However, the role of SPINK1 in malignant tumors remains to be elucidated. We previously demonstrated that SPINK1/Spink3 can bind to EGFR and work as a growth factor through EGFR in the pancreatic cancer, even the chronic pancreatitis. Hence, we hypothesized that SPINK1 plays a role as the growth factor for tissue repair in the inflammatory state, and if prolonged, it works to carcinogenesis in the colon tissue. We first showed that SPINK1 induced proliferation of colon cancer cell lines examined. To clarify the role in the colon cancer of SPINK1 in vivo, we use an efficient animal model for colitis-related carcinogenesis, male C57BL/6 mice were given a single intraperitoneal administration of azoxymethane (AOM), followed by a 1-week oral exposure to dextran sodium sulfate (DSS). We showed that expression of EGFR and Spink3 (its ligand) were observed in DSS induced colitis state. Sixteen weeks after injected AOM, multiple colon cancer occurred in all treated mice. In the Western blot, EGFR and Spink3 overexpressed in the whole colon tissue (cancer tissue and non-cancerous lesion), but Spink3 slightly decreased in the cancer. To determine whether Spink3 has an essential role of carcinogenesis, we further analyzed the tumor incidence of Spink3+/−mice. At 16 weeks, tumor number was 4.6 ± 0.8 (mean ± standard error) in Spink3+/+ mice and 1 ± 0.4 in Spink3+/− mice, and a significant difference was observed between the 2 groups (p&amp;lt;0.05). To further analyze the clinical importance of SPINK1 in the development of colon cancer, we examined the expression of SPINK1 and EGFR in adenoma and adenocarcinoma. SPINK1 express in adenoma and well differentiated adenocarcinoma, but not expressed in poorly differentiated adenocarcinoma. Taken together, these results suggest that SPINK1 stimulates the proliferation of colon cancer cells through the EGFR, and especially role in early carcinogenesis in colon cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3116.
Particulate Levels Are Associated with Early Asthma Worsening in Children with Persistent Disease
Authors: Nathan Rabinovitch, Matthew Strand, Erwin W. Gelfand
Journal: American Journal of Respiratory and Critical Care Medicine (2006)

Ambient particulate concentrations have been associated with variable physiologic effects in children with persistent asthma taking controller medications.To determine whether exposure to particulate matter has immediate effects on asthma control in children with persistent disease.In a school-based cohort, 73 children, primarily with moderate and severe asthma, were followed daily over one or two winters (2001-2002, 2002-2003) in Denver, Colorado. The association among ambient fine particulate, bronchodilator use, and urinary leukotriene E4 levels was assessed.Daily concentrations of fine particulate peaked in the morning hours when children were commuting to school. In a multivariable analysis that controlled for meteorology, time trends, and upper respiratory infections, an increase of one interquartile range in morning maximum fine particulate levels was related to an average increase of 3.8% in bronchodilator usage at school (95% confidence interval [CI], 0.2-7.4; p = 0.04). Children with severe asthma demonstrated significantly stronger associations (8.1% increase; 95% CI, 2.9-13.4; p = 0.003) than those with mild/moderate disease (1.6% increase; 95% CI, -2.2-5.4; p = 0.41; p = 0.03 for difference between groups). Morning maximum fine particulate levels were also associated with urinary leukotriene E4 measured during school hours (average increase of 6.2% per interquartile range increase; 95% CI, 1.9-10.5; p = 0.006). These associations were not discernable when 24-h averaged concentrations were used.Peak concentrations of ambient fine particulate are associated with early increases in bronchodilator use and urinary leukotriene E4 levels among children with persistent asthma, despite the use of controller medications.
An epidemiological investigation of training and injury patterns in British triathletes.
Authors: P K Korkia, D S Tunstall-Pedoe, N Maffulli
Journal: British Journal of Sports Medicine (1994)

During the competitive season of 1990, 155 British triathletes whose competitive distances varied from sprint to full ironman, and who self-classified themselves as recreational, intermediate or élite, kept a training diary for an 8-week period. They gave details of injuries sustained while training for, or competing in, triathlons. The mean(s.d.) distances covered each week were: swimming, 4.2(2.6) km; cycling, 100.2(70.6) km; and running 23.4(15.2) km; mean(s.d.) training time was 7(3.4) h per week, and a mean(s.d.) of 7.9(3.4) training sessions were completed per week. At least one injury was reported by 37% of the participants. The most frequently affected sites were the ankle/foot, thigh, knee, lower leg and the back. Overuse was the reported cause in 41% of the injuries, two-thirds of which occurred during running. The likelihood of an injury was positively associated with experience in triathlon. Average injury rate was 5.4 injuries per 1000 h of training (95% confidence interval: 4-7.2) and 17.4 per 1000 h of competition (95% confidence interval: 10.9-27.9). Injury incidence was unrelated to the mean amount of weekly training or competition, intensity or frequency of training.
The pulmonary physician and critical care. 4. A new look at the pulmonary circulation in acute lung injury.
Authors: G A Fox, D G McCormack
Journal: Thorax (1992)

