tbuckley/cabot-search huggingface dataset:
Heart Rate and Cardiac Rhythm Relationships With Bisoprolol Benefit in Chronic Heart Failure in CIBIS II Trial
Authors: Philippe Lechat, Jean-Sébastien Hulot, Sylvie Escolano, Alain Mallet, Alain Leizorovicz, Marie Werhlen-Grandjean, Gilbert Pochmalicki, Henry Dargie
Journal: Circulation (2001)

beta-Blockade-induced benefit in heart failure (HF) could be related to baseline heart rate and treatment-induced heart rate reduction, but no such relationships have been demonstrated.In CIBIS II, we studied the relationships between baseline heart rate (BHR), heart rate changes at 2 months (HRC), nature of cardiac rhythm (sinus rhythm or atrial fibrillation), and outcomes (mortality and hospitalization for HF). Multivariate analysis of CIBIS II showed that in addition to beta-blocker treatment, BHR and HRC were both significantly related to survival and hospitalization for worsening HF, the lowest BHR and the greatest HRC being associated with best survival and reduction of hospital admissions. No interaction between the 3 variables was observed, meaning that on one hand, HRC-related improvement in survival was similar at all levels of BHR, and on the other hand, bisoprolol-induced benefit over placebo for survival was observed to a similar extent at any level of both BHR and HRC. Bisoprolol reduced mortality in patients with sinus rhythm (relative risk 0.58, P:<0.001) but not in patients with atrial fibrillation (relative risk 1.16, P:=NS). A similar result was observed for cardiovascular mortality and hospitalization for HF worsening.BHR and HRC are significantly related to prognosis in heart failure. beta-Blockade with bisoprolol further improves survival at any level of BHR and HRC and to a similar extent. The benefit of bisoprolol is questionable, however, in patients with atrial fibrillation.
Fetal hemoglobin synthesis in sickle cell anemia: Some molecular considerations
Authors: Kabita Bhaumik
Journal: American Journal of Hematology (1994)

Abstract An ability to maintain high levels of fetal hemoglobin (Hb F) has been associated with the amelioration of the clinical severity of the sickle cell disease (SS). Clinical efforts to increase the Hb F level of the patients have, however, yielded variable therapeutic response. In an attempt to further elucidate the underlying molecular basis, in vitro Hb F synthesis was studied in erythroid progenitor (BFU‐E) cells obtained from SS patients and their heterozygous (AS) relatives with varying genetic backgrounds. This allows us to study the Hb F biosynthesis pattern uncomplicated by the influence of the preferential survival of “F cells” In vivo. The Hb F levels and the relative concentrations of its constituent gamma globin chains, G γ and A γ , were assayed using the reversed phase HPLC method. A percentage increase in the fetal hemoglobin content was observed in the lysates of the erythroid progenitor cells relative to the circulating peripheral blood erythrocyte values in SS patients and their AS relatives with different β s haplotypes reflecting the intrinsic capacity of fetal hemoglobin synthesis in these subjects. No such increase was observed in the patient with the Mor haplotype. Furthermore, the Hb F synthesized in the BFU‐E colonies was more of the adult type, as evidenced by the decrease in the percent G γ level relative to the corresponding peripheral blood values of the subjects in all the haplotype groups studied. The Mor haplotype was again an exception, synthesizing fetal hemoglobin more of the fetal type. © 1994 Wiley‐Liss, Inc.
Anticardiolipin autoantibodies in serum samples and cryoglobulins of patients with chronic hepatitis C infection
Authors: Z. M Sthoeger
Journal: Annals of the Rheumatic Diseases (2000)

