tbuckley/cabot-search huggingface dataset:
Avoiding the V-word: Is volume therapy in hepatorenal syndrome killed by definition?
Authors: A Umgelter, R M Schmid, W Huber
Journal: Gut (2008)

It is generally believed that the hepatorenal syndrome (HRS) is a functional kidney disorder resulting from a disturbed and hyperdynamic circulation leading to central hypovolaemia. Yet there seems to be a strong reluctance to regard it as amenable to volume resuscitation. In this context, the most striking change to the previous definition of HRS Type 1, proposed by the recent consensus workshop ( Gut 2007; 56 :1310–8) is the inclusion among the diagnostic criteria of a failure to respond to plasma expansion with up to 1 g of albumin per kg body weight per day for 2 days. The amount itself is arbitrary and must result in a substantial, if not individually adjusted, increase in total plasma volume.

The authors …
Histopathology peer review of high-grade soft tissue sarcoma: the Scandinavian Sarcoma Group experience.
Authors: T A Alvegård, N O Berg
Journal: Journal of Clinical Oncology (1989)

From 1981 to 1986, a total of 240 patients with a primary soft tissue sarcoma with malignancy grade III or IV were entered into an adjuvant chemotherapy multicenter trial conducted by the Scandinavian Sarcoma Group (SSG). Histopathologic peer review of all the specimens was performed by an expert pathology committee. The most common soft tissue sarcoma after review was malignant fibrous histiocytoma (MFH) (40%), followed by synovial sarcoma (15%), leiomyosarcoma (9%), liposarcoma (8%), and malignant Schwannoma (6%). In 25% of the cases the histologic type of sarcoma was reclassified, and in 40% of the cases the malignancy grade was changed. By survival analyses, the reclassification of malignancy grade seemed to be valid. Also, grading highly malignant soft tissue sarcoma in two grades (III and IV) increased the prognostic information. Of 164 tumors from the centers with the most reported cases (five centers with 25 to 51 tumors each), eight tumors were found to be ineligible for the adjuvant study (5%); of 76 tumors from 13 centers with few tumors (one to 16 tumors per center), 12 tumors were ineligible (16%). We conclude that histologic peer review is important in studies of soft tissue sarcoma.
A clinical score to predict polysomnographic (PSG) results in paediatric sleep disordered breathing (SDB)
Authors: Maria Chiara Paolino, Rosa Castaldo, Filomena Ianniello, Laura Papini, Francesco Biagiarelli, Marco Del Pozzo, Maria Pia Villa
Journal: European Respiratory Journal (2011)

Aims: To develop a reliable tool, PSG validated, for diagnosis of SDB and to reduce the use of PSG.  Methods: Children with referred SDB undergoing a PSG for the first time. We propose the Sleep Clinical Record (SCR) to predict SDB in children, based on clinical experience. It consists of objective data, subjective symptoms, clinical history, behavioural and cognitive problems. These items were used in a model which combine subjective and objective parameters to create the sleep clinical score (SCS) with the higher predictive value.  Results: We studied 289 children (6.2±3.1 yrs, 63.3% M). We found 28% children9s with primary snoring (PS) and 72% with OSAS. The SCS was higher in children with OSAS than children with PS (8.8±2.7 vs 7.4±3.1, p  Conclusion: This SCS is useful to screen SDB in selected population with referred symptoms, and is able to perform diagnosis of OSAS with a positive predictive value of 79% and an accuracy of 73%. It is a useful instrument to select patients with OSAS that could be treated without PSG diagnosis when the study is difficult to perform or is unavailable.
Gender differences in COPD patients
Authors: Valentina Kapustina, Svetlana Ovcharenko
Journal: European Respiratory Journal (2014)

The  aim  of our study was to investigate clinical, functional and laboratory characteristics of COPD in males and females.  Methods : 62 patients with stable COPD (36 males and 26 females, mean age 66.8 ± 7.5 years, GOLD stage I-IV) were included. Demographic, clinical data were collected, pulmonary function testing (PFT) and oxidative stress parameters (reactive oxygen species (ROS) production by granulocytes in peripheral blood, malonyldialdehyde (MDA) level and antioxidant blood capacity measurement) were assessed.  Results : Age, smoking history, 6MWT distance, BODE index score and main PFT parameters didn9t differ significantly between two gender groups. Women experienced less severity of sputum production (0.88 vs 1.71, p Conclusions : Female patient with stable COPD have clinical and laboratory differences compared to male patients such as greater dyspnea severity, less severity of sputum production, increased ROS production combined with greater blood levels of antioxidant protection that may be a reflection of the changed women9s susceptibility to COPD irrespective of smoking intensity and duration.
Enhanced lung inflammatory response to intratracheal CpG-ODN in mice with bleomycin-induced lung fibrosis
Authors: Hideaki Yamasawa, Masayuki Nakayama, Masashi Bando, Yukihiko Sugiyama
Journal: European Respiratory Journal (2011)

