tbuckley/cabot-search huggingface dataset:
A longitudinal prospective study of YKL-40 and matrix metalloproteinase-9 (MMP-9) as serum tumor markers in gliomas
Authors: F. M. Iwamoto, A. F. Hottinger, S. Karimi, E. Riedel, K. Panageas, B. Gu, J. Rao, M. Fleisher, E. Holland, L. M. DeAngelis, A. Hormigo
Journal: Journal of Clinical Oncology (2008)

2038 Background: YKL-40, an extracellular matrix glycoprotein, is overexpressed in high-grade gliomas (HGG). MMP-9, a matrix metalloproteinase associated with tumor infiltration and angiogenesis, has been detected both in tumor and endothelial cells in gliomas. These two proteins are secreted and our previous work suggested that they are serum marker candidates for gliomas. Methods: From 08/02 to 11/06, serum samples were collected prospectively from patients (pts) with histologically confirmed gliomas. Serum was obtained concurrently with MRI scans at multiple time points during the course of the disease. YKL-40 and MMP-9 were determined by ELISA and the values correlated with radiographic disease status and survival. Because the distribution for YKL-40 and MMP-9 were skewed, the data were log transformed. To study the relationship between each serum marker and radiographic disease status all measurements were used in a logit model with generalized estimating equations that corrected for within-patient correlations. The effect of each marker on overall survival was analyzed using each separately as a time-dependent covariate in a Cox model by determining the value of the marker in a log-scale over time. Hazard ratios (HR) were calculated for each doubling in level of serum marker. Results: There were 131 GBM pts, 83 anaplastic gliomas (AG) and 32 low-grade gliomas (LGG). The median number of measurements obtained were 2.5 (range, 1–18) for GBM, 4 (1–14) for AG and 6 (1- 14) for LGG. The median follow-up was 9.6 mos for GBM, 22.5 for AG and 26.9 for LGG. Increase in YKL-40 serum level was associated with risk of death in GBM (HR=1.6, p<0.001), AG (HR=1.6, p=0.02) and the subset of anaplastic astrocytoma (AA) (HR=2.0, p=0.004). Increase in serum MMP-9 was associated with increased risk of death only in AG pts (HR=1.5, p=0.03). YKL-40 levels were associated with radiographic status for GBM (p=0.005), AA (0.02), and LGG (p=0.0005). For MMP-9, there was a correlation with radiographic status for AA (p=0.01) and GBM (p=0.03) but not for AG (p=0.11) or LGG (p=0.13). Conclusions: This longitudinal study shows that YKL-40 is a predictor of survival in patients with HGG and a potential indicator of disease status. MMP-9 may be a potential indicator of disease status in GBM and AA. No significant financial relationships to disclose.
Comparison of conventional forceps biopsy and cryobiopsy in endobronchial lesions
Authors: HamidReza Jabbardarjani, Ramin Sami, Arda Kiani, Mohammadreza Masjedi
Journal: European Respiratory Journal (2012)

Background and objectives:Forceps biopsy has long been the standard method of extracting samples from endobronchial lesions,however diagnostic yield of the specimen obtained by this method(72%)is not very desirable due to small size and artifact.Therefore,in order to increase the diagnostic yield in endobronchial lesions as well as diminish the complications we evaluated a new technique called cryobiopsy(using flexible cryoprobes to obtain frozen samples).  Methods: All patients with endobronchial lesion except for vascular lesions referred to Intervention ward of Masih Daneshvari Hospital were included in this study.For each patient,6 specimen were obtained by conventional forceps,and 2 were extracted through cryobiopsy,one of them 3 seconds after freezing (CB3),and the other one 5 seconds after freezing(CB5).Bleeding during the procedure,and diagnostic yield of the samples were evaluated closely.  Results: Of all 30 patients,diagnosis was achieved for 27 patients(90%).Diagnostic rate of forceps biopsies was 67%,while this rate was 80% and 78% for CB3 and CB5 respectively.Although there was no significant difference between these three rates, total diagnostic yield of both CB3 and CB5 together was significantly higher than conventional biopsy (P-value=0.016).Severe bleeding requiring APC to be controlled occurred in 2 cases during CB5,while no major hemorrhage happened during forceps biopsy.  Conclusion: According to our results,obtaining at least two samples from endobronchial lesions by cryobiopsy technique can lead to a higher rate of diagnosis compared with 6 samples by forceps biopsy.However,duration of freezing(3 or 5 seconds)does not have a significant impact on the quality of specimen.
Abstract 303: Sexual Dimorphisms in Cardiomyocytes Exposed to a Pathological Stimulus
Authors: Christa Blenck, Pamela Harvey, Leslie Leinwand
Journal: Circulation Research (2014)

