tbuckley/cabot-search huggingface dataset:
Abrogating chemotherapy-induced myelosuppression by recombinant granulocyte-macrophage colony-stimulating factor in patients with sarcoma: protection at the progenitor cell level.
Authors: S Vadhan-Raj, H E Broxmeyer, W N Hittelman, N E Papadopoulos, S P Chawla, C Fenoglio, S Cooper, E S Buescher, R W Frenck, A Holian
Journal: Journal of Clinical Oncology (1992)

PURPOSE The purpose of this study was to optimize the dose, schedule, and timing of recombinant granulocyte-macrophage colony-stimulating factor (GM-CSF) administration that would best abrogate myelosuppression in patients with sarcoma. PATIENTS AND METHODS Sarcoma patients who had experienced severe myelosuppression after chemotherapy with Cytoxan (cyclophosphamide; Bristol-Myers Squibb Co, Evansville, IN), Adriamycin (doxorubicin; Adria Laboratories, Columbus, OH), and dacarbazine ([CyADIC], cycle 1) were eligible. GM-CSF was administered during a 14-day period until 1 week before cycle 2 of CyADIC and was resumed 2 days after cycle 2 completion. The schedule subsequently was modified to allow the earlier administration of GM-CSF in which CyADIC was compressed from 5 days to 3 days, and GM-CSF was administered immediately after the discontinuation of CyADIC in cycle 2. To understand better the impact of GM-CSF on bone marrow stem cells, the proliferative status of bone marrow progenitors was examined during treatment. To evaluate the effects of GM-CSF on effector cells, select functions of mature myeloid cells were also examined. RESULTS In the seven patients who were treated on the initial schedule, GM-CSF enhanced the rate of neutrophil recovery; however, severe neutropenia was not abrogated, By using the modified schedule in 17 patients, GM-CSF significantly reduced both the degree and the duration of neutropenia and myeloid (neutrophils, eosinophils, and monocytes) leukopenia. The mean neutrophil and mature myeloid nadir counts were 100/mm3 and 280/mm3 in cycle 1 and 290/mm3 and 1,540/mm3 in cycle 2 (P less than .01 and P less than .001). The duration of severe neutropenia (neutrophil count less than 500/mm3) and myeloid leukopenia (myeloid leukocyte count less than 1,000/mm3) were reduced from 6.2 and 6.8 days in cycle 1 to 2.8 and 1.4 days in cycle 2 (P less than .001). While 16 of 17 patients experienced severe myeloid leukopenia (less than 500/mm3) in cycle 1, only two of 17 experienced severe myeloid leukopenia in cycle 2 (P less than .001). Overall, severe neutropenia was abrogated in seven patients, which made them eligible for dose-escalation of Adriamycin. The fraction of cycling progenitors increased threefold on GM-CSF and decreased dramatically below the baseline within 1 day of GM-CSF discontinuation. CONCLUSIONS The modified schedule improved the beneficial effects of GM-CSF by enhancing myeloprotection and permitting dose-intensification of chemotherapy. The increased myeloid mass and quiescent progenitors at the initiation of chemotherapy suggest that GM-CSF might allow further chemotherapy dose-rate intensification by shortening the interval between courses.
Depression in Cerebral Glioma Patients: A Systematic Review of Observational Studies
Authors: A. G. Rooney, A. Carson, R. Grant
Journal: JNCI Journal of the National Cancer Institute (2010)