<h3>OBJECTIVE</h3> Chronic hepatitis C virus (HCV) has been linked to extrahepatic autoimmune phenomena. In addition, a variety of autoantibodies are found in patients with HCV. The prevalence, nature, and clinical significance of anticardiolipin (aCL) autoantibodies in serum samples of patients with HCV were therefore investigated. <h3>PATIENTS AND METHODS</h3> A prospective study of 48 consecutive patients with chronic HCV with no evidence of previous hepatitis B virus (HBV) infection or any other autoimmune disorder. Thirty patients with HBV and 50 healthy volunteers matched for age and sex served as control groups. Anticardiolipin antibodies in the serum samples and cryoprecipitates were measured by a sensitive enzyme linked immunosorbent assay (ELISA). The β<sub>2</sub> glycoprotein I (β<sub>2</sub>-GPI) dependency was determined by carrying out aCL assays in the presence or absence of fetal calf serum samples. <h3>RESULTS</h3> High levels of IgG aCL antibodies were detected in serum samples of 21/48 (44%) patients with HCV. These autoantibodies showed no β<sub>2</sub>-GPI dependency. The control groups had much lower levels of aCL antibodies (20% in the patients with HBV and none in the normal volunteers). Cryoprecipitates from four patients with HCV (three aCL positive; one aCL negative) were further isolated. In two of the three aCL positive patients, specific cardiolipin reactivity was shown in the cryoprecipitates. The group of patients with HCV and aCL antibodies in their serum showed significantly higher total IgG levels, a higher incidence of antinuclear antibodies, and viraemia (HCV RNA) than the aCL negative patients. None of the patients with HCV and aCL antibodies showed any clinical manifestations related to those autoantibodies. <h3>CONCLUSIONS</h3> This study clearly shows a high prevalence of IgG aCL antibodies in the serum of patients with HCV and the localisation of these antibodies in some cryoprecipitates. The role of these autoantibodies on the course of HCV infection and their clinical significance has not yet been determined.
Absolute lymphocyte count at day 28 independently predicts event‐free and overall survival in adults with newly diagnosed acute lymphoblastic leukemia
Authors: Di Sun, Paul Elson, Michaela Liedtke, Bruno C. Medeiros, Marc Earl, Ash Alizadeh, Jennifer Bates, Mikkael A. Sekeres, Steven Coutre, Matt Kalaycio, Ronald Sobecks, Edward Copelan, Anjali S. Advani
Journal: American Journal of Hematology (2012)

We investigated the prognostic impact of absolute lymphocyte count (ALC) following induction chemotherapy in newly diagnosed adult acute lymphoblastic leukemia (ALL). Patients with ALC ≥350 cells/μL at day 28 had a median overall survival (OS) of 47.4 months when compared with 17.6 months for those with an ALC <350 cells/μL (HR = 1.98, P = 0.007). Among patients who achieved a complete remission, median event-free survival (EFS) for those with ALC ≥350 cells/μL on day 28 was 42.1 months when compared with 13.9 months in those with ALC <350 cells/μL (HR = 2.08, P = 0.006). In multivariable analysis, the ALC on day 28 (<350 cells/μL vs. ≥350 cells/μL, P ≤ .0004 for OS and EFS) along with WBC at diagnosis (≤6.0 or >30.0 K/μL vs. >6.0-30.0 K/μL, P ≤ 0.002 for OS and EFS) and cytogenetics (abnormal vs. normal, P = 0.002 for OS and P = 0.02 for EFS) were independent prognostic factors of both OS and EFS. Combining these three factors segregates patients in three well-defined risk groups. These data suggest that ALC can be used in combination with other prognostic features to better predict outcome and that targeting the immune system to improve ALC may be a worthwhile strategy in ALL.
Overexpression of Transforming Growth Factor β1 in Head and Neck Epithelia Results in Inflammation, Angiogenesis, and Epithelial Hyperproliferation
Authors: Shi-Long Lu, Douglas Reh, Allen G. Li, Jennifer Woods, Christopher L. Corless, Molly Kulesz-Martin, Xiao-Jing Wang
Journal: Cancer Research (2004)

Abstract In the present study, we show that transforming growth factor β1 (TGF-β1) was frequently overexpressed in human head and neck squamous cell carcinomas (HNSCCs) and adjacent tissues in comparison with normal head and neck tissues. To determine the role of TGF-β1 overexpression in HNSCC carcinogenesis, we generated transgenic mice in which TGF-β1 transgene expression can be induced in head and neck epithelia. TGF-β1 transgene induction in head and neck epithelia, at levels similar to those in human HNSCCs, caused severe inflammation and angiogenesis. Consequently, TGF-β1-transgenic epithelia exhibited hyperproliferation. These phenotypes correlated with enhanced Smad signaling in transgenic epithelia and stroma. Our study suggests that TGF-β1 overexpression at early stages of HNSCC formation provides a tumor promoting microenvironment.
Combined treatment with C1 esterase inhibitor and antithrombin III improves survival in severe acute experimental pancreatitis.
Authors: H Yamaguchi, H Weidenbach, H Luhrs, M M Lerch, G Dickneite, G Adler
Journal: Gut (1997)

