tbuckley/cabot-search huggingface dataset:
MRI of delayed-ventilation perfusion matching in COPD
Authors: Helen Marshall, Martin Deppe, Juan Parra-Robles, David Lipson, Rod Lawson, Jim Wild
Journal: European Respiratory Journal (2012)

Introduction Delayed ventilation in COPD may be caused by collateral ventilation, partial obstruction, lung hyperinflation or a mixture of such mechanisms, and allows initially-unventilated lung regions to become ventilated over time. Recently hyperpolarised gas MRI has been used to directly visualise delayed and collateral ventilation in COPD over the period of a single breath-hold. Delayed ventilation will only contribute to gas exchange if there is blood perfusion in these regions.

Objective To image the perfusion matching of lung regions with delayed ventilation in COPD.

Methods Ten patients with moderate to severe COPD as defined by NICE guidelines were scanned using 3He and proton MRI. Delayed-ventilation images; hyperpolarised 3He images with full lung coverage were acquired at six time-points during a single breath-hold. Contrast-enhanced perfusion images with full lung coverage were acquired at breath-hold.

Results Regions of delayed-ventilation were perfused in some cases and were not perfused in others giving an indication of which areas remained active in gas exchange.

![Figure][1] 



Example ventilation and perfusion images are shown in the figure. The defects with delayed-ventilation in patient A are not perfused, whereas the smaller defect in Patient B is perfused.

Conclusions Hyperpolarised gas and proton MRI allow the visualisation of ventilation and perfusion matching, and may aid in the understanding of delayed-ventilation in COPD and its role in gas exchange.

 [1]: pending:yes
Ifosfamide, carboplatin, and etoposide plus granulocyte-macrophage colony-stimulating factor: a phase I study with apparent activity in non-small-cell lung cancer.
Authors: R L Krigel, C S Palackdharry, K Padavic, N Haas, D Kilpatrick, C Langer, R Comis
Journal: Journal of Clinical Oncology (1994)

A phase I trial was performed to evaluate the feasibility of escalating the dose of etoposide in dose-intensive ifosfamide, carboplatin, and etoposide (ICE) with granulocyte-macrophage colony-stimulating factor (GM-CSF).Twenty-four patients were entered between November 1990 and November 1991. Patients received ifosfamide 5 g/m2 by continuous infusion over 48 hours, carboplatin 400 mg/m2 by intravenous bolus, and GM-CSF 5 micrograms/kg/d subcutaneously from day 4 until neutrophil recovery. The etoposide dose was escalated, with six patients receiving 300 mg/m2 total dose (level 1), six receiving 600 mg/m2 (level 2), three receiving 900 mg/m2 (level 3), and five receiving 1,200 mg/m2 (level 4). Level 4B consisted of three patients who received etoposide 1,200 mg/m2 and GM-CSF 10 micrograms/kg/d. Cycles were repeated every 21 days. The maximum-tolerated dose (MTD) was prospectively defined as the dose level at which the next higher level produced greater than 7 days of grade 4 myelosuppression in two or more of six patients.Twenty-three patients were assessable. The median duration of neutropenia was < or = 7 days on cycle 1 at all dose levels. The initial criteria for determination of the MTD was never achieved. However, seven of eight patients treated at levels 4 and 4B required hospitalization for neutropenic fever on cycle 1 of therapy, with three of four septic events occurring at these levels. Cumulative thrombocytopenia occurred at all dose levels, with > or = 50% of patients requiring platelet transfusions on cycle 3. This became the dose-limiting toxicity above level 3. The overall response rate was 48%, with 11 of 23 objective responses, including two complete responses (CRs). Seven of 11 (64%) patients with non-small-cell lung cancer (NSCLC) responded, including one CR. Two of four (50%) heavily pretreated non-Hodgkin's lymphoma (NHL) patients responded, with one CR.The addition of GM-CSF to a dose-intensive ICE regimen permitted dose escalation of etoposide to 900 mg/m2, with cumulative thrombocytopenia as the dose-limiting toxicity. Carboplatin dosing by the area under the curve (AUC) may minimize thrombocytopenia. This appears to be an active regimen for patients with NSCLC and refractory NHL.
Simultaneous imaging of lung structure and function with triple nuclear MRI
Authors: Jim Wild, Helen Marshall, Xiaxun Xu, Graham Norquay, Juan Parra-Robles
Journal: European Respiratory Journal (2012)