Background: Sex is an important modifier of the development of cardiovascular disease; women consistently display less hypertrophy, fewer changes in pathologic gene expression, and less cardiac dysfunction compared to men exposed to the same pathological stimuli. The signaling pathways responsible for these sexual dimorphisms, especially within the cardiomyocyte, are not well understood. Objective: To investigate sexual dimorphisms in activation of signaling pathways and expression of genes related to cardiomyocyte contractility in response to a pathological stimulus in isolated adult rat ventricular myocytes (ARVMs). Methods: ARVMs from both sexes were isolated using a Langendorff perfusion apparatus and treated with the β-adrenergic agonist isoproterenol (ISO) or vehicle (saline) for 24 hours. Activated signaling molecules were detected by performing a phospho-kinase antibody array (R&amp;D Systems) in ARVMs isolated from two rats of each sex treated with ISO or vehicle. Total RNA was isolated from these cells, and real-time PCR was used to determine expression levels of calcium handling genes, including Cav1.2 and sodium calcium exchanger (NCX1). Results: A distinct profile of activated signaling molecules was observed between male and female ARVMs in response to ISO. Female ARVMs displayed activation of kinases such as Akt, ERK1/2, p38α, GSK3α/β and MSK1/2. Male ARVMs were characterized by an activation of signaling molecules such as PLCγ1, RSK1/2/3 and c-Jun. ARVMs of both sexes displayed activation of signaling molecules such as eNOS, STAT3 and mTOR. Because the activated signaling molecules identified with the array can modulate expression of calcium handling genes, expression of these genes was analyzed. In response to ISO treatment, female ARVMs displayed an increase in NCX1 expression normalized to vehicle (1.63 ± 0.079) as well as Cav1.2 expression (1.48 ± 0.072). However, these increases were not observed in male cells. Conclusions: Cardiomyocytes isolated from rats of different sexes display distinct responses to the pathological stimulus ISO. Understanding the mechanisms responsible for these sexual dimorphisms can lead to the development of more effective treatment options for both men and women with cardiovascular disease.
Cardiac diseases in patients with community acquired pneumonia (CAP)
Authors: B.V. Murali Mohan, R. Ranganatha, Tiyas Sen, Ravi Chandra Malapaka
Journal: European Respiratory Journal (2012)

Background: Community Acquired Pneumonia (CAP) and cardiac diseases are mutually aggravating conditions. There is a surge of interest in the association of major cardiac diseases and CAP and this study was done to contribute to the world9s literature from the Indian sub-continent.  Materials and methods: In this retrospective analysis of patients admitted with CAP between January 2011 and January 2012 at a tertiary care referral centre we looked for associated cardiac diseases.  Results: Of the total patients included in the analysis (n=73), 34.24% (25) had an associated cardiac disease. There were 45 instances of cardiac problems. 19.17% (14) had pulmonary hypertension, 16.44% (12) had CCF/Acute LVF, 13.69% (10) had Ischemic heart disease, 4.1% (3) had Rheumatic heart diseases, 2.74% (2) had arrhythmias and there was 1 instance each of Infective endocarditis, acute pulmonary thromboembolism, congenital heart disease and MI (1.36%). 14 (56%) out of 25 patients who had cardiac diseases required ICU care while 9 (18.75%) out of 48 patients who did not have cardiac conditions required ICU care(p=0.001). 6 out of 25 patients had new onset cardiac problems. Two patients in the cardiac disease group died, while in the non cardiac disease group, one patient died.  Conclusions: There is a high degree of correlation between pre existing cardiac disease and CAP as also between CAP and new onset cardiac diseases especially CAD.  The cardiac disease in such patients adversely influences the outcome of the pneumonia.  A careful search for pre existing cardiac disease should be made in patients who present CAP.  Patients with identified heart disease should prophylactically receive vaccines to reduce the incidence of CAP.
Assessing the local impact of a national lung cancer awareness campaign
Authors: Anthony Thanasingam, Lindsey Taylor, Steve Iles, Philip Pearson
Journal: European Respiratory Journal (2013)

The Department of Health in England ran a national lung cancer awareness campaign (“Be Clear on Cancer”), 8th May – 12th June 2012, in particular to encourage patients to present earlier.

Derriford Hospital, Plymouth, and Royal Cornwall Hospital, Truro, are two largest lung cancer centres in the southwest of England (336 & 265 new cases in 2011).