Introduction: Although the etiology of an acute exacerbation of idiopathic pulmonary fibrosis (IPF) is unknown, it may be represented by a clinically occult but biologically distinct condition that often remains undiagnosed, such as viral infections. Unmethylated CpG motifs present in both bacterial and viral DNA initiate an innate immune response mediated by Toll-like receptor 9 (TLR9). We examined the inflammatory response to the intratracheal injection of CpG dinucleotides (CpG-ODN) in bleomycin (BLM)-induced lung fibrosis in mice.

Methods: Lung fibrosis was induced in female C57BL/6 mice by the intraperitoneal injection of BLM. Twenty-eight days after the injection of either BLM or saline, the mice received intratracheal injections of either saline or CpG-ODN. A total number of 4 groups (saline; BLM; saline/CpG; BLM/CpG) were investigated. After 24 h, the mice were killed, and the neutrophil counts and cytokine levels were determined in the bronchoalveolar lavage fluid (BALF).

Results: There were no differences in the neutrophil counts between the saline and BLM groups. The neutrophil counts in the BLM/CpG group were significantly higher than those in the saline/CpG group. The levels of macrophage inflammatory protein (MIP)-2 and interleukin (IL)-6 in the BALF were found to be significantly higher in the BLM/CpG group than in the saline/CpG group. Real-time reverse transcriptase-polymerase chain reaction (RT-PCR) and immunohistochemical analysis of the lung tissue revealed an upregulation of TLR9 expression induced by BLM administration.

Conclusion: These results suggest that the TLR9-mediated lung inflammatory responses are enhanced in BLM-induced lung fibrosis in mice.
Gene Control of Neoplasia. I. Genotypic Mosaicism in Normal and Preneoplastic Mammary Glands of Allophenic Mice&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Beatrice Mintz, Glenn Slemmer
Journal: JNCI Journal of the National Cancer Institute (1969)
Cardiopulmonary exercise response in children with obstructive sleep apnea syndrome
Authors: Labrini Damianidou, Andreas Giannopoulos, Maria Eboriadou, Katerina Haidopoulou, Fotis Kirvasilis, Kalliopi Kontouli, Ioannis Tsanakas, Fani Athanasiadou
Journal: European Respiratory Journal (2012)

Introduction: Cardiopulmonary exercise testing (CPET) is a valuable tool in the evaluation of cardiac and pulmonary function. In adults' patients with obstructive sleep apnea syndrome (OSAS), recent studies addressed reduced exercise capacity, but there is no data in literature for pediatric patient.

Aim: To evaluate cardiopulmonary response to exercise in children with OSAS.

Methods: Twenty seven subjects, without any systematic disease, aged 7 to 14 years (mean age 10,5 ± 1,8 years), referring for evaluation of systematic snoring (≥4 nights/week), underwent overnight polysomnography (PSG) and CPET. According to the Apnea Hypopnea Index (AHI) subjects were divided into two groups: A. mild OSAS (1≤AHI 5, n=12). Control group (group C) consisted of 13 children.

Results: There were no significantly differences in age, sex, BMI, among groups (p<0.05). Mild OSAS had 55,6% of children (group A) and moderate to severe 44,4% (group B). According to CPET children with OSAS had shorter duration of exercise (12,4±2,6min vs 13,3±2min), significantly lower VO2max (40,3±8,4 ml/kg/min vs 47,6±7,9 ml/kg/min, p=0,013), significantly lower VO2max(%) (77,7±15 vs 92,9±10,5, p=0,002), higher VO2AT (%) (48,2±14,7 vs 43,7±19,8) and higher systolic blood pressure level at peak exercise (145±27,4mmHg vs 143,92±20 mmHg) compared to control group. Children with mild OSAS had higher VO2max (%) (80,8±9,3 vs 73,8±19,7) but not statistically significant compared to moderate - severe OSAS.

