tbuckley/cabot-search huggingface dataset:
PREVENTIVE CARE FOR CHILDREN IN THE UNITED STATES: Quality and Barriers
Authors: Paul J. Chung, Tim C. Lee, Janina L. Morrison, Mark A. Schuster
Journal: Annual Review of Public Health (2005)

▪ Abstract Our objective was to examine the academic literature covering quality of childhood preventive care in the United States and to identify barriers that contribute to poor or disparate quality. We systematically reviewed articles related to childhood preventive care published from 1994 through 2003, focusing on 58 large observational studies and interventions addressing well-child visit frequency, developmental and psychosocial surveillance, disease screening, and anticipatory guidance. Although many children attend recommended well-child visits and receive comprehensive preventive care at those visits, many do not attend such visits. Estimates of children who attend all recommended visits range widely (from 37%–81%). In most studies, less than half is the proportion of children who receive developmental or psychosocial surveillance, adolescents who are asked about various health risks, children at risk for lead exposure who are screened, adolescents at risk for Chlamydia who are tested, or children and adolescents who receive anticipatory guidance on various topics. Major barriers include lack of insurance, lack of continuity with a clinician or place of care, lack of privacy for adolescents, lack of clinician awareness or skill, racial/ethnic barriers, language-related barriers, clinician and patient gender-related barriers, and lack of time. In summary, childhood preventive care quality is mixed, with large disparities among populations. Recent research has identified barriers that might be overcome through practice and policy interventions.
ADAM 33: just another asthma gene or a breakthrough in understanding the origins of bronchial hyperresponsiveness?
Authors: S T Holgate
Journal: Thorax (2003)

ADAM 33, the latest of the ADAM proteins to be described, has been identified as a major susceptibility gene in asthma linked to bronchial hyperresponsiveness. It provides an important breakthrough in our understanding of this complex disorder and its variable clinical and physiological presentations.

Asthma is a disorder of the conducting airways in which Th2 mediated inflammation interacts with structural changes to cause variable airflow obstruction. Fundamental to disordered function is the concept of bronchial hyperresponsiveness (BHR) in which the airways constrict too much and too easily. In chronic severe asthma the inflammation and structural changes both become more intense1 and are paralleled by an increase in BHR that is only partially or non-responsive to treatment with corticosteroids.2 Explanations for BHR include mucosal and adventitial swelling causing a disproportionate reduction in airway calibre for a given degree of airways smooth muscle (ASM) shortening,3 excessive ASM shortening,4 an increase in ASM mass causing greater force generation,5 and an excessive velocity of contraction linked to altered crossbridge cycling.6 Morphometric studies have shown a graded increase in ASM mass in proportion to disease severity, and computer modelling has revealed that this and altered contractility are the most plausible explanations for BHR.5,7

Asthma has a high heritability of up to 79%,8 involving a few genes with moderate effects rather than many genes with small effects.9 We have recently reported the first novel asthma related gene identified by positional cloning.10 A genome wide screen was undertaken using phenotypic data and DNA from 362 families in Wessex and 98 in the USA with at least two siblings with asthma. Using 401 microsatellite markers at a density of 9 cM and multipoint linkage analysis, suggestive evidence for linkage (maximum lod score (MLS) 2.24) was found on …
Steroid‐induced hypersegmentation in neutrophiles
Authors: Peter Eichacker, Christine Lawrence
Journal: American Journal of Hematology (1985)

Abstract The effect of glucocorticoid administration on the nuclear segmentation of circulating granulocytes was studied in 13 patients with hematologic disorders and in two normal volunteers. In seventeen of eighteen courses, the granulocyte nuclear lobe count increased from 3.24 ± 0.12 (SD) to 3.41 ± 0.12 by the third day of treatment (P &lt; .001). Nuclear segmentation increased even further with continued therapy during a week of observation. Thus, like deficiencies of folate and of vitamin B 12 , glucocorticoid therapy causes neutrophil hypersegmentation. The cause of this effect is not known.
Response to: ‘Drug survival on TNF inhibitors: 2003–2004 data from Italian National Register (GISEA Register)’ by Iannone<i>et al</i>
Authors: Martin Neovius, Johan Askling
Journal: Annals of the Rheumatic Diseases (2014)

