tbuckley/cabot-search huggingface dataset:
Abstract 3737: The Association Between Therapy With Insulin Glargine Versus Nph And The Risk Of Myocardial Infarction In Patients With Type 2 Diabetes
Authors: Mikhail Kosiborod, Quanwu Zhang, JoAnne Foody
Journal: Circulation (2007)

Background: Prior studies have demonstrated that insulin glargine produces less hypoglycemia, as compared with NPH. Whether these results translate into better long-term cardiovascular outcomes in patients with Type 2 diabetes is unknown. Methods: Using a national managed care administrative database, we evaluated patients with Type 2 diabetes who were on oral antiglycemic agents within 6 months prior to initiating either insulin glargine (n=15,039) or NPH (n=5,666) and had at least 12 months of subsequent continuous plan enrollment during 03/2001–03/2005. Cox proportional hazard models were used to compare the rate of subsequent myocardial infarction (MI) events (defined by ICD-9 codes) following initiation of glargine vs NPH, after adjusting for demographic characteristics, comorbidities, other medications, insulin adherence and baseline Hemoglobin A1C (A1C). Results: Mean age was 56 years, 49% were women; mean duration of follow up was 24 months. Among patients who had available A1C (n=2514), those in glargine group had higher A1C at baseline vs. NPH (9.3 vs 8.9 respectively, p&lt;0.0001). During the 1 st year following insulin initiation, 8.7% patients in NPH vs. 7.5% in glargine group had at least one medical claim for hypoglycemia (OR=1.17, 95% CI: 1.05–1.31). In unadjusted analysis, the rate of MI events was 4.4% in glargine group vs. 7.7% in the NPH group (p&lt;0.0001). After multivariable adjustment, risk of MI events remained lower in glargine group (HR: 0.78, 95% CI: 0.64–0.95). Although hypoglycemic events were associated with higher MI risk (HR 1.3, 95% CI 1.18–1.44 for each quarter with a medical claim for hypoglycemia during 1 st year of follow up), the association between glargine use and lower risk of MI events remained significant even after adjusting for hypoglycemia (HR: 0.79, 95% CI 0.65–0.96). Conclusion: Initiation of insulin glargine in patients with Type 2 diabetes is associated with lower risk of subsequent MI events, as compared with NPH. Lower rate of hypoglycemia associated with glargine use does not completely account for this difference in outcomes. Further studies are needed to validate these results and provide insights into potential physiologic mechanisms.
Detection of Ocular Malignancies
Authors: C J Lyons, J Hungerford
Journal: Journal of the Royal Society of Medicine (1990)

The case notes of new patients attending the oncology clinic at Moorfields Eye Hospital during the first 5 months of 1988 were analysed retrospectively with regard to the origin of the primary referral, the presence of symptoms, the diagnosis and management. Sixty-eight of 94 new patients were diagnosed as having malignant ocular lesions. Of these 68, 47% were first seen and referred by an optician. Half of these patients were asymptomatic at the time of detection.
Impact of Mitral Valve Regurgitation Evaluated by Intraoperative Transesophageal Echocardiography on Long-Term Outcomes After Coronary Artery Bypass Grafting
Authors: Jacob N. Schroder, Matthew L. Williams, Jonathan A. Hata, Lawrence H. Muhlbaier, Madhav Swaminathan, Joseph P. Mathew, Donald D. Glower, Christopher M. O’Connor, Peter K. Smith, Carmelo A. Milano
Journal: Circulation (2005)

