tbuckley/cabot-search huggingface dataset:
THE RELATION OF THE SPLEEN TO BLOOD DESTRUCTION AND REGENERATION AND TO HEMOLYTIC JAUNDICE
Authors: J. Harold Austin, O. H. Perry Pepper
Journal: The Journal of Experimental Medicine (1915)

These experiments indicate, therefore, that when hemoglobin is set free in the portal circulation a larger amount is held by the liver and converted rapidly into bile pigment than is the case when it is set free in the general circulation, and that, under the former condition, over-loading of the liver with bile pigment more readily occurs and jaundice is more apt to develop. This mechanical influence must, therefore, be a factor in the lessened tendency after splenctomy to the jaundice which follows blood destruction due to hemolytic agents, for whether the spleen be an active factor in destroying the erythrocytes or whether it plays merely a passive part as a place for the deposition of the disintegrating cells, there can be no question that in this organ, when it is present, a large number of cells undergo their final disintegration after the action of hemolytic poisons, and that the hemoglobin there liberated passes by the portal system directly to the liver. When the spleen is removed, this disintegration occurs in other organs, notably in the lymph nodes and bone marrow, and the hemoglobin from these organs passes not into the portal but into the general circulation, from which it reaches the liver more gradually and in a more dilute form.
Bronchial responsiveness to inhaled propranolol in asthmatic children and adults
Authors: A Foresi, A Chetta, A Pelucchi, B Mastropasqua, D Moretti, D Olivieri
Journal: European Respiratory Journal (1993)

Inhaled propranolol (P) was administered to a population which included asthmatic children (30 subjects) and adults (43 subjects): 1) to investigate the determinants of induced bronchial response; 2) to examine the relationship with treatment requirements; 3) to determine the relationship with responsiveness to methacholine (M) and ultrasonically nebulized distilled water (UNDW) (50 subjects); and 4) to establish the short-term repeatability of bronchial response to propranolol compared with methacholine (22 subjects). Bronchial response to propranolol and methacholine was expressed as the cumulative provocative dose (PD20 in mumol) and responsiveness to UNDW as the provocative output (PO20 in ml.min-1) producing a 20% fall in forced expiratory volume in one second (FEV1). Response to propranolol was significantly related to the degree of responsiveness to methacholine, but not to age, gender, presence of atopy, age at asthma onset, or baseline FEV1. PD20P was measurable in all but three subjects. A significant difference in mean PD20M but not in PD20P was found between subjects requiring more anti-asthmatic treatments compared to those without therapy. The difference between geometric mean PD20P and geometric mean PD20M was 14.1. PO20UNDW was measurable in only 21 out of 50 subjects. Both PD20P and PD20M were significantly lower in responders to UNDW than in nonresponders. Reproducibility of PD20P was comparable to that of PD20M (coefficients of repeatability: 1.17 and 1.09). We conclude that bronchial responsiveness to propranolol is safely measurable in most children and adults with asthma. Repeatability of bronchial response to propranolol is comparable to that of methacholine. Moreover, responsiveness to propranolol is not a predictor of treatment requirement.(ABSTRACT TRUNCATED AT 250 WORDS)
Variability of a bacterial surface protein and disease expression in a possible mouse model of systemic Lyme borreliosis.
Authors: D Cadavid, D D Thomas, R Crawley, A G Barbour
Journal: The Journal of Experimental Medicine (1994)

During persistent infection of scid mice with Borrelia turicatae, an agent of relapsing fever and neuroborreliosis, there was variation in the surface proteins the bacteria expressed and in disease manifestations over time. Two serotypes, A and B, were isolated from the mice, cloned by limiting dilution, and further characterized. The only discernible difference between the two variants was in the size of the major surface protein they expressed: serotype A had a variable major protein (Vmp) of 23,000, and serotype B had a Vmp of 20,000. When other scid mice were inoculated with clonal populations of A and B, the infections were similar with respect to onset and degree of spirochetemia, involvement of the eye and heart, and occurrence of a peripheral vestibular disorder. However, there were differences between the serotypes in other respects: (a) serotype B but not A caused reddened and significantly enlarged joints, markedly impaired performance on a walking bar, and severe arthritis by histologic examination; (b) serotype A but not B invaded the central nervous system during early infection; and (c) serotype A penetrated monolayers of human umbilical vein endothelial cells more readily than did serotype B. The combination of arthritis, myocarditis, and neurologic disease resembled human Lyme borreliosis. The findings indicate that differences in disease expression are determined by variable surface proteins of the bacterium and that scid mouse infections with B. turicatae provide a model for the study of the pathogenesis of Lyme borreliosis and other persistent spirochetal diseases.
Results of a phase 1-2 study of clofarabine in combination with cytarabine (ara-C) in relapsed and refractory acute leukemias
Authors: Stefan Faderl, Varsha Gandhi, Susan O'Brien, Peter Bonate, Jorge Cortes, Elihu Estey, Miloslav Beran, William Wierda, Guillermo Garcia-Manero, Alessandra Ferrajoli, Zeev Estrov, Francis J. Giles, Min Du, Monica Kwari, Michael Keating, William Plunkett, Hagop Kantarjian
Journal: Blood (2004)
Can clinicians benefit from patient satisfaction surveys? Evaluating the NSF for Older People, 2005–2006
Authors: Steve lliffe, Jane Wilcock, Jill Manthorpe, Jo Moriarty, Michelle Cornes, Roger Clough, Les Bright
Journal: Journal of the Royal Society of Medicine (2008)