Depression is a common and important complication of primary cerebral glioma. However, observational studies of this relationship have not been systematically reviewed. We searched MEDLINE, EMBASE, and PsycINFO for all English-language cross-sectional, case–control, and cohort studies of depression in adults with primary glioma published between January 1, 1980, and September 16, 2009. We identified 42 eligible studies that recruited 4089 individual glioma patients. We conducted a narrative review of these studies regarding the heterogeneity in diagnostic methods, the frequency of depression and its clinical associations, and the quality of study reporting. Most studies of depression in adults with glioma were small, cross-sectional, or retrospective. Depression was most often measured using the Hospital Anxiety and Depression Scale (HADS; n = 10 studies). The Beck Depression Inventory, another frequently used screening instrument, returned a higher frequency of depression (median = 39%, range = 38%–42%) than the Hospital Anxiety and Depression Scale (median = 16%, range = 0%–21%). At clinical interview, the median frequency of depression in glioma was 15% (range = 6%–28%). Depression was consistently associated with reduced physical function, cognitive impairment, and reduced quality of life. It may be associated with reduced survival, although evidence for this association was modest. There was an absence of clear associations between depression and many tumor-related variables. Few observational studies examined the treatment of depression in glioma patients. Multivariable analyses were rare, and study reporting was of variable quality. In glioma, mild to moderate depressive symptoms may only rarely be due to tumor-associated structural or functional disruption of neuronal emotional networks. Improved methodological reporting would help clinicians better evaluate future studies, and facilitate improved evidence-based care of depressed glioma patients.
Prognostic significance of imaging contrast enhancement for WHO grade II gliomas
Authors: Johan Pallud, Laurent Capelle, Luc Taillandier, Denys Fontaine, Emmanuel Mandonnet, Rémy Guillevin, Luc Bauchet, Philippe Peruzzi, Florence Laigle-Donadey, Michèle Kujas, Jacques Guyotat, Marie-Hélène Baron, Karima Mokhtari, Hugues Duffau
Journal: Neuro-Oncology (2008)

In this study, we investigated the prognostic value of MRI contrast enhancement (CE) at the time of histological diagnosis specifically in a selected population of WHO grade II gliomas. We reviewed 927 histologically proven WHO grade II gliomas for which contrast-enhanced MR images were available at the time of histological diagnosis. CE patterns were classified into three categories: "patchy and faint," "nodular-like," and "ring-like." CE progression over time was recorded before oncological treatment on successive MR images, when available. CE was present in 143 cases (15.9%), with 93 patchy and faint, 50 nodular-like, and no ring-like patterns. CE areas were time progressive before oncological treatment in 35 of the 56 available cases (62.5%). Regardless of its pattern, the presence of CE was not significantly associated with a worsened prognosis (p = 0.415) by univariate analysis. Only the nodular-like pattern of CE (p < 0.01) and the time-progressive CE (p < 0.001) in the available subgroup proved to be statistically associated with survival since first oncological treatment. The present results show the necessity, in cases of WHO grade II gliomas, to study CE at the time of histological diagnosis and, whenever possible, to follow its progression over time before oncological treatment. Nodular-like CE and time-progressive CE are associated with a worsened prognosis, both suggesting malignant transformation, even though histopathological examination cannot initially disclose signs of malignancy in those areas.
Inequalities in Premature Death From Colorectal Cancer by State
Authors: Ahmedin Jemal, Rebecca L. Siegel, Jiemin Ma, Farhad Islami, Carol DeSantis, Ann Goding Sauer, Edgar P. Simard, Elizabeth M. Ward
Journal: Journal of Clinical Oncology (2014)

Although disparities in colorectal cancer (CRC) with regard to race, socioeconomic status, and geography are well documented, the extent to which these factors contribute to premature death resulting from CRC nationwide and by state is unknown.We calculated age-standardized CRC death rates for three broad educational categories as a marker of socioeconomic status by race/ethnicity and state among individuals age 25 to 64 years from 2008 through 2010. We also calculated the proportion of premature death resulting from CRC that could potentially be averted in each state by applying the average death rate for the five states with the lowest rates among the most educated whites (Connecticut, North Dakota, Utah, Vermont, and Wisconsin) to all populations.Compared with those with the most education, those with the least education had significantly higher CRC death rates in virtually all states for each racial/ethnic group. For example, rate ratios ranged from 1.15 (95% CI, 0.66 to 2.01) in Delaware to 3.18 (95% CI, 2.01 to 5.05) in New Mexico among whites. Overall, half the premature deaths resulting from CRC that occurred nationwide from 2008 through 2010, or 7,690 deaths annually, would have been avoided if everyone had experienced the lowest death rates of the most educated whites. More premature deaths could be averted in southern states (60% to 70%) than in northern and western states (30% to 40%). Restricting the analyses to persons age 50 to 64 years, for whom CRC screening is recommended, resulted in similar findings.The majority of premature deaths from CRC in southern states and half these deaths nationwide are due to racial/ethnic, socioeconomic, and geographic inequalities.
Outcomes in Patients with Chronic Obstructive Pulmonary Disease and Obstructive Sleep Apnea
Authors: Jose M. Marin, Joan B. Soriano, Santiago J. Carrizo, Ana Boldova, Bartolome R. Celli
Journal: American Journal of Respiratory and Critical Care Medicine (2010)