It is unclear if mild or moderate mitral valve regurgitation (MR) should be repaired at the time of coronary artery bypass grafting (CABG). We sought to determine the long-term effect of uncorrected MR, measured by intraoperative transesophageal echocardiography (TEE), in CABG patients.Between May 1999 and September 2003, data were gathered for 3264 consecutive patients who underwent isolated CABG and had MR graded by intraoperative TEE. MR was graded on the following 5 levels: none, trace, mild, moderate, and severe. Patients who had severe MR or who underwent mitral valve surgery were eliminated from the analysis. The remaining patients were combined into the following 3 groups: none or trace, mild, and moderate MR. Preoperative and follow-up data were 99% complete. The median length of follow-up was 3.0 years. Multivariable analysis controlling for important preoperative risk factors was performed to determine predictors of death and death/hospitalization for heart failure. Increasing MR was a risk factor for death [hazard ratio (HR), 1.44; P<0.001] and death/heart failure hospitalization (HR, 1.34; P<0.01). When patients with moderate MR were eliminated from the analysis, mild MR was a risk factor for death (HR, 1.34; P=0.011) and death/hospitalization for heart failure (HR, 1.34; P<0.001).Even mild MR, identified by intraoperative TEE, predicts worse outcomes after CABG. Revascularization alone did not eliminate the negative long-term effects of mild MR. CABG patients with uncorrected mild or moderate MR are at increased risk for death and heart-failure hospitalization; consideration for surgical repair or more aggressive medical management and follow-up is warranted.
Abstract 13828: Safety During Treadmill Exercise in Patients With High Gradient Hypertrophic Cardiomyopathy.
Authors: Lars L Sorensen, Aurelio Pinheiro, Hsin-Yueh Liang, Miguel S Tomas, Hagit Shatkay, Raimond Winslow, Veronica Dimaano, Blaid Mbiyangandu, Kristian Eskesen, Niels T Olsen, Thomas Fritz-Hansen, Peter Sogaard, Theodore P Abraham
Journal: Circulation (2011)
Abstract B46: Epigenetic alterations associated with platinum resistance in an ovarian cancer cell model
Authors: Sabrina L. Samudio-Ruiz, Michaela L. Granados, Laurie G. Hudson
Journal: Clinical Cancer Research (2015)

Abstract Platinum resistance in ovarian cancer continues to be an impediment to clinical effectiveness. While multiple alterations associated with platinum resistance have been proposed, mechanisms responsible for those alterations, particularly epigenetic alterations, are still under investigation. Epigenetic alterations, specifically epigenetic silencing induced by DNA methylation, to genes involved in drug response is a common occurrence in platinum resistance. We have previously published that activation of the Epidermal Growth Factor Receptor (EGFR) in ovarian cancer cells increases activity of DNA methyltransferases (DNMTs) and extended EGFR activation can also increase global DNA methylation. In a concurrent abstract, we show that acute cisplatin treatment activates the EGFR and increases DNMT activity. Our overarching hypothesis for this work is that the EGFR is a key player in the development of platinum resistance by its ability to regulate DNMT activity and DNA methylation and thereby could be a therapeutic target for preventing acquisition of platinum resistance during chemotherapeutic treatment. Here, we show data obtained using a cellular model of platinum resistance that we have generated in the lab. We show that OVCA 433 cells treated repeatedly with increasing doses of cisplatin acquire resistance and demonstrate resistance in a 3D model which is more indicative of the ovarian cancer cell microenvironment. These cisplatin resistant cells (CPR) also display significantly increased DNMT activity compared to passage control (non-resistant) cells, with modest increases in global DNA methylation. While hyperactivation of the EGFR is not observed in this chronic model of cisplatin treatment, we do see a significant decrease in Copper transporter 1 (CTR1) levels in CPR cells. CTR1 is particularly important in cisplatin drug uptake, thus we believe that platinum resistance in CPR cells is due to downregulation of CTR1 potentially by DNA methylation. Current studies are evaluating DNA methylation of CTR1 and other genes that may be contributing to the development of platinum resistance. Future studies inhibiting the EGFR during cisplatin treatment will be imperative in linking cisplatin induced EGFR activation to the changes in DNMT activity and methylation that we are observing in our model of platinum resistance. This work implicates EGFR driven alterations to DNMT activity and DNA methylation as a novel mechanism for development of platinum resistance. Citation Format: Sabrina L. Samudio-Ruiz, Michaela L. Granados, Laurie G. Hudson. Epigenetic alterations associated with platinum resistance in an ovarian cancer cell model. [abstract]. In: Proceedings of the AACR Precision Medicine Series: Drug Sensitivity and Resistance: Improving Cancer Therapy; Jun 18-21, 2014; Orlando, FL. Philadelphia (PA): AACR; Clin Cancer Res 2015;21(4 Suppl): Abstract nr B46.
Phase II trial of biweekly paclitaxel and cisplatin in advanced breast carcinoma: an Eastern Cooperative Oncology Group study.
Authors: J A Sparano, D Neuberg, J H Glick, N J Robert, L J Goldstein, G W Sledge, W Wood
Journal: Journal of Clinical Oncology (1997)

