tbuckley/cabot-search huggingface dataset:
The epidemiology and treatment of mesothelioma in South East England 1985-2002
Authors: V Mak, E Davies, V Putcha, B Choodari-Oskooei, H Moller
Journal: Thorax (2007)

To describe trends in the incidence of mesothelioma for men and women in South East England and the geographical variation at the level of primary care trust. To describe treatment patterns by cancer network of residence, and relative survival by cancer network, disease stage and treatment modality.5753 cases were extracted from the Thames Cancer Registry database. We calculated age standardised incidence rates for each year, age specific incidence rates in 10 year age groups, and we used linear regression to compute the average annual percentage change in age standardised incidence. We used Poisson regression to analyse generational trends in incidence.Men had five times higher incidence of mesothelioma than women. In men, there was an overall 4% increase per year between 1985 and 2002. Over the same period, the overall increase in incidence for women was 5% per year. The incidence was highest in men aged over 70 years, and men aged over 80 years had the highest increase of 8% per year. The incidence rate ratio increased for men born between 1892 and 1942 and started to slow for those born from 1947 onwards. Areas along the Thames and its estuary had the highest incidence. There was some variation by cancer network in the proportion of patients receiving cancer surgery, radiotherapy and chemotherapy. There were no discernable differences in relative survival by cancer network of residence or disease stage but those receiving combined treatment had higher 5 year survival.Mesothelioma incidence has increased in South East England, particularly for men aged over 70 years. The highest incidence occurs along the Thames and its estuary, reflecting areas of asbestos use in shipbuilding and industry in the past. More research is needed to understand the interrelationships of prognostic factors, treatment choices and survival, and to determine the best care and support for these patients and their families.
Sunitinib malate in solitary fibrous tumor (SFT)
Authors: S Stacchiotti, T Negri, M Libertini, E Palassini, A Marrari, B De Troia, A Gronchi, A P Dei Tos, C Morosi, A Messina, S Pilotti, P G Casali
Journal: Annals of Oncology (2012)
Bone Quality: An Empty Term
Authors: Harri Sievänen, Pekka Kannus, Teppo L. N Järvinen
Journal: PLoS Medicine (2007)

Although the concept of “bone quality” is at least 15 years old [1], the term has recently sparked much discussion and debate among clinicians and clinical researchers [2–5]. At a recent National Institutes of Health conference on bone quality, the term was defined as: “The sum total of characteristics of the bone that influence the bone's resistance to fracture” [6].
The Incidence and Severity of Adverse Events Affecting Patients after Discharge from the Hospital
Authors: Alan J. Forster, Harvey J. Murff, Josh F. Peterson, Tejal K. Gandhi, David W. Bates
Journal: Annals of Internal Medicine (2003)

Background: Studies of hospitalized patients identify safety as a significant problem, but few data are available regarding injuries occurring after discharge. Patients may be vulnerable during this transition period. Objective: To describe the incidence, severity, preventability, and ameliorability of adverse events affecting patients after discharge from the hospital and to develop strategies for improving patient safety during this interval. Design: Prospective cohort study. Setting: A tertiary care academic hospital. Patients: 400 consecutive patients discharged home from the general medical service. Measurements: The three main outcomes were adverse events, defined as injuries occurring as a result of medical management; preventable adverse events, defined as adverse events judged to have been caused by an error; and ameliorable adverse events, defined as adverse events whose severity could have been decreased. Posthospital course was determined by performing a medical record review and a structured telephone interview approximately 3 weeks after each patient's discharge. Outcomes were determined by independent physician reviews. Results: Seventy-six patients had adverse events after discharge (19% [95% CI, 15% to 23%]). Of these, 23 had preventable adverse events (6% [CI, 4% to 9%]) and 24 had ameliorable adverse events (6% [CI, 4% to 9%]). Three percent of injuries were serious laboratory abnormalities, 65% were symptoms, 30% were symptoms associated with a nonpermanent disability, and 3% were permanent disabilities. Adverse drug events were the most common type of adverse event (66% [CI, 55% to 76%]), followed by procedure-related injuries (17% [CI, 8% to 26%]). Of the 25 adverse events resulting in at least a nonpermanent disability, 12 were preventable (48% [CI, 28% to 68%]) and 6 were ameliorable (24% [CI, 7% to 41%]). Conclusion: Adverse events occurred frequently in the peridischarge period, and many could potentially have been prevented or ameliorated with simple strategies.
New concepts for expressing forced expiratory volume in 1 s: conclusions need nuances
Authors: F.A.A. Mohamed Hoesein, P. Zanen
Journal: European Respiratory Journal (2010)

