tbuckley/cabot-search huggingface dataset:
Outcome and prognostic factors in solitary plasmacytoma.
Authors: V. K. Reed, J. J. Shah, A. Mazloom, D. M. Weber, J. Phan, R. Z. Orlowski, S. K. Thomas, M. Wang, R. Alexanian, B. S. Dabaja
Journal: Journal of Clinical Oncology (2010)

e18512 Background: Solitary plasmacytoma is a rare plasma-cell neoplasm. We wanted to assess the outcome and prognostic factors in patients with solitary plasmacytoma. Methods: The data from 79 patients with bone (n=55), and/or extramedullary (n=25) solitary plasmacytoma with no evidence of multiple myeloma treated with definitive radiation at a single institution from 1988-2007 were collected. The median follow-up time was 56 months. A serum myeloma protein was present in 36 patients (46%), and Bence Jones proteinuria was present in 24 patients (31%). The median radiation dose was 45 Gy. Overall-survival, local control, and freedom from multiple-myeloma progression were calculated actuarially. Results: The five-year overall survival rate was 78%. The median overall survival was 11 years. Local control was achieved in 72 patients (91%). Radiation dose above or below 45 Gy was not a predictor of local control (p=0.452). The five-year probability of progression to multiple myeloma in all patients was 47%. The five-year probability of progression to multiple myeloma was higher in patients with bone plasmacytoma than extramedullary plasmacytoma (57% versus 27%, p = 0.008). In patients with solitary plasmacytoma of the bone, the 5-year probability of progression to multiple myeloma was 47% in patients with resolution of serum or urine myeloma protein, versus 75% in patients without resolution of myeloma protein (p =0.056). Conclusions: Local control is excellent in this disease. Progression to multiple myeloma remains the main problem. Patients with extramedullary plasmacytoma had the best outcomes. There was a trend towards a lower rate of progression to multiple myeloma in patients with bone plasmacytoma that had resolution of myeloma protein. No significant financial relationships to disclose.
Cellular DNA content and prognosis of high-grade soft tissue sarcoma: the Scandinavian Sarcoma Group experience.
Authors: T A Alvegard, N O Berg, B Baldetorp, M Fernö, D Killander, J Ranstam, A Rydholm, M Akerman
Journal: Journal of Clinical Oncology (1990)

The nuclear DNA content of 148 high-grade soft tissue sarcomas of the extremities and trunk was determined by flow cytometry, using tumor material from paraffin-embedded tissue. The patients were part of a prospective randomized clinical trial on the efficacy of adjuvant single-agent chemotherapy with doxorubicin. Chemotherapy did not improve the metastasis-free survival (MFS). After a median follow-up time of 48 months (range, 2 to 97), a multivariate analysis of prognostic factors for developing metastatic disease was performed. DNA aneuploidy was found to be an independent prognostic risk factor in addition to histologic malignancy grade IV, intratumoral vascular invasion, tumor size over 10 cm, and male sex. Patients with none or one risk factor had a 5-year MFS of 79%, with two risk factors 65%, with three risk factors 43%, and with four and five risk factors 0%. About one half (78 of 148) of the patients with three factors or less belonged to a group with a MFS over 60%. The combination of different risk factors, including DNA aneuploidy, seems to be a useful prognostic model for soft tissue sarcomas, which could be of value to select high-risk patients for further trials with adjunctive therapy.
Abstract 2789: Iron chelation inhibits mTOR activity in cancer cells
Authors: Chaowei Shang, Hongyu Zhou, Shile Huang
Journal: Cancer Research (2014)

