tbuckley/cabot-search huggingface dataset:
Abstract 240: Electrocardiogram Changes Associated With In-Hospital Cardiac Arrests due to Respiratory Failure
Authors: Derek Phan, Duc Do, Justin Hayase, Xiao Hu, Noel G Boyle
Journal: Circulation (2013)

Introduction: The estimated incidence of in-hospital cardiac arrests (IHCA) in US is over 200,000 annually. Respiratory related causes contribute to approximately 15% of IHCAs. Many arrests due to respiratory problems may be preventable. Thus it may be beneficial to develop methods that can identify patients at increased risk of developing respiratory related cardiac arrests particularly if clinical signs are undetected or develop rapidly. Hypothesis: ECG changes preceding respiratory related cardiac arrests may alert caregivers of an impending cardiac arrest when other clinical signs are not apparent. Methods: We reviewed all IHCA cases that occurred between April 2010 and March 2012 at UCLA Medical Center in patients age &gt; 18 years, with ECG data available at least 3 hours prior to and including the IHCA, and further analyzed cases related primarily to respiratory failure as determined by chart review. ECG data was analyzed for ECG changes prior to arrest. Results: Respiratory failure was designated as the primary cause in 17/65 (26%) of IHCAs reviewed. Of these, the mechanism of IHCA was pulseless electrical activity (PEA) in 70%, and bradyasystolic arrest in 30%; there were no ventricular tachycardia/ventricular fibrillation (VT/VF) arrests. The causes of respiratory failure included: mucous plug (41.2%), aspiration (35.3%), and pneumonia (23.5%). At least one ECG change preceding the arrest was seen in 88% of cases, and at least two ECG changes preceding the arrest was seen in 47% of cases, with an average of 1.6 ECG changes per case. Conclusions: At least one significant ECG change was recorded in approximately 90% of IHCA cases due to respiratory arrest with a median time of approximately 13 minutes prior to the arrest. This may provide an additional alert to physicians and nurses of impending cardiac arrest, and allow for earlier detection and intervention.
Tree pollen allergy
Authors: N. E. Eriksson, J‐Å. Wihl, H. Arrendal, S.‐O. Strandhede
Journal: Allergy (1987)

872 adult hay fever patients were investigated with skin tests, using 20 different tree pollen allergens, and Phadebas RAST®, using eight different tree pollen allergens. Correlation between test results with the different allergens were studied employing the Spearman's correlation coefficient (Rho). Most combinations showed statistically significant correlations. The highest values of Rho (0.8–0.9) were found for pollen from combinations of trees belonging to the families Betulaceae, Corylaceae and Fagaceae (birch, alder, hazel, beech and oak). High values were also found between pollens from aspen and sallow (belonging to Salicaceae ). With several of the trees a high degree of pollen cross sensitization was found, even with trees from a different plant family. Since most of the patients were allergic to birch pollen, some of the reactions to other pollens could be due to allergens shared by birch. To exclude this possibility, a separate analysis was performed for patients having no birch pollen allergy. Even in these patients evidence of cross sensitization was found. It is concluded that cross reactions are common among tree pollens and are most pronounced within botanical families.
Bone marker assessment as a guide to chronic use of aminobisphosphonates in multiple myeloma.
Authors: N. S. Raje, N. C. Munshi, A. K. Mahindra, S. Pozzi, P. G. Richardson, J. Laubach, I. M. Ghobrial, R. L. Schlossman, K. C. Anderson
Journal: Journal of Clinical Oncology (2010)