PURPOSE To determine the efficacy of a biweekly paclitaxel and cisplatin regimen in patients with advanced breast carcinoma, which has previously been reported to produce an 85% response rate in such patients. PATIENTS AND METHODS Sixteen patients with metastatic breast carcinoma who had relapsed after prior doxorubicin-containing adjuvant chemotherapy were treated with paclitaxel (90 mg/m2) by intravenous (i.v.) infusion over 3 hours followed by cisplatin (60 mg/m2) given by i.v. infusion over 1 hour on an outpatient basis. Treatment was repeated every 2 weeks if the absolute neutrophil count was &gt; or = 750/microL and platelet count &gt; or = 75,000/microL. After a maximum of eight cycles of paclitaxel/cisplatin, patients received biweekly paclitaxel alone (90 mg/m2 with dose escalation). Thirteen patients were assessable for response and all for toxicity. Nine of 13 patients assessable for response (69%) had at least three sites of metastases and 10 patients (77%) had visceral-dominant disease. RESULTS Partial response occurred in three of 13 assessable patients (23%; 90% confidence interval, 7% to 49%). All responders had two or fewer sites of metastases. The median time to progression was 4.3 months and the median survival duration was 11.4 months. Patients received a median of seven cycles of therapy (range, two to 21). Severe and/or life-threatening toxicity occurred in 50% and 38%, respectively, and consisted primarily of granulocytopenia, anemia, and neuropathy. The trial was terminated after the first interim analysis as per its two-stage design, since it was unlikely that the response rate would exceed 70%. CONCLUSION Biweekly paclitaxel/cisplatin is not likely to produce a response rate greater than 70% in patients with metastatic breast cancer who have relapsed after prior doxorubicin-containing adjuvant chemotherapy and who have multiple sites of metastases and/or visceral-dominant disease.
Comparison of the fine particle fraction of fluticasone propionate/formoterol fumarate combination with other combination products
Authors: Johal Baljinder, Markus Howald, Manfred Fischer, Jonathan Marshall
Journal: European Respiratory Journal (2012)

Background : A combination of the inhaled corticosteroid, fluticasone propionate, and the long-acting β2-agonist, formoterol fumarate has been developed in an aerosol inhaler (FLUT/FORM). As changes in flow rate have been shown to affect the in-vitro performance of inhalers, which could compromise in-vivo performance, this study evaluated the effect of flow rate on fine particle fraction (FPF) and dose (FPD) of FLUT/FORM and three available combination products.   Methods : Dose strengths used to deliver comparable treatment doses (FLUT/FORM, 250/10µg; beclomethasone/formoterol (BDP/FORM) pMDI, 200/12g; fluticasone/salmeterol (FLUT/SAL) DPI, 250/50µg; budesonide/formoterol (BUD/FORM) DPI, 400/12µg) were compared. Aerodynamic particle size distribution was determined by Andersen Cascade Impaction at 28.3L/min and 60L/min flow rates with a cut-off diameter of 5.0 µM and was calculated as % of label claim.   Results : FLUT/FORM provided a consistent and high FPF of approximately 40% for each component, with less than a 10% relative difference in the FPD emitted between flow rates. FLUT/FORM provided the highest FPF at both flow rates with BUD/FORM and FLUT/SAL delivering a FPF of less than 20% at 28.3L/min. The FPD of all three comparator products evaluated were affected by increases in flow rate from 28.3L/min to 60L/min, with BUD/FORM having a ∼5 fold increase in FPD between flow rates and BDP/FORM showing a 50% difference.  Conclusion:  The data confirm that FLUT/FORM emits a high FPF of approximately 40%. These data also demonstrate that FLUT/FORM has a higher FPF, that is less affected by changes in flow rate, than other combination products assessed.
Position paper of the EAACI: food allergy due to immunological cross-reactions with common inhalant allergens
Authors: T. Werfel, R. Asero, B. K. Ballmer‐Weber, K. Beyer, E. Enrique, A. C. Knulst, A. Mari, A. Muraro, M. Ollert, L. K. Poulsen, S. Vieths, M. Worm, K. Hoffmann‐Sommergruber
Journal: Allergy (2015)