As the largest centres, we have examined the impact of the campaign on our services and looked at the number of referrals for suspected malignancy, the number of new diagnoses, TNM stage at diagnosis and numbers of acute presentations with thoracic malignancy, before (Jan-May 2012) and after (May-Sept 2012) the start of the campaign.

Results:

View this table:

Referrals & new diagnoses before & after the campaign





There was a significant and sustained increase in referrals and a small rise in new diagnoses.

There was little difference in stage or performance status between those diagnosed before or after the start of the campaign, nor was there any effect on patients presenting acutely.

Conclusion:

The “Be Clear On Cancer” campaign in May 2012 led to a sustained increase in referrals for suspected lung cancer. There has been a small rise in the numbers diagnosed to September 2012, but little effect on stage or performance status at presentation, nor upon emergency admissions.
Hemolytic Anemia Induced by Murine Erythroblastosis Virus: Possible Mechanisms of Hemolysis and Effects of an Interferon Inducer2
Authors: Dennis J. Siamon
Journal: JNCI Journal of the National Cancer Institute (1975)

Murine erythroblastosis virus (MuEV), also called murine leukemia virus-Kirsten, is a member of the murine type-C-RNA leukemia-sarcoma group of oncogenic viruses. Like other members of this group, MuEV can elicit both a hemolytiC disorder and an oncogenic response. Neonatal rats infected with MuEV succumb to this hemolytic disorder unless they are treated with the synthetic double-stranded polyribonucleotide, polyinosinic-polycytidylic acid (poly I·poly C). Animals receiving poly I·poly C had markedly reduced levels of virus reproduction as measured by bioassay and electron microscopy. The proliferation of erythroblasts after MuEV infection In animals not receiving poly I·poly C appeared to be an erythropoietin- dependent compensatory response to hemolysis. The hemolysis itself seemed to require virus reproduction in the cell types affected. Administration of poly I·poly C to MuEV-infected rats inhibited virus reproduction and thus may circumvent the hemolytic disease syndrome. The ultrastructure of the virus and of the virus reproduction was also studied.
Role of mitomycin in combination with fluorouracil and radiotherapy, and of salvage chemoradiation in the definitive nonsurgical treatment of epidermoid carcinoma of the anal canal: results of a phase III randomized intergroup study.
Authors: M Flam, M John, T F Pajak, N Petrelli, R Myerson, S Doggett, J Quivey, M Rotman, H Kerman, L Coia, K Murray
Journal: Journal of Clinical Oncology (1996)

PURPOSE Definitive chemoradiation (CR) has replaced radical surgery as the preferred treatment of epidermoid carcinoma of the anal canal. To determine the importance of mitomycin (MMC) in the standard CR regimen and to assess the role of salvage CR in patients who have residual tumor following CR, a phase III randomized trial was undertaken by the Radiation Therapy Oncology Group (RTOG)/Eastern Cooperative Oncology Group (ECOG). PATIENTS AND METHODS Between August 1988 and December 1991, 310 patients were randomized to receive either radiotherapy (RT) and fluorouracil (5-FU) or radiotherapy, 5-FU, and MMC. Of 291 assessable patients, 145 received 45 to 50.4 Gy of pelvic RT plus 5-FU at 1,000 mg/m2/d for 4 days, and 146 received RT, 5-FU, and MMC (10 mg/m2 per dose for two doses). Patients with residual tumor on posttreatment biopsy were treated with a salvage regimen that consisted of additional pelvic RT (9 Gy), 5-FU, and cisplatin (100 mg/m2). RESULTS Posttreatment biopsies were positive in 15% of patients in the 5-FU arm versus 7.7% in the MMC arm (P = .135). At 4 years, colostomy rates were lower (9% v 22%; P = .002), colostomy-free survival higher (71% v 59%; P = .014), and disease-free survival higher (73% v 51%; P = .0003) in the MMC arm. A significant difference in overall survival has not been observed at 4 years. Toxicity was greater in the MMC arm (23% v 7% grade 4 and 5 toxicity; P &lt; or = .001). Of 24 assessable patients who underwent salvage CR, 12 (50%) were rendered disease-free. CONCLUSION Despite greater toxicity, the use of MMC in a definitive CR regimen for anal cancer is justified, particularly in patients with large primary tumors. Salvage CR should be attempted in patients with residual disease following definitive CR before resorting to radical surgery.
Cigarette smoke extract increases the adhesion receptor for S. pneumoniae in vitro
Authors: Naseem Mushtaq, Iain Dickson, Cang-Bao Xu, Lars Edvinsson, Jonathan Grigg
Journal: European Respiratory Journal (2011)

Background: Although the mechanism is unknown, cigarette smoke exposure increases the risk of pneumococcal infections in humans1. We have recently shown that fossil fuel derived particulate matter increases adhesion of S. pneumoniae via upregulation of platelet activating factor receptor (PAFr) expression on airway cells2. We therefore aimed to assess whether cigarette smoke extract (CSE) upregulates the PAFr expression in vitro.