8140 Background: Aminobisphosphonates (aBP) are standard of care for myeloma related bone disease and are recommended every 3-4 weeks. Our previous data suggests altered bone remodeling in osteonecrosis of the jaw (ONJ) patients with h/o aBP use. We therefore hypothesize that pharmacokinetics of aBPs are altered after prolonged treatment and that anti-resorptive agents may be used less frequently as a consequence of this effect. Methods: Here we studied markers of bone turnover after a single dose of zoledronic acid in myeloma patients in remission (NCT00577642). All patients had received 8-12 doses of aBP (pamidronate/ zoledronic acid) prior to study inclusion. Patients were not receiving active anti-myeloma therapy besides maintenance therapy. Our primary objective was to determine the duration of time urinary N- telopeptide (NTX) levels remain suppressed after a single dose of zoledronic acid on study. A secondary objective was the identification and correlation of other markers of bone remodeling with NTX changes and determine if these are predictive of skeletal events. Results: Twenty-four patients have been enrolled on the clinical protocol including 13 men and 11 women. Their ages ranged from 50-85 years and 13/24 patients had advanced stage II/ III myeloma. Myeloma treatment was variable and 10/24 patients were consolidated with transplantation. Twenty patients' have completed 6 month follow up. All patients had suppressed NTX levels with the exception of 1 patient where NTX levels increased at month 3, correlating with disease as well as boney progression. Ongoing studies are correlating other markers of bone formation and resorption. Bone marrow core biopsies on a subset of patients have been studied for osteoclast and osteoblast activity and data will be presented. Conclusions: Our data suggests that NTX levels remain below 50 nMol/L for at least 6 months following a single dose of zoledronic acid once in remission. Increase in NTX level was predictive of boney and disease progression albeit in 1 patient and can potentially be used as a surrogate to tailor aBP therapy. Our data also suggests that less frequent dosing or a treatment holiday may be feasible in MM patients with stable disease. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Amgen, Celgene, Millennium, Novartis Celgene, Millennium, Novartis AstraZeneca, Millennium
Use of therapeutic drug monitoring of cancer chemotherapy to modify initial per-protocol doses.
Authors: J. Rebollo, B. Valenzuela, M. Duart-Duart, V. Escudero-Ortiz, M. S. Gonzalez, A. Brugarolas
Journal: Journal of Clinical Oncology (2010)

e13015 Background: Therapeutic drug monitoring (TDM) is not routinely used for chemotherapy agents. Nonetheless, TDM has the potential to improve the clinical benefit of chemotherapy agents due to their narrow therapeutic index and highly variable pharmacokinetics. The main objective of this study was to evaluate the dose modifications on the standard dosing regimen based on the individual pharmacokinetic (PK) parameters of six antineoplasic drugs (oxaliplatin, cisplatin, doxorubicin, irinotecan, paclitaxel, and 5-fluorouracil). Methods: A total of 187 patients (pts) (764 cycles), treated with either drug tested, were monitored and doses in second or subsequent cycles were pharmacokinetically adjusted until the patients reached the target plasma concentration. Bayesian estimates of individual PK parameters were calculated using a population PK model previously published and were used for pharmacokinetic-based dose adaptation. Patient's toxicities were assessed before each cycle using the National Cancer Institute Common Toxicity Criteria. Results: The main results are shown in the Table. In one out of four patients, the dose was increased an average of 12% without increasing the toxicity. In one out of four patients, the dose was decreased an average 16% due to toxicity caused by the complexity of the therapeutic program but not due to previous dose increases. These results evidence TDM might benefit one out of two oncology patients. Conclusions: Half of the patients evaluated did not achieve the target plasma concentration during the first cycle of chemotherapy. TDM of anticancer drugs is a tool to optimize cancer treatment and ensure that patients receive the right dose. Drug N (pts/cycles) Dose maintenance(% pts) Dose increase (% pts) Dose decrease (% pts) Avg dose increase (%) Avg dose decrease (%) Oxaliplatin 13/51 77 — 23 — 22 Cisplatin 17/62 35 47 18 14 15 Doxorubicin 21/67 52 19 29 13 13 Irinotecan 39/165 31 46 23 13 18 Paclitaxel 46/182 61 4 35 10 12 5-fluorouracil 51/237 37 51 12 12 15 Total 187/764 49 28 23 12 16 No significant financial relationships to disclose.
Abstract 2803: Preclinical models for the development of HER2-specific T-cell therapy
Authors: Christiane Kreutzer, Heinke Conrad, Peter Meyerhuber, Wolfgang Uckert, Philipp Beckhove, Helga Bernhard
Journal: Cancer Research (2014)

