tbuckley/cabot-search huggingface dataset:
Prescription, subjective and objective compliances in patients with obstructive sleep apnea syndrome using positive airway pressure
Authors: Banu Salepci, Benan Caglayan, Nesrin Kiral, Elif Torun Parmaksiz, Gulsen Sarac, Ali Fidan, Sevda Sener Comert, Gulten Aktin Gungor
Journal: European Respiratory Journal (2012)

Gold treatment for obstructive sleep apnea syndrome(OSAS) is continuous positive airway pressure(CPAP).We aimed to assess prospectively prescription,subjective and objective compliances in OSAS patients recommended PAP treatment,factors effecting compliance.648 patients (69.6% men,30.4%women)recommended to use PAP in January 2005-June 2011,were included.Patients using PAP were questioned for adverse effects and assessed with ESS(Epworth Sleepiness Scale)at follow-ups.Prescription,objective and subjective compliances were assessed.Relationship between compliance and demographic data,PSG(polysomnography) findings,ESS scores,adverse effects were analyzed.The mean age was 51.29±9.97 and mean BMI(body mass index) was 33.52±6.56.In the first night PSG;mean AHI(apnea-hypopnea index) was 54.16±26.41 and AI(apnea index)was 31.46±26.95.248(38.3%)cases attended follow-ups,246 (37.9%) were followed by phone visits and 154(23.8%)couldn't be reached.Patients usingPAP for at least 4 hours per night for at least 70% of the days monitored were regarded as compliant and who didn't meet this criteria were considered as noncompliant.In whole population 63.9%obtained PAP machine(prescription).In 248 cases attending follow-ups,subjective compliance was 85.1%;objective compliance was 64.5%.Higher ODI(oxygen desaturation index) and lower SpO2(oxygen saturation) observed in first night PSG were found to positively affect prescription (p<0.05).Improvement in ESS score and satisfactory sleep were significantly correlated with objective compliance(p<0.05).Chest discomfort,difficulty falling asleep and sleep disturbances were significantly higher in noncompliant group (p<0.05).
Web of industry, advocacy, and academia in the management of osteoporosis
Authors: Andrew Grey, Mark Bolland
Journal: BMJ (2015)

Calcium and vitamin D supplementation continue to be recommended to prevent and treat osteoporosis despite evidence of lack of benefit, say <b>Andrew Grey</b> and <b>Mark Bolland</b>. They<b> examine</b> why change is difficult and call for advocacy organisations, academics, and specialist societies to abandon industry ties
Immunologic, Virologic, and Genetic Aspects of Mammary Tumor Virus-Induced Cell-Surface Antigens: Presence of These Antigens and the Thy 1.2 Antigen on Murine Mammary Gland and Tumor Cells 2
Authors: J. Hilgers, J. Haverman, R. Nusse, W. J. van Blitterswijk, F. J. Cleton, Ph. C. Hageman, R. van Nie, J. Calafat
Journal: JNCI Journal of the National Cancer Institute (1975)

The distribution of the normal differentiation antigen Thy 1 and the mammary tumor virus (MTV)-induced antigens or antigen complexes MLm and MLr were studied in mouse mammary gland cells, mammary tumor cells, and other cell types, by use of ascites leukemia cells of the GR mouse strain as target cells in the cytotoxicity test. The Thy 1.2 antigen was detected by an AKR antiserum to C3Hf thymocytes. MLm was shown by a homologous C57BL antiserum to GRSL2 leukemia (absorbed in vivo in GR mice); MLr was detected by a rabbit heterologous antiserum (absorbed in vivo in C57BL or GR mice and in vitro with BALB/c milk) prepared against Tween 80- and ether-treated purified B particles. Sera from Sprague-Dawley rats bearing murine leukemia virus (MuLV)-producing syngeneic tumors were not cytotoxic or only slightly cytotoxic for GR leukemias transplanted in vivo, which indicated that MuLV-induced antigens were absent or present in very low quantity in such leukemias. The MLr and MLn antigens or antigen complexes were possibly identical to the mammary leukemia (ML) antigen, since they could be detected not only on GR but also on DBA/2 leukemia cells and since their distribution was exactly the same as that of MTV. Both the MLr and MLm antigens were present in purified B particles, and antigenic activity were present in purified B particles, and antigenic activity was enhanced by destruction of the purified virus particles. The antigens were about eightfold enriched in a preparation of B-particle envelopes, as shown by quantitative cytotoxicity absorption (CYTA) tests. Purified nucleoid fractions of B particles were only lightly positive for the antigen, probably due to envelope contamination. One dominant gene was responsible for the expression of MLr, as shown by CYTA tests with mammary glands of individual animals of segregating crosses between the GR strain with high mammary cancer incidence and strains with low incidence. This gene was closely linked with or was possibly identical to 1) the gene for cytoplasmic MTV gs antigen expression as seen by fixed cell immunofluorescence, and 2) the gene causing mammary tumors in the GR mouse strain.
Impact of doxorubicin on survival in advanced ovarian cancer.
Authors: R P A'Hern, M E Gore
Journal: Journal of Clinical Oncology (1995)