Patients with chronic obstructive pulmonary disease (COPD) and obstructive sleep apnea (OSA) (overlap syndrome) are more likely to develop pulmonary hypertension than patients with either condition alone.To assess the relation of overlap syndrome to mortality and first-time hospitalization because of COPD exacerbation and the effect of continuous positive airway pressure (CPAP) on these major outcomes.We included 228 patients with overlap syndrome treated with CPAP, 213 patients with overlap syndrome not treated with CPAP, and 210 patients with COPD without OSA. All were free of heart failure, myocardial infarction, or stroke. Median follow-up was 9.4 years (range, 3.3-12.7). End points were all-cause mortality and first-time COPD exacerbation leading to hospitalization.After adjustment for age, sex, body mass index, smoking status, alcohol consumption, comorbidities, severity of COPD, apnea-hypopnea index, and daytime sleepiness, patients with overlap syndrome not treated with CPAP had a higher mortality (relative risk, 1.79; 95% confidence interval, 1.16-2.77) and were more likely to suffer a severe COPD exacerbation leading to hospitalization (relative risk, 1.70; 95% confidence interval, 1.21-2.38) versus the COPD-only group. Patients with overlap syndrome treated with CPAP had no increased risk for either outcome compared with patients with COPD-only.The overlap syndrome is associated with an increased risk of death and hospitalization because of COPD exacerbation. CPAP treatment was associated with improved survival and decreased hospitalizations in patients with overlap syndrome.
Prostate Cancer Mortality Reduction by Prostate-Specific Antigen–Based Screening Adjusted for Nonattendance and Contamination in the European Randomised Study of Screening for Prostate Cancer (ERSPC)
Authors: Monique J. Roobol, Melissa Kerkhof, Fritz H. Schröder, Jack Cuzick, Peter Sasieni, Matti Hakama, Ulf Hakan Stenman, Stefano Ciatto, Vera Nelen, Maciej Kwiatkowski, Marcos Lujan, Hans Lilja, Marco Zappa, Louis Denis, Franz Recker, Antonio Berenguer, Mirja Ruutu, Paula Kujala, Chris H. Bangma, Gunnar Aus, Teuvo L.J. Tammela, Arnauld Villers, Xavier Rebillard, Sue M. Moss, Harry J. de Koning, Jonas Hugosson, Anssi Auvinen
Journal: European Urology (2009)
Basic biology and role of interleukin‐17 in immunity and inflammation
Authors: Camille Zenobia, George Hajishengallis
Journal: Periodontology 2000 (2015)

Abstract Interleukin‐17 (also known as interleukin‐17A) is a key cytokine that links T‐cell activation to neutrophil mobilization and activation. As such, interleukin‐17 can mediate protective innate immunity to pathogens or contribute to the pathogenesis of inflammatory diseases, such as psoriasis and rheumatoid arthritis. This review summarizes the basic biology of interleukin‐17 and discusses its emerging role in periodontal disease. The current burden of evidence from human and animal model studies suggests that the net effect of interleukin‐17 signaling promotes disease development. In addition to promoting neutrophilic inflammation, interleukin‐17 has potent pro‐osteoclastogenic effects that are likely to contribute to the pathogenesis of periodontitis, rheumatoid arthritis and other diseases involving bone immunopathology. Systemic treatments with anti‐interleukin‐17 biologics have shown promising results in clinical trials for psoriasis and rheumatoid arthritis; however, their impact on the highly prevalent periodontal disease has not been investigated or reported. Future clinical trials, preferably using locally administered interleukin‐17 blockers, are required to implicate conclusivelyinterleukin‐17 in periodontitis and, more importantly, to establish an effective adjunctive treatment for this oral inflammatory disease.
Erythroderma in a child with coeliac disease
Authors: HAROLD WOOLFSON, ALEXANDER McQUEEN, MARY STEPHEN
Journal: British Journal of Dermatology (1974)