Hybrid medical imaging scanners (eg PET-CT) allow imaging with different detection modalities at the same time, providing complementary anatomical and functional information within the same physiological time course. Here, we re-engineer a standard clinical MRI scanner for the simultaneous acquisition of lung MR images from three different nuclei (1H, 3He and 129Xe) in a single breath-hold. The temporal and spatial registration of these images is impossible to achieve in separate breath-hold scans. This new system opens up the possibility of simultaneous capture of regional lung function from the 3He and 129Xe gases and lung structure from the 1H MRI without reliance on ionising radiation.  Figure shows images of 3He, 1H and 129Xe acquired from a healthy volunteer in the same breath; the anatomical 1H images show excellent spatial registration with the 3He and 129Xe ventilation images.  The method has multiple potential applications, allowing side-by-side quantitative analysis of early signs of impaired lung function from the 3He and 129Xe images and anatomical signs of disease from 1H MRI. For a variety of lung diseases, registration of ventilation MRI to anatomical 1H MRI would allow subsequent image registration to the radiological gold standard for anatomy, CT, which serves as the clinical gold standard in diseases such as emphysema.
Selective enhancement of endothelial BMPR-II with BMP9 reverses pulmonary arterial hypertension
Authors: Lu Long, Mark L Ormiston, Xudong Yang, Mark Southwood, Stefan Gräf, Rajiv D Machado, Matthias Mueller, Bernd Kinzel, Lai Ming Yung, Janine M Wilkinson, Stephen D Moore, Kylie M Drake, Micheala A Aldred, Paul B Yu, Paul D Upton, Nicholas W Morrell
Journal: Nature Medicine (2015)
Prognostic Utility of Molecular Factors by Age at Diagnosis of Colorectal Cancer
Authors: Nadine J. McCleary, Kaori Sato, Reiko Nishihara, Kentaro Inamura, Teppei Morikawa, Xuehong Zhang, Kana Wu, Mai Yamauchi, Sun A. Kim, Yasutaka Sukawa, Kosuke Mima, Zhi Rong Qian, Charles S. Fuchs, Shuji Ogino, Jeffrey A. Meyerhardt
Journal: Clinical Cancer Research (2015)

We hypothesized that adverse prognostic associations of specific tumor molecular factors vary by patient age at colorectal cancer diagnosis.
Studies on the Utilization of Asparagine by Mouse Leukemia Cells&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Toshihiko Ubuka, Alton Meister
Journal: JNCI Journal of the National Cancer Institute (1971)

Asparaginase-sensitive (EARAD1) and asparaginase-resistant (RADA1) mouse leukemia cells were incubated with RPMl 1630 medium containing 15% fetal calf serum and 14C-, amide-15N-L-asparagine, amide-15N-L-glutamine, or 15NH4CI for 24 or 48 hours. The protein and nucleic acid fractions were then isolated and the incorporation of isotopes was determined. In both tumors the incorporation of asparagine carbon and amide nitrogen into nucleic acid was very low, but there was substantial incorporation into protein. The incorporation of glutamine amide nitrogen into nucleic acid and protein was considerable, whereas the incorporation of 15N from 15N-ammonia into nucleic acid and protein was very low. In in vivo experiments mice bearing EARAD1 or RADA1 tumors were given injections of amide-15N-gIutamine, amide-15N-asparagine, or 15NH4CI, and the protein and nucleic acid fractions were isolated 24 hours later. There was substantial incorporation of 15N from glutamine amide and asparagine amide into proteins but such incorporation was only about 10% of that observed in the in vitro experiments. The incorporation of asparagine amide nitrogen into nucleic acids was much less than that of glutamine amide nitrogen, and there was appreciable incorporation of N from ammonium into both nucleic acids and proteins.
Influence of an acute exacerbation during pulmonary rehabilitation (PR) on outcomes of PR in COPD patients awaiting lung transplantation
Authors: Inga Heinzelmann, Isabelle Ningel, Rainer Gloeckl, Andreas Jerrentrup, Klaus Kenn
Journal: European Respiratory Journal (2014)