BACKGROUND: Patients with severe acute pancreatitis die of complications closely related to the systemic activation of protease cascades. AIM: To examine the effects of human C1 esterase inhibitor (C1 INH) and antithrombin III (AT III) on two experimental models of acute pancreatitis. METHODS: Oedematous pancreatitis was induced by continuous intravenous infusion of caerulein and haemorrhagic pancreatitis by retrograde injection of sodium taurocholate into the biliopancreatic duct. C1 INH and AT III were given intravenously, either before or after the induction of pancreatitis. Treatment with C1 INH and AT III had no beneficial effect on oedematous pancreatitis. On the other hand, combined C1 INH and AT III therapy improved the survival in haemorrhagic pancreatitis compared with treatment with human serum albumin. This reduction in mortality was found regardless of whether the treatment was given prophylactically or therapeutically. CONCLUSIONS: Treatment with C1 INH and AT III represents a promising therapeutic concept for patients with severe haemorrhagic pancreatitis.
Interleukin-1β–Driven Inflammation Promotes the Development and Invasiveness of Chemical Carcinogen–Induced Tumors
Authors: Yakov Krelin, Elena Voronov, Shahar Dotan, Moshe Elkabets, Eli Reich, Mina Fogel, Monika Huszar, Yoichiro Iwakura, Shraga Segal, Charles A. Dinarello, Ron N. Apte
Journal: Cancer Research (2007)

Abstract The role of microenvironment interleukin 1 (IL-1) on 3-methylcholanthrene (3-MCA)–induced carcinogenesis was assessed in IL-1–deficient mice, i.e., IL-1β−/−, IL-1α−/−, IL-1α/β−/− (double knockout), and mice deficient in the naturally occurring inhibitor of IL-1, the IL-1 receptor antagonist (IL-1Ra). Tumors developed in all wild-type (WT) mice, whereas in IL-1β–deficient mice, tumors developed slower and only in some of the mice. In IL-1Ra–deficient mice, tumor development was the most rapid. Tumor incidence was similar in WT and IL-1α–deficient mice. Histologic analyses revealed fibrotic structures forming a capsule surrounding droplets of the carcinogen in olive oil, resembling foreign body–like granulomas, which appeared 10 days after injection of 3-MCA and persisted until the development of local tumors. A sparse leukocyte infiltrate was found at the site of carcinogen injection in IL-1β–deficient mice, whereas in IL-1Ra–deficient mice, a dense neutrophilic infiltrate was observed. Treatment of IL-1Ra–deficient mice with recombinant IL-1Ra but not with an inhibitor of tumor necrosis factor abrogated the early leukocytic infiltrate. The late leukocyte infiltrate (day 70), which was dominated by macrophages, was also apparent in WT and IL-1α–deficient mice, but was nearly absent in IL-1β–deficient mice. Fibrosarcoma cell lines, established from 3-MCA–induced tumors from IL-1Ra–deficient mice, were more aggressive and metastatic than lines from WT mice; cell lines from IL-1–deficient mice were the least invasive. These observations show the crucial role of microenvironment-derived IL-1β, rather than IL-1α, in chemical carcinogenesis and in determining the invasive potential of malignant cells. [Cancer Res 2007;67(3):1062–71]
Peripartum cardiomyopathy: a case series
Authors: Manuel Ruiz-Bailén, Asunción López-Martínez, José Ángel Ramos-Cuadra, Miguel Ángel Díaz-Castellanos, Antonio Cárdenas-Cruz, Manuel Rodríguez-Elvira, Ángel Montiel-Trujillo
Journal: Intensive Care Medicine (2000)
Complications Associated With Revision of Sprint Fidelis Leads
Authors: Ratika Parkash, Eugene Crystal, Jamil Bashir, Christopher Simpson, David Birnie, Laurence Sterns, Derek Exner, Bernard Thibault, Sean Connors, Jeffrey S. Healey, Jean Champagne, Doug Cameron, Iqwal Mangat, Atul Verma, Kevin Wolfe, Vidal Essebag, Teresa Kus, Felix Ayala-Paredes, Ted Davies, Shubhayan Sanatani, Robert Gow, Benoit Coutu, Soori Sivakumaran, Elizabeth Stephenson, Andrew Krahn
Journal: Circulation (2010)