We read with interest the recent publication by MILLER and PEDERSEN [1] on determining the best way of expressing lung function impairment for prediction of mortality.The authors ranked the methods of expressing forced expiratory volume in 1 s (FEV1).It was concluded that the FEV1 quotient (Q) was the best predictor.We believe that this outcome is in need for some nuances.This ranking is, in our view, only suitable when the parameters under investigation are all valid and when based on proper testing.We feel that this is not the case.We will illustrate this via the FEV1 standardised residuals (SR) and focus on the receiver operating curve (ROC) comparison chosen for the ranking.
A double-blind trial of ibuprofen and aspirin in the treatment of soft-tissue injuries sustained in professional football.
Authors: D. S. Muckle
Journal: British Journal of Sports Medicine (1980)

Of ten thousand patients seen in the Orthopaedic Department of the Middlesbrough General Hospital, about one thousand are sportsmen, and overall the majority suffer an injury or disease of the collagen tissues with or without bone involvement.An important factor in soft-tissue lesions is the bio-feedback neuro- logical mechanisms controlling joint movement, bone and muscle growth, and calcification of bone.
Increase of Ascites and Pleural Effusion Misleading Assessment of Antitumor Response to Erlotinib in Adenocarcinoma of the Lung
Authors: Motoko Tachihara, Kenichi Misa, Manabu Uematsu, Hiroyuki Minemura, Yutaka Katsuura, Takashi Ishida, Mitsuru Munakata
Journal: Journal of Clinical Oncology (2011)
RETRACTED ARTICLE:Differential modulatory effects of GSK-3β and HDM2 on sorafenib-induced AIF nuclear translocation (programmed necrosis) in melanoma
Authors: Qingjun Liu, James W Mier, David J Panka
Journal: Molecular Cancer (2011)

Abstract Background GSK-3β phosphorylates numerous substrates that govern cell survival. It phosphorylates p53, for example, and induces its nuclear export, HDM2-dependent ubiquitination, and proteasomal degradation. GSK-3β can either enhance or inhibit programmed cell death, depending on the nature of the pro-apoptotic stimulus. We previously showed that the multikinase inhibitor sorafenib activated GSK-3β and that this activation attenuated the cytotoxic effects of the drug in various BRAF-mutant melanoma cell lines. In this report, we describe the results of studies exploring the effects of GSK-3β on the cytotoxicity and antitumor activity of sorafenib combined with the HDM2 antagonist MI-319. Results MI-319 alone increased p53 levels and p53-dependent gene expression in melanoma cells but did not induce programmed cell death. Its cytotoxicity, however, was augmented in some melanoma cell lines by the addition of sorafenib. In responsive cell lines, the MI-319/sorafenib combination induced the disappearance of p53 from the nucleus, the down modulation of Bcl-2 and Bcl-x L , the translocation of p53 to the mitochondria and that of AIF to the nuclei. These events were all GSK-3β-dependent in that they were blocked with a GSK-3β shRNA and facilitated in otherwise unresponsive melanoma cell lines by the introduction of a constitutively active form of the kinase (GSK-3β-S9A). These modulatory effects of GSK-3β on the activities of the sorafenib/MI-319 combination were the exact reverse of its effects on the activities of sorafenib alone, which induced the down modulation of Bcl-2 and Bcl-x L and the nuclear translocation of AIF only in cells in which GSK-3β activity was either down modulated or constitutively low. In A375 xenografts, the antitumor effects of sorafenib and MI-319 were additive and associated with the down modulation of Bcl-2 and Bcl-x L , the nuclear translocation of AIF, and increased suppression of tumor angiogenesis. Conclusions Our data demonstrate a complex partnership between GSK-3β and HDM2 in the regulation of p53 function in the nucleus and mitochondria. The data suggest that the ability of sorafenib to activate GSK-3β and alter the intracellular distribution of p53 may be exploitable as an adjunct to agents that prevent the HDM2-dependent degradation of p53 in the treatment of melanoma.
A Marker of Endotoxemia Is Associated With Obesity and Related Metabolic Disorders in Apparently Healthy Chinese
Authors: Liang Sun, Zhijie Yu, Xingwang Ye, Shurong Zou, Huaixing Li, Danxia Yu, Hongyu Wu, Yan Chen, Joel Dore, Karine Clément, Frank B. Hu, Xu Lin
Journal: Diabetes Care (2010)

