tbuckley/cabot-search huggingface dataset:
Altering Overuse of Cardiac Telemetry in Non–Intensive Care Unit Settings by Hardwiring the Use of American Heart Association Guidelines
Authors: Robert Dressler, Marylou M. Dryer, Christian Coletti, Donna Mahoney, Andrew J. Doorey
Journal: JAMA Internal Medicine (2014)

cant decreases in blood pressure following renal denervation, but this sham-controlled study identified no such benefit.While these findings also may be influenced by patient selection, they should concern those inclined to recommend interventional treatment of resistant hypertension presumed due to renovascular causes.Keeping in mind that blood pressure reduction can only be considered a surrogate for "hard end points" such as death, myocardial infarction, stroke, congestive heart failure, and renal failure, we seem to be very far removed from any convincing evidence that renal artery interventions reduce cardiovascular or renal morbidity or mortality.With these issues in mind, where do we go from here?While awaiting further studies to investigate the possibility of a clinical benefit to renal artery interventions, we must focus on aggressive medical management of patients with refractory hypertension.We should not overlook the consistent evidence that sodium restriction, increased potassium intake, exercise and weight loss are associated with blood pressure reduction in patients with hypertension.Furthermore, the recent Eighth Joint National Committee guidelines 9 suggest that for nonblack patients, first-line therapy for hypertension should consist of 1 or a combination of thiazide diuretics, calcium channel blockers, angiotensin-converting enzyme inhibitors and angiotensin receptor blockers.For black patients, firstline therapy should consist of thiazide diuretics and calcium channel blockers.Emphasis on the importance of lifestyle measures and medication compliance, and consideration of secondary causes such as sleep apnea, drug-induced hypertension, hypercortisolism, hyperaldosteronism, hyperthyroidism or hypothyroidism, or hyperparathyroidism is warranted in patients with resistant hypertension.Focus on proven therapies while we await more concrete data supporting the use of interventional procedures for resistant hypertension is the most reasonable approach, at least until the next big thing comes along.
Reticulon 4B (Nogo-B) is a novel regulator of hepatic fibrosis
Authors: Dahai Zhang, Teruo Utsumi, Hui-Chun Huang, Lili Gao, Panjamaporn Sangwung, Chuhan Chung, Kazunori Shibao, Kohji Okamoto, Koji Yamaguchi, Roberto J. Groszmann, Levente Jozsef, Zhengrong Hao, William C. Sessa, Yasuko Iwakiri
Journal: Hepatology (2011)

Nogo-B, also known as Reticulon 4B, plays important roles in vascular injuries. Its function in the liver is not understood. The aim of this study was to characterize Nogo-B in liver fibrosis and cirrhosis. Nogo-B distribution was assessed in normal and cirrhotic human liver sections. We also determined the levels of liver fibrosis in wild-type (WT) and Nogo-A/B knockout (NGB KO) mice after sham operation or bile duct ligation (BDL). To investigate the mechanisms of Nogo-B's involvement in fibrosis, hepatic stellate cells were isolated from WT and NGB KO mice and transformed into myofibroblasts. Portal pressure was measured to test whether Nogo-B gene deletion could ameliorate portal hypertension. In normal livers, Nogo-B expression was found in nonparenchymal cells, whereas its expression in hepatocytes was minimal. Nogo-B staining was significantly elevated in cirrhotic livers. Fibrosis was significantly increased in WT mice 4 weeks after BDL compared with NGB KO mice. The absence of Nogo-B significantly reduced phosphorylation of Smad2 levels upon transforming growth factor β (TGF-β) stimulation. Reconstitution of the Nogo-B gene into NGB KO fibroblasts restored Smad2 phosphorylation. Four weeks after BDL, portal pressure was significantly increased in WT mice by 47%, compared with sham-operated controls (P = 0.03), whereas such an increase in portal pressure was not observed in NGB KO mice (P = NS).Nogo-B regulates liver fibrosis, at least in part, by facilitating the TGFβ/Smad2 signaling pathway in myofibroblasts. Because absence of Nogo-B ameliorates liver fibrosis and portal hypertension, Nogo-B blockade may be a potential therapeutic target in fibrosis/cirrhosis.
High- and Low-Fat Dairy Intake, Recurrence, and Mortality After Breast Cancer Diagnosis
Authors: C. H. Kroenke, M. L. Kwan, C. Sweeney, A. Castillo, B. J. Caan
Journal: JNCI Journal of the National Cancer Institute (2013)