Abstract The adoptive transfer of autologous, tumor-reactive T cells to treat cancer patients is a promising tool in immunotherapy. One of our clinical goals is the adoptive transfer of autologous T cells transduced with a human epidermal growth factor receptor 2 (HER2)-directed TCR in patients with advanced breast cancer. We successfully established cytotoxic T-cell clones and CD8+ T cells transduced with a TCR specific for the tumor and self-antigen HER2 and tested their lytic capability in vitro. Since HER2 is a self antigen that is not only expressed by malignant cells but also in normal tissue, e.g. the heart, we tested the recognition of normal HER2+-cell lines by HER2-directed T cells in vitro. For this purpose HER2-directed CD8+ T cells were used to analyze the recognition and lysis of HLA-A2+ cardiomyocyte cell lines in IFNγ-ELISA and chromium-release-assay. Compared to HER2-overexpressing breast cancer cell lines recognition of the cardiomyocytes by HER2-directed T cells was much lower. From these data we hypothesize that there might be a therapeutic window, which may allow the treatment with HER2-directed T cells without having any unwanted side effects, like cardiac dysfunction. To further analyse this, we are establishing a mouse model using HLA-A2-transgenic NOD/SCID-HHDII mice. We injected a human breast cancer cell line s.c. into NOD/SCID-HHDII mice, waited until a solid tumor had been established, and evaluated the responsiveness of tumor cells towards adoptive T cell transfer. Our data show an improvement in tumor growth inhibition after adoptive T cell transfer and IL-15 treatment; however, no significant tumor reduction was observed yet. Furthermore, in the NOD/SCID-HHDII mice we are able to detect potential autoimmune reactions. Subsequent experiments will analyze the combination therapy of transferred HER2-directed T cells with HER2-directed antibody treatment (Trastuzumab and/or Pertuzumab) in order to increase the anti-tumor response. These pre-clinical studies, as well as the in vitro tests, are important for the evaluation of possible unwanted side effects after adoptive transfer of TCR-transduced T cells specific for self-antigens like HER2. Citation Format: Christiane Kreutzer, Heinke Conrad, Peter Meyerhuber, Wolfgang Uckert, Philipp Beckhove, Helga Bernhard. Preclinical models for the development of HER2-specific T-cell therapy. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2803. doi:10.1158/1538-7445.AM2014-2803
Drug hypersensitivity in children: report from the pediatric task force of the<scp>EAACI</scp>Drug Allergy Interest Group
Authors: E. R. Gomes, K. Brockow, S. Kuyucu, F. Saretta, F. Mori, N. Blanca‐Lopez, H. Ott, M. Atanaskovic‐Markovic, M. Kidon, J.‐C. Caubet, I. Terreehorst
Journal: Allergy (2015)

When questioned, about 10% of the parents report suspected hypersensitivity to at least one drug in their children. However, only a few of these reactions can be confirmed as allergic after a diagnostic workup. There is still a lack of knowledge on drug hypersensitivity (DH) epidemiology, clinical spectrum, and appropriate diagnostic methods particularly in children. Meanwhile, the tools used for DH management in adults are applied also for children. Whereas this appears generally acceptable, some aspects of DH and management differ with age. Most reactions in children are still attributed to betalactams. Some manifestations, such as nonsteroidal anti-inflammatory drug-associated angioedema and serum sickness-like reactions, are more frequent among young patients as compared to adults. Risk factors such as viral infections are particularly frequent in children, making the diagnosis challenging. The practicability and validity of skin test and other diagnostic procedures need further assessment in children. This study presents an up-to-date review on epidemiology, clinical spectrum, diagnostic tools, and current management of DH in children. A new general algorithm for the study of these reactions in children is proposed. Data are presented focusing on reported differences between pediatric and adult patients, also identifying unmet needs to be addressed in further research.
Mitochondrial DNA Variation in the Northern Flicker (Colaptes auratus, Aves)
Authors: WS Moore, JH Graham, JT Price
Journal: Molecular Biology and Evolution (1991)