We thank Iannone et al for their comment1 on our recent study on drug survival on etanercept, infliximab and adalimumab in patients with rheumatoid arthritis (RA).2 They noted similarities between our findings and their previously published data3 on 853 Italian patients starting tumour necrosis factor (TNF) inhibitor treatment in 2003–2004 in terms of best drug survival on etanercept, similar 4- versus 5-year drug survival for etanercept and infliximab, and some shared findings regarding predictors. We agree that there are several similarities, but also differences. We also apologise for not including their study in our non-exhaustive review in the appendix, and not citing their study together with the study by Kievit et al .4

Specifically, we …
EMFs and Childhood Leukemia
Authors: Michael Kundi
Journal: Environmental Health Perspectives (2007)

ADHD in those subjects with low ferritin levels.Given that lead exposure may contribute to ADHD and iron deficiency may exacerbate deleterious effects caused by lead, we recommend systematically seeking for iron deficiency in children with ADHD.We also think that controlled studies assessing the potential effectiveness of iron supplementation on ADHD symptoms should be encouraged.Such studies could aid the understanding of the complex pathophysiology underlying ADHD and provide effective therapeutic strategies for this disorder.
Mitochondrial KATP channels: role in cardioprotection
Authors: O Oldenburg
Journal: Cardiovascular Research (2002)

The role of the mitochondrial ATP-sensitive potassium channel (mKATP) in ischemic preconditioning and cardioprotection is reviewed. A great deal of accumulated evidence implicatese opening of this channel as an important step in the anti-infarct effect of ischemic preconditioning. Recent studies, however, reveal that channel opening can actually serve as a signal transduction element. Data indicate that mKATP opening causes mitochondria to generate reactive oxygen species (ROS) which then activate downstream kinases. Opening of mKATP prior to ischemia can serve as a trigger since the critical time for its opening is prior to the onset of the lethal ischemic insult. Most Gi-coupled receptors trigger protection through the mKATP/ROS pathway except for the adenosine receptor which uses some other, as yet unidentified, pathway. Possible coupling schemes between the receptors and the mKATP are discussed. Protection from preconditioning can also be aborted when a mKATP blocker is present only during the lethal ischemic insult (mediator phase), but a much higher concentration of the blocker is required. Thus the mKATP probably serves a dual role as both a trigger and a mediator. Possible end-effectors of preconditioning's protection are discussed including the mKATP itself.
A High-Throughput Pharmaceutical Screen Identifies Compounds with Specific Toxicity against BRCA2-Deficient Tumors
Authors: Bastiaan Evers, Eva Schut, Eline van der Burg, Tanya M. Braumuller, David A. Egan, Henne Holstege, Pauline Edser, David J. Adams, Richard Wade-Martins, Peter Bouwman, Jos Jonkers
Journal: Clinical Cancer Research (2009)

Hereditary breast cancer is partly explained by germline mutations in BRCA1 and BRCA2. Although patients carry heterozygous mutations, their tumors have typically lost the remaining wild-type allele. Selectively targeting BRCA deficiency may therefore constitute an important therapeutic approach. Clinical trials applying this principle are underway, but it is unknown whether the compounds tested are optimal. It is therefore important to identify alternative compounds that specifically target BRCA deficiency and to test new combination therapies to establish optimal treatment strategies.
Interaction of sympathetic and parasympathetic nervous system on ventricular refractoriness assessed by local fibrillation intervals in the canine heart
Authors: T. Opthof, L. R C Dekker, R. Coronel, J. T Vermeulen, F. J L v. Capelle, M. J Janse
Journal: Cardiovascular Research (1993)

