tbuckley/cabot-search huggingface dataset:
Intensive Chemotherapy Followed by Hematopoietic Stem-Cell Rescue for Refractory and Recurrent Primary CNS and Intraocular Lymphoma: Société Française de Greffe de Moëlle Osseuse-Thérapie Cellulaire
Authors: Carole Soussain, Khê Hoang-Xuan, Luc Taillandier, Emmanuelle Fourme, Sylvain Choquet, Francis Witz, Olivier Casasnovas, Brigitte Dupriez, Bertrand Souleau, Anne-Laure Taksin, Christian Gisselbrecht, Arnaud Jaccard, Antonio Omuro, Marc Sanson, Maud Janvier, Brigitte Kolb, Jean-Marc Zini, Véronique Leblond
Journal: Journal of Clinical Oncology (2008)

The prognosis of relapsing primary CNS lymphoma (PCNSL) is poor. We report the results of a prospective multicenter trial of intensive chemotherapy followed by autologous hematopoietic stem-cell rescue (IC + HCR) in immunocompetent adult patients with PCNSL or intraocular lymphoma (IOL) after failure of high-dose methotrexate-based treatment.Salvage treatment consisted of two cycles of high-dose cytarabine and etoposide (CYVE). Intensive chemotherapy combined thiotepa, busulfan, and cyclophosphamide. Forty-three patients (median age, 52 years; range, 23 to 65 years) were included, with relapse (n = 22), refractory disease (n = 17), or a partial response to first-line treatment (n = 4). The response to CYVE was not assessable in three cases because of treatment-related death. Twenty patients (47%) were chemosensitive to CYVE: 15 of them proceeded to IC + HCR. IC + HCR was also administered to 12 patients who did not respond to CYVE. All but one of the 27 patients who underwent IC + HCR entered complete remission.With a median follow-up of 36 months, the median overall survival was 18.3 months in the overall population, and 58.6 months among patients who completed IC + HCR. The respective median progression-free survival (PFS) times after IC + HCR were 11.6 and 41.1 months. The 2-year overall survival probability was 45% in the whole population and 69% among the 27 patients who received IC + HCR. The 2-year PFS probability was 43% among all the patients and 58% in the IC + HCR subpopulation.IC + HCR is an effective treatment for refractory and recurrent PCNSL.
Microalbuminuria in patients with rheumatoid arthritis.
Authors: L M Pedersen, H Nordin, B Svensson, H Bliddal
Journal: Annals of the Rheumatic Diseases (1995)

To assess (a) the prevalence of microalbuminuria in patients with rheumatoid arthritis, (b) the association between urinary albumin excretion and disease activity as estimated by the erythrocyte sedimentation rate and C reactive protein (CRP), and (c) the association between urinary albumin excretion and treatment with antirheumatic drugs.Sixty five patients with rheumatoid arthritis attending two rheumatology clinics were compared with 51 control subjects matched by age and sex. The controls consisted of 20 healthy subjects, 16 patients with osteoarthritis and 15 with non-articular rheumatism. Patients with hypertension, diabetes mellitus, or evidence of previous renal disease were not included. Urinary albumin was assayed by immunoturbidimetry in random urine samples on two occasions within seven months. The results were expressed as the ratio of urinary albumin to urinary creatinine ratio. Disease activity was assessed by the erythrocyte sedimentation rate and CRP. A drug history for the year before entry to the study was obtained for each patient.Urinary albumin to creatinine ratio in patients with rheumatoid arthritis was significantly greater than in controls (p < 0.01). Microalbuminuria (urinary albumin to creatinine ratio 3-30 mg/mmol in either or both urine samples) was present in 27.7% of patients with rheumatoid arthritis and 7.8% of the control subjects. A significant relation was noted between urinary albumin to creatinine ratio and CRP, and the duration of disease. The number of patients treated with either gold or penicillamine was significantly greater in patients with microalbuminuria than in patients with normoalbuminuria.Microalbuminuria is frequently present in patients with rheumatoid arthritis. Treatment with gold and penicillamine seems to increase the risk of developing microalbuminuria. Urinary albumin measured by immunochemical methods is a simple and sensitive test to detect early subclinical renal dysfunction and drug induced renal damage in rheumatoid arthritis. Urinary albumin excretion was found to be significantly correlated with CRP and may be a sensitive indicator of disease activity in patients with rheumatoid arthritis.
MLK3 Regulates Paxillin Phosphorylation in Chemokine-Mediated Breast Cancer Cell Migration and Invasion to Drive Metastasis
Authors: Jian Chen, Kathleen A. Gallo
Journal: Cancer Research (2012)