Abstract Mammalian target of rapamycin (mTOR) plays a critical role in regulating cell proliferation and survival through sensing environmental cues. mTOR functions as at least two complexes (mTORC1/2). In cancer cells, mTOR activity is often deregulated. Intracellular iron levels are higher in cancer cells than in normal cells mainly due to the increased requirement of iron for proliferation. Thus, cancer cells are more sensitive to iron chelation than normal cells. Iron chelators have been used as traditional treatment for iron overload diseases. Recent studies have shown that iron chelators possess potent anticancer activity. However, the underlying mechanism is not well understood. In this study, we found that ciclopirox olamine (CPX), an iron chelator and off-patent antifungal drug, inhibited cell proliferation and induced cell death in human head and neck cancer cells (PCI-13 and FaDu), breast adenocarcinoma (MDA-MB-231), human rhabdomyosarcoma (Rh30), and skin squamous cell carcinoma (SRB-M7) cells. Similar results were observed using Dp44mT, another iron chelator. Concurrently, CPX and Dp44mT inhibited mTORC1 signaling in the cells. This is evidenced by the findings that treatment with the iron chelators inhibited phosphorylation of 4E-BP1 and S6K1, two best known effector molecules of mTORC1, which could be blocked by addition of ferrous sulfate, but not cuprous sulfate. At the same time, the addition of ferrous sulfate prevented cancer cell death. The findings suggest that the inhibitory effect of CPX or Dp44mT on mTORC1 function was attributed to selective chelation of iron in the cells. Mechanistically, chelation of iron did not activate protein phosphatase 2A (PP2A), but induced raptor (S792) phosphorylation and disrupted mTORC1 integrity. Of note, the effect of iron chelation on mTORC2 was cell line dependent. Further research may enhance our understanding the role of iron in the regulation of mTOR signaling. Citation Format: Chaowei Shang, Hongyu Zhou, Shile Huang. Iron chelation inhibits mTOR activity in cancer cells. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2789. doi:10.1158/1538-7445.AM2014-2789
Abstract 10987: Mitral Valve Annular, Leaflet and Papillary Muscle Geometry and Function in Functional Ischemic Mitral Regurgitation: New Insights from Cardiovascular Magnetic Resonance
Authors: K. M. John Chan, Ricardo Wage, Karen Symmonds, Isabelle Roussin, Marcus Flather, Dudley J Pennell, Sanjay K Prasad, Philip J Kilner, John R Pepper
Journal: Circulation (2011)
Ethnic differences in the vitamin D levels of foreign-born tuberculosis patients in south London not reflected in patients born in the UK
Authors: Nicole Penn, Sharenja Ratnakunar, Jessie Randhawa, Heather Milburn
Journal: European Respiratory Journal (2012)

Vitamin D deficiency is more common in tuberculosis (TB) patients, and within certain ethnic groups. 70% of TB in the UK occurs in foreign-born persons. We investigated the roles of ethnicity and immigration on the vitamin D levels of TB patients in south London.  We analysed the vitamin D levels of all patients at the time of diagnosis. We compared results by country of birth, ethnicity, age and length of residency in the UK.  There were 470 patients; the mean serum 25(OH)D level was 29.1nmol/L (95% CI 27.2-31.0) and 90.6% had insufficient (  TB patients born in the horn of Africa and the Indian subcontinent have an increased risk of very low vitamin D levels. As there is little difference in ambient sunshine this raises the possibility of significant differences in diet or genetics. Children born in the UK had high levels of vitamin D not attributed to ethnicity.
Characterization of Feline T- and B-Lymphocytes and Identification of an Experimentally Induced T-Cell Neoplasm in the Cat23
Authors: G. L. Cockerell, S. Krakowka, E. A. Hoover, R. G. Olsen, D. S. Yohn
Journal: JNCI Journal of the National Cancer Institute (1976)

Membrane markers of feline T- and B-lymphocytes were identified for further investigation of leukemogenesis In the cat. Feline T-cells formed spontaneous erythrocyte rosettes with guinea pig (GPE) and rat erythrocytes (RE). The receptors for GPE and RE were separate entities and expressed independently on lymphoid cell membranes. The RE receptor appeared to be present only on more mature or differentiated T-cells, whereas the GPE receptor reacted with a broader population that included less differentiated T-cells. Feline B-cells bore a complement receptor that was detected by adherence of SE coated with antibody and complement. Malignant lymphoblasts obtained from thoracic fluid of cats with feline leukemia virus (FeLV)-induced thymic lymphosarcomas, as well as FL-74 cells (a FeLV-transformed feline lymphoblastoid cell line) expressed T-cell markers. These resuHs provided definitive evidence for markers of feline T- and B-cells and identified an experimentally Induced T-cell lymphosarcoma.
CPFE (combined pulmonary fibrosis and emphysema): A case series
Authors: Giovanna Calabrese, Maria Martino, Giovanna Caccavo, Maria D'Amato, Anna Agnese Stanziola
Journal: European Respiratory Journal (2014)