It has been observed that replacement of an implantable cardioverter-defibrillator generator in response to a device advisory may be associated with a substantial rate of complications, including death. The risk of lead revision in response to a lead advisory has not been determined previously.Twenty-five implantable cardioverter-defibrillator implantation and follow-up centers from the Canadian Heart Rhythm Society Device Advisory Committee were surveyed to assess complication rates as a result of lead revisions due to the Sprint Fidelis advisory issued in October 2007. As of June 1, 2009, there had been 310 lead failures found in 6237 Sprint Fidelis leads in Canada (4.97%) over a follow-up of 40 months. There were 469 leads to be revised, 66% for confirmed fracture. Of the patients who underwent revision, 95% had a new lead inserted, whereas 4% had a pace/sense lead added. The lead was removed in 248 cases (53%), by simple traction in 61% and by laser lead extraction in 33%. Complications were encountered in 14.5% of the lead revisions; 7.25% of these were major, whereas 7.25% were minor. There were 2 deaths (0.43%). The overall risk of complications (19.8%) was greater in those who underwent lead removal at the time of revision than in those whose leads were abandoned (8.6%; P=0.0008).The overall rate of major complications that arose from lead revision due to the Sprint Fidelis advisory was significant. This must be taken into account when lead revision is planned in those patients who have not yet demonstrated an abnormality in lead performance.
Abstract 2873: Epithelial NF-κB signaling is required for different functions in Kras- and EGFR-mediated lung tumorigenesis.
Authors: Jamie A. Ausborn, Taylor Sherrill, Rinat Zaynagetdinov, Vasiliy Polosukhin, Frank McMahon, Fiona Yull, Timothy Blackwell
Journal: Cancer Research (2013)

Abstract The transcription factor nuclear factor-κB (NF-κB) is a key mediator of the inflammatory response, and its activation correlates with poor prognosis in non-small cell lung cancer patients. Oncogenic KRAS and epidermal growth factor receptor (EGFR) mutations occur frequently in lung adenocarcinoma and are associated with increased NF-κB activation in lung tumors. Recent papers have shown that inhibition of epithelial NF-κB signaling in a mouse model of Kras-mediated lung tumorigenesis decreases tumor formation. However, the mechanisms linking NF-κB signaling to tumor formation remain unclear. We hypothesize that epithelial NF-κB signaling is a common requirement for lung tumorigenesis. For our studies, we used mice that inducibly express oncogenic KrasG12D or EGFRL858R+T790M as well as a dominant negative inhibitor of κB signaling (DN-IκB) in Clara Cell Specific Protein (CCSP)-expressing lung epithelium (designated KrasDN or EGFRDN mice). EGFRDN mice developed smaller and fewer tumors after two months of doxycycline administration compared to mice expressing EGFRL858R+T790M alone, while KrasDN mice did not develop any tumors. In KrasDN mice, loss of Kras transgene expression and increased cell death were observed after one week of doxycycline, suggesting that NF-κB signaling may be required for survival of Kras mutant cells in vivo. In EGFRDN mice, NF-κB inhibition led to a significant reduction in the percentage of BAL neutrophils when compared to mice expressing EGFRL858R+T790M alone. In addition, NF-κB inhibition led to reduced expression of CXCR2 ligands CXCL1 and CXCL2, which are known NF-κB-regulated neutrophil chemoattractants. In vitro inhibition of CXCR2 did not affect proliferation of EGFR-mutant cells, suggesting that the critical function of CXCL1 and CXCL2 may be inflammatory cell recruitment/activation. Future studies will investigate the effects of CXCR2 inhibition and neutrophil depletion on EGFR-mediated tumor formation in vivo. Together, these results suggest that NF-κB signaling is required for both Kras- and EGFR-mediated lung tumorigenesis, but NF-κB's function in a tumor may depend on the driver mutation. From these studies, we hope to identify NF-κB-regulated genes critical for tumor formation as potential targets for the development of better therapeutic strategies for lung cancer patients. Citation Format: Jamie A. Ausborn, Taylor Sherrill, Rinat Zaynagetdinov, Vasiliy Polosukhin, Frank McMahon, Fiona Yull, Timothy Blackwell. Epithelial NF-κB signaling is required for different functions in Kras- and EGFR-mediated lung tumorigenesis. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2873. doi:10.1158/1538-7445.AM2013-2873
Abstract 5445: Universal bioluminescent HTS-formatted assay for quantitation of ADP production in kinase and ATPase reactions
Authors: Said A. Goueli, Kevin Hsiao, Marina Zdanovskaia, Jolanta Vidugiriene, Hicham Zegzouti
Journal: Cancer Research (2011)