Summary Background A transformation of healthcare is underway, from a sellers' market to a consumers' market, where the satisfaction of the patient's needs is part of the definition of quality. Patient satisfaction surveys are widely used to judge service quality, but clinicians are sceptical about them because they are too often poorly designed measures that do not lead to improvements in the quality of care. Aim To explore the use of patient satisfaction survey data in identifying problems with the provision of inpatient care for older people. Methods A case study using secondary analysis of postal survey data about older people's experiences of health and social care services, obtained during the evaluation of the National Service Framework for Older People in 2005–2006. The survey asked about experiences of inpatient care and of discharge from hospital, and sought perceptions of the avoidability of the admission. Settings and participants A total of 4170 people aged 50 years and over returned a postal questionnaire in six local authority areas of England. Responses from 584 who had experienced a recent overnight stay in hospital are reported and discussed. Findings The response rate was 35%, ranging from 26% to 44% in the six areas surveyed. The great majority of those who had recent direct experience of inpatient care reported that they had been engaged in decision-making, that staff promoted their independence and maintained their dignity. There were widespread examples, however, of the opposite experiences. Discharge from hospital was problematic for about one-third of survey respondents with this experience, and there were different accounts of poorly managed discharges from all areas. Conclusions Case studies using local survey data can be used as formative assessments of services. The response rate to the survey and the likelihood of responder bias mean that patient satisfaction survey data of this sort cannot be used to judge or compare services in a summative way, but can highlight areas where remedial action is needed. Small-scale local surveys may seem to lack the robustness of larger studies, but do identify similar areas of concern. Commissioners and clinicians could use the findings of such surveys to inform dialogues about the quality of hospital care for older people.
Diabetes-Induced Oxidative Stress and Low-Grade Inflammation in Porcine Coronary Arteries
Authors: LiFeng Zhang, Andrew Zalewski, Yuchuan Liu, Tomasz Mazurek, Scott Cowan, Jack L. Martin, Susanna M. Hofmann, Helen Vlassara, Yi Shi
Journal: Circulation (2003)

Multiple pathways contribute to accelerated coronary atherosclerosis in diabetics, including increased oxidative stress and inflammatory burden. Accordingly, the mechanisms of abnormal formation of reactive oxygen species and the changes in inflammatory gene expression were examined in diabetic coronary arteries.In pigs with streptozotocin-induced diabetes, superoxide formation was augmented in coronary media and adventitia because of increased NAD(P)H oxidase activity (3 months) accompanied by upregulated expression of its cytosolic subunit, p22phox. Diabetes-induced oxidative stress resulted in the inflammatory response in the adventitia (increased expression of interleukin-6, tumor necrosis factor-alpha, monocyte chemotactic protein-1, vascular cell adhesion molecule-1 [VCAM-1]) and in the media (VCAM-1). To examine the mechanisms of these changes, studies with isolated coronary fibroblasts were undertaken. Advanced glycation end products (AGEs), rather than glucose itself, upregulated expression of interleukin-6, VCAM-1, and monocyte chemotactic protein-1 mRNAs. These results were paralleled by increased interleukin-6 secretion (P<0.01) and augmented leukocyte adhesion to AGE-stimulated coronary cells (P<0.001). AGEs increased expression of phosphorylated forms of mitogen-activated protein kinases in coronary cells (ERK1/2 and JNK) and resulted in redox-sensitive expression of inflammatory genes that was inhibited by several inhibitors of oxidative pathways [NAD(P)H oxidase inhibitors, N-acetylcysteine, and pyrrolidine dithiocarbamate].Diabetes increased NAD(P)H oxidase activity and oxidative stress, producing inflammatory responses in porcine coronary media and adventitia. AGEs activated ERK1/2 and JNK signaling pathways and induced the expression of several inflammatory genes in coronary cells in a redox-sensitive manner. These results suggest the involvement of AGEs in the development of accelerated coronary atherosclerosis in diabetes.
Identification in Administrative Databases of Women Dying of Breast Cancer
Authors: Bruno Gagnon, Nancy E. Mayo, Carroll Laurin, James A. Hanley, Neil McDonald
Journal: Journal of Clinical Oncology (2006)