The northern flicker is a common woodpecker that inhabits open woodlands throughout North America.A narrow hybrid zone occurs along the range boundaries between the eastern yellow-shafted and western red-shafted subspecies.Mitochondrial DNA (mtDNA) was isolated from 20 1 flickers from 27 locales, primarily along two transects that cross the hybrid zone, one across the northern United States and one across the southern United States.Analysis of restriction-fragment patterns revealed substantial mtDNA polymorphism.Three restriction endonucleases--HindHI, PvuII, and AvaI--together define eight haplotypes.Geographic variation in haplotype frequencies is highly significant.UPGMA analysis of haplotype frequencies reveals two major clusters of populations, a northern-and-eastern cluster and a southwestern cluster; 86% of the variance in haplotype frequency occurs between the two clusters.Geographic variation in haplotype frequencies is not clearly associated with the hybrid zone.This pattern of divergence may reflect a history of isolation of southwestern populations; alternatively, it is possible that the group of related southwestern haplotypes is adapted to hot, arid conditions common in the deserts of the American Southwest.The gilded flicker is a third subspecies that occurs in the Sonoran Desert.Gilded flickers from Arizona have an mtDNA haplotype closely related to the haplotypes observed in red-shafted flickers of the Southwest.1.
Abstract 817: Glucose Loading Increases Adiponectin Levels in Subjects With Impaired Glucose Tolerance and Impairs Endothelial Function
Authors: Aikaterini Konniari, Dimitris Tousoulis, Charalambos Antoniades, Aggeliki Nikolopoulou, Nikolaos Papageorgiou, Antigoni Miliou, Costas Tentolouris, Anastasios Giolis, Athanasios Trikas, Kyriakoula Marinou, Ioannis Ntarladimas, Pavlos Stougiannos, Christodoulos Stefanadis
Journal: Circulation (2009)

Background: Adiponectin is an adipokine with beneficial effect on vascular function. Although adiponectin levels are decreased in patients with diabetes mellitus (DM), it is unclear whether impaire...
Identification of Legionella spp. by 19 European reference laboratories: results of the European Working Group for Legionella Infections External Quality Assessment Scheme using DNA sequencing of the macrophage infectivity potentiator gene and dedicated online tools
Authors: N.K. Fry, B. Afshar, W. Bellamy, A.P. Underwood, R.M. Ratcliff, T.G. Harrison
Journal: Clinical Microbiology and Infection (2007)
Hypercapnic ventilatory response in patients with Steinert's myotonic dystrophy type 1
Authors: François Bughin, Fares Gouzi, Matthieu Desplan, Yves Dauvilliers, Maurice Hayot
Journal: European Respiratory Journal (2013)

Steinert9s myotonic dystrophy type 1 (DM 1 ) leads to hypercapnic respiratory failure which is often considered as secondary to respiratory muscle weakness. Because of frequent central sleep disorder breathing, low central ventilatory drive is likely to be involved in the pathogenesis of hypercapnia but data are scarce and conflicting.  Thus, the aim of our study was to compare the hypercapnic ventilatory response in 20 consecutive DM 1  patients versus 22 matched healthy subjects (HS) of similar age (33±10 vs.39±14 yrs).  The ventilatory response to carbon dioxide was assessed by the rebreathing method with measures of occlusion pressure (P0.1). DM 1  patients performed spirometry, arterial blood gas analysis (ABG) and inspiratory maximal pressure (PImax). In response to hypercapnia, DM 1  patients vs. HS showed lower forced vital capacity, minute ventilation (VE), mean inspiratory flow rate (VT/Ti), and P0.1 (p  In DM 1  patients, HCO3- was significantly correlated with cHCVR (r=-0.48; p  In contrast to previous studies, our results suggest a contribution of ventilatory control dysfunction to chronic respiratory failure in DM 1  patients. More data are now needed to identify the phenotypes of patients experiencing such central abnormalities.
Blood pressure indices in patients with obstructive sleep apnea and overlap syndrome
Authors: Ksenia Nazarenko, Marina Polianskaja, Inna Zvol, Svetlana Moskalenko
Journal: European Respiratory Journal (2014)

Many studies demonstrate huge prevalence of arterial hypertension (AH) in patients with obstructive sleep apnea (OSA).  The purpose of this study was to identify blood pressure parameters in patients with OSA and its combination with COPD (overlap syndrome (OS)).  Material and methods: 50 patients with excessive daytime sleepiness and OSA (verified by polysomnography), age 47,12±2,16 years, 54 patients with OS (Post BD FEV1/FVC (58,57±2,03)%, FEV1 (66,71±3,14)%), age 57,85±1,36 years and 10 healthy subjects(age 54,1±4,31years). All patients were not previously aware of their cardiovascular pathology. All patients underwent ambulatory blood pressure monitoring (ABPM).AH diagnosed in patients with office systolic blood pressure (SBP)≥140 and diastolic blood pressure (DBP)≥90 mmHg.  Results.  Office SBP and DBP in OSA group were 12 and 10% higher vs healthy subjects (p  Office SBP and DBP in OS group were 17 and 13% higher vs healthy subjects (p  SBP24 in OS group was 7% higher vs OSA group (p  AH was diagnosed in 38% patients with OSA and 65% patients with OS.  Conclusion. COPD in combination with OSA has more negative effects on blood pressure then isolated OSA. Prevalence of AH in OS group was 27% higher than in patients with OSA.
Intensive Diabetes Treatment and Cardiovascular Disease in Patients with Type 1 Diabetes
Authors: David M Nathan, Patricia A Cleary, Jye-Yu C Backlund, Saul M Genuth, John M Lachin, Trevor J Orchard, Philip Raskin, Bernard Zinman
Journal: New England Journal of Medicine (2005)