MLK3 kinase activates multiple mitogen-activated protein kinases and plays a critical role in cancer cell migration and invasion. In the tumor microenvironment, prometastatic factors drive breast cancer invasion and metastasis, but their associated signaling pathways are not well-known. Here, we provide evidence that MLK3 is required for chemokine (CXCL12)-induced invasion of basal breast cancer cells. We found that MLK3 induced robust phosphorylation of the focal adhesion scaffold paxillin on Ser 178 and Tyr 118, which was blocked by silencing or inhibition of MLK3-JNK. Silencing or inhibition of MLK3, inhibition of JNK, or expression of paxillin S178A all led to enhanced Rho activity, indicating that the MLK3-JNK-paxillin axis limits Rho activity to promote focal adhesion turnover and migration. Consistent with this, MLK3 silencing increased focal adhesions and stress fibers in breast cancer cells. MLK3 silencing also decreased the formation of breast cancer lung metastases in vivo, and breast cancer cells derived from mouse lung metastases showed enhanced Ser 178 paxillin phosphorylation. Taken together, our findings suggest that the MLK3-JNK-paxillin signaling axis may represent a potential therapeutic target and/or prognostic marker in breast cancer metastasis.
Information systems introduced carefully can aid clinicians
Authors: R C Baldwin
Journal: BMJ (1998)

EDITOR—The article by Simpson and Gordon on clinical information technology is free of jargon and relevant.1 It is also realistic. I have seen three software systems come and go in the trust where I am based. All were management tools; clinicians were merely encouraged to believe in them. Then four years ago I had the opportunity to purchase an early version of a medical information management system (the Advanced Medical Information Guidance and Organisational System manufactured by AVC Multimedia, Norwich); this system …
Granulocytes cause reperfusion ventricular dysfunction after 15-minute ischemia in the dog.
Authors: R Engler, J W Covell
Journal: Circulation Research (1987)

Regional ventricular dysfunction (the stunned myocardium) persists for several hours after 15 minutes of ischemia and reperfusion in the dog. Superoxide-radical-induced damage appears to be one of the mechanisms of this injury. We tested whether granulocytes were a direct source of injury in the stunned myocardium in the 15-minute ischemia dog model. Regional function during agranulocytic extracorporeal coronary perfusion (using Leukopak filters) with ischemia and reperfusion was compared with function during a second period of ischemia and reperfusion after removal of the filters (granulocytopenia). Flow reduction and reperfusion flow, preload, afterload, and inotropic stimulation were the same during agranulocytic and granulocytopenic perfusion. During agranulocytic perfusion, stunning did not occur (greater than 100% of preischemic function during reperfusion), but when the filters were removed and about 10% of the normal granulocyte count was present, stunning occurred with only 76% return of function at 60 minutes of reperfusion (p less than 0.01). A second series of studied animals with extracorporeal perfusion and granulocyte replete perfusion all had less than 75% return of regional function, indicating that the agranulocytic perfusion and not the extracorporeal aspects of the experiment prevented stunning. We conclude that granulocytes are the direct source of the injury in stunned myocardium and apparently the main source of superoxide in the 15-minute ischemia dog model. Other possible granulocyte-related mechanisms of reperfusion injury include capillary no-reflow, causing microvascular ischemia and degranulation leading to enzyme-induced damage.
Microenvironment-Modulated Metastatic CD133+/CXCR4+/EpCAM− Lung Cancer–Initiating Cells Sustain Tumor Dissemination and Correlate with Poor Prognosis
Authors: Giulia Bertolini, Lucia D'Amico, Massimo Moro, Elena Landoni, Paola Perego, Rosalba Miceli, Laura Gatti, Francesca Andriani, Donald Wong, Roberto Caserini, Monica Tortoreto, Massimo Milione, Riccardo Ferracini, Luigi Mariani, Ugo Pastorino, Ilaria Roato, Gabriella Sozzi, Luca Roz
Journal: Cancer Research (2015)