Purpose Palliative care is an essential component of cancer care, and population-based research is needed to monitor its impact. Administrative databases are the cornerstone of health services research. Their limitation is that cause of death is not sufficient to readily classify decedents as terminally ill for the study of the health services they received at the end of life. The study purpose is to develop and test the validity of an algorithm allowing the classification of the decedents as dying of breast cancer (BC), using administrative data. Methods Validation was carried out through a chart review of 119 BC decedents extracted from hospital-based databases. This algorithm was applied to 3,384 deceased women with BC representative of the whole population. The effect of the classification by the algorithm was illustrated by the shift in the distributions of age and place of death. Results The validation showed a sensitivity of 95%, a specificity of 89%, a positive predictive value of 98%, and negative predictive value of 77% for the classification of women dying of BC. Of the 3,384 decedents, 2,293 were classified as dying of, and 1,091 as not dying of BC. Women dying of BC were younger, died less often at home (6.9% v 17.9%), and in chronic care institutions (4.1% v 14.8%), and more often in acute-care beds (69.9% v 57.1%). Conclusion This novel way to classify decedents is conceptually based and empirically validated through chart review and impact on distribution of age and place of death.
Social Status and Child Psychiatric Practice: The Influence of the Clinician's Socioeconomic Origin
Authors: SAUL I. HARRISON, JOHN F. McDERMOTT, JULES SCHRAGER, EARL R. SHOWERMAN
Journal: American Journal of Psychiatry (1970)

The authors report on an investigation into the influences of class background on the diagnoses, clinical perceptions, prognoses, and recommendations for treatment of two groups of child psychiatrists: those who were born into the upper middle class and those whose childhood was spent in the lower class or lower middle class. The differences found in this study point up the need for clinical training to draw the psychiatrist's attention to understanding the role his social background may play in his interaction with his patients.
BG9719 (CVT-124), an A <sub>1</sub> Adenosine Receptor Antagonist, Protects Against the Decline in Renal Function Observed With Diuretic Therapy
Authors: Stephen S. Gottlieb, D. Craig Brater, Ignatius Thomas, Edward Havranek, Robert Bourge, Steven Goldman, Farere Dyer, Miguel Gomez, Donald Bennett, Barry Ticho, Evan Beckman, William T. Abraham
Journal: Circulation (2002)

Adenosine may adversely affect renal function via its effects on renal arterioles and tubuloglomerular feedback, but effects of adenosine blockade in humans receiving furosemide and ACE inhibitors is unknown.This was a randomized, double-blind, ascending-dose, crossover study evaluating 3 doses of BG9719 in 63 patients with congestive heart failure. Patients received placebo or 1 of 3 doses of BG9719 on 1 day and the same medication plus furosemide on a separate day. Renal function and electrolyte and water excretion were assessed. BG9719 alone caused an increase in urine output and sodium excretion (P<0.05). Although administration of furosemide alone caused a large diuresis, addition of BG9719 to furosemide increased diuresis, which was significant at the 0.75-microg/mL concentration. BG9719 alone improved glomerular filtration rate (GFR) at the 2 lower doses. Furosemide alone caused a decline in GFR. When BG9719 was added to furosemide, however, creatinine clearance remained at baseline at the 2 lower doses.In patients with congestive heart failure on standard therapy, including ACE inhibitors, BG9719 increased both urine output and GFR. In these same patients, furosemide increased urine output at the expense of decreased GFR. When BG9719 was given in addition to furosemide, urine volume additionally increased and there was no deterioration in GFR. A1 adenosine antagonism might preserve renal function while simultaneously promoting natriuresis during treatment for heart failure.
Activation of Mitogen-Activated Protein Kinases in Human Heart During Cardiopulmonary Bypass
Authors: Daniel Talmor, Azai Applebaum, Assaf Rudich, Yoram Shapira, Amir Tirosh
Journal: Circulation Research (2000)