PURPOSE Our study examined the impact of the addition of doxorubicin to ovarian cancer regimens in general, while removing the confounding influence of other drugs. MATERIALS AND METHODS We performed an overview using the data from two large analyses, the Advanced Ovarian Cancer Trialists Group (AOCTG [Br Med J 303:884-893, 1991] and Williams et al [Seminars in Oncol 19:120-128, 1992 (suppl 2)]) and the Ovarian Cancer Meta-Analysis Project (OCMP [J Clin Oncol 9:1668-1674, 1991]). RESULTS Our data suggest that the addition of doxorubicin significantly improves survival (hazards ratio, 0.85; 95% confidence interval [CI], 0.76 to 0.95; P = .003) and that the size of this benefit is of a similar magnitude to that of platinum. CONCLUSION The implication of our results is that the basic drugs for the standard treatment of advanced ovarian should be a combination of platinum and doxorubicin. The addition of an alkylating agent may add toxicity and lead to a dose reduction of these two drugs. In view of recent data on combination therapy with paclitaxel and platinum, it would be appropriate to compare this regimen with a combination of doxorubicin and platinum.
Dysregulated metabolism contributes to oncogenesis
Authors: Matthew D. Hirschey, Ralph J. DeBerardinis, Anna Mae E. Diehl, Janice E. Drew, Christian Frezza, Michelle F. Green, Lee W. Jones, Young H. Ko, Anne Le, Michael A. Lea, Jason W. Locasale, Valter D. Longo, Costas A. Lyssiotis, Eoin McDonnell, Mahya Mehrmohamadi, Gregory Michelotti, Vinayak Muralidhar, Michael P. Murphy, Peter L. Pedersen, Brad Poore, Lizzia Raffaghello, Jeffrey C. Rathmell, Sharanya Sivanand, Matthew G. Vander Heiden, Kathryn E. Wellen
Journal: Seminars in Cancer Biology (2015)

Cancer is a disease characterized by unrestrained cellular proliferation. In order to sustain growth, cancer cells undergo a complex metabolic rearrangement characterized by changes in metabolic pathways involved in energy production and biosynthetic processes. The relevance of the metabolic transformation of cancer cells has been recently included in the updated version of the review "Hallmarks of Cancer", where dysregulation of cellular metabolism was included as an emerging hallmark. While several lines of evidence suggest that metabolic rewiring is orchestrated by the concerted action of oncogenes and tumor suppressor genes, in some circumstances altered metabolism can play a primary role in oncogenesis. Recently, mutations of cytosolic and mitochondrial enzymes involved in key metabolic pathways have been associated with hereditary and sporadic forms of cancer. Together, these results demonstrate that aberrant metabolism, once seen just as an epiphenomenon of oncogenic reprogramming, plays a key role in oncogenesis with the power to control both genetic and epigenetic events in cells. In this review, we discuss the relationship between metabolism and cancer, as part of a larger effort to identify a broad-spectrum of therapeutic approaches. We focus on major alterations in nutrient metabolism and the emerging link between metabolism and epigenetics. Finally, we discuss potential strategies to manipulate metabolism in cancer and tradeoffs that should be considered. More research on the suite of metabolic alterations in cancer holds the potential to discover novel approaches to treat it.
Failure of Interferon to Inhibit Plutonium-Induced Osteosarcomas in Mice&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: G N Taylor, E R Kern, B Braaten, L A Glasgow, M E Wrenn, D A Atherton, C W Mays, K Charrier, G Ayoroa
Journal: JNCI Journal of the National Cancer Institute (1984)