Metastasis is the main reason for lung cancer-related mortality, but little is known about specific determinants of successful dissemination from primary tumors and metastasis initiation. Here, we show that CD133(+)/CXCR4(+) cancer-initiating cells (CIC) directly isolated from patient-derived xenografts (PDX) of non-small cell lung cancer are endowed with superior ability to seed and initiate metastasis at distant organs. We additionally report that CXCR4 inhibition successfully prevents the increase of cisplatin-resistant CD133(+)/CXCR4(+) cells in residual tumors and their metastatization. Immunophenotypic analysis of lung tumor cells intravenously injected or spontaneously disseminated to murine lungs demonstrated the survival advantage and increased colonization ability of a specific subset of CD133(+)/CXCR4(+) with reduced expression of epithelial cell adhesion molecule (EpCAM(-)), which also shows the greatest in vitro invasive potential. We next prove that recovered disseminated cells from lungs of PDX-bearing mice enriched for CD133(+)/CXCR4(+)/EpCAM(-) CICs are highly tumorigenic and metastatic. Importantly, microenvironment stimuli eliciting epithelial-to-mesenchymal transition, including signals from cancer-associated fibroblasts, are able to increase the dissemination potential of lung cancer cells through the generation of the CD133(+)/CXCR4(+)/EpCAM(-) subset. These findings also have correlates in patient samples where disseminating CICs are enriched in metastatic lymph nodes (20-fold, P = 0.006) and their detection in primary tumors is correlated with poor clinical outcome (disease-free survival: P = 0.03; overall survival: P = 0.05). Overall, these results highlight the importance of specific cellular subsets in the metastatic process, the need for in-depth characterization of disseminating tumor cells, and the potential of therapeutic strategies targeting both primary tumor and tumor-microenvironment interactions.
Axillary dissection in primary breast cancer.
Authors: P J O'Dwyer
Journal: BMJ (1991)

will not be influenced purely by the expected workload.A survey explicitly focused on which factors necessitate compensation seems to be needed.Similar considerations apply to the other uses to which underprivileged area scores have been put.In the (now superseded) RAWP review the index was included in the resource allocation formula after criticism that the original formula did not take account of social deprivation.20The research commissioned for the RAWP review did not, however, show that the use of this index would improve the fit between resource allocation and either need or demand for health services.2'There is no reason to believe that the use of other deprivation indices would do any better.22The use of indices requires that a relation has been shown between measurements and the underlying factors which they are supposedly indexing.Stating that the underprivileged area score "is a measure of workload or pressure on the services of general practitioners"23 is premature, and the index cannot adequately substitute for empirically validated measures in the fields in which it is being used.
Regional melanoma incidence in England, 1996-2006: reversal of north-south latitude trends among the young female population
Authors: S.C. Wallingford, R.D. Alston, J.M. Birch, A.C. Green
Journal: British Journal of Dermatology (2013)

Journal Article Regional melanoma incidence in England, 1996–2006: reversal of north–south latitude trends among the young female population Get access S.C. Wallingford, S.C. Wallingford Manchester Academic Health Science Centre Institute of Inflammation and Repair University of Manchester Oxford Road Manchester M13 9PT U.KCancer Research U.K. Paediatric and Familial Cancer Research Group Institute of Cancer Sciences Manchester Academic Health Science Centre University of Manchester Oxford Road Manchester M13 9PT U.K Correspondence Sarah C. Wallingford. E‐mail: sarah.wallingford@manchester.ac.uk Search for other works by this author on: Oxford Academic Google Scholar R.D. Alston, R.D. Alston Cancer Research U.K. Paediatric and Familial Cancer Research Group Institute of Cancer Sciences Manchester Academic Health Science Centre University of Manchester Oxford Road Manchester M13 9PT U.K Search for other works by this author on: Oxford Academic Google Scholar J.M. Birch, J.M. Birch Cancer Research U.K. Paediatric and Familial Cancer Research Group Institute of Cancer Sciences Manchester Academic Health Science Centre University of Manchester Oxford Road Manchester M13 9PT U.K Search for other works by this author on: Oxford Academic Google Scholar A.C. Green A.C. Green Manchester Academic Health Science Centre Institute of Inflammation and Repair University of Manchester Oxford Road Manchester M13 9PT U.KCancer and Population Studies Group Queensland Institute of Medical Research Brisbane Qld 4029 Australia Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 169, Issue 4, 1 October 2013, Pages 880–888, https://doi.org/10.1111/bjd.12460 Published: 01 October 2013
Mallory bodies in alcoholic and non-alcoholic liver disease contain a common antigenic determinant.
Authors: K A Fleming, J A Morton, C Barbatis, J Burns, S Canning, J O McGee
Journal: Gut (1981)