Background:  Pulmonary rehabilitation (PR) can be an effective intervention also in patients with very severe COPD awaiting lung transplantation (ltx). However, up to now the role and the influence of an acute exacerbation (AE) during PR on the outcome of PR are unknown.  Methods:  In this retrospective analysis n=462 COPD patients (age: 54±7y, FEV 1 : 26±9% pred.) awaiting lung transplantation were enrolled for an inpatient PR. 401 patients completed PR (34±13days) without AE and 61 patients acquired an AE while performing PR (40±16 days; p=0.002). Patients with an AE continued PR in an individually tailored fashion. 6-minute walking distance, lung function testing and health-related quality of life questionnaire (SF-36) were performed on admission and discharge.  Results:  Patients with and without AE showed a comparable 6-minute walking distance (6MWD) (236±108m versus 253±122m; p=n.s.) and lung function (FEV 1 : 26±9% pred. versus 26±10% pred.; p=n.s.) at baseline. At discharge patients with and without AE were able to increase their 6MWD by 65±62m and 56±62m, respectively (both p  Conclusion:  It seems that patients with end-stage COPD significantly benefit from PR with regards to exercise capacity and HRQL even if they acquire an AE during PR. Thus AE seems not to be a reason to discontinue PR.
Neutrophilic leukemoid reaction in multiple myeloma
Authors: Dragana Milojkovic, Ann Hunter, Linda Barton, Nicholas C. P. Cross, Barbara J. Bain
Journal: American Journal of Hematology (2015)

A 52-year-old man with asymptomatic multiple myeloma was referred for assessment of a high white cell count and neutrophil count. He had already been commenced on hydroxycarbamide and while on this drug in a dose of 2.5 g daily, his white cell count was 22.5 × 109/l and neutrophil count was 18.9 × 109/l. His blood film showed toxic granulation and Döhle bodies (images), although not all neutrophils were abnormal. He was found to have an immunoglobulin G lambda paraprotein in a concentration of 80 g/l. Bone marrow showed 10–15% plasma cells and granulocytic hyperplasia. Molecular analysis for JAK2 V617F and CSF3R exon 14 and 17 mutations was negative. A diagnosis of neutrophilic leukaemoid reaction to multiple myeloma was made. Isolated neutrophilia without dysplasia is characteristic of chronic neutrophilic leukemia. However, before making this diagnosis it is essential to exclude an underlying plasma cell neoplasm. About a quarter of the reported patients with either chronic neutrophilic leukemia (CNL), or a condition resembling it, have had coexisting monoclonal gammopathy of undetermined significance or multiple myeloma 1. A diagnosis of CNL is not appropriate in patients with a coexisting plasma cell neoplasm unless there is demonstrated clonality of myeloid cells or other clear evidence that the myeloid condition is neoplastic. Rarely, by chance, CNL and a plasma cell neoplasm have coexisted 2, 3. Patients with a plasma cell neoplasm and neutrophilia often have toxic granultion and Döhle bodies, as shown in the current patient. Synthesis of granulocyte colony-stimulating factor (G-CSF) by neoplastic plasma cells and high levels of serum G-CSF have been demonstrated, indicating that this is a reactive, cytokine-driven process. Similar changes can also be seen in CNL, albeit somewhat less often; in these patients the cytological changes are likely to result from a mutation that directly affects neutrophil biology, particularly but not only mutation of CSFR3, encoding the G-CSF receptor 4.
Prognostic significance of MYCN oncogene expression in childhood neuroblastoma.
Authors: S B Bordow, M D Norris, P S Haber, G M Marshall, M Haber
Journal: Journal of Clinical Oncology (1998)