OBJECTIVE Elevated lipopolysaccharide-binding protein (LBP), a marker of subclinical endotoxemia, may be involved in the pathogenesis of obesity and metabolic risk. We aimed to investigate the association between plasma LBP and metabolic disorders in apparently healthy Chinese. RESEARCH DESIGN AND METHODS A population-based study including 559 overweight/obese (BMI ≥24.0 kg/m2) and 500 normal-weight (18.0 ≤ BMI &amp;lt;24.0 kg/m2) subjects aged 35–54 years was conducted in Shanghai, China. Fasting plasma glucose, lipid profile, LBP, high-sensitivity C-reactive protein, interleukin-6, high-molecular-weight (HMW) adiponectin, leptin, hepatic enzymes, and body composition were measured. Metabolic syndrome was defined by the updated National Cholesterol Education Program Adult Treatment Panel III criterion for Asian Americans. RESULTS LBP levels were significantly higher in overweight/obese individuals than in normal-weight individuals (geometric mean 27.6 [95% CI 25.2–30.3] vs. 10.0 [9.1–11.1] μg/ml; P &amp;lt; 0.001). After multiple adjustments including BMI, the odds ratios were 3.54 (95% CI 2.05–6.09) and 5.53 (95% CI 2.64–11.59) for metabolic syndrome and type 2 diabetes, respectively, comparing the highest with the lowest LBP quartile. Further adjustments for inflammatory markers almost abolished the significant association of LBP with metabolic syndrome but not that with type 2 diabetes, and controlling for adipokines and hepatic enzymes did not substantially alter the results. CONCLUSIONS Elevated circulating LBP was associated with obesity, metabolic syndrome, and type 2 diabetes in apparently healthy Chinese. These findings suggested a role of lipopolysaccharide via initiation of innate immune mechanism(s) in metabolic disorders. Prospective studies are needed to confirm these results.
Epitope-specific antibodies to the 43-kD glomerular membrane protein podoplanin cause proteinuria and rapid flattening of podocytes.
Authors: K Matsui, S Breiteneder-Geleff, D Kerjaschki
Journal: Journal of the American Society of Nephrology (1998)

The 43-kD integral membrane protein podoplanin is localized on the surface of rat podocytes, and transcriptionally downregulated in rat puromycin nephrosis. In this study, a single intravenous injection of polyclonal rabbit anti-podoplanin IgG resulted in selective binding of IgG to the entire podocyte's surface. Some IgG produced by different rabbits rapidly induced transient proteinuria (approximately 350 mg/24 h at day 1, normal levels around day 5), whereas other IgG were ineffective. All anti-podoplanin IgG shared a common binding site at amino acids 39 to 47 (DDMVNPGLE), whereas IgG inducing glomerular damage specifically bound to an additional epitope at amino acids 74 to 79 (PIEELP), as observed by a SPOTs analysis on overlapping synthetic peptides. Proteinuria was not prevented by complement depletion or by treatment with the oxygen radical scavenger dimethylthiourea. Injection of Fab fragments failed to induce glomerular pathology, indicating that dimerization of podoplanin by divalent IgG was required. Proteinuria was paralleled by extensive flattening of foot processes that was also induced by blood-free perfusion of isolated rat kidneys with anti-podoplanin IgG. Thus, glomerular changes were due to direct interaction of distinct epitope(s) of podoplanin and divalent IgG. These results provide evidence that podoplanin plays a role in maintaining the unique shape of podocyte foot processes and glomerular permeability.
Choice of Oxygen-Conserving Treatment Regimen Determines the Inflammatory Response and Outcome of Photodynamic Therapy of Tumors
Authors: Barbara W. Henderson, Sandra O. Gollnick, John W. Snyder, Theresa M. Busch, Philaretos C. Kousis, Richard T. Cheney, Janet Morgan
Journal: Cancer Research (2004)

