tbuckley/cabot-search huggingface dataset:
Calling on Reserves
Authors: Ebo D. de Muinck, Michael Simons
Journal: Circulation (2005)

issue injury elicits a regenerative response designed to restore its function through replacement of damaged cells.2][3] The effectiveness of this repair ranges from minimal to complete, depending, among other factors, on the involved organ and the age of the individual in question, with certain organs such as the brain or the heart thought to have very low repair potential.Furthermore, little role has been ascribed to bone marrow-derived progenitors in adult tissue repair.Recent studies, however, have challenged both of these paradigms.The notion that the heart is a terminally differentiated organ without the capability of self-renewal has been challenged by the discovery of cardiac-specific progenitor cells residing in the myocardium. 3However, it is unclear how much functional effect such repair processes have and whether they can be effectively stimulated with pharmacological or biological therapies.
Stem-Cell Transplantation in Children With Acute Lymphoblastic Leukemia: A Prospective International Multicenter Trial Comparing Sibling Donors With Matched Unrelated Donors—The ALL-SCT-BFM-2003 Trial
Authors: Christina Peters, Martin Schrappe, Arend von Stackelberg, André Schrauder, Peter Bader, Wolfram Ebell, Peter Lang, Karl-Walter Sykora, Johanna Schrum, Bernhard Kremens, Karoline Ehlert, Michael H. Albert, Roland Meisel, Susanne Matthes-Martin, Tayfun Gungor, Wolfgang Holter, Brigitte Strahm, Bernd Gruhn, Ansgar Schulz, Wilhelm Woessmann, Ulrike Poetschger, Martin Zimmermann, Thomas Klingebiel
Journal: Journal of Clinical Oncology (2015)

Purpose Although hematopoietic stem-cell transplantation is widely performed in children with high-risk acute lymphoblastic leukemia (ALL), the influence of donor types is poorly understood. Thus, transplantation outcomes were compared in the prospective multinational Berlin-Frankfurt-Muenster (BFM) study group trial: ALL-SCT-BFM 2003 (Allogeneic Stem Cell Transplantation in Children and Adolescents with Acute Lymphoblastic Leukemia). Patients and Methods After conditioning with total-body irradiation and etoposide, 411 children with high-risk ALL received highly standardized stem-cell transplantations during the first or later remissions. Depending on donor availability, grafts originated from HLA-genoidentical siblings or from HLA-matched unrelated donors who were identified and matched by high-resolution allelic typing and were compatible in at least 9 of 10 HLA loci. Results Four-year event-free survival (± standard deviation [SD]) did not differ between patients with transplantations from unrelated or sibling donors (0.67 ± 0.03 v 0.71 ± 0.05; P = .405), with cumulative incidences of nonrelapse mortality (± SD) of 0.10 ± 0.02 and 0.03 ± 0.02 (P = .017) and relapse rates (± SD) of 0.22 ± 0.02 and 0.24 ± 0.04 (P = .732), respectively. Among recipients of transplantations from unrelated donors, no significant differences in event-free survival, overall survival, or nonrelapse mortality were observed between 9/10 and 10/10 matched grafts or between peripheral blood stem cells and bone marrow. The absence of chronic graft-versus-host disease had no effect on event-free survival. Engraftment was faster after bone marrow transplantation from siblings and was associated with fewer severe infections and pulmonary complications. Conclusion Outcome among high-risk pediatric patients with ALL after hematopoietic stem-cell transplantation was not affected by donor type. Standardized myeloablative conditioning produced a low incidence of treatment-related mortality and effective control of leukemia.
Coronary Plaque Classification With Intravascular Ultrasound Radiofrequency Data Analysis
Authors: Anuja Nair, Barry D. Kuban, E. Murat Tuzcu, Paul Schoenhagen, Steven E. Nissen, D. Geoffrey Vince
Journal: Circulation (2002)

