tbuckley/cabot-search huggingface dataset:
Ambulatory oxygen therapy in stable kyphoscoliosis
Authors: DJ Jones, EA Paul, JH Bell, JA Wedzicha
Journal: European Respiratory Journal (1995)

Patients with chronic obstructive pulmonary disease (COPD) may benefit from ambulatory oxygen; however, the effect of exercise on arterial oxygen saturation (Sa,O2) in patients with kyphoscoliosis and of correction with ambulatory oxygen have not been previously reported. Twelve patients with stable kyphoscoliosis (mean (SD) Cobb angle 79 (26) degrees) were studied, with mean (SD) arterial oxygen tension (Pa,O2) 8.96 (0.93) kPa, arterial carbon dioxide tension (Pa,CO2) 6.52 (0.66), forced expiratory volume in one second (FEV1) 0.90 (0.15) L, forced vital capacity (FVC) 1.34 (0.46) L. Six-minute walking tests with oximetry and visual analogue scores (VAS) for breathlessness were performed on air (baseline), and with cylinders containing air and oxygen at 2 L-min-1. Cylinder walks were in random order, with patients blinded to cylinder content. Patients showed oxygen desaturation at each stage of the study. At baseline, oxygen desaturation during exercise was correlated with deterioration in VAS breathlessness scores. Ambulatory oxygen produced significant improvements in desaturation, breathlessness scores and recovery time compared to baseline and air cylinder walks. There was no relationship between baseline desaturation and changes in walking distance. Although exercise desaturation, breathlessness and recovery times were significantly improved with ambulatory oxygen at 2 L.min-1, walking distance was unaffected. We conclude that patients with moderate to severe kyphoscoliosis have significant oxygen desaturation on exercise and should thus routinely receive oximetry on exercise and assessment for ambulatory oxygen therapy.
Carcinogenicity and Chronic Toxicity of 2,4-Toluenediamine in F344 Rats&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: R H Cardy
Journal: JNCI Journal of the National Cancer Institute (1979)

The aromatic amine 2,4-toluenediamine was fed at levels of 50 and 100 ppm to inbred, barrier-raised F344 rats for 2 years. The high dose induced a statistically significant increase in the incidence of hepatic neoplasia in males, and it induced a significant dose-related positive trend in the incidence of liver neoplasms in both sexes. Hepatocellular changes considered to be associated with neoplasia were increased at a high level of statistical significance in both sexes. In addition, the compound caused statistically significant increases in the incidence of mammary tumors in females and an increase of mammary tumors in males which, although not significant statistically, was nevertheless considered to be related to the chemical. The compound was hepatotoxic and accelerated the development of chronic renal disease in this strain, an effect that contributed to a marked decrease in the survival of dosed animals.
Audit shows shortfall in care for emergency bowel surgery patients
Authors: J. Wise
Journal: BMJ (2015)

The death rate in emergency bowel surgery is up to five times greater than that in high risk elective surgery, shows an audit carried out by the Royal College of Anaesthetists.1

The first national emergency laparotomy audit included data on over 20 000 patients (83% of those eligible) from 192 NHS hospitals in England and Wales between 1 December 2013 and 30 November 2014. It found that 11% of patients who underwent emergency laparotomy died within 30 days of the operation. Although this figure was lower than the 15% reported in other studies, it was nevertheless still much higher …
(18)F-FDG positron emission tomography/computed tomography and pulmonary function in sarcoidosis
Authors: Claudia Ravaglia, Carlo Gurioli, Micaela Romagnoli, GianLuca Casoni, Sara Tomassetti, Christian Gurioli, Venerino Poletti
Journal: European Respiratory Journal (2013)

Introduction : (18)F-fluorodeoxyglucose PET has recently been proposed as marker of active disease in Sarcoidosis, although we do not know if it could add value to pulmonary lung function tests and chest radiography.

Objectives : a retrospective analysis to assess whether metabolic activity imaged by (18)F-FDG PET can reflect impairment of lung function or gas exchange in patients with sarcoidosis.

Methods : 44 newly diagnosed pulmonary sarcoidosis patients underwent pulmonary function tests (FVC, FEV1, DLCO) and (18)F-FDG PET. Based on (18)F-FDG PET, patients were diagnosed with exclusively mediastinal/hilar activity (group A), with activity in the lung parenchyma (group B) and without signs of activity (group C). Per group, pulmonary function tests results were compared with the extent of metabolic activity expressed as the maximum standardized uptake value (SUV-max).