Methods: The human lung epithelial (A549) cell line was incubated with very low concentrations of CSE (0.01%, 0.02% and 0.05%) for 4 hr. PAFr expression, adjusted for non-specific staining, was then assessed by flow cytometry using a PAFr human monoclonal antibody.

Results: CSE stimulated dose-dependent increase in PAFr expression, with an increase in mean PAFr fluorescence and % positivity (Figure 1 and Table 1).

View this table:

FACs analysis showing dose (%) of CSE vs mean fluorescence





![Figure][1] 



Conclusion: CSE stimulates PAFr, the receptor for S. pneumoniae adhesion to lower airway cells, and may be the mechanisms underlying the epidemiological association between active and passive cigarette exposure and invasive pneumococcal disease in adults and children.

FACs analysis showing a dose response relationship between CSE and PAFr expression.

 [1]: pending:yes
Prevalence of emm types 1 and 12 from invasive Streptococcus pyogenes disease in Greece—results of enhanced surveillance
Authors: A. Stathi, J. Papaparaskevas, L. Zachariadou, A. Pangalis, N.J. Legakis, A. Tseleni-Kotsovili, P.T. Tassios
Journal: Clinical Microbiology and Infection (2008)
Modern Treatment Strategies for Patients with Epilepsy: A Review
Authors: J S Duncan
Journal: Journal of the Royal Society of Medicine (1991)

Of patients who develop epilepsy 70–80% will become seizure free, the remaining 20% are the most difficult to treat satisfactorily. Eighty per cent of patients are best treated with a single drug. Stepwise treatment plans for the treatment of newly diagnosed patients and for the evaluation of patients with chronic epilepsy are suggested. There is a lack of consensus regarding the rate at which to taper antiepileptic drugs being discontinued in patients with active epilepsy. There are arguments for making drug changes rapidly; these arguments and strategies for managing the withdrawal of individual drugs are presented.
Accelerated Induction of Kidney Neoplasms in Mice After X Radiation (690 Had) and Unilateral Nephrectomy&lt;xref ref-type="fn" rid="fn1"&gt;2&lt;/xref&gt;
Authors: Victor J. Rosen, Leonard J. Cole
Journal: JNCI Journal of the National Cancer Institute (1962)

Groups of young adult (C57L × A)F1 mice were subjected to several different treatments: (a) 690 rad whole-body X radiation; (b) unilateral nephrectomy and no irradiation; (c) 690 rad followed by unilateral nephrectomy 1 hour later; (d) unilateral nephrectomy followed by 690 rad 3 hours later; (e) unilateral nephrectomy followed by 690 rad 48 hours later. The mice were examined 1 year or 18 months later for kidney neoplasms. The grdup nephrectomized and irradiated 3 hours later showed a high incidence (10 out of 19) of kidney adenomas, as compared with none in the mice irradiated only, or nephrectomized only. In addition, a high incidence (11 out of 15) of tubular and Bowman's capsule proliferations was observed in the mice subjected to irradiation first and nephrectomy 1 hour later. These proliferations are considered to be early stages in the development of the frank renal adenoma. The findings suggest that the occurrence of renal neoplasms in these X-irradiated mice was greatly increased as a consequence of the interaction of the specific proliferative stimulus (unilateral nephrectomy) on radiation-altered kidney cells.
Phase I and pharmacokinetic study of etoposide phosphate by protracted venous infusion in patients with advanced cancer.
Authors: N Soni, N J Meropol, L Pendyala, D Noel, L P Schacter, K E Gunton, P J Creaven
Journal: Journal of Clinical Oncology (1997)

