tbuckley/cabot-search huggingface dataset:
Universal Screening for Methicillin-Resistant &lt;emph type="ital"&gt;Staphylococcus aureus&lt;/emph&gt; at Hospital Admission and Nosocomial Infection in Surgical Patients
Authors: Stephan Harbarth
Journal: JAMA (2008)

Experts and policy makers have repeatedly called for universal screening at hospital admission to reduce nosocomial methicillin-resistant Staphylococcus aureus (MRSA) infection.To determine the effect of an early MRSA detection strategy on nosocomial MRSA infection rates in surgical patients.Prospective, interventional cohort study conducted between July 2004 and May 2006 among 21 754 surgical patients at a Swiss teaching hospital using a crossover design to compare 2 MRSA control strategies (rapid screening on admission plus standard infection control measures vs standard infection control alone). Twelve surgical wards including different surgical specialties were enrolled according to a prespecified agenda, assigned to either the control or intervention group for a 9-month period, then switched over to the other group for a further 9 months.During the rapid screening intervention periods, patients admitted to the intervention wards for more than 24 hours were screened before or on admission by rapid, multiplex polymerase chain reaction. For both intervention (n=10 844) and control (n=10 910) periods, standard infection control measures were used for patients with MRSA in all wards and consisted of contact isolation of MRSA carriers, use of dedicated material (eg, gown, gloves, mask if indicated), adjustment of perioperative antibiotic prophylaxis of MRSA carriers, computerized MRSA alert system, and topical decolonization (nasal mupirocin ointment and chlorhexidine body washing) for 5 days.Incidence of nosocomial MRSA infection, MRSA surgical site infection, and rates of nosocomial acquisition of MRSA.Overall, 10 193 of 10 844 patients (94%) were screened during the intervention periods. Screening identified 515 MRSA-positive patients (5.1%), including 337 previously unknown MRSA carriers. Median time from screening to notification of test results was 22.5 hours (interquartile range, 12.2-28.2 hours). In the intervention periods, 93 patients (1.11 per 1000 patient-days) developed nosocomial MRSA infection compared with 76 in the control periods (0.91 per 1000 patient-days; adjusted incidence rate ratio, 1.20; 95% confidence interval, 0.85-1.69; P = .29). The rate of MRSA surgical site infection and nosocomial MRSA acquisition did not change significantly. Fifty-three of 93 infected patients (57%) in the intervention wards were MRSA-free on admission and developed MRSA infection during hospitalization.A universal, rapid MRSA admission screening strategy did not reduce nosocomial MRSA infection in a surgical department with endemic MRSA prevalence but relatively low rates of MRSA infection.isrctn.org Identifier: ISRCTN06603006.
Factors of importance for the long term prognosis after hospital treated pneumonia.
Authors: J U Hedlund, A B Ortqvist, M E Kalin, F Granath
Journal: Thorax (1993)

Elderly patients admitted to hospital for community acquired pneumonia have a high risk of recurrence of pneumonia and of death during the years after discharge. In this study potential factors of importance for the long term prognosis after hospital treated pneumonia were retrospectively investigated.A total of 241 patients (103 men) with a mean age of 60 (range 18-102) years discharged from hospital after treatment for community acquired pneumonia were studied. After an average follow up period of 31 months, 18 independent variables present during hospital treatment of the initial pneumonia were examined for association with the following end points: recurrence of pneumonia, death from any cause, and death from pneumonia.Age adjusted analysis showed that systemic treatment with corticosteroids correlated significantly with recurrence of pneumonia and with death. The presence of low serum albumin levels on admission or colonisation of the respiratory tract with Gram negative enteric bacteria seemed to be important negative prognostic factors for the outcome during pneumonia recurrences after discharge.Patients who are admitted to hospital with pneumonia are at risk of subsequent pneumonia and death after discharge. This risk seems to be even higher in patients who are treated with corticosteroids systemically, who have a low serum albumin level on admission, or who become colonised in the respiratory tract with Gram negative enteric bacteria during their hospital stay.
beta 2-Microglobulin levels in serum and urine of rheumatoid arthritis patients on gold therapy.
Authors: D Latt, J.B Weiss, M.I Jayson
Journal: Annals of the Rheumatic Diseases (1981)