In older children, adolescents, and adults, a substantial part of all IgE-mediated food allergies is caused by cross-reacting allergenic structures shared by inhalants and foods. IgE stimulated by a cross-reactive inhalant allergen can result in diverse patterns of allergic reactions to various foods. Local, mild, or severe systemic reactions may occur already after the first consumption of a food containing a cross-reactive allergen. In clinical practice, clinically relevant sensitizations are elucidated by skin prick testing or by the determination of specific IgE in vitro. Component-resolved diagnosis may help to reach a diagnosis and may predict the risk of a systemic reaction. Allergy needs to be confirmed in cases of unclear history by oral challenge tests. The therapeutic potential of allergen immunotherapy with inhalant allergens in pollen-related food allergy is not clear, and more placebo-controlled studies are needed. As we are facing an increasing incidence of pollen allergies, a shift in sensitization patterns and changes in nutritional habits, and the occurrence of new, so far unknown allergies due to cross-reactions are expected.
Bradykinin Preconditioning Improves the Profile of Cell Survival Proteins and Limits Apoptosis After Cardioplegic Arrest
Authors: Jun Feng, Cesario Bianchi, Jennifer L. Sandmeyer, Frank W. Sellke
Journal: Circulation (2005)

Background— We hypothesized that preconditioning the heart with bradykinin (BK) would improve the profile of antiapoptotic proteins and inhibit myocardial apoptosis. Methods and Results— Eighteen rabbit hearts were retrogradely perfused with Krebs-Henseleit buffer (KHB). Six control hearts were perfused with KHB for 90 minutes without cardioplegia ischemia. Six hearts were arrested for 30 minutes (37°C) with crystalloid cardioplegia (CCP). Six BK preconditioning (BKPC) hearts received a 10-minute coronary infusion of 10 −8 M BK-enriched KHB followed by a 5-minute recovery period and were then arrested for 30 minutes with CCP. The hearts were reperfused for 30 minutes with KHB. BKPC significantly improved the recovery of left ventricular pressure (73±5 versus 51±4 mm Hg; P &lt;0.05) and reduced the percentage of myocardial apoptosis (3.4±0.3% versus 1.2±0.2%; P &lt;0.05) as compared with CCP. There were no significant differences in total protein levels of caspase 3, Bcl-2, Bad, and Bax, among the groups. Both BKPC and CCP induced phosphorylation of Bad at Ser 112 , but the BKPC group had higher phosphorylated Bad than CCP (4.4±0.5 versus 2.0±0.3; P &lt;0.05). Both BKPC and CCP alone increased caspase 3 cleavage and activity as compared with controls ( P &lt;0.05 and P &lt;0.01, respectively), but BKPC caused less cleavage and activation of caspase 3 than CCP alone ( P &lt;0.05). Conclusions— BKPC increased Bad phosphorylation, inhibited caspase 3 activation, and limited myocardial apoptosis, which were associated with improvement of left-ventricular performance. These results identify novel molecular mechanisms underlying the protective effects of BKPC during cardiac surgery.
COPD and work absenteeism: Birmingham COPD cohort
Authors: Kiran Kalirai, Peymane Adab, Rachel Jordan, David Fitzmaurice, Jon Ayres
Journal: European Respiratory Journal (2014)

Introduction 

Around 5% of UK sickness absence (absenteeism) is due to COPD. However we know little about which factors are related to absenteeism in COPD patients to inform future interventions.

Aims and objectives 

To carry out a cross-sectional analysis to assess factors associated with absenteeism in a primary care COPD cohort

Methods 

Interim baseline data from a primary care cohort of COPD patients was used. We examine the associations between absenteeism and sociodemographic, clinical and occupational characteristics.

Results 

Of 1700 COPD patients, 16.7% (n=283) were in work, of which ∼49% (n=139) reported absenteeism (> 1 day over 12m). Patients with absenteeism were more likely to be female (57.0% vs 44.4%), slightly younger (mean age 59.2 vs. 61.1) and to have ever smoked (47.8% vs. 42.1%) compared to those without. They were also more likely to report dyspnoea (p for trend  3). However there were no significant associations with disease severity (GOLD stage). Using a logistic regression model including income level in addition to all the above covariates, increasing number of exacerbations (p for trend > 0.01) remained the only factor independently associated with self-reported absenteeism.