PURPOSE Etoposide has schedule-dependent cytotoxic activity, and clinical resistance may be overcome with prolonged low-dose therapy. Oral bioavailability is variable, and protracted intravenous administration is limited by water insolubility, which requires large infusion volumes. Etoposide phosphate (EP) is a water-soluble prodrug that is rapidly converted in vivo to etoposide, and may be administered in concentrated solution. A phase I study was conducted to determine the toxicity, pharmacokinetics, and pharmacodynamics of EP administered as a protracted venous infusion in the ambulatory setting. METHODS Twenty-three patients with advanced cancer were treated with a continuous infusion of EP using ambulatory pumps for 6 weeks followed by a 2-week rest. Cohorts were treated with EP at 10, 20, 25, and 30 mg/m2/d. Steady-state plasma etoposide levels (Css) and stability of EP in infusion pumps were measured using high performance liquid chromatography (HPLC). RESULTS Myelosuppression, mucositis, and fatigue were dose-limiting. The maximum-tolerated dose (MTD) of EP was 20 mg/m2/d. The mean Css (+/- SD) of etoposide were 0.67 +/- 0.25, 1.14 +/- 0.24, 1.38 +/- 0.64, and 2.19 +/- 0.52 microg/mL at daily EP doses of 10, 20, 25, and 30 mg/m2, respectively. Neutropenia correlated with Css (r = 0.65, P = .008). EP was stable in infusion pumps for at least 7 days. Partial responses were observed in patients with hepatoma and non-small-cell lung cancer (one each). CONCLUSION EP may be conveniently and safely administered as a low-volume protracted venous infusion in the ambulatory setting. Cytotoxic plasma concentrations of etoposide are obtained at the MTD. The pharmacodynamic relationships observed suggest the possibility of pharmacologically based dosing of EP.
Risk Factors for Ocular Melanoma: Western Canada Melanoma Study&lt;xref ref-type="fn" rid="FN1"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN2"&gt;3&lt;/xref&gt;
Authors: R P Gallagher, J M Elwood, J Rootman, J J Spinelli, G B Hill, W J Threlfall, J M Birdsell
Journal: JNCI Journal of the National Cancer Institute (1985)

Between April 1, 1979, and March 31, 1981, 90 individuals in the four western provinces of Canada were diagnosed as having ocular melanomas. Of 87 age-eligible cases (age 20-79 yr), 65 (75%) were interviewed along with age- and sex-matched controls chosen at random from the provincial populations. Individuals with blue eyes had a significantly greater crude risk of ocular melanoma than those with brown eyes [odds ratio (OR)=3.0, P=.04]. Subjects with red or blonde hair were at higher risk of having ocular melanoma than those with black or dark-brown hair (OR=7.7, P=.03). Indoor workers appeared to be at elevated risk for ocular melanoma even after controlling for eye and hair color (OR=3.5, P=.006).
Bronchoconstriction and alveolar derecruitment following cardiopulmonary bypass
Authors: Adam L. Balogh, Ferenc Petak, Kitti Nevery, Jozsef Tolnai, Barna Babik
Journal: European Respiratory Journal (2014)

Evidence is accumulating for the adverse pulmonary consequences of cardiopulmonary bypass (CPB), its effects on the airway and lung tissue mechanics, ventilation heterogeneities, and dead space parameters have not been characterized.

Anaesthetized, mechanically ventilated patients (n=46) undergoing elective cardiac surgery were studied in open-chest condition before and 5 min after weaning from CPB. Airway resistance (Raw), inertance (Iaw), tissue damping (G) and elastance (H) were derived from the lung impedance spectra. The third phase slope of the expired CO2 concentration (SIII) and the respiratory dead space indices were determined by using mainstream capnography. Fowler's dead space (VDF) reflecting the volume of the conductive airways, Bohr's dead space (VDB) including also the unperfused alveolar volume, and Enghoff's dead space (VDE)comprising additionally the volume of the perfused but not ventilated alveoli were assessed. VDE-VDB reflects the intrapulmonary shunt.

Raw significantly increased (143±15[SE]%) while Iaw (-178±25%) and VDF (-10±0.1%) decreased after CPB. SIII (38±17%), G (130±6%) and H (7±0.5%, p=0.024) elevated post-CPB. The lowering in VDB (-12±0.1%) was associated with increased VDE-VDB (38±0.6%) following CPB (p<0.001 for all).

The rise of Raw with concomitant drops of Iaw and VDF implies that the airway narrowing was associated with their shortening after CPB. The changes in SIII, G and H suggest the development of ventilation heterogeneities. The increased VDE-VDB indicates enhanced intrapulmonary shunting. Bedside volumetric capnography may serve as a good indicator for loss of alveoli and ventilation/perfusion mismatch.

Grant: OTKA K81179 and TAMOP-4.2.4.A/2-11/1-2012-0001.