The injection of murine interferon three times weekly in dose levels of 1,250, 5,000, or 20,000 U produced no significant antitumor effect against primary 239Pu-induced osteosarcomas in C57BL/6J mice. The interferon treatment was begun 94 days after the plutonium injection, which is well before the radiographic or microscopic appearance of neoplasia, and was continued until the moribund state or death. The average radiation dose accumulated by the skeleton at the time of first treatment was approximately 300 rad. The largest dose of interferon studied, 20,000 U/injection, was approximately 3 X 10(6) U/m2 of body surface, or 10(6) U/kg body weight.
COPD monocytes differentiate into pro-inflammatory macrophages regardless of environment
Authors: Amy Day, Peter Barnes, Louise Donnelly
Journal: European Respiratory Journal (2013)

COPD is a chronic inflammatory lung disease associated with an increased pro-inflammatory macrophage (mφ) response whereby cells produce increased pro-inflammatory mediators CXCL8 and TNFα and decreased anti-inflammatory mediator IL-10.  A monocyte-derived macrophage (MDM) model was used to study the effect of adherence and fetal calf serum (FCS) on mφ phenotype in non-smokers (NS n=3), smokers (S n=3) and COPD patients (COPD n=3).  Monocytes were isolated and cultured for 12d in either adherent or non-adherent plates in the presence or absence of FCS and addition of either GM-CSF (G-mφ, M1) or M-CSF (M-mφ, M2). MDM were stimulated for 24h with either LPS or IL-4 and levels of CXCL8, TNFα and IL-10 measured by ELISA.  Baseline cytokine production was minimal and did not differ between groups. G-mφ from COPD patients stimulated with LPS produced significantly more TNFα and CXCL8 compared to NS and S (Table 1).  This persisted when G-mφ were cultured without serum or adherence. Lower levels of cytokines were released by M-mφ, although COPD MDM remained pro-inflammatory. M-mφ from S and COPD patients stimulated with IL-4 released less IL-10 than cells from NS (Table 2). This effect was lost in FCS-free media.  COPD MDM consistently produce more pro-inflammatory cytokines and less IL-10 regardless of culture condition. FCS may be priming MDM to produce more cytokines when stimulated  ex-vivo . These data suggest that circulating monocytes are primed in patients with COPD to generate a pro-inflammatory mφ regardless of environment.
Extracorporeal Detoxification Using the Molecular Adsorbent Recirculating System for Critically Ill Patients with Liver Failure
Authors: STEFFEN R. MITZNER, JAN STANGE, SEBASTIAN KLAMMT, PIOTR PESZYNSKI, REINHARDT SCHMIDT, GABRIELE NO[Combining Diaeresis]LDGE-SCHOMBURG
Journal: Journal of the American Society of Nephrology (2001)

Liver failure resulting from different causes and its concomitant complications represent difficult-to-treat conditions with high mortality rates, despite improved therapeutic modalities in intensive care medicine. The accumulation of albumin-bound metabolites that are normally cleared by the liver, such as bilirubin and bile acids, contributes substantially to the development of multiorgan dysfunction in these clinical situations. The molecular adsorbent recirculating system (MARS) represents a cell-free, extracorporeal, liver assistance method for the selective removal of albumin-bound substances. Moreover, it enables the removal of excess water and water-soluble substances via an inbuilt dialysis step. Since 1993, >400 patients have been treated in 53 centers in Europe, the United States, and Asia. Diseases treated with MARS included acute exacerbation of chronic hepatic failure, hepatorenal syndrome, acute hepatic failure, and primary nonfunction/poor function after liver transplantation and major liver resection. Treatments were well tolerated. No severe adverse events were observed. Six- to 8-h MARS treatments resulted in significant (P < 0.05) removal of bilirubin, bile acids, tryptophan, short- and middle-chain fatty acids, aromatic amino acids, and ammonia. Clearance rates for strongly albumin-bound substances were between 10 and 60 ml/min. The removal of albumin-bound toxins resulted in decreases in hepatic encephalopathy, increases in mean arterial pressure, and improvements in kidney and liver function. In the first randomized clinical trial of the MARS method for treatment of the hepatorenal syndrome, significant prolongation of survival was observed for the MARS-treated group. It is concluded that the MARS method can contribute to the treatment of critically ill patients with liver failure and different underlying diseases.
Targeting CHK1 pathway to induce cytotoxic response to histone deactylase inhibitors and evaluating the synergistic effects of CHK1 and HDAC inhibitors in human soft tissue sarcoma cell lines and primary tumor xenografts.
Authors: D. R. Reed, W. Brazelle, J. Gemmer, S. Altiok
Journal: Journal of Clinical Oncology (2010)