Background: The syndrome of combined pulmonary fibrosis and emphysema (CPFE) is characterized by preserved lung volume indices contrasted by markedly impaired diffusion capacity.   Methods: A cohort of 48 consecutive patients (43M/5F) with both emphysema of the upper zones and diffuse parenchymal lung disease with fibrosis of the lower zones of the lungs on chest computed tomography is reported. Demographic and clinical characteristics, past medical history, respiratory profile (spyrometric and arterial blood gasanalysis values, meters walked at 6 MWT), management and outcomes were prospectively recorded. All patients performed a HRCT and transthoracic Doppler echocardiography (TTE).   Results: The mean age was 72.5years (range 63-80), 40/48 patients were smokers. Pulmonary function tests were FVC 92 ± 26 % , FEV1% 90 ±22 , DLCO 34 ±15, carbon monoxide transfer coefficient 48 ±19% . All patients were hypoxemic with mild hypocapnia, pO 2  58 ± 15mmHg, pCO 2  35.5 ± 4.7 mmHg, and had an important exercise functional limitation (6 MWT mt 300 ± 150). Pulmonary hypertension, as calculated by TTE, was present in 73% of patients (PAPs 62 ±18 mmHg). Nine pts underwent right heart catheterization with PAPm 42 ± 8 mmHg.   Conclusions:  The indirect correlation (r = -0,61) between PAPs and DLCO/VA and PAPs and pO 2  (r = -0,40 ) confirms the onset of pulmonary hypertension and reflects the deterioration of the respiratory function.
State funding of elderly care in England has fallen by 40% in five years
Authors: C. White
Journal: BMJ (2015)

England has seen an “unprecedented” fall over the past five years in the number of people aged 65 or over who receive social care packages, despite a rise in the need for such services, delegates to a seminar on the care of older people heard on 9 June.

Speaking at the Westminster Health Forum’s keynote seminar on improving care for older people in London, Jose-Luis Fernandez, principal research fellow and deputy director of the Personal Social Services Research Unit at the London School of Economics and Political Science, said that care packages funded by local authorities in England for people aged 65 or over had plummeted since 2009-10.

“There has been a very steep decrease in the absolute numbers of people receiving services over the past five years,” he said. “When you control for the demographic effect, where more people are in …
OC-096 The rising incidence of early-onset inflammatory bowel disease in Scotland
Authors: P Henderson, R Hansen, F L Cameron, K Gerasimidis, E L Reynish, H E Drummond, W M Bisset, J Satsangi, R K Russell, D C Wilson
Journal: Gut (2010)

Introduction The incidence of early-onset inflammatory bowel disease (IBD) is high in Europe and North America with numbers rising in recent decades. An accurate indication of the current incidence and temporal trends experienced by a whole population is useful in understanding possible aetiological factors and is essential for the planning of future specialist healthcare provision. Methods This study reports the incidence of early-onset IBD within the Scottish population over a 6-year period (2003–2008), comparing the incidence and demographic attributes to previous figures. Three paediatric gastroenterology networks provide care for all paediatric IBD patients in Scotland. Retrospective data regarding incident cases of IBD diagnosed <16 years old were collected using a centrally coordinated database. Duplicates and diagnoses outwith Scotland were excluded. General Register Office for Scotland population statistics were used to calculate incidence. Statistical comparisons were made by Mann–Whitney U test. Results During the study period 430 patients <16 years were diagnosed with IBD in Scotland giving an overall incidence of 7.7/100 000/year. The incidence of Crohn's disease (CD) was 4.7/100 000/year, ulcerative colitis (UC) 2.0/100 000/year and inflammatory bowel disease unspecified (IBDU) 1.0/100 000/year. When compared with previous data from 1990 to 1995, significant rises in the incidence of IBD from 4.4/100 000/year (p=0.002) and CD from 2.8/100 000/year (p=0.002) were seen. The rise in UC from 1.6/100 000/year was not significant (p=0.13). The median age at diagnosis between 2003 and 2008 was 11.8 years for IBD and UC, and 11.9 years for CD. When compared with 1990–1995 data, there was a significant decrease in the age at diagnosis of CD from 12.8 years (p=0.009), but not in UC from 12.3 years (p=0.49). The male to female ratio was 1.5:1 for CD and 1.1:1 for UC during 2003–2008 compared to 1.2:1 for CD and 0.9:1 for UC between 1990 and 1995. Conclusion The number of Scottish children diagnosed with IBD continues to rise with the rates of IBD and CD rising significantly by 70% and 61%, respectively. Although UC has risen by 25%, this was not significant. This continuing rise has clear implications for the health of Scotland's children and the local provision of specialist healthcare. A greater understanding of the changing demographic of early-onset IBD may give us clues as to the aetiology of this chronic condition and aid future disease prevention measures.
STUDIES IN EXPERIMENTAL EXTRACORPOREAL THROMBOSIS
Authors: Walter R. Johnson, Takuji Shionoya, Leonard G. Rowntree
Journal: The Journal of Experimental Medicine (1928)