Background— Atherosclerotic plaque stability is related to histological composition. However, current diagnostic tools do not allow adequate in vivo identification and characterization of plaques. Spectral analysis of backscattered intravascular ultrasound (IVUS) data has potential for real-time in vivo plaque classification. Methods and Results— Eighty-eight plaques from 51 left anterior descending coronary arteries were imaged ex vivo at physiological pressure with the use of 30-MHz IVUS transducers. After IVUS imaging, the arteries were pressure-fixed and corresponding histology was collected in matched images. Regions of interest, selected from histology, were 101 fibrous, 56 fibrolipidic, 50 calcified, and 70 calcified-necrotic regions. Classification schemes for model building were computed for autoregressive and classic Fourier spectra by using 75% of the data. The remaining data were used for validation. Autoregressive classification schemes performed better than those from classic Fourier spectra with accuracies of 90.4% for fibrous, 92.8% for fibrolipidic, 90.9% for calcified, and 89.5% for calcified-necrotic regions in the training data set and 79.7%, 81.2%, 92.8%, and 85.5% in the test data, respectively. Tissue maps were reconstructed with the use of accurate predictions of plaque composition from the autoregressive classification scheme. Conclusions— Coronary plaque composition can be predicted through the use of IVUS radiofrequency data analysis. Autoregressive classification schemes performed better than classic Fourier methods. These techniques allow real-time analysis of IVUS data, enabling in vivo plaque characterization.
A Phase I Trial of Erlotinib and Concurrent Chemoradiotherapy for Stage III and IV (M0) Squamous Cell Carcinoma of the Head and Neck
Authors: Jill Gilbert, Michelle A. Rudek, Michaela J. Higgins, Ming Zhao, Sara Bienvenu, Nancy Tsottles, Richard Wahl, Arlene Forastiere, Maura Gillison
Journal: Clinical Cancer Research (2012)

Erlotinib, an orally active selective inhibitor of the epidermal growth factor receptor (EGFR) tyrosine kinase, has synergistic activity with radiation and with cisplatin. The EGFR is overexpressed in the majority of head and neck cancers. The primary objective of this phase I study was to determine the maximum-tolerated dose (MTD) of erlotinib in combination with low-dose daily cisplatin and radiotherapy. We also sought evidence of biologic activity of erlotinib alone using serial 18-FDG positron emission tomography (PET) imaging.Oral erlotinib was taken daily starting with a 14-day run-in and continued until radiation therapy (RT) was completed. Low-dose daily cisplatin, 6 mg/m(2) i.v. was given concurrently with standard fractionation RT to a total dose of 66 to 70 Gy. Dose escalation followed a modified Fibonacci dose escalation design.Twenty-two patients were enrolled and 18 patients received therapy on protocol. MTD of the combination of erlotinib, cisplatin, and RT was not reached. The recommended phase II dose of erlotinib is 150 mg per day in combination with cisplatin and RT, the highest dose of erlotinib evaluated in this study. 18F-FDG PET showed evidence for metabolic response to single-agent erlotinib. Per PERCIST criteria, the overall metabolic response rate at day 14 was 38.8% (95% CI: 17.3-64.3). On completion of concurrent chemoradiotherapy, overall response rate derived from tumor measurements based on imaging studies was 83% for all dose levels combined.Erlotinib in combination with low-dose daily cisplatin and RT is well tolerated and shows evidence of clinical efficacy. The combination should be evaluated further.
Expert witnesses are issued with new advice after high profile failings
Authors: Clare Dyer
Journal: BMJ (2006)

Expert witnesses for the prosecution in legal cases are for the first time to be issued with a guide to their duties, after a high profile case in which experts' failings led the Court of Appeal to quash a mother's convictions for murdering her babies.

The booklet was launched this week as the attorney general, Peter Goldsmith, said that three “shaken baby” cases raised concerns about the safety of the convictions.

The three emerged from a review of 88 convictions in cases involving shaken baby syndrome in the past 10 years. The review was undertaken after an appeal court judgment in four test cases last July. The court ruled that …
Caffeine as a Substitute for Schedule II Stimulants in Hyperkinetic Children
Authors: ROBERT C. SCHNACKENBERG
Journal: American Journal of Psychiatry (1973)

Children being treated with methylphenidate or dextroamphetamine for minimal brain dysfunction syndrome and subsequent hyperkinetic impulse disorder may develop annoying side effects. A pilot study substituting caffeine, in the form of two cups of regular coffee a day, suggests that caffeine may be a suitable alternative to Schedule II drugs. The author points out the advantages of treatment with caffeine and suggests some specific aspects for further studies in this area.
Effects of lung volume reduction surgery in hamsters with elastase-induced emphysema
Authors: E. Marchand, P. De Leyn, G. Gayan-Ramirez, F. Palecek, E. Verbeken, M. Decramer
Journal: European Respiratory Journal (2002)