Abstract Protein Kinases are implicated in metabolic and cellular disorders including cancer and thus they represent a very important target for the development of novel therapeutics. The process of developing new drug requires an innovative and low cost strategy to screen and identify compounds that can be used for lead optimization that incorporate the required desirable features. It will be idea to have a universal technology that can be used for the various stages of drug discovery such as assay development, compound screening, lead optimization, and enzyme profiling using the same technology platform. The technology should provide high sensitivity, robustness, and low cost. Towards that goal, we have expanded our luminescent platform for monitoring kinase activity to enable us to detect enzyme activity using low amount of enzymes, measure initial rates at very early substrate conversion, and generate reliable and robust data. This luminescent assay monitors enzyme activity by measuring ADP production using a homogenous and high through put formatted assay. The assay is also ideal for profiling compounds against various kinases since it detects ADP, the universal product of all kinases. Thus, the new homogenous assay is most suitable for drug discovery targeting kinases since it can be used in all various stages of drug development leading to animal or cellular studies. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 5445. doi:10.1158/1538-7445.AM2011-5445
The Effect of High-Dose Radioiodine Treatment on Lacrimal Gland Function in Patients With Differentiated Thyroid Carcinoma
Authors: Armaghan Fard-Esfahani, Hossein Mirshekarpour, Babak Fallahi, Mohammad Eftekhari, Mohsen Saghari, Davood Beiki, Kianoush Ansari-Gilani, Abbas Takavar
Journal: Clinical Nuclear Medicine (2007)

Purpose: There are a limited number of case reports confirming the radioiodine (I-131) presence in tears and only a few case reports of lacrimal gland dysfunction after I-131 therapy. This study was designed to clarify whether lacrimal gland function can be affected by I-131 therapy. Materials and Methods: We studied 100 eyes of 50 patients who had received high doses of I-131 for treatment of differentiated thyroid carcinoma and 100 eyes of 50 age- and sex-matched control individuals without a history of interfering conditions. The exposed group was studied at least 3 months after their last I-131 therapy. Dry eye symptoms and Schirmer test values (wetting level in millimeters per 5 minutes) of an exposed group were compared with those of an unexposed group. Results: Fifty-one percent of the exposed eyes and 50% of the unexposed ones revealed at least 1 of the dry eye symptoms. There was no significant difference in symptoms between 2 groups, except for burning sensation and eye redness, which were significantly higher in the exposed eyes. A lower Schirmer test value was noted in the exposed group, 14.5 ± 10.8 mm, when compared with that in controls, 18.2 ± 11.0 mm (P = 0.016), and the relative risk of an abnormal Schirmer test in exposed cases to control group was 1.78 ± 0.62. Correlation coefficient analysis showed no significant relationship between Schirmer test values and cumulative doses of administered I-131. Conclusions: Reduction in the tear secretion from lacrimal glands is seen after high-dose I-131 therapy; however, their symptoms are no greater than an unexposed population.
Hazards of Microwave Ovens
Authors: Milton M. Zaret
Journal: JAMA (1971)

To the Editor.—  The EDITORIAL, Microwave Ovens ( 215 :1661, 1971), contains much misleading information. My ophthalmological examinations of more than 1,000 microwave workers yielded 42 with pathognomonic signs of microwave cataract ( posterior capsular opacification), a form of thermal injury. No worker volunteered a history of sensing heat, even when specifically questioned. Hirsch and Parker in 1952 and Shimkowicz and Shilyaev in 1959 published cases of microwave cataract without reporting any sensory effects.  All of the known biological effects of microwaves, except those which may be dependent upon pulse characteristics, are relatable, no matter what the source. For example, microwave diathermy, which more closely simulates oven rather than radar application, has produced mircowave cataracts in a patient of mine.  That microwave ovens are manufactured to stringent safety standards does not make them harmless. Although these appliances have been used since 1950 without reported injuries, recently has it been discovered that the
An Intracardiac Pacemaker for Stokes-Adams Seizures
Authors: Seymour Furman, John B. Schwedel
Journal: New England Journal of Medicine (1959)

THIS paper is a report of the clinical application of an intracardiac pacemaker in the therapy of severe or intractable Stokes–Adams seizures associated with heart block. This is the first recorded description of such clinical use.The resuscitation of the heart in asystole has been a goal sought for many years. It has been known for a considerable time that the mammalian heart, either as the intact organ or as a strip of tissue, is sensitive to stimulation by an electric current. Only recently, however, has clinical use been made of this knowledge. Zoll employed an extrathoracic cardiac pacemaker in . . .