Results: PET revealed exclusively mediastinal/hilar activity in 16 patients (36,4 %), activity in the lung parenchyma in 18 patients (40,9 %) and no signs of activity in 10 patients (22,7 %). When considered together, SUV(max) did not correlate with the considered pulmonary function tests; overall, in group A, a significant negative correlation between SUV (max) of the mediastinum/hila and FVC and FEV1 was found, while SUV(max) of the mediastinum/hila did not correlate with DLCO. In group B, SUV (max) of lung parenchyma did not correlate with FVC, FEV1 and DLCO.

Conclusions : these results suggest that PET scanning could be considered in the multidisciplinary evaluation of pulmonary disease in sarcoidosis as it could add value to the pulmonary lung function tests.
<i>SF3B1</i>in Chronic Lymphocytic Leukemia
Authors: Jinichi Mori, Yukie Takahashi, Tetsuya Tanimoto
Journal: New England Journal of Medicine (2012)

To the Editor: Wang et al. (Dec. 29 issue)1 report that SF3B1 mutation is associated with a shorter time to initiation of treatment in patients with chronic lymphocytic leukemia. However, this result should be interpreted with caution. In the discovery cohort of 91 patients, 29 were classified as having stage 0 disease, 43 as having stage I, and 19 as having stage III–IV according to the Rai classification (ranging from 0 [low risk] to I or II [intermediate risk] to III or IV [high risk]). At the time of the sampling, 61 of the patients had not received chemotherapy, whereas 30 had prior exposure to chemotherapy. It should be noted that the SF3B1 mutations could be acquired during progression of the disease, as shown in a recent article in which the mutations appeared in two of three cases in the serial analysis during the clinical course.2 These findings suggest that a number of SF3B1 mutations were acquired after initiation of treatment in the present study. Clinicians need information on whether SF3B1 mutation in patients who have not received chemotherapy is predictive of the time to initiation of treatment. Would the authors provide us with the data limited to the population in the discovery cohort?
Cost-effectiveness of cancer chemotherapy: an economic evaluation of a randomized trial in small-cell lung cancer.
Authors: P J Goodwin, R Feld, W K Evans, J Pater
Journal: Journal of Clinical Oncology (1988)

An economic evaluation of a randomized trial of cyclophosphamide, Adriamycin (doxorubicin; Adria Laboratories, Columbus, OH), and vincristine alone or alternating with etoposide (VP-16) and cisplatin in extensive small-cell lung cancer (SCLC) was undertaken. A survival benefit of 1.6 months in favor of alternating chemotherapy was associated with an additional cost of $450 (1984 Canadian dollars) per patient. This translated to a cost of $3,370 per year of life gained. Sensitivity analyses demonstrated that the cost-effectiveness (CEA) of alternating chemotherapy was greatest when treatment was given on an outpatient basis. The results of the evaluation were sensitive to hospitalization rates, but even the most unfavorable analyses revealed the CEA of alternating chemotherapy to be comparable to that of treatments of common nonmalignant diseases. It is concluded that the CEA of alternating chemotherapy for SCLC was favorable when compared with accepted treatments for nonmalignant diseases. The survival benefit seen with alternating chemotherapy was felt to be clinically significant and alternating chemotherapy is recommended as routine therapy for extensive SCLC.
A Randomized Phase 3 Study of Peripheral Blood Progenitor Cell Mobilization With Stem Cell Factor and Filgrastim in High-Risk Breast Cancer Patients
Authors: Elizabeth J. Shpall, Catherine A. Wheeler, Stewart A. Turner, Saul Yanovich, Randy A. Brown, Andrew L. Pecora, Thomas C. Shea, Kenneth F. Mangan, Stephanie F. Williams, C. Fred LeMaistre, Gwynn D. Long, Roy Jones, Mark W. Davis, Robyn Murphy-Filkins, William R.L. Parker, John A. Glaspy
Journal: Blood (1999)
Tumor and liver drug uptake following hepatic artery and portal vein infusion.
Authors: E R Sigurdson, J A Ridge, N Kemeny, J M Daly
Journal: Journal of Clinical Oncology (1987)