Erythroderma is described in a 2‐year‐old child with coeliac disease, who died of fungal pneumonia. The skin eruption commenced the day after a gluten‐free diet was instituted and proved intractable to treatment, whereas the signs of malabsorption were swiftly controlled. We could establish no connection between the cutaneous and intestinal disorders.
Effect of proprioception training on knee joint position sense in female team handball players
Authors: G Pánics, A Tállay, A Pavlik, I Berkes
Journal: British Journal of Sports Medicine (2008)

A number of studies have shown that proprioception training can reduce the risk of injuries in pivoting sports, but the mechanism is not clearly understood.To determine the contributing effects of propioception on knee joint position sense among team handball players.Prospective cohort study.Two professional female handball teams were followed prospectively for the 2005-6 season. 20 players in the intervention team followed a prescribed proprioceptive training programme while 19 players in the control team did not have a specific propioceptive training programme. The coaches recorded all exposures of the individual players. The location and nature of injuries were recorded. Joint position sense (JPS) was measured by a goniometer on both knees in three angle intervals, testing each angle five times. Assessments were performed before and after the season by the same examiner for both teams. In the intervention team a third assessment was also performed during the season. Complete data were obtained for 15 subjects in the intervention team and 16 in the control team. Absolute error score, error of variation score and SEM were calculated and the results of the intervention and control teams were compared.The proprioception sensory function of the players in the intervention team was significantly improved between the assessments made at the start and the end of the season (mean (SD) absolute error 9.78-8.21 degrees (7.19-6.08 degrees ) vs 3.61-4.04 degrees (3.71-3.20 degrees ), p<0.05). No improvement was seen in the sensory function in the control team between the start and the end of the season (mean (SD) absolute error 6.31-6.22 degrees (6.12-3.59 degrees ) vs 6.13-6.69 degrees (7.46-6.49 degrees ), p>0.05).This is the first study to show that proprioception training improves the joint position sense in elite female handball players. This may explain the effect of neuromuscular training in reducing the injury rate.
Frontiers in Nephrology
Authors: Joshua N. Beilke, Ronald G. Gill
Journal: Journal of the American Society of Nephrology (2007)

Natural killer (NK) cells are recognized for providing an important early innate immune response to viral and bacterial pathogens and for the surveillance of stressed and transformed autologous cells. However, with the exception of a pronounced role in allogeneic hematopoietic stem cell rejection, it has been challenging to ascribe the precise roles for NK cells in reactivity to tissue and solid-organ transplants. In general, NK cells initiate a rapid, proinflammatory environment that is conducive to many forms of effective immune host defense. This reactivity is often considered deleterious to allograft survival because NK cells are implicated in promoting both acute and chronic graft injury. However, more recent findings indicate that NK cells can also play a surprisingly profound role in allograft tolerance induction. This duality of function requires a reconsideration of the nature and consequence of NK cell reactivity during the allograft response. This review focuses on the differing "faces" of NK cells, especially the unexpected role of NK cells in allograft tolerance induction.
Interferon-gamma and interleukin-4 gene polymorphisms in Caucasian idiopathic inflammatory myopathy patients in UK
Authors: H. Chinoy, F. Salway, S. John, N. Fertig, B. D Tait, C. V Oddis, W. E R Ollier, R. G Cooper
Journal: Annals of the Rheumatic Diseases (2007)