PURPOSE To assess the significance of MYCN gene expression as a prognostic factor in patients with neuroblastoma of various ages, and to determine whether it can predict for outcome independently of MYCN gene amplification. PATIENTS AND METHODS The level of MYCN gene expression in 60 specimens of primary untreated neuroblastoma was determined by reverse-transcriptase polymerase chain reaction (RT-PCR) analysis. RESULTS High levels of MYCN gene expression were associated with advanced tumor stage (P=.0005), with the presence of MYCN gene amplification (P &lt; .0001), but not with older age at diagnosis. Among patients who lacked MYCN gene amplification, the levels of MYCN gene expression were significantly greater in the tumors of infants compared with those of older children (P &lt; .0005). High MYCN expression was strongly associated with reduced survival and event-free survival in the overall study population (P &lt; .005), and also in the subset of patients aged older than 1 year at diagnosis (P &lt; .001). In contrast, MYCN expression did not appear to be predictive of outcome in infants. After adjustment for the effect of MYCN amplification, high levels of MYCN expression retained significant prognostic value for poor survival (relative hazards, 30.3; P=.003) in children aged older than 12 months at diagnosis. CONCLUSION High MYCN gene expression is strongly predictive of poor outcome in older children with neuroblastoma, but not in infants. The findings help explain the controversy in the literature about the prognostic value of MYCN gene expression and highlight the different biology of neuroblastoma that presents in infants and older children.
The polarity protein Scrib mediates epidermal development and exerts a tumor suppressive function during skin carcinogenesis
Authors: Helen B. Pearson, Edwina McGlinn, Toby J. Phesse, Holger Schlüter, Anuratha Srikumar, Nathan J. Gödde, Christina B. Woelwer, Andrew Ryan, Wayne A. Phillips, Matthias Ernst, Pritinder Kaur, Patrick Humbert
Journal: Molecular Cancer (2015)

The establishment and maintenance of polarity is vital for embryonic development and loss of polarity is a frequent characteristic of epithelial cancers, however the underlying molecular mechanisms remain unclear. Here, we identify a novel role for the polarity protein Scrib as a mediator of epidermal permeability barrier acquisition, skeletal morphogenesis, and as a potent tumor suppressor in cutaneous carcinogenesis. To explore the role of Scrib during epidermal development, we compared the permeability of toluidine blue dye in wild-type, Scrib heterozygous and Scrib KO embryonic epidermis at E16.5, E17.5 and E18.5. Mouse embryos were stained with alcian blue and alizarin red for skeletal analysis. To establish whether Scrib plays a tumor suppressive role during skin tumorigenesis and/or progression, we evaluated an autochthonous mouse model of skin carcinogenesis in the context of Scrib loss. We utilised Cre-LoxP technology to conditionally deplete Scrib in adult epidermis, since Scrib KO embryos are neonatal lethal. We establish that Scrib perturbs keratinocyte maturation during embryonic development, causing impaired epidermal barrier formation, and that Scrib is required for skeletal morphogenesis in mice. Analysis of conditional transgenic mice deficient for Scrib specifically within the epidermis revealed no skin pathologies, indicating that Scrib is dispensable for normal adult epidermal homeostasis. Nevertheless, bi-allelic loss of Scrib significantly enhanced tumor multiplicity and progression in an autochthonous model of epidermal carcinogenesis in vivo, demonstrating Scrib is an epidermal tumor suppressor. Mechanistically, we show that apoptosis is the critical effector of Scrib tumor suppressor activity during skin carcinogenesis and provide new insight into the function of polarity proteins during DNA damage repair. For the first time, we provide genetic evidence of a unique link between skin carcinogenesis and loss of the epithelial polarity regulator Scrib, emphasizing that Scrib exerts a wide-spread tumor suppressive function in epithelia.
Vitamin D in Tunisian young asthmatics
Authors: Eya Tangour, Haifa Maalmi, Jamel Ammar, Anissa Berraies, Hanadi Abid, Kamel Hamzaoui, Sadok Yaalaoui, Agnes Hamzaoui
Journal: European Respiratory Journal (2011)

Vitamin D deficiency has been described in numerous chronic inflammatory diseases.