The levels of beta 2-microglobulin (beta 2-m) in serum and urine of 24 seropositive patients with rheumatoid arthritis (RA) treated with regular gold (sodium aurothiomalate) injections have been investigated. The values obtained were compared with levels from 20 seropositive patients with RA treated only with nonsteroidal anti-inflammatory drugs and 20 age and sex matched normal controls who had received no medication. A significant increase of urinary beta 2-m levels was found in the gold-treated RA group. No correlation between dose of gold received and the levels of beta 2-m in the urine could be established. There was also no correlation between the erythrocyte sedimentation rate (ESR) or total lymphocyte count and beta 2-m levels in serum or urine. We conclude that serum and urinary beta 2-m levels appear to be poor indices of joint inflammation, but sequential urinary beta 2-m levels may prove valuable in monitoring the development of renal tubular lesions due to gold therapy.
Erythropoietin and mesenchymal stromal cells in angiogenesis and myocardial regeneration: one plus one equals three?
Authors: M. R. Ward, D. J. Stewart
Journal: Cardiovascular Research (2008)

There is an increasing interest in cellular therapy for cardiovascular diseases. The first well-designed clinical trials have shown tantalizing hints that bone marrow cells may improve cardiac function post-myocardial infarction (post-MI)1,2 and enhance perfusion in patients with critical limb ischaemia.3 This cautious optimism comes on the heels of the great disappointment with pro-angiogenic gene therapy, which failed to live up to the promise based on encouraging pre-clinical studies and early, largely anecdotal clinical experience.4 However, even accepting that cell therapy may have a significant beneficial effect, the magnitude of this benefit would seem to be rather modest.5 Although there are many reasons for this, related both to the host (age, cardiovascular risk factors, and co-morbidities) as well as the cells themselves (type, ‘dose’, delivery route, and activity), it seems clear that strategies to enhance the regenerative capacity of stem or progenitor cells will be needed to effect robust clinical improvements.

Bone marrow-derived mesenchymal stromal cells (MSCs) offer exciting potential in therapy of cardiovascular diseases and have been studied extensively. They have been reported to induce angiogenesis in models of myocardial6,7 and hindlimb ischaemia.8 They have also been shown to inhibit cardiomyocyte apoptosis, reduce remodelling, and improve myocardial function in the post-infarct myocardium.9 Their functional benefit in the heart was originally attributed to their ability to differentiate into cardiomyocytes,10 although evidence of engraftment and differentiation is often lacking. Greater attention has recently been placed on their ability to secrete paracrine growth factors,11 which act to reduce cardiomyocyte apoptosis and immune cell proliferation,12 together reducing inflammation and fibrosis. MSCs have been shown to secrete several mitogenic and angiogenic growth factors, including VEGF, IGF-1, EGF, angiopoietin-1, and SDF-1.12 In … 

*Corresponding author. Tel: +1 613 761 5341; fax: +1 613 761 4920. E-mail address: djstewart{at}ohri.ca
Two receptor forms for ouabain in sarcolemma-enriched preparations from canine ventricle.
Authors: N V Wellsmith, G E Lindenmayer
Journal: Circulation Research (1980)

Some evidence indicates that the inotropic effect of cardiac glycosides occurs at concentrations too low to affect Na+,K+-ATPase activity. This suggests that some receptor other than Na+,K+-ATPase mediates the inotropic effect. We studied ouabain binding to sarcolemma-enriched preparations from canine ventricle under conditions known to promote binding to Na+,K+-ATPase. Profiles for binding and dissociation were characterized by two kinetic components: (1) fast association and slow dissociation; (2) slow association and fast dissociation. Profiles in the absence of supporting ligands were consistent with a single species of receptors with slow association, fast dissociation and minimal effect on Na+,K+-ATPase activity. Binding supported by magnesium plus inorganic phosphate inhibited Na+,K+-ATPase activity by 86%. The two binding components were affected differentially by heating at 55 degrees C. It was concluded that the preparation possesses two receptors for ouabain: the Na+,K+-ATPase and a "new" receptor. The latter may be different chemically from the Na+,K+-ATPase. The more likely possibility is that the "new" receptor is the Na+,K+-ATPase in a state characterized by low catalytic activity, low affinity for ouabain, and no requirement of specific ligands for ouabain binding. Further, the data suggest an interdependence between the two forms. This leads to a mechanism which allows an inotropic effect to precede loss of Na+,K+-ATPase activity even though both result from glycoside binding to Na+,K+-ATPase. The mechanism involves an equilibrium between inactive and active forms of the Na+,K+-ATPase such that the inactive form buffers loss of the active form upon exposure to a cardiac glycoside.
Multifaceted Dysregulation of the Epidermal Growth Factor Receptor Pathway in Clear Cell Sarcoma of the Kidney
Authors: Suzanne E. Little, Dorine A. Bax, Maria Rodriguez-Pinilla, Rachael Natrajan, Boo Messahel, Kathy Pritchard-Jones, Gordan M. Vujanic, Jorge S. Reis-Filho, Chris Jones
Journal: Clinical Cancer Research (2007)