Dietary fat in dairy is a source of estrogenic hormones and may be related to worse breast cancer survival. We evaluated associations between high- and low-fat dairy intake, recurrence, and mortality after breast cancer diagnosis.We included 1893 women from the Life After Cancer Epidemiology study diagnosed with early-stage invasive breast cancer from 1997 to 2000, who completed the Fred Hutchinson Cancer Research Center Food Frequency Questionnaire after diagnosis. A total of 349 women had a recurrence and 372 died during a median follow-up of 11.8 years, with 189 deaths from breast cancer. We used delayed entry Cox proportional hazards regression to evaluate associations between categories of the cumulative average of dairy fat at baseline and at follow-up 5 to 6 years later and subsequent outcomes. Tests of statistical significance were two-sided.In multivariable-adjusted analyses, overall dairy intake was unrelated to breast cancer-specific outcomes, although it was positively related to overall mortality. Low-fat dairy intake was unrelated to recurrence or survival. However, high-fat dairy intake was positively associated with outcomes. Compared with the reference (0 to <0.5 servings/day), those consuming larger amounts of high-fat dairy had higher breast cancer mortality (0.5 to <1.0 servings/day: hazard ratio [HR] = 1.20, 95% confidence interval [CI] = 0.82 to 1.77; and ≥1.0 servings/day: HR = 1.49, 95% CI = 1.00 to 2.24, P trend = .05), higher all-cause mortality (P trend < .001), and higher non-breast cancer mortality (P trend = .007); the relationship with breast cancer recurrence was positive but not statistically significant. The higher risk appeared consistent across different types of high-fat dairy products.Intake of high-fat dairy, but not low-fat dairy, was related to a higher risk of mortality after breast cancer diagnosis.
Psychiatric Disorders and Mental Health Service Use Among Caregivers of Advanced Cancer Patients
Authors: Lauren C. Vanderwerker, Rachel E. Laff, Nina S. Kadan-Lottick, Suzanne McColl, Holly G. Prigerson
Journal: Journal of Clinical Oncology (2005)

Purpose Despite research demonstrating the psychological burden of caregiving for advanced cancer patients, limited information exists on the prevalence of psychiatric disorders and mental health service use among these informal caregivers. Methods Two hundred informal caregivers of advanced cancer patients were interviewed and administered the Structured Clinical Interview of the Diagnostic and Statistical Manual of Mental Disorders Fourth Edition and an assessment of mental health service use. Results Thirteen percent of caregivers met criteria for a psychiatric disorder; 25% accessed treatment for mental health concerns since the patient's cancer diagnosis. The frequencies of current psychiatric disorders were as follows: panic disorder, 8.0% (95% CI, 4.6% to 12.7%), major depressive disorder, 4.5% (95% CI, 2.1% to 8.4%), post-traumatic stress disorder, 4.0% (95% CI, 1.7% to 7.7%), and generalized anxiety disorder, 3.5% (95% CI, 1.4% to 7.1%). Among caregivers with a current psychiatric disorder, 81% discussed mental health concerns with a health professional before the patient's cancer diagnosis compared with 46% after the diagnosis (McNemar test = 5.40; P = .02). Only 46% of caregivers with a current psychiatric disorder accessed mental health services. Caregivers who discussed mental health concerns with a clinician before the patient's cancer diagnosis (odds ratio [OR] = 3.51; 95% CI, 1.42 to 8.71) and after the diagnosis (OR = 21.23; 95% CI, 9.02 to 49.94) were more likely than caregivers not having these discussions to receive mental health services. Conclusion Many caregivers of advanced cancer patients either meet criteria or are being treated for psychiatric problems. Discussing mental health issues positively influences the receipt of mental health services and should be actively pursued in this vulnerable population.
Renin-Angiotensin System and Cardiac Rupture After Myocardial Infarction
Authors: Scott D. Solomon, Marc A. Pfeffer
Journal: Circulation (2002)