We sought to investigate vitamin D in children with asthma and its interaction with disease variables and inflammatory responses.

Methods: Thirty-nine children with asthma in a stable state were enrolled. Samples were obtained in summer. Lung function was measured on the same day. Serum concentrations of vitamin D were assayed with a radioimmunoassay kit, 30 healthy children acted as controls. CD4+ blood lymphocytes were investigated for cytokines expression (IFNg, IL4, IL10, IL17) by intracytoplasmic cytokines expression quantified by cytofluorometry. CD4+ CD25+FoxP3+ cells were identified as regulatory T cells.

Only 15% of our patients had a sufficient serum 25(OH) D ((33.83 + 3.31 ng/ml). Deficient values were observed in 43% of asthmatic patients (14.40 + 3.30; P = 0.0001). A positive correlation was found between FVC percent predicted and vitamin D (r = 0.35; P = 0.027). A negative correlation was observed between serum IL-17 and vitamin D (r = - 0.617; P = 0.001). Th1/Th2 ratios of controls were higher (27.26 + 14.35%) than those of patients (13.48 + 8.55%; P = 0.0001). In asthma, Th1/Th2 ratio was correlated with vitamin D (r= 0.68; P = 0.0001). Tr1/Th17 ratio was significantly decreased in asthmatic children. A positive correlation was observed between vitamin D and IL-10+ cells (r = 0.428; P = 0.008). A correlation was observed between the percentage of CD25+FoxP3+ Treg cells and vitamin D values in asthmatics (r = 0.368)

Conclusions: Asthma was associated with lower serum Vitamin D levels despite high levels of sun exposure. Our findings suggest that vitamin D is an important promoter of T cell regulation in vivo in asthma patients.
A lifestyle physical activity intervention is associated with decline in health care utilization (HCU) among patients with COPD
Authors: David Coultas, Rennie Russo, Jennifer Peoples, Jamile Ashmore, John Sloan, Bradford Jackson, Minyong Uhm, Karan Singh, Sejong Bae
Journal: European Respiratory Journal (2014)

Rationale : Among patients with COPD physical inactivity is associated with increased hospitalizations. The purpose of this investigation was to examine the effect of an intervention to increase physical activity on HCU.   Methods : This was a randomized trial among patients with COPD comparing a physical activity intervention (PAI) to usual care (UC). Self-reported HCU during previous 6 months was measured for clinic visits for lung disease (CLD) and non-lung disease (CNLD), emergency/urgent visits for lung disease (ELD) and non-lung disease (ENLD), and hospitalization for lung disease (HLD) and non-lung disease (HNLD). Both cross-sectional differences and longitudinal changes in HCU were examined.   Results : A total of 305 were randomized (156 UC, 149 I) and 6-month outcome results available for 92% (144) and 83% (123), respectively. In cross-sectional analysis there were no statistical differences in the prevalence of any HCU (Table). In longitudinal analysis the majority of both groups had no change in HCU. However, the odds of decline vs. increase for each type of HCU were greatest among PAI-group. (Table).   Conclusion : After an intervention to increase physical activity there were no overall differences in HCU. In longitudinal sub-group analyses the intervention was consistently associated with less HCU for both lung- and non-lung related disorders.
Macrolide therapy is associated with lower 30-day mortality in patients with non-pneumonia and pneumonia severe sepsis
Authors: Marcos Restrepo, Eric Mortensen, Laurel Copeland, Brandie Nakashima, MaryJo Pugh, Antonio Anzueto
Journal: European Respiratory Journal (2011)