Anatomic dye injection studies of the blood supply of colorectal hepatic metastases suggest that tumors are supplied predominantly by the hepatic artery. Using 13N amino acids with dynamic gamma camera imaging in patients with colorectal hepatic metastases, it has been shown that hepatic artery infusion results in a significantly greater nutrient delivery to tumor compared with portal vein infusion. However, direct measurements of drug levels in tumor following hepatic artery and portal vein infusion in humans have not previously been reported. Patients with metastatic colorectal cancer confined to the liver received fluorodeoxyuridine (FUdR) through the hepatic artery or through the portal vein. All patients had previously failed systemic chemotherapy. Five patients with hepatic artery catheters were matched (by age, serum lactic dehydrogenase levels, percent hepatic replacement, and tumor size) with five patients with portal vein catheters. At operation, 3H-FUdR (1 microCi/kg) and 99mTc-macroaggregated albumin (MAA) (6 mCi) were injected into the hepatic artery or portal vein. Liver and tumor biopsies were obtained two and five minutes later. 3H and 99mTc were measured per gram tissue by scintillation and gamma counting. The mean liver levels following hepatic artery infusion (23.9 +/- 11.4 nmol/g) and portal vein infusion (18.4 +/- 14.5 nmol/g) did not differ. However, the mean tumor FUdR level following hepatic artery infusion was 12.4 +/- 12.2 nmol/g, compared with a mean tumor FUdR level following portal vein infusion of 0.8 +/- 0.7 nmol/g (P less than .01). This low level of tumor drug uptake after portal vein infusion of FUdR predicts minimal tumor response to treatment via this route. Thus, regional chemotherapy for established colorectal hepatic metastases should be administered through the hepatic artery.
Worsening bone scan in the evaluation of antitumor response during hormonal therapy of breast cancer.
Authors: C L Vogel, J Schoenfelder, I Shemano, D F Hayes, R A Gams
Journal: Journal of Clinical Oncology (1995)

PURPOSE Scintigraphic flare in association with response to therapy has been well described in the medical literature. During the course of a recent breast cancer trial, it became apparent that several patients with worsening bone scan but no other clinical evidence of disease progression might have potentially benefited from continued therapy, but had therapy discontinued. A retrospective analysis of this issue was performed to assess the magnitude and scope of this problem. MATERIALS AND METHODS A total of 648 patients with hormone receptor-positive or unknown advanced breast cancer were treated as part of a large-scale trial of first-line hormonal therapy. Patients were assessed for response to therapy, including response duration, progression-free interval (PFI), overall survival, and quality of life. The retrospective analysis presented here was performed to assess whether patients with a possible scintigraphic flare within the first 16 weeks of therapy might have had therapy discontinued prematurely due to a worsening bone scan attributable to tumor flare, rather than due to disease progression. RESULTS Analysis of the hormonal trial showed that of 376 assessable patients 108 (29%) with bone disease had a possible scintigraphic flare by week 8 or 16 of the trial, based on data on the case report forms and radiology reports (bone scans and x-rays). Of these, 69 patients (64%) were continued on study therapy, which resulted in clinical benefit in 50 (72%) of those patients. In contrast, 39 patients (36%) with possible scintigraphic flare were removed from the trial. CONCLUSION We conclude that changes in bone scintigraphy that mimic progressive disease early in the course of hormonal treatment of patients with breast cancer metastatic to bone may represent scintigraphic flare associated with response. Thus, clinicians must be cognizant of the phenomenon of scintigraphic flare to avoid premature discontinuation of a potentially beneficial treatment.
The transcription factors ZEB2 and T-bet cooperate to program cytotoxic T cell terminal differentiation in response to LCMV viral infection
Authors: Claudia X. Dominguez, Robert A. Amezquita, Tianxia Guan, Heather D. Marshall, Nikhil S. Joshi, Steven H. Kleinstein, Susan M. Kaech
Journal: The Journal of Experimental Medicine (2015)

The transcription factor T-bet is critical for cytotoxic T lymphocyte (CTL) differentiation, but it is unclear how it operates in a graded manner in the formation of both terminal effector and memory precursor cells during viral infection. We find that, at high concentrations, T-bet induced expression of Zeb2 mRNA, which then triggered CTLs to adopt terminally differentiated states. ZEB2 and T-bet cooperate to switch on a terminal CTL differentiation program, while simultaneously repressing genes necessary for central memory CTL development. Chromatin immunoprecipitation sequencing showed that a large proportion of these genes were bound by T-bet, and this binding was altered by ZEB2 deficiency. Furthermore, T-bet overexpression could not fully bypass ZEB2 function. Thus, the coordinated actions of T-bet and ZEB2 outline a novel genetic pathway that forces commitment of CTLs to terminal differentiation, thereby restricting their memory cell potential.
Novel type of red blood cell pyruvate kinase hyperactivity predicts a remote regulatory locus involved in <i>PKLR</i> gene expression
Authors: Brigitte Antoinette van Oirschot, Jerney Johanna Jeanette Maria Francois, Wouter Willem van Solinge, Annet Cornelia Wilhelmina van Wesel, Gert Rijksen, Hans Kristian Ploos van Amstel, Richard van Wijk
Journal: American Journal of Hematology (2013)