Conclusion: The present study demonstrates that young patients (mean age 10,5 ± 1,8 years) with OSAS, even with mild OSAS, had reduced exercise capacity (lower VO2max) as compared to control group.
The importance of early treatment with tranexamic acid in bleeding trauma patients: an exploratory analysis of the CRASH-2 randomised controlled trial
Authors: Ian Roberts, Haleema Shakur, Adefemi Afolabi, Karim Brohi, Tim Coats, Yashbir Dewan, Satoshi Gando, Gordon Guyatt, B J Hunt, Carlos Morales, Pablo Perel, David Prieto-Merino, Tom Woolley
Journal: The Lancet (2011)
Abstract 3235: Twenty Years of Percutaneous Coronary Intervention - The Evolution and the Impact. A Report from the National Heart, Lung and Blood Institute-Sponsored PTCA (1985 86) and Dynamic (1997 2004) Registries
Authors: Lakshmi Venkitachalam, Kevin E Kip, Faith Selzer, Robert L Wilensky, Peter Block, David O Williams, Sheryl F Kelsey, Dynamic Registries Investigators
Journal: Circulation (2006)

Background: Technological advancements in percutaneous coronary intervention (PCI), since the pre-stent era, have widened the scope of its use. The NHLBI-sponsored 1985– 86 PTCA (pre-stent) registr...
Effect of Different Levels of Dietary Zinc on Longevity of BALB/c Mice Inoculated With Plasmacytoma MOPC 104E&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: M K Song, N F Adham, N V Costea
Journal: JNCI Journal of the National Cancer Institute (1984)

The effect of different levels of Zn intake on survival was studied in 6 groups of 4-week-old BALB/c mice inoculated with MOPC 104E tumor cells. The first 3 groups received either a Zn-deficient (0.5 microgram Zn/g), a Zn-supplemented (1 mg Zn/g), or a control diet (37.5 micrograms Zn/g) starting 11 days after tumor inoculation (T11). The remaining 3 groups received the same diets starting the day the tumor was implanted (T0). The mean survival of rats beginning the Zn-deficient diet at T11 was significantly increased compared with that of the control group. However, when the same diet was begun at T0, the mean survival of the Zn-deficient group was significantly reduced; for this group the results probably related to the combined adverse effects from prolonged Zn deficiency and to those effects of the tumor itself. Similarly, excess Zn intake significantly prolonged the mean survival when given at T11. However, excess Zn intake at T0 produced no significant effect on survival, probably because of the elevation of plasma Zn level following oral Zn intake that occurred before the establishment of the tumor or possibly because of the inability of the small intestine to absorb excess Zn at T11 when the tumor was fully developed.
Organoids as Models for Neoplastic Transformation
Authors: James T. Neal, Calvin J. Kuo
Journal: Annual Review of Pathology Mechanisms of Disease (2016)

Cancer models strive to recapitulate the incredible diversity inherent in human tumors. A key challenge in accurate tumor modeling lies in capturing the panoply of homo- and heterotypic cellular interactions within the context of a three-dimensional tissue microenvironment. To address this challenge, researchers have developed organotypic cancer models (organoids) that combine the 3D architecture of in vivo tissues with the experimental facility of 2D cell lines. Here we address the benefits and drawbacks of these systems, as well as their most recent advances. In particular, we focus on the application of such models to the discovery of novel cancer drivers, the study of tumor biology, and the development of novel therapeutic approaches for the treatment of cancer.
Oral etoposide is active against platinum-resistant epithelial ovarian cancer.
Authors: P J Hoskins, K D Swenerton
Journal: Journal of Clinical Oncology (1994)

PURPOSE To determine whether etoposide (VP16) is more effective when administered on a chronic schedule, women with clinically defined platinum-resistant epithelial ovarian cancer (EOC) were studied. PATIENTS AND METHODS Thirty-one eligible women were treated with oral VP16. The first seven received a dose that varied depending on their body-surface area, but this proved too toxic, and so a fixed dose of 100 mg orally per day for 14 days every 3 weeks was used for the other subjects. RESULTS The response rate was 26% (95% confidence interval [CI], 11% to 41%). The 28 women with cancer that had progressed while they were receiving a platinum analog had a response rate of 21% (95% CI, 6% to 36%). Response durations were short. CONCLUSION When administered on this chronic schedule, VP16 has activity against platinum-resistant EOC.
Ifosfamide, mesna, and nephrotoxicity in children.
Authors: R Skinner, I M Sharkey, A D Pearson, A W Craft
Journal: Journal of Clinical Oncology (1993)