Background:  Recent studies suggest that macrolides may have beneficial effects for patients at risk for certain infections. However, the evidence is limited to events associated with pneumonia.   Aim:  We examined the effect of macrolide therapy on 30-day mortality for patients with severe sepsis caused by pneumonia compared to non-pneumonia severe sepsis.   Methods:  A retrospective administrative data of hospitalized inpatients aged >/=65 years with a discharge diagnosis of sepsis (by ICD-9 codes 0.38 and 0.20) in fiscal years 2002-2007, and at least 1 year of Department of Veterans Affairs outpatient care before the index admission were included. Severe sepsis was defined as sepsis with at least one organ failure. Stratification was done according to the source in severe sepsis secondary to community acquired pneumonia (SSCAP) vs. non-pneumonia severe sepsis NCAP-SS). Primary outcome was 30-day mortality.   Results:  Severe sepsis was present in 15,308 subjects, out of whom 1,817 (12%) received macrolides. SSCAP occurred in 24% of the patients vs. 76% in NCAP-SS. Mortality was 46% at 30 days for the severe sepsis group. The use of macrolide therapy was associated with decreased mortality at 30 days in the SSCAP group (31% vs. 51%, p   Conclusion:  Macrolide use was associated with decreased 30-day mortality in patients with severe sepsis due to pneumonia and non-pneumonia, respectively. Confirmatory randomized control trials are needed to determine whether macrolide therapy may be protective for patients with sepsis and the mechanism of this association.
Lymph node staging in non-small-cell lung cancer with FDG-PET scan: a prospective study on 690 lymph node stations from 68 patients.
Authors: J F Vansteenkiste, S G Stroobants, P R De Leyn, P J Dupont, J Bogaert, A Maes, G J Deneffe, K L Nackaerts, J A Verschakelen, T E Lerut, L A Mortelmans, M G Demedts
Journal: Journal of Clinical Oncology (1998)

PURPOSE To compare the accuracy of computed tomography-(CT) scan and the radiolabeled glucose analog 18F-fluoro-2-deoxy-D-glucose (FDG) positron emission tomography (PET) visually correlated with CT (PET + CT) in the locoregional lymph node (LN) staging of non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS Sixty-eight patients with potentially operable NSCLC underwent thoracic CT, PET, and invasive surgical staging (ISS). Imaging studies were read prospectively and blinded to the surgical and pathologic data. A five-point visual scale was used for the interpretation of LNs on PET. Afterwards, with knowledge of the pathology, the relationship between standardized uptake values (SUVs) and the presence of metastasis in LNs was explored in a receiver operating characteristic (ROC) analysis, and the likelihood ratios (LRs) for SUVs of LNs were determined. RESULTS ISS was available for 690 LN stations. CT correctly identified the nodal stage in 40 of 68 patients (59%), with understaging in 12 patients and overstaging in 16 patients. PET + CT was accurate in 59 patients (87%), with understaging in five patients and overstaging in four patients. In the detection of locally advanced disease (N2/N3), the sensitivity, specificity, and accuracy of CT were 75%, 63%, and 68%, respectively. For PET + CT, this was 93%, 95%, and 94% (P = .0004). In the ROC curve, the best SUV threshold to distinguish benign from malignant LNs was 4.40. The analysis with this SUV threshold was not superior to the use of a five-point visual scale. The LR of a SUV less than 3.5 in an LN was 0.152; for a SUV between 3.5 and 4.5, it was 3.157; and for a SUV greater than 4.5, it was 253.096. CONCLUSION PET + CT is significantly more accurate than CT alone in LN staging of NSCLC. A five-point visual scale is as accurate as the use of an SUV threshold for LNs in the distinction between benign and malignant nodes. The very high negative predictive value of mediastinal PET could reduce the need for mediastinal ISS in NSCLC substantially.