Red blood cell pyruvate kinase (PK-R) is a key regulatory enzyme of red cell metabolism. Hereditary deficiency of PK-R is caused by mutations in the PKLR gene, leading to chronic nonspherocytic hemolytic anemia. In contrast to PK deficiency, inherited PK hyperactivity has also been described. This very rare abnormality of RBC metabolism has been documented in only two families and appears to be without clinical consequences. Thus far, it has been attributed to either a gain of function mutation in PKLR or to persistent expression of the fetal PK isozyme PK-M2 in mature red blood cells. We here report on a novel type of inherited PK hyperactivity that is characterized by solely increased expression of a kinetically normal PK-R. In line with the latter, no mutations were detected in PKLR. Mutations in regulatory regions as well as variations in PKLR copy number were also absent. In addition, linkage analysis suggested that PK hyperactivity segregated independently from the PKLR locus. We therefore postulate that the causative mutation resides in a novel yet-unidentified locus, and upregulates PKLR gene expression. Other mutations of the same locus may be involved in those cases of PK deficiency that fail to reveal mutations in PKLR.
Transbronchial cryobiopsy and open lung biopsy in interstitial lung disease: Comparison of two diagnostic tools
Authors: Lars Hagmeyer, Dirk Theegarten, Jeremias Wohlschläger, Christina Priegnitz, Marcel Treml, Winfried Randerath
Journal: European Respiratory Journal (2013)

Background: Transbronchial cryobiopsy (TCB) allows representative sampling of lung tissue. It has not yet been evaluated whether this procedure is a reliable diagnostic tool in the work-up of interstitial lung diseases (ILD). Until now, open lung biopsy (OLB) is the gold standard, obtaining lung tissue from ILD patients (pts.).

Materials und Methods: We retrospectively analyzed data of 8 ILD pts.who underwent both, TCB and OLB. Pathological results of both methods were analyzed in conjunction with clinical and radiological findings. Tissue samples after OLB and TCB have been investigated independently by two expertized pathologists.

Results: In all pts.3-4 TCBs were sampled from 2 different lobes. After TCB, complication were observed: pneumothorax 0/8 pts.; postinterventional bleeding mild in 5/8 pts., moderate in 1/8 pts. No life-threatening events occurred after TCB within 30 days. OLB was performed more than 30 days after TCB in all pts. (2 OLBs from 2 different lobes). After OLB no prolonged chest tube therapy or bleeding was observed, but 2/8 pts. died within 30 days due to acute exacerbation of ILD.

Histological findings showed a good correlation between TCB and OLB in 6 cases (75%). In one pt. the findings were discordant (TCB probable NSIP pattern, OLB possible UIP pattern). In one pt. TCB samples showed unspecific changes, whereas OLB showed a definite UIP pattern.

Conclusion: OLB may be afflicted with a higher risk for postinterventional 30 days-mortality. Specific histological patterns after TCB may allow to abstain from OLB in many ILD patients. Furthermore, TCB may be an option in pts. who either do not give their consent or are at high-risk for OLB.
The Role and Therapeutic Potential of Autophagy Modulation in Controlling Virus‐Induced Cell Death
Authors: Gordana Tovilovic, Biljana Ristic, Marina Milenkovic, Maja Stanojevic, Vladimir Trajkovic
Journal: Medicinal Research Reviews (2013)

Abstract Macroautophagy (hereafter referred to as autophagy) is an evolutionary conserved catabolic process in which the cytoplasmic content is sequestered and degraded by the lysosomal machinery in order to maintain cellular homeostasis or provide energy during metabolic and hypoxic stress. It also represents an important component of the host response against infectious agents, performing surveillance and effector functions involved in detection and clearance of pathogens, including viruses. Moreover, it appears that autophagy plays a major role in determining the fate of both virally infected and uninfected cells by blocking or promoting their death in a virus‐ and cell‐type‐dependent manner. We here review the current knowledge on the complex involvement of autophagy in survival and death of the host cells during viral infection, focusing on the molecular mechanisms underlying viral modulation of autophagic response and its interference with the cell death pathways. We also discuss a possible significance of the autophagy‐dependent modulation of cell death for the outcome and therapy of viral infections, emphasizing the need for a time‐ and cell‐type‐dependent fine‐tuning of the autophagic response in achieving an optimal balance between beneficial and adverse effects.
Helicobacter pylori and myocardial infection
Authors: C. Armitage
Journal: BMJ (2000)