An immunohistochemical technique is described for the detection of Mallory bodies (MBs) in paraffin sections of liver tissue. This is based on proteolytic digestion of sections before exposure to an antiserum which recognises a unique antigenic determinant in MBs. With the use of this procedure it has been shown in alcoholic liver disease, primary biliary cirrhosis. Indian childhood cirrhosis, Wilson9s disease, diabetes mellitus, and hepatocellular cancer that the MBs found in these disorders contain this unique antigenic determinant. It is postulated, therefore, that the mechanism of formation of MBs is similar in liver diseases of diverse aetiology. In addition, it has been demonstrated that the immunohistochemical procedure is more sensitive than routine staining; MBs were detected in five out of 12 fatty livers by immunohistochemical and only in one by H and E staining. As MBs in fatty livers were not associated with polymorph filtration or fibrogenesis it is argued that MB formation is not an absolute prerequisite for the progression of acute to chronic liver disease.
Guillain–Barré syndrome in a patient receiving anti-tumour necrosis factor α for rheumatoid arthritis: a case report and discussion of literature
Authors: S Silburn, E McIvor, A McEntegart, H Wilson
Journal: Annals of the Rheumatic Diseases (2008)

Tumour necrosis factor α (TNFα) is a proinflammatory cytokine that is involved in the pathogenesis of rheumatoid arthritis (RA).1 Anti-TNFα has been shown to have a significant effect in delaying the joint destruction associated with this condition, and is being used with increasing frequency. The side effects are well documented, but further information continues to emerge and advice regarding how to proceed thereafter remains limited.2

We report on a 46-year-old woman with a 6-year history of seropositive erosive RA. Despite combination disease-modifying antirheumatic drugs (DMARDs) she remained symptomatic and had a 28-joint Disease Activity Score (DAS28) …
Molybdenum: An Essential Trace Element in Human Nutrition
Authors: K V Rajagopalan
Journal: Annual Review of Nutrition (1988)

Abstract: The goal of this review is to evaluate several different facets of the present state of knowledge regarding the nutritional aspects of Mo and to provide a basis for future directions in research dealing with complete characterization of its biological functions, as a means of recognizing possible isolated or epidemiological instances of nutritional deficiency of the metal.
The Chronic Kidney Disease Epidemic
Authors: Bryce Kiberd
Journal: Journal of the American Society of Nephrology (2006)