f all the mechanical complications after acute myocardial infarction (MI), cardiac rupture remains the most devastating, dramatic, and deadly.Continued improvements in the care of patients with acute MI have decreased the incidence of cardiac rupture over the past decade to under 3% in patients receiving reperfusion therapy, 1 although autopsy evaluation of patients who died suddenly with acute MI has suggested a higher incidence. 2,3ithout extremely prompt surgical intervention, patients with cardiac rupture rarely survive.
Survival After a Psychoeducational Intervention for Patients With Cutaneous Malignant Melanoma: A Replication Study
Authors: Ellen H. Boesen, Sidsel H. Boesen, Kirsten Frederiksen, Lone Ross, Karin Dahlstrøm, Grethe Schmidt, Jesper Næsted, Christen Krag, Christoffer Johansen
Journal: Journal of Clinical Oncology (2007)

The results of a randomized, intervention study done in 1993 of psychoeducation for patients with early-stage malignant melanoma showed a beneficial effect on recurrence and survival 6 years after the intervention. In the present study, we replicated the study with 258 Danish patients with malignant melanoma. We also compared recurrence and survival among the participants in the randomized study with 137 patients who refused to participate.We randomly assigned 262 patients with primary malignant melanoma to a control or an intervention group. Patients in the intervention group were offered six weekly 2-hour sessions of psychoeducation. Participants and nonparticipants were followed up for vital status and recurrence 4 to 6 years after surgical treatment. Prognostic factors (thickness of the tumor and lymph node status), sex, and age were adjusted for in a Cox regression model (proportional hazards regression) to derive an adjusted survival rate ratio and an adjusted relapse-free survival rate ratio, with 95% CIs.The hazard ratio was 1.30 (95% CI, 0.5 to 3.5) for survival and 0.73 (95% CI, 0.3 to 1.9) for recurrence. Being a nonparticipant increased the risk for death by more than two-fold (hazard ratio, 2.26; 95% CI, 1.0 to 5.2) over that of participants.Psychoeducation did not increase survival or the recurrence-free interval among patients with malignant melanoma; however, nonparticipants had a statistically significantly greater risk for death than participants.
Occurrence of Autoantibodies to Annexin I, 14-3-3 Theta and LAMR1 in Prediagnostic Lung Cancer Sera
Authors: Ji Qiu, Gina Choi, Lin Li, Hong Wang, Sharon J. Pitteri, Sandra R. Pereira-Faca, Alexei L. Krasnoselsky, Timothy W. Randolph, Gilbert S. Omenn, Cim Edelstein, Matt J. Barnett, Mark D. Thornquist, Gary E. Goodman, Dean E. Brenner, Ziding Feng, Samir M. Hanash
Journal: Journal of Clinical Oncology (2008)

We have implemented a high throughput platform for quantitative analysis of serum autoantibodies, which we have applied to lung cancer for discovery of novel antigens and for validation in prediagnostic sera of autoantibodies to antigens previously defined based on analysis of sera collected at the time of diagnosis.Proteins from human lung adenocarcinoma cell line A549 lysates were subjected to extensive fractionation. The resulting 1,824 fractions were spotted in duplicate on nitrocellulose-coated slides. The microarrays produced were used in a blinded validation study to determine whether annexin I, PGP9.5, and 14-3-3 theta antigens previously found to be targets of autoantibodies in newly diagnosed patients with lung cancer are associated with autoantibodies in sera collected at the presymptomatic stage and to determine whether additional antigens may be identified in prediagnostic sera. Individual sera collected from 85 patients within 1 year before a diagnosis of lung cancer and 85 matched controls from the Carotene and Retinol Efficacy Trial (CARET) cohort were hybridized to individual microarrays.We present evidence for the occurrence in lung cancer sera of autoantibodies to annexin I, 14-3-3 theta, and a novel lung cancer antigen, LAMR1, which precede onset of symptoms and diagnosis.Our findings suggest potential utility of an approach to diagnosis of lung cancer before onset of symptoms that includes screening for autoantibodies to defined antigens.
Abstract 3336: Upregulated inflammatory cytokines in glioma stem cells: Targets for glioma therapies
Authors: Lei Wang, Dalila Del Real, Gwi-Moon Seo, Marla Pyle, Dery Troyer
Journal: Cancer Research (2010)