Lung volume reduction surgery (LVRS) has been shown to improve respiratory mechanics in selected patients with severe emphysema. This is thought to be due to an improvement in lung elastic recoil. This study was aimed at gaining further understanding about the effects of LVRS on respiratory mechanics and airway function. Control hamsters instilled with saline (Ctrl; n=8) were compared with emphysematous animals that underwent either a sham operation (Sham; n=7) or an LVRS (LVRS; n=7). As expected, there was a significant increase in the static lung volumes in the Sham as compared to the Ctrl group and a significant decrease of these volumes in LVRS as compared to the Sham group. Surprisingly, emphysema was associated with a significant increase and LVRS with a significant decrease in vital capacity. Despite a tendency toward an increase in lung compliance as compared to Sham, indices of maximal expiratory flows tended to decrease with LVRS. As opposed to humans, there was no change in the distribution of airway diameters in Sham compared to Ctrl. These findings appear to be largely explained by the high compliance of the hamster chest wall. This allows for better matching between the emphysematous lung and the chest-wall sizes than in humans.
Exposures That Alter The Early Life Microbiome and The Risk Of Asthma
Authors: Amy S. Feldman, Pingsheng Wu, Kristina James, Tebeb Gebretsadik, Gabriel Escobar, Kecia N. Carroll, Sherian Xu Li, Eileen Walsh, Ed Mitchel, Tina V. Hartert
Journal: Journal of Allergy and Clinical Immunology (2014)
Biologic Cost of Caring for a Cancer Patient: Dysregulation of Pro- and Anti-Inflammatory Signaling Pathways
Authors: Nicolas Rohleder, Teresa J. Marin, Roy Ma, Gregory E. Miller
Journal: Journal of Clinical Oncology (2009)

Caring for a family member with cancer is a psychologically demanding experience. However, it remains unclear whether the distress that caregiving provokes also takes a physiologic toll on the body. This study observed familial caregivers of patients with brain cancer for a year after diagnosis and tracked changes in neurohormonal and inflammatory processes.Eighteen caregivers (age 50.4 +/- 3.5 years) and 19 controls (age 50.2 +/- 2.6 years) were assessed four times during a year (before and after radiotherapy, as well as 6 weeks and 4 months thereafter). Salivary biomarkers of hypothalamus-pituitary-adrenal axis and sympathetic nervous system (SNS) activity were collected, and blood was drawn for assessment of the systemic inflammatory markers C-reactive protein (CRP) and interleukin-6 (IL-6). Blood was also used to monitor in vitro IL-6 production by endotoxin-stimulated leukocytes and expression of mRNA for pro- and anti-inflammatory signaling molecules.Caregivers showed marked changes over time in diurnal output of salivary amylase, a marker of SNS activity, whereas secretions in controls were stable during follow-up. Cortisol output was similar in caregivers and controls. During the year, caregivers showed a profound linear increase in systemic inflammation, as indexed by CRP. At the same time, they displayed a linear decline in mRNA for anti-inflammatory signaling molecules and diminished in vitro glucocorticoid sensitivity.These preliminary data show that familial caregivers of patients with cancer experience marked changes in neurohormonal and inflammatory processes in the year after diagnosis. These changes may place them at risk for morbidity and mortality from diseases fostered by excessive inflammation.
Plasma Brain Natriuretic Peptide Levels Increase in Proportion to the Extent of Right Ventricular Dysfunction in Pulmonary Hypertension
Authors: Noritoshi Nagaya, Toshio Nishikimi, Yoshiaki Okano, Masaaki Uematsu, Toru Satoh, Shingo Kyotani, Sachio Kuribayashi, Seiki Hamada, Mikio Kakishita, Norifumi Nakanishi, Makoto Takamiya, Takeyoshi Kunieda, Hisayuki Matsuo, Kenji Kangawa
Journal: Journal of the American College of Cardiology (1998)
Recombinant Hirudin (Lepirudin) Provides Safe and Effective Anticoagulation in Patients With Heparin-Induced Thrombocytopenia
Authors: A. Greinacher, H. Völpel, U. Janssens, V. Hach-Wunderle, B. Kemkes-Matthes, P. Eichler, H. G. Mueller-Velten, B. Pötzsch
Journal: Circulation (1999)