Intensive diabetes therapy aimed at achieving near normoglycemia reduces the risk of microvascular and neurologic complications of type 1 diabetes. We studied whether the use of intensive therapy as compared with conventional therapy during the Diabetes Control and Complications Trial (DCCT) affected the long-term incidence of cardiovascular disease.The DCCT randomly assigned 1441 patients with type 1 diabetes to intensive or conventional therapy, treating them for a mean of 6.5 years between 1983 and 1993. Ninety-three percent were subsequently followed until February 1, 2005, during the observational Epidemiology of Diabetes Interventions and Complications study. Cardiovascular disease (defined as nonfatal myocardial infarction, stroke, death from cardiovascular disease, confirmed angina, or the need for coronary-artery revascularization) was assessed with standardized measures and classified by an independent committee.During the mean 17 years of follow-up, 46 cardiovascular disease events occurred in 31 patients who had received intensive treatment in the DCCT, as compared with 98 events in 52 patients who had received conventional treatment. Intensive treatment reduced the risk of any cardiovascular disease event by 42 percent (95 percent confidence interval, 9 to 63 percent; P=0.02) and the risk of nonfatal myocardial infarction, stroke, or death from cardiovascular disease by 57 percent (95 percent confidence interval, 12 to 79 percent; P=0.02). The decrease in glycosylated hemoglobin values during the DCCT was significantly associated with most of the positive effects of intensive treatment on the risk of cardiovascular disease. Microalbuminuria and albuminuria were associated with a significant increase in the risk of cardiovascular disease, but differences between treatment groups remained significant (P< or =0.05) after adjusting for these factors.Intensive diabetes therapy has long-term beneficial effects on the risk of cardiovascular disease in patients with type 1 diabetes.
Circulating Immune Complexes in Cutaneous Vasculitis
Authors: Susan E. Mackel, Gerhard Tappeiner, Hilton Brumfield, Robert E. Jordon
Journal: Journal of Clinical Investigation (1979)

To investigate the pathogeneic significance of immune complexes in cutaneous vasculitis, 107 patients with various forms of cutaneous vasculitis, including 59 patients with necrotizing (leukocytoclastic) vasculitis (group 1), and 48 patients with lymphocytic vasculitis, or a predominately lymphocytic perivascular infiltrate (group 2), were studied. Immunoglobulins or complement components in cutaneous blood vessels were detected by direct immunofluorescence in high frequency in both groups (91 and 88%, respectively). Using two radioassays for circulating immune complexes, Clq or monoclonal rheumatoid factor (mRF) reactive material was detected in 68% of the patients with necrotizing vasculitis but only 44% of the patients in the lymphocytic-perivascular group. The mRF radioassay was elevated in 58% of the first group of patients and 41% of the patients in group 2, although Clq binding activity was increased in 54% of the patients with necrotizing vasculitis but only in 9% of the patients with a lymphocytic vasculitis or lymphocytic perivascular infiltrate. By using both sucrose density gradient ultracentrifugation and Sepharose 6B gel filtration, the Clq and mRF reactive material detected in some patients with necrotizing vasculitis eluted in high molecular weight fractions that were also anticomplementary. In one patient with necrotizing vasculitis and hepatitis B antigenemia, these heavy molecular weight Clq and mRF reactive fractions contained a two- to three-fold increase in hepatitis B surface antigen when compared with lighter molecular weight fractions. Heavy and light molecular weight mRF reactive material could be detected in selected patients in the lymphocytic-perivascular group as well as in the necrotizing vasculitis group. These studies suggest that cutaneous vasculitis, including acute necrotizing (leukocytoclastic) vasculitis and some forms of lymphocytic vasculitis, and perhaps some diseases characterized by a lymphocytic perivascular infiltrate, may represent cutaneous expressions of immune complex disease.