Abstract Gliomas are the most common primary brain tumors in adults. With the highly invasive growth pattern, gliomas often escape current therapeutic modalities including combinations of surgery, radiotherapy and chemotherapy. Recent studies implicate that a minority population of glioma stem cells (GSCs) are responsible for glioma maintenance and recurrence. Interleukin (IL)-1 beta, IL-6 and IL-8 are pleiotropic proinflammatory cytokines and their excessive production in the tumor microenvironment is associated with poor disease outcome in many cancer types, including glioma. These cytokines promote tumor growth via induction of proteins associated with tumor invasion and angiogenesis and anti-apoptosis. We hypothesize that GSCs acquire their chemo-resistance and invasion by excessive cytokine production. To test the hypothesis, we compared the cytokine gene expression of a human GSC-enriched population in serum-free medium (SFM) in the presence of epidermal growth factor and fibroblast growth factor, to that of glioma cells in serum-containing medium (SCM). SFM is the neural stem/progenitor cell (NPC) medium in which NPCs proliferate in neurospheres and this medium also has been used to enrich GSCs. We found that IL-1 beta and IL-6 were upregulated in GSC-enriched population along with increased expression of Nestin, a marker of neural stem cells. More interestingly, Smad interacting protein 1 (SIP1), which is thought to be involved in glioma cell migration and invasion, was also increased in the GSC-enriched population. The paralleled upregulation of IL-1 beta and IL-6 with Nestin and SIP1 in GSC-enriched population suggest that there is a possible correlation between them. The correlation is now under investigation. Since IL-1 beta is elevated in GSC enriched population, we further determined whether IL-1 beta plays a critical role in glioma growth. Glioma cells were co-cultured with mouse NPCs expressing IL-1 receptor antagonist (IL-1ra), which can bind to IL-1 receptors without transmitting activation signals and represents a competitive inhibitor of IL-1. Proliferation of glioma cells, which were modified to express Renilla luciferase, was measured using bioluminescence imaging. Our results showed that proliferation of glioma cells was inhibited in the co-culture with NPCs expressing IL-1ra, but not in the co-culture with NPCs without expression of IL-1ra, compared to glioma cells cultured alone. The results suggest that IL-1 has an important role in glioma cell growth and NPCs engineered to express IL-1ra have therapeutic potential for gliomas. 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 3336.
Endomysial antibody: is it the best screening test for coeliac disease?
Authors: M Ferreira, S L Davies, M Butler, D Scott, M Clark, P Kumar
Journal: Gut (1992)

The sensitivities and specificities of the IgA and IgG antigliadin antibody and the IgA antireticulin antibody have been compared with the recently described endomysial antibody directed against the basement membrane of smooth muscle in monkey oesophagus. One hundred and seventeen patients with adult coeliac disease (21 untreated), 84 patients with inflammatory bowel disease, systemic lupus erythematosus and rheumatoid arthritis (comprising the disease control group), 47 normal controls and a miscellaneous group of 29 patients, who were selected because of a positive reticulin staining pattern, were investigated. These results were correlated with the degree of abnormality of the intestinal mucosa in patients with adult coeliac disease. Endomysial antibodies were found in all patients with untreated coeliac disease and subtotal villous atrophy and in 47% of patients on a non-strict gluten free diet. One patient on a strict gluten free diet was positive and had partial villous atrophy while all patients in disease control groups were negative. Results were variable with the antireticulin and antigliadin antibodies. Sensitivity and correlation with subtotal villous atrophy in the untreated patients was 100%. It is concluded that the endomysial antibody is superior to other current antibody tests and should be used in preference for the diagnosis of coeliac disease.
Abnormal Tissue Oxygenation and Cardiovascular Changes in Endotoxemia
Authors: PETER B. ANNING, MARK SAIR, C. PETER WINLOVE, TIMOTHY W. EVANS
Journal: American Journal of Respiratory and Critical Care Medicine (1999)