Objective: The aim was to assess the effects of autonomic nerve stimulation on local ventricular refractoriness by measuring local ventricular fibrillation intervals. Methods: In 10 dogs on cardiopulmonary bypass, ventricular fibrillation intervals were recorded simultaneously at up to 32 sites before and after neural stimulation. In four dogs (group 1) the response to bilateral stellate ganglion stimulation was measured before and after bilateral cervical vagotomy. In three dogs (group 2) bilateral stellate ganglion stimulation, vagal nerve stimulation, and combined vagal and stellate ganglia stimulation were performed. In three dogs (group 3) the same protocol was applied after total decentralisation of the autonomic nervous system. Results: Bilateral stellate ganglion stimulation shortened the ventricular fibrillation interval at 44-50% of myocardial sites before and after vagotomy, whereas prolongation of the interval was observed at 14-18% of the sites. At higher stimulus strength shortening of the interval was measured at 85% of the sites in the intact and decentralised groups. No prolongation was observed. The shortening was largest in the decentralised group (11.1 ms). Dispersion in refractoriness increased in hearts from all groups, but not in each individual heart. Left, right, or bilateral vagal stimulation was without effect at about 75% of the tested sites. The fact that the response to autonomic nerve stimulation varies from site to site warrants our approach of simultaneous recordings at multiple sites. Dispersion in refractoriness was not affected by vagal stimulation. Combined autonomic stimulation had approximately the same effect on dispersion in refractoriness as bilateral stellate ganglion stimulation alone. However, vagal stimulation attenuated the responses to bilateral stellate ganglion stimulation by some 20% in the decentralised group. Conclusions: Vagal stimulation has minor effects on ventricular refractoriness, but this is not due to sparse innervation, since vagal stimulation is able to mitigate the effects of sympathetic stimulation in decentralised hearts. Cardiovascular Research 1993;27:753-759
Impact of Critical Care Physician Staffing on Patients With Septic Shock in a University Hospital Medical Intensive Care Unit
Authors: H N Reynolds, M T Haupt, M C Thill-Baharozian, R W Carlson
Journal: JAMA (1988)

To evaluate the effects of reorganizing physician resources in a medical intensive care unit (MICU), we studied the impact of these changes in patients with septic shock. Patients were compared during two consecutive 12-month periods: (1) an interval in which faculty without critical care medicine (CCM) training supervised the MICU (before CCM, n = 100) and (2) following staffing with physicians formally trained in CCM (after CCM, n = 112). Acute Physiology and Chronic Health Evaluation scores were utilized to compare severity of illness and were similar for each group (29 ±11 before CCM vs 28 ± 10 after CCM). However, mortality was significantly lower during the post-CCM interval (74% vs 57%, respectively). There was no significant difference in the frequency of use of mechanical ventilation (83% vs 87%), although pulmonary artery catheters (48% vs 64%) and arterial catheters (24% vs 73%) were employed more frequently after CCM. The number of subspecialty consultations and MICU and hospital length of stay were similar for both intervals. We conclude that the implementation of dedicated staffing by CCM physicians in a university hospital MICU was associated with a favorable impact on patients with septic shock. (<i>JAMA</i>1988;260:3446-3450)
Effects of Screening on Radical Prostatectomy Efficacy: The Prostate Cancer Intervention Versus Observation Trial
Authors: Jing Xia, Roman Gulati, Margaret Au, John L. Gore, Daniel W. Lin, Ruth Etzioni
Journal: JNCI Journal of the National Cancer Institute (2013)

The Scandinavian Prostate Cancer Group Study Number 4 (SPCG-4) trial showed that radical prostatectomy (RP) reduced prostate cancer deaths with an absolute mortality difference (AMD) between the RP and watchful waiting arms of 6.1% (95% confidence interval [CI] = 0.2% to 12.0%) after 15 years. In the United States, the Prostate Cancer Intervention Versus Observation Trial (PIVOT) produced an AMD of 3% (95% CI = -1.1% to 6.5%) after 12 years. It is not known whether a higher frequency of screen detection in PIVOT explains the lower AMD.We assumed the SPCG-4 trial represents RP efficacy and prostate cancer survival in an unscreened population. Given the fraction of screen-detected prostate cancers in PIVOT, we adjusted prostate cancer survival using published estimates of overdiagnosis and lead time to project the effect of screen detection on disease-specific deaths.On the basis of published estimates, we assumed that 32% of screen-detected cancers were overdiagnosed and a mean lead time among non-overdiagnosed cancers of 7.7 years. When we adjusted prostate cancer survival for the 76% of case patients in PIVOT who were screen detected, we projected that the AMD after 12 years would be 2.0% (95% CI = -1.6% to 5.6%) based on variation in published estimates of overdiagnosis and mean lead time in the United States.If RP efficacy and prostate cancer survival in the absence of screening are similar to that in the SPCG-4 trial, then overdiagnosis and lead time largely explain the lower AMD in PIVOT. If these artifacts of screening are the correct explanation, then there is a subset of case subjects that should not be treated with RP, and identifying this subset should lead to a clearer understanding of the benefit of RP in the remaining cases.
Palifermin for Oral Mucositis after Intensive Therapy for Hematologic Cancers
Authors: Ricardo Spielberger, Patrick Stiff, William Bensinger, Teresa Gentile, Daniel Weisdorf, Tarun Kewalramani, Thomas Shea, Saul Yanovich, Keith Hansen, Stephen Noga, John McCarty, C. Frederick LeMaistre, Eric C. Sung, Bruce R. Blazar, Dieter Elhardt, Mon-Gy Chen, Christos Emmanouilides
Journal: New England Journal of Medicine (2004)