In experimental obstructive jaundice in rabbits, thrombosis is definitely delayed in the extracorporeal loop. White thrombi are laid down at the normal rate in many instances; in others there is a delay in deposition of platelets, while in still others cauliflower-like masses of platelets are rapidly deposited and tend to slow or even stop the blood stream before much fibrin is apparent. Fibrin deposits and formation of the red thrombus usually appear late in the experiment and often only at the ends of the collodion tubes. In vigorous animals, the thrombi rarely tend to obstruct and usually cease growing when they have made up the difference between the lumen of the glass tube and of the collodion tube. On the other hand, if the animal's general condition is poor and its circulation depressed, red thrombus forms more rapidly and tends to encroach progressively on the lumen until obstruction takes place. Even in such cases circulation through the loop persists for periods much longer than in the normal animal. Judging from the gross appearance of the thrombus the quantity and quality of fibrin seem deficient. Single injections of bile salts yield pictures similar to those seen in experimental obstructive jaundice. White thrombi are deposited but obstruction of the lumen is delayed because of inadequate formation of fibrin. The continuous intravenous injection of bile salts resulted in a progressive increase of the clotting time and in the level of bile acids of the blood. The state of the extracorporeal loop was likewise similar in many respects to that seen in obstructive jaundice. There was, however, a definite decrease in the size and numbers of white thrombi deposited on the collodion membrane. From the evidence presented it is obvious that the processes of blood coagulation and of thrombosis in the extracorporeal loop are definitely delayed in experimental obstructive jaundice and in animals that have received intravenous injections of bile salts. No attempt is made to explain the changes found in jaundice on the basis of the increased levels of bile acids in the blood although these experiments would indicate that such a possibility has not been ruled out.
PCR-based DNA fingerprinting (REP-PCR, AP-PCR) and pulsed-field gel electrophoresis characterization of a nosocomial outbreak caused by imipenem- and meropenem-resistant Acinetobacter baumannii
Authors: G. Bou, G. Cerveró, M.A. Domínguez, C. Quereda, J. Martínez-Beltrán
Journal: Clinical Microbiology and Infection (2000)
Clinical application of autologous technetium-99m-labelled eosinophils to detect focal eosinophilic inflammation in the lung: Figure 1
Authors: Chrystalla Loutsios, Neda Farahi, Rosalind Simmonds, Ian Cullum, Daniel Gillett, Chandra Solanki, Kishor Solanki, John Buscombe, Alison M Condliffe, A Mike Peters, Edwin R Chilvers
Journal: Thorax (2015)

<h3>Abstract</h3> The detection of focal eosinophilic inflammation by non-invasive means may aid the diagnosis and follow-up of a variety of pulmonary pathologies. All current methods of detection involve invasive sampling, which may be contraindicated or too high-risk to be performed safely. The use of injected autologous technetium-99m (Tc-99m)-labelled eosinophils coupled to single-photon emission computed tomography (SPECT) has been demonstrated to localise eosinophilic inflammation in the lungs of a patient with antineutrophil cytoplasmic antibody-positive vasculitis. Here, we report on the utility of this technique to detect active eosinophilic inflammation in a patient with focal lung inflammation where a biopsy was contraindicated.
Comparison of bronchodilator effect of salbutamol delivered via MDI + spacer and DPI in children with asthma
Authors: Laszlo Kadar
Journal: European Respiratory Journal (2012)

Background: Inhaled short acting beta2-agonists are widely used in asthma treatment. Studies comparing the efficacy of salbutamol containing pressurized metered dose inhalers (pMDI) and dry powder inhalers (DPI) in the paediatric asthma population are limited.

Aim: This study aimed to compare the bronchodilator response to a salbutamol pMDI plus spacer and to a salbutamol DPI by children and adolescents with asthma related bronchoconstriction.

Methods: 80 patients aged 5 to 18 years with physician diagnosed asthma with a forced expiratory volume in one second (FEV1) < 85% were enrolled in a single centre, randomized, open label study. Patients were randomized to salbutamol 200 ug via pMDI (Ventolin HFA Inhalation Aerosol, GlaxoSmithKline, UK) plus large volume spacer (Volumatic, GlaxoSmithKline, UK), or salbumatol 200 ug via DPI (Buventol Easyhaler, Orion Pharma, Finland). The primary variable was FEV1 change from baseline, the co-primary endpoint was forced expiratory flow 25–75% (FEF25-75%) change from baseline 20 minutes after administration of salbutamol.