<b>Objective:</b> To determine whether interferon-gamma (IFN-γ) and interleukin-4 (IL-4) genes confer susceptibility for the idiopathic inflammatory myopathies (IIMs). <b>Methods:</b> A large cross-sectional study of UK caucasian adults with polymyositis (PM, n = 101), dermatomyositis (DM, n = 94) and myositis overlapping with a connective tissue disease (myositis/CTD-overlap, n = 70) was completed. 177 ethnically matched controls were available for comparison. Single-nucleotide polymorphisms (SNPs) within intronic regions coding for IL-4, IFN-γ and a microsatellite marker within intron 1 of the IFN-γ gene were typed. <b>Results:</b> Strong linkage disequilibrium was present between SNPs in each gene. In the IFN-γ gene, a weak allelic association was observed in PM versus controls at rs1861493 (odds ratio (OR) 1.6, 95% confidence interval (CI) 1.03 to 2.4). The microsatellite IFN-γ CA(14) allele was associated with risk for IIMs overall (OR 3.3, 95% CI 1.4 to 7.8), the strongest association being observed within the anti-U1-ribonucleoprotein (RNP) group (OR 6.0, 95% CI 1.5 to 23.1), and persisting after adjustment for known myositis human leucocyte antigen (HLA) class II associations. <b>Conclusions:</b> Genetic markers in the IFN-γ gene demonstrate significant allelic associations with the IIMs in a UK Caucasian population. The SNPs tested in this study within the region coding for IL-4 fail to show significant associations with susceptibility to IIM disease.
Chromatin modifications remodel cardiac gene expression
Authors: Prabhu Mathiyalagan, Samuel T. Keating, Xiao-Jun Du, Assam El-Osta
Journal: Cardiovascular Research (2014)

Signalling and transcriptional control involve precise programmes of gene activation and suppression necessary for cardiovascular physiology. Deep sequencing of DNA-bound transcription factors reveals a remarkable complexity of co-activators or co-repressors that serve to alter chromatin modification and regulate gene expression. The regulated complexes characterized by genome-wide mapping implicate the recruitment and exchange of proteins with specific enzymatic activities that include roles for histone acetylation and methylation in key developmental programmes of the heart. As for transcriptional changes in response to pathological stress, co-regulatory complexes are also differentially utilized to regulate genes in cardiac disease. Members of the histone deacetylase (HDAC) family catalyse the removal of acetyl groups from proteins whose pharmacological inhibition has profound effects preventing heart failure. HDACs interact with a complex co-regulatory network of transcription factors, chromatin-remodelling complexes, and specific histone modifiers to regulate gene expression in the heart. For example, the histone methyltransferase (HMT), enhancer of zeste homolog 2 (Ezh2), is regulated by HDAC inhibition and associated with pathological cardiac hypertrophy. The challenge now is to target the activity of enzymes involved in protein modification to prevent or reverse the expression of genes implicated with cardiac hypertrophy. In this review, we discuss the role of HDACs and HMTs with a focus on chromatin modification and gene function as well as the clinical treatment of heart failure.
Translation Initiation Factor eIF4E Is a Target for Tumor Cell Radiosensitization
Authors: Thomas J. Hayman, Eli S. Williams, Muhammad Jamal, Uma T. Shankavaram, Kevin Camphausen, Philip J. Tofilon
Journal: Cancer Research (2012)

A core component in the cellular response to radiation occurs at the level of translational control of gene expression. Because a critical element in translation control is the availability of the initiation factor eIF4E, which selectively enhances the cap-dependent translation of mRNAs, we investigated a regulatory role for eIF4E in cellular radiosensitivity. eIF4E silencing enhanced the radiosensitivity of tumor cell lines but not normal cells. Similarly, pharmacologic inhibition of eIF4E with ribavirin also enhanced tumor cell radiosensitivity. eIF4E attenuation did not affect cell-cycle phase distribution or radiation-induced apoptosis, but it delayed the dispersion of radiation-induced γH2AX foci and increased the frequency of radiation-induced mitotic catastrophe. Radiation did not affect 4E-BP1 phosphorylation or cap-complex formation but it increased eIF4E binding to more than 1,000 unique transcripts including many implicated in DNA replication, recombination, and repair. Taken together, our findings suggest that eIF4E represents a logical therapeutic target to increase tumor cell radiosensitivity.
GnRH agonist for triggering of final oocyte maturation: time for a change of practice?
Authors: P. Humaidan, S. Kol, E. Papanikolaou
Journal: Human Reproduction Update (2011)

BACKGROUNDGnRH agonist (GnRHa) triggering has been shown to significantly reduce the occurrence of ovarian hyperstimulation syndrome (OHSS) compared with hCG triggering; however, initially a poor reproductive outcome was reported after GnRHa triggering, due to an apparently uncorrectable luteal phase deficiency. Therefore, the challenge has been to rescue the luteal phase. Studies now report a luteal phase rescue, with a reproductive outcome comparable to that seen after hCG triggering.