Oral mucositis is a complication of intensive chemotherapy and radiotherapy with no effective treatment. We tested the ability of palifermin (recombinant human keratinocyte growth factor) to decrease oral mucosal injury induced by cytotoxic therapy.This double-blind study compared the effect of palifermin with that of a placebo on the development of oral mucositis in 212 patients with hematologic cancers; 106 patients received palifermin (60 microg per kilogram of body weight per day) and 106 received a placebo intravenously for three consecutive days immediately before the initiation of conditioning therapy (fractionated total-body irradiation plus high-dose chemotherapy) and after autologous hematopoietic stem-cell transplantation. Oral mucositis was evaluated daily for 28 days after transplantation.The incidence of oral mucositis of World Health Organization (WHO) grade 3 or 4 was 63 percent in the palifermin group and 98 percent in the placebo group (P<0.001). Among patients with this degree of mucositis, the median duration of mucositis was 6 days (range, 1 to 22) in the palifermin group and 9 days (range, 1 to 27) in the placebo group. Among all patients, regardless of the occurrence of mucositis, the median duration of oral mucositis of WHO grade 3 or 4 was 3 days (range, 0 to 22) in the palifermin group and 9 days (range, 0 to 27) in the placebo group (P<0.001). As compared with placebo, palifermin was associated with significant reductions in the incidence of grade 4 oral mucositis (20 percent vs. 62 percent, P<0.001), patient-reported soreness of the mouth and throat (area-under-the-curve score, 29.0 [range, 0 to 98] vs. 46.8 [range, 0 to 110]; P<0.001), the use of opioid analgesics (median, 212 mg of morphine equivalents [range, 0 to 9418] vs. 535 mg of morphine equivalents [range, 0 to 9418], P<0.001), and the incidence of use of total parenteral nutrition (31 percent vs. 55 percent, P<0.001). Adverse events, mainly rash, pruritus, erythema, mouth and tongue disorders, and taste alteration, were mild to moderate in severity and were transient.Palifermin reduced the duration and severity of oral mucositis after intensive chemotherapy and radiotherapy for hematologic cancers.
Abstract IA5: Discovering the distal fallopian tube as the origin for high-grade serous ovarian cancer
Authors: Ronny Drapkin
Journal: Clinical Cancer Research (2013)