Abstract —Mitogen-activated protein kinases (MAPKs) have been shown to be activated in both in vitro and in vivo models of cardiac tissue in response to ischemia/reperfusion injury. We investigated whether MAPKs are activated in human heart during coronary artery bypass grafting (CABG) surgery. During elective CABG surgery of 8 patients, 3 right atrial appendage biopsies were obtained at baseline, at the end of cross-clamping, and after coronary reperfusion. The expression of the p38-MAPK, c-Jun N-terminal kinase (JNK), and extracellular signal–regulated kinases (ERK1/2) MAPKs was not altered during CABG. The phosphorylation and activation of both ERK1/2 and p38-MAPK were increased ≈2-fold by ischemia and even more (8- and 4-fold, respectively) by reperfusion. Although the ischemic period did not result in a significant activation of JNK, an ≈6-fold increase in JNK activity could be observed after reperfusion. In conclusion, distinct activation patterns of ERK1/2, p38, and JNK MAPKs can be observed in human heart during CABG.
PLEKHA5 as a Biomarker and Potential Mediator of Melanoma Brain Metastasis
Authors: Lucia B. Jilaveanu, Fabio Parisi, Meaghan L. Barr, Christopher R. Zito, William Cruz-Munoz, Robert S. Kerbel, David L. Rimm, Marcus W. Bosenberg, Ruth Halaban, Yuval Kluger, Harriet M. Kluger
Journal: Clinical Cancer Research (2014)

Approximately 40% of patients with metastatic melanoma develop brain metastases. Our purpose was to identify genes aberrantly expressed in melanoma that might be associated with propensity for brain homing.We studied gene expression profiles in a cell line model of brain metastasis (cerebrotropic A375Br cells vs. parental A375P cells) and compared them with profiles of patients who developed early brain metastases and who did not. A tissue microarray containing 169 metastatic melanoma cases with variable time to brain metastasis was constructed to further study marker expression by quantitative immunofluorescence. An in vitro model of the blood brain barrier (BBB) was generated to evaluate potential mediators of brain metastases.PLEKHA5 was differentially expressed in both the A375 cell line model and patient samples subjected to gene expression profiling. At the protein level, by quantitative immunofluorescence, PLEKHA5 was associated with decreased brain metastasis-free survival. PLEKHA5 overexpression was not associated with other metastatic sites. Knockdown of PLEKHA5 decreases the viability of A375Br cells, inhibits BBB transmigration and invasion in vitro. Similar results were found with YUMUL cells, cultured from a patient with overwhelming brain metastases. PLEKHA5 knockdown did not affect the viability of A375P cells.PLEKHA5 expression in melanoma tumors was associated with early development of brain metastases. Inhibition of PLEKHA5 might decrease passage across the BBB and decrease proliferation and survival of melanoma cells both in the brain and in extracerebral sites.
Antisense Bcl&amp;ndash;2 Oligonucleotide Uptake in Human Transitional Cell Carcinoma
Authors: Brian J. Duggan, Finbarr E. Cotter, John D. Kelly, Peter W. Hamilton, Kevin McCallion, Denis Harkin, Tom Gardiner, Neil Anderson, Patrick F. Keane, Samuel R. Johnston, Kate E. Williamson
Journal: European Urology (2001)
Clinical guide to sports injuries
Authors: P McCrory
Journal: British Journal of Sports Medicine (2006)

Edited by Roald Bahr and Sverre Maehlum. Published by Human Kinetics, 2004, $95 USD (Amazon), ISBN 0736041176

A new book from Scandinavia raises the bar (no pun intended) in sports medicine textbooks. The main strength of this book is its use of lavish high quality illustrations throughout with over 400 …
PFI projects cost the taxpayer an extra 1bn at the height of the credit crisis
Authors: A. O'Dowd
Journal: BMJ (2010)

Private finance initiative (PFI) projects such as new hospitals cost the taxpayer an additional £1bn (€1.2bn; $1.6bn) at the height of the United Kingdom’s 2008 credit crisis, it has been shown.

The PFI projects, in which private companies build hospitals with NHS trusts repaying them typically over 30 years, proved to be even more expensive when the country faced financial problems in 2008, according to a report published on 9 December by the parliamentary public accounts committee.