Acute lung injury or the adult respiratory distress syndrome (ARDS) refers to the non- specific pulmonary response to various insults, acting either directly (for example, gastric acid aspiration, inhalation of toxic fumes, and oxygen toxicity) or indirectly (for example, sepsis syndrome, pancreatitis, and fat embo- lism syndrome).'The injury leads to reduced pulmonary compliance2 and a defect in gas transfer,3 both of which may occur in the absence of an appreciable increase in extra- vascular lung water.After acute lung injury the pulmonary vasculature may be affected at various levels:(1) pulmonary resistance vessels may be stimulated to contract with a resultant increase in pulmonary artery pressure; (2) pulmonary vascular reactivity may be attenuated, causing increased ventilation-perfusion mismatching; and (3) the pulmonary microvascular endothe- lium may be disrupted with a consequent increase in permeability.The purpose of this article is to provide an update on new developments regarding the pulmonary circulation in Neurohumoral factors: Cyclooxygenase products -thromboxane A2 Lipoxygenase products -leukotrienes Other -serotonin 5 cm
An international survey of the health economics of IVF and ICSI
Authors: J. A. Collins
Journal: Human Reproduction Update (2002)

The health economics of IVF and ICSI involve assessments of utilization, cost, cost-effectiveness and ability to pay. In 48 countries, utilization averaged 289 IVF/ICSI cycles per million of population per annum, ranging from two in Kazachstan, to 1657 in Israel. Higher national utilization of IVF/ICSI was associated with higher quality of health services, as indicated by lower infant mortality rates. IVF and ICSI are scientifically demanding and personnel-intensive, and are therefore expensive procedures. The average cost per IVF/ICSI cycle in 2002 would be US$9547 in the USA, and US$3518 in 25 other countries. Price elasticity estimates suggest that a 10% decrease in IVF/ICSI cost would generate a 30% increase in utilization. The average cost-effectiveness ratios in 2002 would be US$58 394 per live birth in the USA, and US$22 048 in other countries. In three randomized controlled trials, incremental costs per additional live birth with IVF compared with conventional therapy were US$ –26 586, $79 472 and $47 749. The national costs of IVF/ICSI treatment would be US$1.00 per capita in one current model, but the costs to individual couples range from 10% of annual household expenditures in European countries to 25% in Canada and the USA.
B Cell Antigen Receptor Specificity and Surface Density Together Determine B-1 versus B-2 Cell Development
Authors: Kong-Peng Lam, Klaus Rajewsky
Journal: The Journal of Experimental Medicine (1999)

Mice expressing the immunoglobulin (Ig) heavy (H) chain variable (V) region from a rearranged VH12 gene inserted into the IgH locus generate predominantly B-1 cells, whereas expression of two other VH region transgenes (VHB1-8 and VHglD42) leads to the almost exclusive generation of conventional, or B-2, cells. To determine the developmental potential of B cells bearing two distinct B cell antigen receptors (BCRs), one favoring B-1 and the other favoring B-2 cell development, we crossed VH12 insertion mice with mice bearing either VHB1-8 or VHglD42. B cells coexpressing VH12 and one of the other VH genes are readily detected in the double IgH insertion mice, and are of the B-2 phenotype. In mice coexpressing VH12, VHB1-8 and a transgenic κ chain able to pair with both H chains, double H chain–expressing B-2 cells, and B-1 cells that have lost VHB1-8 are generated, whereas VHB1-8 single producers are undetectable. These data suggest that B-1 but not B-2 cells are selected by antigenic stimuli in whose delivery BCR specificity and surface density are of critical importance.
Sir Geoffrey Bateman Susan Caroline Bellman Patrick Ernest George Clements Robert Quayle ("Robin") Crellin Henry ("Harry") Doberman Frederick George Barclay Dodd John Ewell Anne Ferguson Henry Angus Fraser Thomas Frederick Rathbone Griffin Maria Elizabeth Grossman Herman Frank Harwood
Authors: N T Bateman, G. Levin, C. Morgan, P. Crellin, B J Murray, M. Dodd, M. Boll and partners, G. Collee, D. J Fraser, A. Jackson, J. Lawrie, A J Eisinger
Journal: BMJ (1999)

He served with the Royal Air Force during the war, reaching the rank of wing commander, before returning to the bomb damaged St Thomas's.His department developed a popular training programme, which launched the