Editor—We are writing in response to the paper by Danesh et al on infection with Helicobacter pylori and early onset myocardial infarction.1 We believe that this thorough study is of interest because of its large sample size, and inclusion of sibling pairs and young people. We would, however, like to address the following points. Firstly, Danesh et al did not explain clearly how the controls were selected for the early onset case-control study. We concluded that they were chosen from the pool of spouses and relatives of the cases, which would make them unrepresentative of the general population.

Secondly, Danesh et al say that exclusion of cases with any history of gastrointestinal bleeding or peptic ulceration (both of which could be caused by certain cytotoxic strains of H pylori) would not have caused any underestimation as controls who reported these conditions were also excluded. Excluding this group with potentially higher rates of infection with H pylori could, however, bias the estimate of the odds ratio. For example, considering the case-control study, if we assume the same numbers (183) of controls as cases were excluded, and that 50% of the excluded cases and controls were positive for H pylori, the odds ratio calculation would be as in the table. 

The odds ratio in the study was calculated as 2.28. Using our adjusted results, the odds ratio is decreased to 1.97. This shows that exclusion could have a significant effect. We have identified the following residual confounding factors. Danesh et al used current smoking as an indicator of smoking status. This may be inadequate as it does not take into account the duration and amount smoked. Also, they have not controlled for hypertension or diabetes, which are more prevalent in the cases than in the controls.
Utilization of sequential oxygenation index and organ dysfunction assessment within the first 3 days of mechanical ventilation to predict the outcome of adult patients with severe acute respiratory failure
Authors: Wen-Feng Fang, Hsu-Ching Kao, Ting-Yu Lai, Heui-Ling Hung, Yu-Mu Chen, Po-An Chou, Chin-Chou Wang, Meng-Chih Lin
Journal: European Respiratory Journal (2013)

Objective: Early prediction of outcome of patients with acute respiratory failure enables prompted adjustment of treatment strategy and more efficient allocation of medical resources. We though to determine early predictors of outcome of adult patients with severe acute respiratory failure.  Method: 100 consecutive adult patients with severe acute respiratory failure were evaluated in this retrospective study. Data including co-morbidities, Sequential Organ Failure Assessment (SOFA) score, Acute Physiological Assessment and Chronic Health Evaluation II (APACHE II) score, PaO2, FiO2, PaO2/FiO2, PEEP, mean airway pressure (mPaw), and oxygenation index (OI) on the 1st and the 3rd day of mechanical ventilation, and change in OI within 3 days were recorded. Primary outcome was hospital mortality; secondary outcome measure was ventilator weaning failure.  Results: 38 out of 100 (38%) patients died within the study period. 48 patients (48%) failed to wean from ventilator. Multivariate analysis showed day 3 OI (p=0.004) and SOFA (p=0.02) score were independent predictors of hospital mortality. Pre-existing CVA (cerebrovascular accident) (p=0.002) was the predictor of weaning failure. Results from Kaplan-Meier method demonstrated higher day 3 OI was associated with shorter survival time (log-Rank test, p  Conclusion: Early OI (within 3 days) and SOFA score were predictors of mortality in severe acute respiratory failure.
Surface Antigen Expressed in Hematopoietic Cells Derived From <italic>Fv-4</italic><sup><italic>r</italic></sup> Mouse Strains<xref ref-type="fn" rid="FN2">2</xref>
Authors: H Yoshikura, T Odaka
Journal: JNCI Journal of the National Cancer Institute (1982)

Fv-4 locus controls the susceptibility of mice to ecotropic murine leukemia virus (MuLV). Antiserum against Fv-4r/s mice with BALB/c background was raised in inbred BALB/c mice. In the complement-dependent cytotoxicity test, the antiserum killed the hematopoietic cells derived from Fv-4r/- mice but not these from Fv-4s/s mice, and the genetic cross experiments located the locus controlling the expression of the target molecule of the antibody in the close vicinity of Fv-4. In addition, the antigenic expression of the exogenously infecting MuLV suppressed the expression of the target molecule of the antiserum. The expressions of these two antigens appear to compete with each other on the cell surface.