Conclusions 

This is the first UK primary care study to assess associations between COPD and absenteeism. Interventions to reduce COPD exacerbations should be a focus in trials aimed at improving work productivity.
Polymorphisms in Genes Encoding Potential Mercury Transporters and Urine Mercury Concentrations in Populations Exposed to Mercury Vapor from Gold Mining
Authors: Karin Engström, Shegufta Ameer, Ludovic Bernaudat, Gustav Drasch, Jennifer Baeuml, Staffan Skerfving, Stephan Bose-O’Reilly, Karin Broberg
Journal: Environmental Health Perspectives (2012)

Background: Elemental mercury (Hg0) is widely used in small-scale gold mining. Persons working or living in mining areas have high urinary concentrations of Hg (U-Hg). Differences in genes encoding potential Hg-transporters may affect uptake and elimination of Hg.Objective: We aimed to identify single nucleotide polymorphisms (SNPs) in Hg-transporter genes that modify U-Hg.Methods: Men and women (1,017) from Indonesia, the Philippines, Tanzania, and Zimbabwe were classified either as controls (no Hg exposure from gold mining) or as having low (living in a gold-mining area) or high exposure (working as gold miners). U-Hg was analyzed by cold-vapor atomic absorption spectrometry. Eighteen SNPs in eight Hg-transporter genes were analyzed.Results: U-Hg concentrations were higher among ABCC2/MRP2 rs1885301 A–allele carriers than among GG homozygotes in all populations, though differences were not statistically significant in most cases. MRP2 SNPs showed particularly strong associations with U-Hg in the subgroup with highest exposure (miners in Zimbabwe), whereas rs1885301 A–allele carriers had higher U-Hg than GG homozygotes [geometric mean (GM): 36.4 µg/g creatinine vs. 21.9; p = 0.027], rs2273697 GG homozygotes had higher U-Hg than A–allele carriers (GM: 37.4 vs. 16.7; p = 0.001), and rs717620 A–allele carriers had higher U-Hg than GG homozygotes (GM: 83 vs. 28; p = 0.084). The SLC7A5/LAT1 rs33916661 GG genotype was associated with higher U-Hg in all populations (statistically significant for all Tanzanians combined). SNPs in SLC22A6/OAT1 (rs4149170) and SLC22A8/OAT3 (rs4149182) were associated with U-Hg mainly in the Tanzanian study groups.Conclusions: SNPs in putative Hg-transporter genes may influence U-Hg concentrations.
Impact of cytogenetic classification on outcomes following early high-dose therapy in multiple myeloma
Authors: G P Kaufman, M A Gertz, A Dispenzieri, M Q Lacy, F K Buadi, D Dingli, S R Hayman, P Kapoor, J A Lust, S Russell, R S Go, Y L Hwa, R A Kyle, S V Rajkumar, S K Kumar
Journal: Leukemia (2015)
Allogeneic versus autologous purged bone marrow transplantation for neuroblastoma: a report from the Childrens Cancer Group.
Authors: K K Matthay, R C Seeger, C P Reynolds, D O Stram, M C O'Leary, R E Harris, M Selch, J B Atkinson, G M Haase, N K Ramsay
Journal: Journal of Clinical Oncology (1994)

PURPOSE We have compared the toxicity, relapse rate, and progression-free survival (PFS) of high-risk neuroblastoma patients receiving identical induction therapy and myeloablative chemotherapy plus total-body irradiation (TBI) followed by allogeneic or autologous purged bone marrow transplantation (BMT). PATIENTS AND METHODS Fifty-six patients with high-risk neuroblastoma underwent BMT at investigator and parent option if they did not have progressive disease after induction chemotherapy with cisplatin, cyclophosphamide, doxorubicin, and etoposide. After surgery and local radiation to residual tumor, myeloablative therapy consisting of etoposide, melphalan, cisplatin, and TBI was given followed by BMT. Patients with human leukocyte antigen (HLA)-compatible siblings received allogeneic bone marrow (n = 20). The remaining patients (n = 36) received autologous bone marrow that had undergone multimodality purging and had no remaining detectable tumor cells by immunocytology. RESULTS Four of 20 allogeneic patients had a treatment-related death, compared with three of 36 autologous patients (P = .21). The relapse rate among allogeneic BMT patients was 69%, compared with 46% for autologous BMT patients (P = .14). The estimated PFS rates 4 years after BMT were 25% for allogeneic BMT patients and 49% for autologous BMT patients (P = .051). CONCLUSION Overall outcome for patients with neuroblastoma given this same induction therapy followed by autologous purged marrow was similar to that with allogeneic marrow, although bias in patients selection cannot be excluded in a nonrandomized comparison.