Results: FEV1 change from baseline was 19.77% (SD: 15.519) and 13.93% (SD: 12.828) in the PMDI + spacer group and in DPI group respectively. The difference was not significant (p=0.069, 95% CI: -12.149, 0.472). FEF25-75% change from baseline 37.11% (SD: 35.293) and 30.20% (SD: 31.241) in the PMDI + spacer group and in DPI group respectively. The difference was not significant (p = 0.3564, 95% CI: -21.75, 7.923).

Conclusion: The present study shows that salbutamol DPI is a valid alternative for relieving bronchoconstriction in children (5 to 18 years of age) with asthma.
8-isoprostane in exhaled breath condensate in healthy and asthmatic children, and its relationship with tobacco smoke exposure
Authors: Belda Ramírez, Caballero Balanzá, Martorell Aragonés, Escribano Montaner
Journal: European Respiratory Journal (2011)

Introduction: 8-Isoprostane is an oxidative stress marker, which rises in asthma and in exposure to tobacco smoke.

Objectives: 1) Differences in the concentration of 8-isoprostane in exhaled breath condensate (EBC) between asthmatics and healthy children. And also between children with recurrent wheezes and healthy preschool children. 2) Relationship between levels of 8-isoprostane and passive smoke exposure.

Methods: 70 children (6 to 14 years) were recruited in 2 groups: 40 asthmatic and 30 healthy children. Also 46 children (8 months to 5 years) were recruited in other 2 groups: 25 with recurrent wheezes and 25 as controls. EBC was colleted through the exhaled condenser. 8-isoprostane was determined by enzyme immunoassay. Data about number of smokers living with the child, cigarettes/day and the smoking place was asked.

Results: 8-isoprostane concentrations were lower between in the group of healthy children than in children with asthma (p<0.004, Mann-Whitney U: 343, mean difference: 6.2 (4.7)). Moreover 8-isoprostane levels differ according to smoking habits of parents (ANOVA F=8.28, P<0.001) and children whose parents smoke at home have higher levels than those of nonsmoking parents (mean difference 22.4, p=0.003). Similarly happened to children from 8 months to 5 years (ANOVA F=8.23, p<0.001) and (mean difference = 141.3, p<0.001).

Conclusions: 1. There are significant differences in the concentrations of 8-isoprostane in EBC from asthmatic children 6-14 years old and healthy and also in preschool children. 2. Passive exposure to tobacco smoke increases concentrations of 8-isoprostane, in the EBC of children in both age groups.
Re-sequencing of IL33 and IL1RL1 in severe asthma patients identifies novel variation
Authors: Michael Portelli, Nick Shrine, Yize Wan, Louise Wain, Tricia McKeever, Adel Mansur, Neil Thomson, Rekha Chaudhuri, Chris Brightling, A. Singapuri, Ian Hall, Ian Sayers
Journal: European Respiratory Journal (2014)

Background:  IL33  (9p24.1) and IL33 receptor ( IL1RL1,  2q12) have been reproducibly identified as asthma susceptibility genes. However, the variants driving genetic associations are not yet fully defined. Using re-sequencing we aimed to i) identify novel common and rare variants and ii) determine if these variants are differentially represented in severe asthma and control subjects.   Method:  200 UK severe asthma patients (GINA ≥3) and 200 non-asthma/non-atopic controls were sequenced. Samples were multiplexed, with each group split into 3 pools (n=66, 66 and 68). Target enrichment was carried out using the Agilent SureSelect kit for 9p24.1 (243kb) and 2q12 (470kb) regions. Paired-end sequencing was utilised and 100bp reads for cases and controls were run on the Illumina HiSeq2000™ System. Realignment around insertion deletions, recalibration of quality scores and variant detection were carried out using the GATK and Syzgy software packages.   Results:  Mean coverage was 46x for 2q12 and 40x for 9p24.1. 4107 and 2475 total variants were identified with 1644 (1231 rare) and 1125 (779 rare) being novel variants, respectively. We identified 14 exon variants in  IL1RL1  and 7 in  IL33 , of which 11 and 1 were predicted to be functional, respectively. Several variants were unique to cases or controls. On correcting for multiple testing, we identified 3 differentially expressed variants at 2q12 and 9 at 9p24.1. Variants at 9p24.1 were upstream of  IL33,  within  KIAA2026  and in a 50bp cluster. On 2q12, variants were upstream of  IL1RL1 , within  IL1RL1  and located in the 39UTR.   Conclusion:  Re-sequencing of  IL33  and  IL1RL1  loci has identified novel common and rare variants that may be of relevance to asthma.