10049 Background: Histone deacetylase inhibitors (HDACis) are promising anticancer drugs; however, the molecular mechanisms leading to cell death by HDACis have not been well understood and no clear mechanism of resistance has been elucidated to explain limited efficacy of HDACis in clinical trials. Methods: In vitro treatment of cell lines with HDACi and Chk1 inhibitors, time course experiments, protein analysis by western blot, and ex vivo evaluation of sarcoma xenografts were performed. Results: In HDACi- treated sarcoma cell lines, Chk1 downregulation was functional as indicated by decreased inhibitory phosphorylation of cdc25c and its downstream target cdc2. Chk1 downregulation occurred upon HDACi treatment and preceded apoptosis, as assessed by poly(ADP-ribose) polymerase cleavage. Pharmacological inhibition of Chk1 showed strong synergistic effect with LBH589 in sarcoma cells in vitro. Serial sampling of mouse xenografts of these sarcoma cell lines using FNAB indicates that downregulation of Chk1 upon HDACi treatment occurs in vivo and can be used to assess and predict efficacy of treatment. Conclusions: Taken together these results suggest that Chk1 could be an early pharmacodynamic marker to assess HDACi efficacy in clinical samples. A combination of drugs targeting HDAC and Chk1 enzymes may be clinically useful for sarcoma treatment. We show that expression of checkpoint kinase 1 (Chk1), which has a major role in G2 cell cycle checkpoint regulation, was markedly reduced in multiple sarcoma cell lines both in vitro and in vivo as well as in human sarcoma samples tested ex vivo when cells were treated with the HDACi LBH589, scriptaid, valproic acid, or apicidin. No significant financial relationships to disclose.
Measurement of cardiac troponin identifies patients with moderate to large pulmonary emboli and right ventricular strain
Authors: Jack Andrews, William MacNee, John Murchison
Journal: European Respiratory Journal (2014)

Introduction   Moderate to large acute pulmonary embolism (PE) is associated with a rise in serum cardiac troponins. The proposed mechanism is through acute right heart overload. Acute right ventricular failure is associated with a higher mortality in those with PE.   Aims   In patients with CT Pulmonary Angiogram (CTPA) confirmed PE, we studied the association between raised troponin I, right ventricular strain and mortality.   Methods   We conducted a retrospective cohort study in 369 patients over 1 year with a CTPA diagnosis of PE in those with troponin I measurements and assessed the association between elevated troponin I (>0.05 ng/l), right ventricular dilatation on CT (right ventricular to left ventricular ratio > 1.0) and clot burden (Miller score).   Results   106 patients had troponin I measurements. Of those 58 (55%) were positive. The degree of elevation of troponin I is associated with an increase in the RV:LV axial ratio on CT.  RV:LV   RV:LV 1-1.5 – average troponin I 0.68 ng/l.  RV:LV >1.5 – average troponin I 1.64 ng/l.   Conclusions   We conclude that there is an association between the level of Troponin I, clot burden and the degree of right ventricular dysfunction in acute PE. Thus Troponin I could be used to identify those most at risk of cardiovascular collapse in acute PE.
Hemodynamic assessment of pulmonary hypertension in grown-up congenital heart disease
Authors: Mario Gerges, Christian Gerges, Marie Lang, Irene Lang
Journal: European Respiratory Journal (2012)

PURPOSE: Pulmonary arterial hypertension (PAH) associated with congenital heart disease (CHD) is included in group 1 of the pulmonary hypertension (PH) clinical classification. The persistent exposure of the pulmonary vasculature to increased blood flow due to systemic-to-pulmonary shunts as well as increased pressure may result in a typical pulmonary arteriopathy that leads to an increase in invasively measured mean pulmonary arterial pressure (mPAP) ≥25mmHg at rest.  METHODS: 3107 right and left heart catheterizations were analyzed. Diagnoses were validated on the grounds of patient histories, imaging, clinical data and patho-anatomic evidence (2369 complete data sets). 257 data sets were from patients with CHD.  RESULTS: Underlying diagnoses were: pre-tricuspid defects in 172 patients, post-tricuspid defects in 38 patients and complex lesions in 47 patients. Of the 257 patients with CHD (38 were corrected), 141 patients had normal hemodynamics (“Non-PH” mPAP 15mmHg; Table 1).  CONCLUSION: The data demonstrate that a significant proportion (almost 50%) of patients with PH in grown-up congenital heart disease suffer from post-capillary pulmonary hypertension.
Shift training from NHS trusts to skills laboratories ...
Authors: Julie Michelle Walton
Journal: BMJ (2008)