Epidermal growth factor receptor (EGFR) is a receptor tyrosine kinase overexpressed in a variety of human malignancies, against which targeted therapies have shown efficacy in lung and brain tumors. Clinical responses to EGFR inhibitors have been found to be highly dependent on the presence of activating mutations, whereas gene amplification, downstream activation of Akt, and abnormalities in PTEN are also reported predictive factors. We sought to evaluate these variables in pediatric renal tumors.We screened a series of 307 pediatric renal tumors for EGFR expression by immunohistochemistry and gene amplification by chromogenic in situ hybridization. In identifying a striking predilection for certain tumor types, we further analyzed the clear cell sarcomas of the kidney (CCSK) for mutations in EGFR and PTEN.Although only 23 of 177 (13.0%) nonanaplastic Wilms' tumors were EGFR positive, 4 of 11 (36.4%) anaplastic tumors showed receptor overexpression. In addition, 5 of 9 (55.6%) mesoblastic nephromas and 12 of 12 (100%) CCSKs were strongly immunoreactive for EGFR. In studying the CCSKs in more detail, we identified gene amplification in 1 of 12 (8.3%) cases and a somatic T790M EGFR mutation in a further case. These two samples additionally harbored mutations in PTEN. Downstream pathway activation, as assayed by phosphorylated Akt expression, was observed in 8 of 12 (66.7%) cases.Together, these data show dysregulation of the EGFR pathway at multiple levels in CCSKs. Identification of factors predictive of poor response to targeted therapy, including the drug resistance T790M mutation, may provide a rationale for upfront trials with irreversible inhibitors of EGFR in children with these tumors.
Long-Term Risk of Cardiovascular Disease in 10-Year Survivors of Breast Cancer
Authors: Maartje J Hooning, Akke Botma, Berthe M P Aleman, Margreet H A Baaijens, Harry Bartelink, Jan G M Klijn, Carolyn W Taylor, Flora E van Leeuwen
Journal: JNCI Journal of the National Cancer Institute (2007)

Radiotherapy for breast cancer as delivered in the 1970s has been associated with increased risk of cardiovascular disease, but recent studies of associations with modern regimens have been inconclusive. Few data on long-term cardiovascular disease risk according to specific radiation fields are available, and interaction with known cardiovascular risk factors has not been examined.We studied treatment-specific incidence of cardiovascular disease in 4414 10-year survivors of breast cancer who were treated from 1970 through 1986. Risk of cardiovascular disease in these patients was compared with general population rates and evaluated in Cox proportional hazards regression models. All statistical tests were two-sided.After a median follow-up of 18 years, 942 cardiovascular events were observed (standardized incidence ratio = 1.30, 95% confidence interval [CI] = 1.22 to 1.38; corresponding to 62.9 excess cases per 10,000 patient-years). Breast irradiation only was not associated with increased risk of cardiovascular disease. However, radiotherapy to either the left or right side of the internal mammary chain was associated with increased cardiovascular disease risk for the treatment period 1970-1979 (for myocardial infarction, hazard ratio [HR] = 2.55, 95% CI = 1.55 to 4.19; P<.001; for congestive heart failure, HR = 1.72, 95% CI = 1.22 to 2.41; P = .002) compared with no radiotherapy. Among patients who received internal mammary chain radiotherapy after 1979, risk of myocardial infarction declined over time toward unity, whereas the risks of congestive heart failure (HR = 2.66, 95% CI = 1.27 to 5.61; P = .01) and valvular dysfunction (HR = 3.17, 95% CI = 1.90 to 5.29; P<.001) remained increased. Patients who underwent radiotherapy plus adjuvant chemotherapy (cyclophosphamide, methotrexate, and fluorouracil) after 1979 had a higher risk of congestive heart failure than patients who were treated with radiotherapy only (HR = 1.85, 95% CI = 1.25 to 2.73; P = .002). Smoking and radiotherapy together were associated with a more than additive effect on risk of myocardial infarction (HR = 3.04, 95% CI = 2.03 to 4.55; P for departure from additivity = .039).Radiotherapy as administered from the 1980s onward is associated with an increased risk of cardiovascular disease. Irradiated breast cancer patients should be advised to refrain from smoking to reduce their risk for cardiovascular disease.
Bronchodilator drug efficacy via cyclic AMP.
Authors: P E Duncan, J P Griffin, S S Solomon
Journal: Thorax (1975)