Background —The immunological type of heparin-induced thrombocytopenia (HIT) is the most frequent drug-induced thrombocytopenia. This study evaluated the efficacy of recombinant hirudin (r-hirudin or lepirudin), a potent thrombin inhibitor, for anticoagulation in patients with confirmed HIT. Methods and Results —Eighty-two patients in this prospective, multicenter study received 1 of 4 intravenous r-hirudin regimens: A1, HIT patients with thrombosis (n=51), 0.4-mg/kg bolus and then 0.15 mg · kg −1 · h −1 ; A2, HIT patients with thrombosis receiving thrombolysis (n=5), 0.2-mg/kg bolus and then 0.1 mg · kg −1 · h −1 ; B, HIT patients without thrombosis (n=18), 0.1 mg · kg −1 · h −1 ; and C, during cardiopulmonary bypass surgery (n=8), 0.25-mg/kg bolus and then 5-mg boluses as needed. Response criteria were increase in platelet count by ≥30% to &gt;10 9 /L and activated partial thromboplastin time (aPTT) values 1.5 to 3.0 times baseline values achieved with a maximum of 2 dose increases. No placebo control was used for ethical reasons. Outcomes of a subset of r-hirudin–treated patients who met predefined inclusion criteria (n=71) were compared with those of a historical control group (n=120) for combined and individual incidences of death, amputations, new thromboembolic complications, and incidences of bleeding. Platelet counts increased rapidly in 88.7% of r-hirudin–treated patients with acute HIT. In regimens A1 and A2, the 25% and 75% quartiles of the aPTT were within the target range at all but 1 time point. The incidence of the combined end point (death, amputation, new thromboembolic complications) was significantly reduced in r-hirudin patients compared with historical control patients ( P =0.014). During first selected treatment, the adjusted hazard ratio for r-hirudin patients versus historical control was 0.279 (95% CI, 0.112 to 0.699; P =0.003). Bleeding rates were similar in both groups. Conclusions —r-Hirudin treatment is associated with a rapid and sustained recovery of platelet counts, sufficient aPTT prolongations, and true clinical benefits for patients with HIT.
Melanoma Proliferation and Chemoresistance Controlled by the DEK Oncogene
Authors: Michael S. Khodadoust, Monique Verhaegen, Ferdinand Kappes, Erica Riveiro-Falkenbach, Juan C. Cigudosa, David S.L. Kim, Arul M. Chinnaiyan, David M. Markovitz, María S. Soengas
Journal: Cancer Research (2009)

Abstract Gain of chromosome 6p is a consistent feature of advanced melanomas. However, the identity of putative oncogene(s) associated with this amplification has remained elusive. The chromatin remodeling factor DEK is an attractive candidate as it maps to 6p (within common melanoma-amplified loci). Moreover, DEK expression is increased in metastatic melanomas, although the functional relevance of this induction remains unclear. Importantly, in other tumor types, DEK can display various tumorigenic effects in part through its ability to promote proliferation and inhibit p53-dependent apoptosis. Here, we report a generalized up-regulation of DEK protein in aggressive melanoma cells and tumors. In addition, we provide genetic and mechanistic evidence to support a key role of DEK in the maintenance of malignant phenotypes of melanoma cells. Specifically, we show that long-term DEK down-regulation by independent short hairpin RNAs resulted in premature senescence of a variety of melanoma cell lines. Short-term abrogation of DEK expression was also functionally relevant, as it attenuated the traditional resistance of melanomas to DNA-damaging agents. Unexpectedly, DEK short hairpin RNA had no effect on p53 levels or p53-dependent apoptosis. Instead, we identified a new role for DEK in the transcriptional activation of the antiapoptotic MCL-1. Other MCL-1–related factors such as BCL-2 or BCL-xL were unaffected by changes in the endogenous levels of DEK, indicating a selective effect of this gene on the apoptotic machinery of melanoma cells. These results provide support for DEK as a long sought-after oncogene mapping at chromosome 6, with novel functions in melanoma proliferation and chemoresistance. [Cancer Res 2009;69(16):6405–13]
Effect of Multifactorial Intervention on Diabetic Macular Edema
Authors: Ramandeep Singh, Vidya Abhiramamurthy, Vishali Gupta, Amod Gupta, Anil Bhansali
Journal: Diabetes Care (2006)

Clinical trials (1, 2) have shown that intensive control of blood glucose and hypertension reduce development of clinically significant macular edema (CSME). Elevated HbA1c (A1C) is a risk for persistent CSME (3). Gross proteinuria is associated with a 95% increase in the incidence of macular edema (4). However, the effect of control of systemic factors before focal laser photocoagulation is not known. We aimed to determine whether multifactorial intervention over 4–6 weeks before focal laser photocoagulation would reduce …
Juvenile and adult types of chronic granulocytic leukemia of childhood: Growth patterns and characteristics of granulocyte‐macrophage colony forming cells
Authors: Y. Barak, S. Levin, R. Vogel, I. J. Cohen, B. Wallach, E. Nir, R. Zaizov
Journal: American Journal of Hematology (1981)