The report, Financing PFI projects in the credit crisis and the Treasury’s response , using evidence from the Treasury, examined its response to financing PFI projects in the …
Increased levels of interleukin-8 in BAL fluid from smokers susceptible to pulmonary emphysema
Authors: M Tanino
Journal: Thorax (2002)

Background: It has previously been shown that smokers with computed tomographic (CT) evidence of subclinical emphysema have signs of neutrophil activation, despite having no appreciable increase in the number of neutrophils in their bronchoalveolar lavage (BAL) fluid. Methods: The levels of the following chemoattractants in BAL fluid from 61 community based older volunteers classified into four groups according to current smoking status and the presence or absence of emphysema were determined: interleukin 8 (IL-8), epithelial neutrophil activating protein 78 (ENA-78) and leukotriene B<sub>4</sub> (LTB<sub>4</sub>) which are primarily chemotactic for neutrophils; monocyte chemoattractant protein 1 (MCP-1) and macrophage inflammatory protein-1α (MIP-1α) which are predominantly chemotactic for mononuclear leucocytes. Results: Of the five chemoattractants studied, only the level of IL-8 in BAL fluid clearly distinguished between subjects with and without emphysema among current smokers (median values 34.7 and 12.2 pg/ml, respectively, p&lt;0.01). In addition, the levels of IL-8 and neutrophil elastase-α<sub>1</sub> protease inhibitor complex in BAL fluid were significantly correlated (<i>r</i>=0.65, p&lt;0.01). There was no difference in either the release of IL-8 from cultured alveolar macrophages at 24 hours or the expression of IL-8 messenger RNA of alveolar macrophages in the two groups of current smokers with and without emphysema. Conclusion: An accelerated response of IL-8 to chronic smoking is a factor that characterises those smokers who are susceptible to pulmonary emphysema, although the cellular source of IL-8 remains to be determined.
Soluble interleukin-2 receptors, antineutrophil cytoplasmic antibodies, and other autoantibodies in patients with ulcerative colitis.
Authors: G N Dalekos, M N Manoussakis, A C Goussia, E V Tsianos, H M Moutsopoulos
Journal: Gut (1993)

Ulcerative colitis (UC) is an inflammatory bowel disease of unknown aetiology. In this study, serum samples from 80 patients with UC were studied for the presence of various autoantibodies and soluble interleukin-2 receptor molecules (sIL-2Rs) in an attempt to determine the degree of activation of the immune system in this disease process. Autoantibodies detected included rheumatoid factors (in 5% of patients), antinuclear antibodies (in 51.3%), anti-Ro(SSA) (in 1.3%), anticardiolipin antibodies (IgG and/or IgM classes in 26.3%), anti-double stranded DNA (IgG or IgM classes in 45%), and antineutrophil cytoplasmic antibodies (ANCAs, in 30%). The ANCAs had a perinuclear pattern (p-ANCA) in 95.8%, without anti-myeloperoxidase activity, at least in an enzyme linked immunosorbent assay (ELISA) system. Raised concentrations of sIL-2R were found in 32.5% of patients (26/80, 18 with active and eight with inactive UC). The mean (SD) sIL-2R concentrations were significantly higher in patients with active UC (595 (219) u/ml v 406 (162) u/ml, p = 0.0001) and in patients with ANCAs (584 (177) u/ml in ANCA positive v 447 (212) u/ml in ANCA negative patients, p < 0.01). The sIL-2R concentrations were correlated with increased serum concentrations of C3c (r = 0.23, p < 0.05) or C4 (r = 0.4, p < 0.001) components of the complement system and erythrocyte sedimentation rate (ESR, r = 0.44, p = 0.0001). Platelets, ESR, and C3c were not associated with disease activity (p = 0.06, 0.33 and 0.86) whereas mean (SD) serum concentrations of C4 were higher in active disease (37.4 (11.9) mg/dl v 32.3 (10.3) mg/dl, p < 0.05). The sIL-2Rs had 53% sensitivity and 82.6% specificity for disease activity whereas platelet counts had 53% sensitivity and 58.7% specificity. To conclude, UC is accompanied by an autoimmune response that results in the production of several autoantibodies and cellular immune activation, as shown by the high sIL-2R concentration, is also present. The identification of the target antigen(s) of p-ANCA would possibly act as an indicator of disease activity if this distinct subset of ANCAs can be attributed to the pathogenesis of UC. The sIL-2R concentrations seem to be a useful laboratory marker for assessing activity of the disease.