Abstract The rate of light delivery (fluence rate) plays a critical role in photodynamic therapy (PDT) through its control of tumor oxygenation. This study tests the hypothesis that fluence rate also influences the inflammatory responses associated with PDT. PDT regimens of two different fluences (48 and 128 J/cm2) were designed for the Colo 26 murine tumor that either conserved or depleted tissue oxygen during PDT using two fluence rates (14 and 112 mW/cm2). Tumor oxygenation, extent and regional distribution of tumor damage, and vascular damage were correlated with induction of inflammation as measured by interleukin 6, macrophage inflammatory protein 1 and 2 expression, presence of inflammatory cells, and treatment outcome. Oxygen-conserving low fluence rate PDT of 14 mW/cm2 at a fluence of 128 J/cm2 yielded ∼70–80% tumor cures, whereas the same fluence at the oxygen-depleting fluence rate of 112 mW/cm2 yielded ∼10–15% tumor cures. Low fluence rate induced higher levels of apoptosis than high fluence rate PDT as indicated by caspase-3 activity and terminal deoxynucleotidyl transferase-mediated nick end labeling analysis. The latter revealed PDT-protected tumor regions distant from vessels in the high fluence rate conditions, confirming regional tumor hypoxia shown by 2-(2-nitroimidazol-1[H]-yl)-N-(3,3,3-trifluoropropyl) acetamide staining. High fluence at a low fluence rate led to ablation of CD31-stained endothelium, whereas the same fluence at a high fluence rate maintained vessel endothelium. The highest levels of inflammatory cytokines and chemokines and neutrophilic infiltrates were measured with 48 J/cm2 delivered at 14 mW/cm2 (∼10–20% cures). The optimally curative PDT regimen (128 J/cm2 at 14 mW/cm2) produced minimal inflammation. Depletion of neutrophils did not significantly change the high cure rates of that regimen but abolished curability in the maximally inflammatory regimen. The data show that a strong inflammatory response can contribute substantially to local tumor control when the PDT regimen is suboptimal. Local inflammation is not a critical factor for tumor control under optimal PDT treatment conditions.
Prevalence and risk factors of discordance in diagnosis of osteoporosis using spine and hip bone densitometry
Authors: A. El Maghraoui, D. A Mouinga Abayi, I. Ghozlani, A. Mounach, A. Nouijai, M. Ghazi, L. Achemlal, A. Bezza
Journal: Annals of the Rheumatic Diseases (2006)

Dual x ray absorptiometry is the reference method to measure bone mineral density (BMD) accurately and reproducibly. The World Health Organization defines osteoporosis on the basis of the T score (which is the difference between the measured BMD and the mean value of young adults, expressed in standard deviations for a normative population of the same ethnicity).1 Although the BMD at different anatomical regions is correlated, the agreement between sites is low when it comes to classifying individual subjects as having osteoporosis.2 Various studies have analysed the prevalence and effect of T score discordance on the management of osteoporosis.3–7 However, most of these studies did not evaluate risk factors for this phenomenon. Thus, …
What Are the Risks and Benefits to Increasing Dietary Bone Minerals and Vitamin D Intake in Infants and Small Children?
Authors: Steven A. Abrams
Journal: Annual Review of Nutrition (2011)

Bone minerals and vitamin D are crucial for infants and small children. Human milk has little vitamin D, and supplemental vitamin D must be given to all infants either via drops or as contained in infant formula or foods. The calcium and phosphorus in human milk are adequate for infants in the first six months of life, with supplemental minerals coming from weaning foods after six months. Long-term benefits to providing bone minerals at greater levels than in human milk have not been shown. There is no evidence to support high-dose bone mineral supplementation or high-dose vitamin D supplementation in infancy, and controlled trials are needed before these can be advocated.
Urinary incontinence in physically active women and female athletes
Authors: Orly Goldstick, Naama Constantini
Journal: British Journal of Sports Medicine (2013)