PURPOSE With the increasing use of ifosfamide in pediatric malignancies, nephrotoxicity has emerged as a potentially serious adverse effect, which may be dose-limiting or may cause severe chronic morbidity, including glomerular impairment and/or Fanconi's syndrome. The purpose of this review was (1) to improve the documentation of ifosfamide nephrotoxicity in children, and (2) to consider the possible causative role of ifosfamide metabolites. DESIGN (1) A grading system was developed that allowed documentation of the nature and severity of published reports of ifosfamide-induced nephrotoxicity, and evaluation of patient and treatment-related risk factors. (2) The relationship between the pharmacology of ifosfamide/mesna and nephrotoxicity was investigated by examination of published data, especially that concerning the quantitative differences in the metabolism of ifosfamide and its nonnephrotoxic structural isomer, cyclophosphamide. RESULTS (1) Examination of 16 published reports (with assessable data from 40 children) demonstrated that ifosfamide-induced nephrotoxicity was associated with a wide range of patient ages and ifosfamide cumulative doses given by different administration schedules. (2) Chloroacetaldehyde, a major metabolite of ifosfamide only, may be at least partly responsible for the renal toxicity of this drug. Although mesna may be capable of detoxifying the toxic metabolite(s), delivery to the renal tubule may not be sufficient to provide adequate protection of tubular glutathione from depletion by the metabolite(s), which results in a failure to prevent nephrotoxicity. CONCLUSION Increased understanding of the interindividual variability in the extent and nature of ifosfamide metabolism, which may be a major determinant of susceptibility to renal damage, may lead to improved use of the drug with less nephrotoxicity.
Treatment Response Assessment in IDH-Mutant Glioma Patients by Noninvasive 3D Functional Spectroscopic Mapping of 2-Hydroxyglutarate
Authors: Ovidiu C. Andronesi, Franziska Loebel, Wolfgang Bogner, Małgorzata Marjańska, Matthew G. Vander Heiden, A. John Iafrate, Jorg Dietrich, Tracy T. Batchelor, Elizabeth R. Gerstner, William G. Kaelin, Andrew S. Chi, Bruce R. Rosen, Daniel P. Cahill
Journal: Clinical Cancer Research (2015)

Abstract Purpose: Measurements of objective response rates are critical to evaluate new glioma therapies. The hallmark metabolic alteration in gliomas with mutant isocitrate dehydrogenase (IDH) is the overproduction of oncometabolite 2-hydroxyglutarate (2HG), which plays a key role in malignant transformation. 2HG represents an ideal biomarker to probe treatment response in IDH-mutant glioma patients, and we hypothesized a decrease in 2HG levels would be measureable by in vivo magnetic resonance spectroscopy (MRS) as a result of antitumor therapy. Experimental Design: We report a prospective longitudinal imaging study performed in 25 IDH-mutant glioma patients receiving adjuvant radiation and chemotherapy. A newly developed 3D MRS imaging was used to noninvasively image 2HG. Paired Student t test was used to compare pre- and posttreatment tumor 2HG values. Test–retest measurements were performed to determine the threshold for 2HG functional spectroscopic maps (fSM). Univariate and multivariate regression were performed to correlate 2HG changes with Karnofsky performance score (KPS). Results: We found that mean 2HG (2HG/Cre) levels decreased significantly (median = 48.1%; 95% confidence interval = 27.3%–56.5%; P = 0.007) in the posttreatment scan. The volume of decreased 2HG correlates (R2 = 0.88, P = 0.002) with clinical status evaluated by KPS. Conclusions: We demonstrate that dynamic measurements of 2HG are feasible by 3D fSM, and the decrease of 2HG levels can monitor treatment response in patients with IDH-mutant gliomas. Our results indicate that quantitative in vivo 2HG imaging may be used for precision medicine and early response assessment in clinical trials of therapies targeting IDH-mutant gliomas. Clin Cancer Res; 22(7); 1632–41. ©2015 AACR.
Randomized phase III trial evaluating the role of erythropoietin in the prevention of chemotherapy-induced anemia.
Authors: L Del Mastro, M Venturini, R Lionetto, O Garrone, G Melioli, W Pasquetti, M R Sertoli, G Bertelli, G Canavese, M Costantini, R Rosso
Journal: Journal of Clinical Oncology (1997)