Cyclic adenosine 39, 59-monophosphosphate (cyclic AMP) as measured by radioimmunoassay is found in diced rat lung in an amount approximating one picomole per milligram of wet weight lung tissue. Incubation of rat lung with adrenaline, a beta adrenergic agent, produced a rapid increase in cyclic AMP, 100% increase at 15 seconds and 340% at 2 minutes. Isoprenaline was more stimulatory than adrenaline; noradrenaline was less stimulatory, and ephedrine produced a negligible effect. The methylxanthines, caffeine and theophylline, produced an increase in cyclic AMP concentration. Of these, caffeine was more potent, and synergism with adrenaline was demonstrated. The beta adrenergic blocking agent, propranolol, completely inhibited the expected rise in cyclic AMP secondary to adrenaline stimulation. In contrast, the alpha blocker, phentolamine, produced no effect. This animal model offers evidence that adrenergic agents and methylxanthines act to increase cyclic AMP in lung tissue. It is likely that many of the beneficial effects of these drugs in pulmonary patients occur through similar changes and modulation of the cyclic AMP system.
Donepezil and Memantine for Moderate-to-Severe Alzheimer's Disease
Authors: Robert Howard, Rupert McShane, James Lindesay, Craig Ritchie, Ashley Baldwin, Robert Barber, Alistair Burns, Tom Dening, David Findlay, Clive Holmes, Alan Hughes, Robin Jacoby, Rob Jones, Roy Jones, Ian McKeith, Ajay Macharouthu, John O'Brien, Peter Passmore, Bart Sheehan, Edmund Juszczak, Cornelius Katona, Robert Hills, Martin Knapp, Clive Ballard, Richard Brown, Sube Banerjee, Caroline Onions, Mary Griffin, Jessica Adams, Richard Gray, Tony Johnson, Peter Bentham, Patrick Phillips
Journal: New England Journal of Medicine (2012)

Clinical trials have shown the benefits of cholinesterase inhibitors for the treatment of mild-to-moderate Alzheimer's disease. It is not known whether treatment benefits continue after the progression to moderate-to-severe disease.
Association of Brominated Flame Retardants With Diabetes and Metabolic Syndrome in the U.S. Population, 2003–2004
Authors: Ji-Sun Lim, Duk-Hee Lee, David R. Jacobs
Journal: Diabetes Care (2008)

Chlorinated persistent organic pollutants (POPs), endocrine disruptors accumulated in adipose tissue, were associated with diabetes and metabolic syndrome. Brominated flame retardants (BFRs), such as polybrominated diphenyl ethers (PBDEs) or polybrominated biphenyls (PBBs), are another class of POPs for which body burden is increasing. Cross-sectional associations of serum concentrations of BFRs with diabetes and metabolic syndrome were studied.In the National Health and Nutrition Examination Survey 2003-2004, 1,367 adults were examined with respect to diabetes status. Five PBDEs and one PBB were selected, detectable in >or=60% of participants. For the outcome metabolic syndrome, we restricted the analysis to 637 participants with a morning fasting sample.Compared with subjects with serum concentrations below the limit of detection, prevalent diabetes had differing dose-response associations with serum concentrations of PBB-153 and PBDE-153. Adjusted odds ratios across quartiles of serum concentrations for PBB-153 or PBDE-153 were 1.0, 0.7, 1.4, 1.6, and 1.9 (P for trend <0.01) and 1.0, 1.6, 2.6, 2.7, and 1.8 (P for quadratic term <0.01), respectively. PBB-153 was also positively associated with the prevalence of metabolic syndrome with adjusted odds ratios of 1.0, 1.5, 3.1, 3.1, and 3.1 (P for trend<0.01). As in its association with diabetes, PBDE-153 showed an inverted U-shaped association with metabolic syndrome.Pending confirmation in prospective studies, lipophilic xenobiotics, including brominated POPs stored in adipose tissue, may be involved in the pathogenesis of diabetes and metabolic syndrome.
TRAIL Induces Apoptosis in Human Colorectal Adenoma Cell Lines and Human Colorectal Adenomas
Authors: Mathilde Jalving, Steven de Jong, Jan J. Koornstra, Wytske Boersma-van Ek, Nynke Zwart, Jelle Wesseling, Elisabeth G.E. de Vries, Jan H. Kleibeuker
Journal: Clinical Cancer Research (2006)