Abstract Peripheral blood and bone marrow cells from three children with the juvenile (Ph 1 negative) type of chronic granulocytic leukemia and from one with the adult (Ph 1 positive) type were cultured in soft agar, and their specific growth patterns were evaluated. Greatly increased numbers of colonies were obtained in all cases, particularly from peripheral blood cells. By morphologic, cytochemical and ultrastructural criteria, colonies from one juvenile type and from the single adult type patients were found to be almost exclusively granulocytic, whereas in the other two juvenile type leukemia patients colonies were either granulocytic or macrophage. Moreover, both growth patterns were obtained in the same patients on different occasions. It appears that the leukemic cell populations of the juvenile and the adult forms of chronic granulocytic leukemia do not arise from different cell lines. Rather, both are the progeny of the common monocyte‐granulocyte progenitor cell, whose abnormal proliferation and differentiation along either the granulocytic or the monocytic pathway is probably directed by fluctuations in humoral and/or microenvironmental factors.
The contribution of airway smooth muscle to airway narrowing and airway hyperresponsiveness in disease
Authors: J.G. Martin, A. Duguet, D.H. Eidelman
Journal: European Respiratory Journal (2000)

Airway hyperresponsiveness (AHR), the exaggerated response to constrictor agonists in asthmatic subjects, is incompletely understood. Changes in either the quantity or properties of airway smooth muscle (ASM) are possible explanations for AHR. Morphometric analyses demonstrate structural changes in asthmatic airways, including subepithelial fibrosis, gland hyperplasia/hypertrophy, neovascularization and an increase in ASM mass. Mathematical modelling of airway narrowing suggests that, of all the changes in structure, the increase in ASM mass is the most probable cause of AHR. An increase in ASM mass in the large airways is more closely associated with a greater likelihood of dying from asthma than increases in ASM mass in other locations within the airway tree. ASM contraction is opposed by the elastic recoil of the lungs and airways, which appears to limit the degree of bronchoconstriction in vivo. The cyclical nature of tidal breathing applies stresses to the airway wall that enhance the bronchodilating influence of the lung tissues on the contracting ASM, in all probability by disrupting cross-bridges. However, the increase in ASM mass in asthma may overcome the limitation resulting from the impedances to ASM shortening imposed by the lung parenchyma and airway wall tissues. Additionally, ASM with the capacity to shorten rapidly may achieve shorter lengths and cause a greater degree of bronchoconstriction when stimulated to contract than slower ASM. Changes in ASM properties are induced by the process of sensitization and allergen-exposure such as enhancement of phospholipase C activity and inositol phosphate turnover, and increases in myosin light chain kinase activity. Whether changes in ASM mass or biochemical/biomechanical properties form the basis for asthma remains to be determined.
Do exercises used in injury prevention programmes modify cutting task biomechanics? A systematic review with meta-analysis
Authors: Evangelos Pappas, Elizabeth J Nightingale, Milena Simic, Kevin R Ford, Timothy E Hewett, Gregory D Myer
Journal: British Journal of Sports Medicine (2014)

Objective Some injury prevention programmes aim to reduce the risk of ACL rupture. Although the most common athletic task leading to ACL rupture is cutting, there is currently no consensus on how injury prevention programmes influence cutting task biomechanics. To systematically review and synthesise the scientific literature regarding the influence of injury prevention programme exercises on cutting task biomechanics. Design The three largest databases (Medline, EMBASE and CINAHL) were searched for studies that investigated the effect of injury prevention programmes on cutting task biomechanics. When possible meta-analyses were performed. Results Seven studies met the inclusion criteria. Across all studies, a total of 100 participants received exercises that are part of ACL injury prevention programmes and 76 participants served in control groups. Most studies evaluated variables associated with the quadriceps dominance theory. The meta-analysis revealed decreased lateral hamstrings electromyography activity (p≤0.05) while single studies revealed decreased quadriceps and increased medial hamstrings activity and decreased peak knee flexion moment. Findings from single studies reported that ACL injury prevention exercises reduce neuromuscular deficits (knee valgus moment, lateral trunk leaning) associated with the ligament and trunk dominance theories, respectively. The programmes we analysed appear most effective when they emphasise individualised biomechanical technique correction and target postpubertal women. Conclusions The exercises used in injury prevention programmes have the potential to improve cutting task biomechanics by ameliorating neuromuscular deficits linked to ACL rupture, especially when they emphasise individualised biomechanical technique correction and target postpubertal female athletes.