Experimental sepsis induces disturbances in microcirculatory flow and nutrient exchange that may result in impaired tissue oxygenation. Volume resuscitation is a principal clinical intervention in patients with sepsis. Nitric oxide (NO) has been implicated in the pathophysiology of endotoxemia, but few data exist concerning the effects of either NO synthase inhibition (NOSi) or volume resuscitation on microvascular regulation and tissue oxygenation. Amperometric measurements were made of skeletal muscle (tissue) oxygen tension (PtO2 ) and its response to changes in fraction of inspired oxygen (Fi O2 ) in rats rendered endotoxemic. Simultaneous measurements were made of systemic hemodynamic indices and arterial blood gas tensions. At normal PaO2 , PtO2 in endotoxemic animals was significantly lower than in control animals, with marked attenuation of the response to increasing Fi O2 . These changes were associated with significant metabolic acidemia. In volume-resuscitated endotoxemic rats, PtO2 and blood pH were unchanged. A significant reduction in the PtO2 response to hyperoxia was observed in animals treated with the NOS inhibitor N G-nitro-l-arginine methyl ester (l-NAME), an effect not reversed by fluid resuscitation. These data suggest that significant tissue hypoxia and abnormal microvascular control occur in endotoxemia. Volume resuscitation can reverse the changes in PtO2 , whereas nitric oxide synthase (NOS) inhibition has deleterious effects on muscle PtO2 in both control and endotoxemic animals.
Antioxidant Intervention Attenuates Myocardial Neovascularization in Hypercholesterolemia
Authors: Xiang-Yang Zhu, Martin Rodriguez-Porcel, Michael D. Bentley, Alejandro R. Chade, Vincenzo Sica, Claudio Napoli, Noel Caplice, Erik L. Ritman, Amir Lerman, Lilach O. Lerman
Journal: Circulation (2004)

Hypercholesterolemia (HC) and atherosclerosis can elicit oxidative stress, coronary endothelial dysfunction, and myocardial ischemia, which may induce growth-factor expression and lead to myocardial neovascularization. We tested the hypothesis that chronic antioxidant intervention in HC would attenuate neovascularization and preserve the expression of hypoxia-inducible factor (HIF)-1alpha and vascular endothelial growth factor (VEGF).Three groups of pigs (n=6 each) were studied after 12 weeks of normal or 2% HC diet or HC+antioxidant supplementation (100 IU/kg vitamin E and 1 g vitamin C daily). Myocardial samples were scanned ex vivo with a novel 3D micro-CT scanner, and the spatial density and tortuosity of myocardial microvessels were determined in situ. VEGF mRNA, protein levels of VEGF and VEGF receptor-1, HIF-1alpha, nitrotyrosine, and superoxide dismutase (SOD) were determined in myocardial tissue. The HC and HC+antioxidant groups had similar increases in serum cholesterol levels. HC animals showed an increase in subendocardial spatial density of microvessels compared with normal (160.5+/-11.8 versus 95.3+/-8.2 vessels/cm2, P<0.05), which was normalized in HC+antioxidant (92.5+/-20.5 vessels/cm2, P<0.05 versus HC), as was arteriolar tortuosity. In addition, HC induced upregulation of VEGF, HIF-1alpha, and nitrotyrosine expression and decreased SOD expression and activity, all of which were preserved by antioxidant intervention.Changes in myocardial microvascular architecture invoked by HC are accompanied by increases in HIF-1alpha and VEGF expression and attenuated by antioxidant intervention. This underscores a role of increased oxidative stress in modulating myocardial microvascular architecture in early atherogenesis.
The study of varicocele through the use of animal models
Authors: T. T. Turner
Journal: Human Reproduction Update (2001)

The pathophysiology of the varicocele has received considerable study, both in humans and in animal models. Mechanistic information is difficult to obtain from human subjects because study designs must not be invasive and the subject population is variable in the status of the varicocele, patient age, fertility or other health-related issues. Because of these limitations, animal models of varicocele have been developed in several species, the most common being the rat. Surgery to establish the varicocele involves partial obstruction of the left renal vein, causing a varicosity of the left spermatic vein, including the pampiniform plexus. Studies using this model have shown that experimental left varicocele induces bilateral increases in testicular blood flow and temperature contemporaneous with decreases in intratesticular testosterone and testicular sperm output. Spermatic vein reflux is not related to the pathophysiological consequences of experimental varicocele. Many questions remain regarding the mechanism by which varicocele induces testicular dysfunction, chief among them being how the unilateral varicocele causes a bilateral testicular response in the first place.