A literature review was performed on the topic of urinary incontinence during physical activity and sports. This paper reviews the prevalence, risk factors, pathophysiology and treatment modalities of urinary incontinence in physically active women and female athletes. Urinary incontinence affects women of all ages, including top female athletes, but is often under-reported. The highest prevalence of urinary incontinence is reported in those participating in high impact sports. Pelvic floor muscle training is considered the first-line treatment, although more research is needed to determine optimal treatment protocols for exercising women and athletes. Trainers, coaches and other athletes’ caregivers should be educated and made aware of the need for proper urogynaecological assessment.
Targeting of the VEGF-kinase inhibitor PTK787 to angiogenic vasculature using RGD-equipped albumin carrier molecules
Authors: K. Temming, M. Lacombe, H.E. Moorlag, S.A. Asgeirsdottir, L. Orfi, G. Kéri, K. Poelstra, G. Molema, R.J. Kok
Journal: Journal of Controlled Release (2006)
Health-Related Quality of Life As a Survival Predictor for Patients With Localized Head and Neck Cancer Treated With Radiation Therapy
Authors: François Meyer, André Fortin, Michel Gélinas, Abdenour Nabid, François Brochet, Bernard Têtu, Isabelle Bairati
Journal: Journal of Clinical Oncology (2009)

Purpose To assess the added prognostic value for overall survival (OS) of baseline health-related quality of life (HRQOL) and of early changes in HRQOL among patients with localized head and neck cancer (HNC) treated with radiation therapy. Patients and Methods All 540 patients with HNC who participated in a randomized trial completed two HRQOL instruments before radiation therapy: the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30 (EORTC QLQ-C30) and the Head and Neck Radiotherapy Questionnaire. Six months after the end of radiation therapy, 497 trial participants again completed the two HRQOL instruments. During the follow-up, 179 deaths were observed. Multivariate Cox proportional hazards models were used to test whether HRQOL variables, baseline and change, provided additional prognostic value beyond recognized prognostic factors. Results The baseline EORTC QLQ-C30 physical functioning (PF) score was an independent predictor of OS. The hazard ratio (HR) associated with a 10-point increment in baseline PF was 0.87 (95% CI, 0.81 to 0.94). In multivariate models, the change in HRQOL was significantly associated with OS for most HRQOL dimensions. Among these, PF change was the strongest predictor. The magnitude of the association between PF change and survival decreased over time. At 1 year, the HR associated with a positive PF change of 10 points was 0.75 (95% CI, 0.68 to 0.83). After PF is taken into account, no other HRQOL variable was associated with survival. Conclusion Our findings indicate that both baseline PF and PF change provide added prognostic value for OS beyond established predictors in patients with HNC. Assessing HRQOL could help better predict survival of cancer patients.
Chymase Inhibition Prevents Cardiac Fibrosis and Improves Diastolic Dysfunction in the Progression of Heart Failure
Authors: Takehiro Matsumoto, Atsuyuki Wada, Takayoshi Tsutamoto, Masato Ohnishi, Takahiro Isono, Masahiko Kinoshita
Journal: Circulation (2003)

Angiotensin (Ang) II, which plays a crucial role in the cardiac remodeling process, is generated via angiotensin-converting enzyme (ACE); however, an alternative generation pathway, chymase, which is stored in the mast cells, also exists in the heart. Cardiac chymase is insensitive to ACE inhibitors (ACEIs), and heart chymase promotes interstitial fibrosis by affecting collagen metabolism via transforming growth factor-beta in vitro. Therefore, selective chymase blockade seems to be an important strategy in the prevention of cardiac remodelingWe evaluated the effects of a specific chymase inhibitor, SUNC8257 (Chy I; 10 mg/kg twice a day; n=7), on changes in cardiac structures, Ang II levels, and gene expressions, which are characterized as molecular markers for fibrosis, in dogs with tachycardia induced heart failure (HF). In HF, the number of chymase enzyme-positive mast cells increased in the left ventricle (LV) compared with the normal group; however, Chy I significantly decreased the mast cell density and cardiac Ang II levels. Despite no significant differences in LV systolic function compared with the vehicle group, Chy I decreased LV end-diastolic pressure and shortened the prolongation of tau. Chy I suppressed collagen-type I and III and transforming growth factor-beta mRNA levels and decreased fibrosis in the LV compared with the vehicle.The chymase pathway may be critical for cardiac diastolic dysfunction accompanied with fibrosis. Chronic chymase inhibition may therefore become an important strategy in the prevention of cardiac remodeling in HF.