Abstract Purpose: Recombinant human (rh) tumor necrosis factor–related apoptosis-inducing ligand (TRAIL) is a potential new anticancer drug which can induce apoptosis in colorectal cancer cell lines. The aim of this study was to investigate whether it is possible to induce apoptosis in human adenoma cell lines and human adenomas using rhTRAIL. Experimental Design: Two human adenoma cell lines were exposed to 0.1 μg/mL of rhTRAIL for 5 hours. Apoptosis and caspase activation in cell lines were evaluated using immunocytochemistry, fluorimetric caspase assays, and Western blotting. Short-term explant cultures were established from freshly removed human adenomas (n = 38) and biopsies of normal colon epithelium (n = 15), and these were incubated for 5 hours in the presence or absence of 1 μg/mL of rhTRAIL. Apoptosis was determined in paraffin-embedded tissue using morphologic criteria and cleaved caspase-3 staining. Results: In the adenoma cell lines, rhTRAIL induced up to 55% apoptosis. This coincided with caspase-8 and caspase-3 activation and could be inhibited by a pan-caspase inhibitor. rhTRAIL induced caspase-dependent apoptosis in adenomas with high-grade dysplasia (n = 21) compared with the paired untreated counterparts (apoptotic index, 34 ± 5% versus 17 ± 2%, mean ± SE; P = 0.002), but not in adenomas with low-grade dysplasia (n = 17) or in normal colon epithelium (n = 15). Conclusions: Colorectal adenoma cell lines and adenomas with high-grade dysplasia are sensitive to rhTRAIL-induced apoptosis, whereas normal colon epithelium is not. This suggests the potential application of rhTRAIL in the treatment of adenomas with high-grade dysplasia.
Sodium and Potassium Balance Depends on αENaC Expression in Connecting Tubule
Authors: Birgitte Mønster Christensen, Romain Perrier, Qing Wang, Annie Mercier Zuber, Marc Maillard, David Mordasini, Sumedha Malsure, Caroline Ronzaud, Jean-Christophe Stehle, Bernard C. Rossier, Edith Hummler
Journal: Journal of the American Society of Nephrology (2010)

Mutations in α, β, or γ subunits of the epithelial sodium channel (ENaC) can downregulate ENaC activity and cause a severe salt-losing syndrome with hyperkalemia and metabolic acidosis, designated pseudohypoaldosteronism type 1 in humans. In contrast, mice with selective inactivation of αENaC in the collecting duct (CD) maintain sodium and potassium balance, suggesting that the late distal convoluted tubule (DCT2) and/or the connecting tubule (CNT) participates in sodium homeostasis. To investigate the relative importance of ENaC-mediated sodium absorption in the CNT, we used Cre-lox technology to generate mice lacking αENaC in the aquaporin 2–expressing CNT and CD. Western blot analysis of microdissected cortical CD (CCD) and CNT revealed absence of αENaC in the CCD and weak αENaC expression in the CNT. These mice exhibited a significantly higher urinary sodium excretion, a lower urine osmolality, and an increased urine volume compared with control mice. Furthermore, serum sodium was lower and potassium levels were higher in the genetically modified mice. With dietary sodium restriction, these mice experienced significant weight loss, increased urinary sodium excretion, and hyperkalemia. Plasma aldosterone levels were significantly elevated under both standard and sodium-restricted diets. In summary, αENaC expression within the CNT/CD is crucial for sodium and potassium homeostasis and causes signs and symptoms of pseudohypoaldosteronism type 1 if missing.
Plasma insulin, serum lipids and lipoproteins in gall stone disease in non-insulin dependent diabetic subjects: a case control study.
Authors: M Laakso, M Suhonen, R Julkunen, K Pyorala
Journal: Gut (1990)

Fasting insulin, lipids and lipoproteins were measured in 22 middle aged female non-insulin dependent diabetics with gall stone disease (cases) and in 22 non-insulin dependent diabetics without gall stone disease (controls). The groups were matched for sex, age, obesity, and fasting glucose concentrations. No differences were observed between the cases and controls in duration of diabetes, glycated haemoglobin A1, alcohol intake, smoking, use of cardiovascular drugs or a history of myocardial infarction. Diabetics with gall stone disease had higher fasting insulin concentrations (p less than 0.5), lower total (p less than 0.01) and low density lipoprotein cholesterol (p less than 0.01) and high density lipoprotein cholesterol (not statistically significant) concentrations than diabetics without gall stone disease. These changes in insulin, lipids and lipoproteins are similar to reported changes in non-diabetic subjects with gall stone disease. Therefore, they are characteristic for gall stone disease and not as such explanatory to an increased risk of gall stones in patients with non-insulin dependent diabetes.