Estimating the prevalence of chronic kidney disease (CKD) is no simple task. The overall prevalence is relatively low but may be higher in select populations that are not accessible to surveys (e.g., certain ethnic groups, the sick or elderly). Moreover, the tests that define CKD lack precision and transportability to healthy populations. During the past decade, it is not clear that CKD has grown substantially. Some epidemiologic factors that are associated with CKD (obesity and diabetes) are increasing, whereas others (uncontrolled hypertension and smoking) are decreasing. Reasons for the discrepancy between a stable CKD population and ongoing ESRD growth remain speculative. There is evidence that ESRD rates may be stabilizing and that efforts to reduce progression in high-risk groups may be starting to show benefit. Expanding the definition of CKD and increasing detection may be required to reduce overall ESRD prevalence. One concern is that many of the well-defined high-risk patient groups (diabetes and black) are still undertreated. Increasing the investigation and treatment of low-risk patients may not be the answer. Clinical inertia (failure to initiate or change therapy) may be a more significant and modifiable barrier toward reducing ESRD, and this deserves increased attention. Furthermore, reducing CKD prevalence will require controlling the precipitating causes. The incremental benefit of detecting CKD in low-risk patients, use of expensive therapies in CKD, or new strategies such as the treatment of prehypertension require solid evidence, not only of the variety that shows benefit (hard end points) but also to whom, when, and at what cost.
A rapid translocation of CD45RO but not CD45RA to lipid rafts in IL-6-induced proliferation in myeloma
Authors: Fu-Jun Li, Naohiro Tsuyama, Hideaki Ishikawa, Masanori Obata, Saeid Abroun, Shangqin Liu, Ken-ichiro Otsuyama, Xu Zheng, Zi Ma, Yasuko Maki, Michio M. Kawano
Journal: Blood (2004)
Acute-phase proteins and serum immunoglobulins in ankylosing spondylitis.
Authors: M R Laurent, G S Panayi
Journal: Annals of the Rheumatic Diseases (1983)

The erythrocyte sedimentation rate (ESR) and the serum acute-phase proteins (APP), C-reactive protein (CRP), fibrinogen, 9th component of complement (C9), and alpha, antitrypsin were measured on 231 occasions in 80 patients with ankylosing spondylitis and compared with those in 30 controls. APP levels did not correlate with clinical assessment of disease activity. However, there were significant correlations between CRP, C9, and fibrinogen (p = less than 0.01), suggesting that these APP may be more reliable indicators of disease activity. The mean values of the APP in those patients with a peripheral arthritis were significantly higher than in those with pelvospondylitis alone for ESR (p less than 0.01), CRP (p less than 0.01), and fibrinogen (p less than 0.05). The only significant difference between those patients with an iritis and those with only pelvospondylitis was an elevated CRP in the iritis group (p less than 0.01). This suggests that a peripheral arthritis is the most important cause of an elevated ESR or APP in ankylosing spondylitis. Serum immunoglobulins were also measured and they showed a significant elevation of IgA in all 3 patients groups, there being no difference between each group. Serum IgG was raised only in those patients with an iritis or peripheral arthritis, the IgM levels being within the normal range for all patient groups.
Incidence of anaerobes in ventilator-associated pneumonia with use of a protected specimen brush.
Authors: P Doré, R Robert, G Grollier, J Rouffineau, H Lanquetot, J M Charrière, J L Fauchère
Journal: American Journal of Respiratory and Critical Care Medicine (1996)

The role of anaerobic bacteria in ventilator-associated pneumonia (VAP) has been little investigated. In this study we analyzed the incidence of anaerobes in patients with a first episode of bacteriologically documented VAP (> 10(3)CFU/ml), using protected specimen brushes (PSB). We particularly took care to preserve anaerobic conditions during transport and the microbiological procedure. Two groups were considered: group A with anaerobic bacteria recovered from PSB, with or without anaerobes, and group B with aerobic bacteria only. One hundred and thirty patients were included, 30 (23%) in group A, and 100 (77%) in group B. The main anaerobic strains isolated were Prevotella melaninogenica (36%), Fusobacterium nucleatum (17%), and Veillonella parvula (12%). Univariate analysis demonstrated that patients in group A were younger than those in group B (p < 0.05) and their simplified acute physiologic score was higher (p < 0.02). The percentage of patients receiving antibiotics before PSB did not differ significantly between group A (57%) and group B (35%). VAP with anaerobes occurred more often in patients orotracheally intubated than nasotracheally intubated (p < 0.02). Episodes of VAP involving anaerobic bacteria occurred more often in the first five days (early VAP) than after the fifth day (late VAP) (p < 0.05). The 3-mo mortality rate was similar in the two groups, but death occurred earlier in group B (p < 0.01). Multivariate analysis demonstrated that presence of altered level of consciousness (p = 0.0002), higher simplified acute physiologic score (p = 0.003), and admission to the medical ICU (p = 0.02) were the factors independently predisposing to the development of VAP with anaerobes.