Although erythropoietin (EPO) is known to be useful in treating chemotherapy-induced anemia, few data are available on its potential preventive role. The aim of this study was to evaluate the ability of EPO in preventing the development of clinically significant anemia in patients treated with chemotherapy.Sixty-two early-stage breast cancer patients undergoing accelerated adjuvant chemotherapy were randomized to receive EPO 150 U/kg three times a week or no additional treatment. Chemotherapy consisted of six cycles of cyclophosphamide 600 mg/m2, epirubicin 60 mg/m2, and fluorouracil 600 mg/m2 (CEF) intravenously on day 1, every 2 weeks with the support of granulocyte colony-stimulating factor (G-CSF), 5 microg/kg subcutaneously from day 4 to day 11.Throughout the six cycles of chemotherapy, EPO-treated patients maintained stable values of hemoglobin, whereas control patients developed a progressive anemia. At the end of chemotherapy, the mean (+/- SD) hemoglobin decrease in the control group was 3.05 g/dL (+/- 1.0; 95% confidence interval [CI], 2.6 to 3.5), whereas in the EPO group it was 0.8 (+/- 1.4; 95% CI, 0.3 to 1.4). Clinically significant anemia (hemoglobin < or = 10 g/dL) occurred in 16 patients (52%; 95% CI, 33 to 69) in the control arm and in no patient (0%; 95% CI, 0 to 14) in the EPO arm (P = .00001).EPO prevents anemia in patients undergoing chemotherapy. Further trials are required to identify subsets of patients in which the preventive use of this drug could be cost-effective.
Quality of life, symptoms and pulmonary function in asthma: long-term treatment with nedocromil sodium examined in a controlled multicentre trial. Nedocromil Sodium Quality of Life Study Group
Authors: PW Jones
Journal: European Respiratory Journal (1994)

This study was designed to measure improvement in quality of life of patients with asthma, using a standardized disease-specific questionnaire, the St George's Respiratory Questionnaire, in a year long double-blind, placebo-controlled, group comparative study with nedocromil sodium. Two other questionnaires were used: the Sickness Impact Profile (a measure of general health) and the Hospital Anxiety and Depression Scale. Measurements were made at baseline and following 24 and 48 weeks of treatment. Response to therapy was also evaluated using daily diary card and peak flow measurements, clinic assessments and spirometry. Following a 4 week baseline, 719 adult asthmatics were randomized to treatment with 4 mg nedocromil sodium or placebo. Patients currently maintained on inhaled corticosteroids received treatments four times daily, those on bronchodilator alone received treatments twice daily. The Impacts component of the St George's Respiratory Questionnaire was significantly improved in patients receiving nedocromil sodium, as were night-time asthma, asthma severity at clinic, and daytime inhaled bronchodilator use. In patients receiving placebo, most of the traditional variables improved, and all three questionnaires recorded significant improvements in health. Patients and clinicians judged nedocromil sodium more effective than placebo. The improvement in St George's Questionnaire score in the nedocromil sodium treated patients was approximately double the change considered to be clinically significant. The study has shown that improvements in health with prophylactic therapy for asthma may be quantified by the use of a standardized disease-specific questionnaire.
Resolving lesions in human cutaneous leishmaniasis predominantly harbour chemokine receptor CXCR3-positive T helper 1/T cytotoxic type 1 cells
Authors: B. Geiger, J. Wenzel, M. Hantschke, I. Haase, S. Ständer, E. Von Stebut
Journal: British Journal of Dermatology (2009)

Background Cutaneous leishmaniasis (CL) is an epidemic disease affecting millions of individuals worldwide. Treatment options have several side‐effects and a vaccine does not exist at present. Objectives To translate information about protection against CL from mice to man, we studied the local immune response in CL skin biopsies and correlated these findings with clinical information. Methods The frequency of inflammatory cells was determined in skin biopsies of 20 patients diagnosed with CL using immunohistochemistry. In addition, the nature of the resulting adaptive immune response was assessed by (double) immunostaining against CD4 and chemokine receptors CXCR3 (T helper 1, Th1)/CCR4 (Th2). Results All lesions contained CD4+ and CD8+ T cells, B cells and CD68+ macrophages. CD1a+ epidermal Langerhans cells were absent above the centre of the lesions, but normally distributed in the surrounding tissue. Mast cell and CD56+ natural killer cell numbers were not affected. Interestingly, CCR4+ Th2 cells were not detected in any of the 20 samples. In contrast, the number of infiltrating CXCR3+ cells was high and the majority of these were CD4+ or CD8+ indicating that they represent interferon‐γ‐producing Th1/T cytotoxic type 1 (Tc1) cells. Finally, these findings did not correlate with clinical information about the country where the infection was acquired, or age or sex of the patients. However, lesions that had already persisted for more than 6 months contained fewer CXCR3+ CD4 and CD8 T cells than those that had persisted for less than 6 months. Conclusions Our data on the inflammatory infiltrate of human CL lesions underline the relevance of findings obtained in experimental models. Both Th1 and Tc1 cells appear to be critical for healing in CL in mouse and man.