Abstract Recent developments in the study of epithelial ovarian cancer have called into question the traditional views regarding the site of tumor initiation. Histopathologic studies and genomic analyses suggest that extra-ovarian sites, like the fallopian tube (FT) epithelium, may harbor the coveted cell of origin and could therefore contribute significantly to the development of high-grade serous ovarian carcinoma (HGSOC). Our ability to validate these emerging genomic and pathologic observations and characterize the early transformation events of HGSOC hinges on the development of novel model systems. The tubal hypothesis of serous tumorigenesis has led us to develop a number of experimental platforms. These platforms provide us with a unique view into the susceptibilities of the FT epithelium to neoplastic transformation and provide a vehicle to query the contribution of any given genetic alteration to tumor development in vitro and in vivo. These models include the ex-vivo bioanalytical platform of benign FT epithelium, the in vitro FT secretory cell transformation model, a series of patient-derived primary tumor xenograft (PDX) models that retain the phenotypic and genotypic properties of the original patient tumors, and a genetically-engineered mouse model (GEMM) that specifically targets the FT epithelium in vivo. Our GEM model specifically targets the Müllerian secretory cell. It uses the Pax8 promoter to drive expression of the Cre recombinase in the fallopian tube (FT) secretory cells. Pax8 is a lineage marker for the Müllerian system. It is necessary for the development of the female reproductive tract and its expression is retained in the adult FT secretory cell and in nearly all HGSOCs. By crossing our Pax8-Cre deletor mouse with mice carrying floxed alleles of BRCA genes, TP53 (or mutant) and/or PTEN, we could specifically manipulate the expression of these genes in the FT secretory cell. Using this approach, in collaboration with the laboratory of Daniela Dinulescu, we showed that HGSOC can originate in secretory cell of the FT and also established that serous tubal intraepithelial carcinoma (STIC) is the precursor lesion to high-grade serous ovarian and peritoneal carcinomas. Importantly, the tumors that arise in this model not only look like high-grade serous carcinomas but they also retain the genomic complexity that is a hallmark of human HGSOC. In addition to providing mechanistic insight into the origin and pathogenesis of HGSC, this model provides a platform to explore HGSOC sensitivity to novel therapeutic strategies and to develop better detection strategies for early tumor diagnosis in high-risk women. Citation Format: Ronny Drapkin. Discovering the distal fallopian tube as the origin for high-grade serous ovarian cancer. [abstract]. In: Proceedings of the AACR Special Conference on Advances in Ovarian Cancer Research: From Concept to Clinic; Sep 18-21, 2013; Miami, FL. Philadelphia (PA): AACR; Clin Cancer Res 2013;19(19 Suppl):Abstract nr IA5.
Respiratory virus–induced EGFR activation suppresses IRF1-dependent interferon λ and antiviral defense in airway epithelium
Authors: Iris F. Ueki, Gundula Min-Oo, April Kalinowski, Eric Ballon-Landa, Lewis L. Lanier, Jay A. Nadel, Jonathan L. Koff
Journal: The Journal of Experimental Medicine (2013)

Viruses suppress host responses to increase infection, and understanding these mechanisms has provided insights into cellular signaling and led to novel therapies. Many viruses (e.g., Influenza virus, Rhinovirus [RV], Cytomegalovirus, Epstein-Barr virus, and Hepatitis C virus) activate epithelial epidermal growth factor receptor (EGFR), a tyrosine kinase receptor, but the role of EGFR in viral pathogenesis is not clear. Interferon (IFN) signaling is a critical innate antiviral host response and recent experiments have implicated IFN-λ, a type III IFN, as the most significant IFN for mucosal antiviral immune responses. Despite the importance of IFN-λ in epithelial antiviral responses, the role and mechanisms of epithelial IFN-λ signaling have not been fully elucidated. We report that respiratory virus-induced EGFR activation suppresses endogenous airway epithelial antiviral signaling. We found that Influenza virus– and RV-induced EGFR activation suppressed IFN regulatory factor (IRF) 1–induced IFN-λ production and increased viral infection. In addition, inhibition of EGFR during viral infection augmented IRF1 and IFN-λ, which resulted in decreased viral titers in vitro and in vivo. These findings describe a novel mechanism that viruses use to suppress endogenous antiviral defenses, and provide potential targets for future therapies.
Compendium of Unpublished Phase III Trials in Oncology: Characteristics and Impact on Clinical Practice
Authors: Vincent C. Tam, Ian F. Tannock, Christine Massey, Jennifer Rauw, Monika K. Krzyzanowska
Journal: Journal of Clinical Oncology (2011)

Many phase III trials presented at annual meetings of the American Society of Clinical Oncology (ASCO) remain unpublished. The results of these unpublished trials, if more generally known, might have an impact on clinical practice.Abstracts of large phase III trials evaluating systemic cancer treatment were identified from conference proceedings of the 1989 to 2003 ASCO annual meetings. PubMed, Medline, and Embase were searched for corresponding publications. A compendium of unpublished phase III trials was assembled. Clinical significance of nonpublication was determined by disease site-specific oncology experts from two academic cancer centers in Canada.A total of 709 phase III trials were identified of which 66 (9.3%) remain without a subsequent publication at a minimum of 6.5 years of follow-up and 94 (13%) were published after a delay of ≥ 5 years from their initial presentation. Of the unpublished trials, 48% were presented as oral sessions at an ASCO meeting, and 71% of the abstracts reported negative results. The experts judged that 70% of the unpublished trials addressed an important question and 59% might have had clinical impact if their results had been published promptly.A substantial number of cancer clinical trials with potential influence on clinical practice remain unpublished and many other trials are published after a substantial delay. Nonpublication of clinical trials breaks an implicit contract with participants, institutional review boards, and sponsors.