Wise’s article is timely.1 All ultrasound trainees currently require a clinical placement that is supported by specialist trainers and these are typically situated in NHS trusts. Where these placements already exist, there is already “competition” for machine time for training by sonographers and specialist trainees in radiology. Access to ultrasound systems for training is also becoming increasingly difficult in …
Low numbers of CSF blasts at diagnosis do not predict for the development of CNS leukemia in children with intermediate-risk acute lymphoblastic leukemia: a Childrens Cancer Group report.
Authors: G S Gilchrist, D G Tubergen, H N Sather, P F Coccia, R T O'Brien, M J Waskerwitz, G D Hammond
Journal: Journal of Clinical Oncology (1994)

PURPOSE This study was designed to evaluate the effect on CNS relapse (CNSR) and overall relapse rates of blast cells in the CSF containing &lt; or = 5 cells/microL at the time of diagnosis of intermediate-risk acute lymphoblastic leukemia (ALL) in children entered onto a large randomized multicenter prospective therapeutic trial (Childrens Cancer Group [CCG]-105). PATIENTS AND METHODS We studied outcome in terms of CNSR and event-free survival (EFS) in 1,544 patients who successfully completed remission-induction therapy and had been randomized to one of four systemic chemotherapy regimens and to one of two CNS prophylaxis regimens. We compared outcome between 1,450 patients who had varying degrees of pleocytosis but no blasts in the CSF at diagnosis (blast-negative group) with 94 who had blasts detected in the CSF after cytocentrifugation but had a total CSF WBC count of &lt; or = 5/microL (blast-positive group). RESULTS No statistically significant differences in overall CNSR or EFS rates were observed between the two groups and no differences were found when analyzed according to age or WBC count at diagnosis, sex, or type of CNS prophylaxis (intrathecal [IT] methotrexate [MTX] alone v IT MTX plus 18 Gy cranial irradiation [CXRT]). CONCLUSION In intermediate-risk ALL, there was no significant difference in CNSR and systemic relapse rates after standard presymptomatic CNS therapy between patients with a CSF WBC count &lt; or = 5/microL and those without identifiable blasts in the CSF. These findings suggest that certain approaches to therapy, such as that used in this study, may eliminate the need for any additional special treatment directed at this subset of patients with CSF blasts.
Predictors of treatment outcome in multidrug-resistant tuberculosis
Authors: Olena Oliveira, Miguel Villar, Raquel Duarte
Journal: European Respiratory Journal (2011)

Multidrug-resistant tuberculosis (MDR-TB) is a challenge to control programs.In these cases, treatment is more complex, more expensive and very often less successful.  The purpose of this study was to analyze the factors that could influence (positively or negatively)the outcome.  To examine this issue we used data from the National Tuberculosis Program in Portugal SVIG-TB.For the study,we included all MDR-TB cases reported from January 2000 to December 2008. To identify the predictive factors related to the outcome of treatment we used univariate and multiple logistic regression models with the clinical variables.  During the studied period 130 patients with MDR-TB were notified, of these 94 (72,3%) were male and 36 (27,7%) female, mean age 42 years old (range 40-44). Forty-six patients (35,5%) had a previous treatment and 39 (30%) were HIV positive. Treatment success (cured or completed treatment) was observed in 80 (61,5%) patients. Susceptibility and use of pyrazinamide or ethambutol, susceptibility and use of a fluoroquinolone, the use of five or more drugs in the treatmant regimen, sputum culture conversion after 2 months of treatment were predictors of successful outcome of treatment. Treatment insucess (death, default and failure) was observed in 47 (36,1%) patients. Previous treatment, HIV co-infection, presence of cavitation on the chest radiograph, resistance of two more drugs than just isoniazid and rifampicin and positive cultures after 2 to 3 month of treatment were predictors of poor treatment outcome.  Rapid diagnosis of drug resistance and an appropriate therapy for effective treatment are important conditions for the prevention of spread of resistant strains and control of MDR-TB.