tbuckley/cabot-search huggingface dataset:
Privatisation of NHS prescribing
Authors: S Head
Journal: BMJ (1994)

we took the average cost for a specialty as a starting point.Day cases were included in this cost.Korner data for 1990-1 were used to estimate outpatient activity, but later data were used when available.We agree on the shortcomings of these data, but in North Thames region KMmer data are the main source of information on outpatients.The cost of each outpatient attendance was taken from work by the Department of Health.'Until out- patient care is contracted for separately, it may not be possible to move far from such gross assumptions.We welcome advice to help improve our methods.Consistent biases can produce consistent results.But, as shown above, it is not clear in which direction biases may have operated in our study.A working party with representatives from health authorities in North Thames Regional Health Authority is now developing the methodology further.Also under discussion is whether health authorities should contract separately for fundholding-type hospital care.We agree that estimating and comparing the prices paid by fundholders and health authorities are difficult and that a more detailed analysis is needed.The data illustrated in our paper suggested that prices between fundholders and health authorities were different within specific health agencies but not across the region as a whole.It is therefore difficult to make the case that fundholders were systematically charged more than health authorities.Finally, we believe that our analysis was as robust as was possible with current data and in the time available.While it would be easy to wait for perfect methods and perfect data, decisions about funding for fundholders are being made with little knowledge of the impact on health authorities.We hope that others will see the importance of investigating this issue without delay, especially as fundholding is extended.
Determining Risk of Biochemical Recurrence in Prostate Cancer by Immunohistochemical Detection of PTEN Expression and Akt Activation
Authors: Roble Bedolla, Thomas J. Prihoda, Jeffrey I. Kreisberg, Shazli N. Malik, Naveen K. Krishnegowda, Dean A. Troyer, Paramita M. Ghosh
Journal: Clinical Cancer Research (2007)

Abstract Purpose: A considerable fraction of patients who undergo radical prostatectomy as treatment for primary prostate cancer experience biochemical recurrence detected by elevated serum levels of prostate-specific antigen. In this study, we investigate whether loss of expression of the tumor suppressor phosphatase and tensin homologue deleted on chromosome 10 (PTEN) and the phosphorylated form of the cell survival protein Akt (pAkt) predicts biochemical recurrence. Experimental Design: Expression of PTEN and pAkt was detected by immunohistochemistry in paraffin-embedded prostate cancer tissue obtained from men undergoing radical prostatectomy. Outcome was determined by 60-month follow-up determining serum prostate-specific antigen levels. Results: By itself, PTEN was not a good predictor of biochemical recurrence; however, in combination with pAkt, it was a better predictor of the risk of biochemical recurrence compared with pAkt alone. Ninety percent of all cases with high pAkt and negative PTEN were recurrent whereas 88.2% of those with low pAkt and positive PTEN were nonrecurrent. In addition, high Gleason scores resulted in reduced protection from decreased pAkt and increased PTEN. By univariate logistic regression, pAkt alone gives an area under the receiver-operator characteristic curve of 0.82 whereas the area under the receiver-operator characteristic curve for the combination of PTEN, pAkt, and Gleason based on a stepwise selection model is 0.89, indicating excellent discrimination. Conclusions: Our results indicate that loss of PTEN expression, together with increased Akt phosphorylation and Gleason score, is of significant predictive value for determining, at the time of prostatectomy, the risk of biochemical recurrence.
Bacterial colonisation in patients with bronchiectasis: microbiological pattern and risk factors
Authors: J Angrill
Journal: Thorax (2002)

Background: A study was undertaken to investigate the incidence, diagnostic yield of non-invasive and bronchoscopic techniques, and risk factors of airway colonisation in patients with bronchiectasis in a stable clinical situation. Methods: A 2 year prospective study of 77 patients with bronchiectasis in a stable clinical condition was performed in an 800 bed tertiary university hospital. The interventions used were pharyngeal swabs, sputum cultures and quantitative protected specimen brush (PSB) bacterial cultures (cut off point ≥10<sup>2</sup> cfu/ml) and bronchoalveolar lavage (BAL) (cut off point ≥10<sup>3</sup> cfu/ml). Results: The incidence of bronchial colonisation with potential pathogenic microorganisms (PPMs) was 64%. The most frequent PPMs isolated were <i>Haemophilus influenzae</i> (55%) and <i>Pseudomonas</i> spp (26%). Resistance to antibiotics was found in 30% of the isolated pathogens. When the sample was appropriate, the operative characteristics of the sputum cultures were similar to those obtained with the PSB taken as a gold standard. Risk factors associated with bronchial colonisation by PPMs in the multivariate analysis were: (1) diagnosis of bronchiectasis before the age of 14 years (odds ratio (OR)=3.92, 95% CI 1.29 to 11.95), (2) forced expiratory volume in 1 second (FEV<sub>1</sub>) &lt;80% predicted (OR=3.91, 95% CI 1.30 to 11.78), and (3) presence of varicose or cystic bronchiectasis (OR=4.80, 95% CI 1.11 to 21.46). Conclusions: Clinically stable patients with bronchiectasis have a high prevalence of bronchial colonisation by PPMs. Sputum culture is a good alternative to bronchoscopic procedures for evaluation of this colonisation. Early diagnosis of bronchiectasis, presence of varicose-cystic bronchiectasis, and FEV<sub>1</sub> &lt;80% predicted appear to be risk factors for bronchial colonisation with PPMs.
Regulation of Bile Salt Sulfotransferase Isoenzymes by Gonadal Hormones
Authors: Robert E. Kane, Lee J. Chen, Michael M. Thaler
Journal: Hepatology (1984)

We studied the regulation of hepatic bile salt sulfotransferase activity by gonadal hormones and the effect of gonadal hormones on two bile salt sulfotransferase isoenzymes. Bile salt sulfotransferase enzyme activity was three times greater in the female than in the male rats. Oophorectomy significantly decreased bile salt sulfotransferase activity in the female, but orchidectomy had no effect on bile salt sulfotransferase activity in the male. Estrogen treatment of intact as well as orchidectomized males markedly stimulated the enzyme activity, while testosterone treatment of intact or oophorectomized females did not effect bile salt sulfotransferase activity. We concluded that the 3-fold greater activity in female rats is due to the striking stimulatory effect of estrogen on bile salt sulfotransferase activity, and the testosterone has little or no role in the sexually related differences in bile salt sulfotransferase activity in mature rats. These sex-related differences in bile salt sulfotransferase activity were investigated further using DEAE-Sephadex A50 ion-exchange chromatography of rat hepatic cytosol. Two bile salt sulfotransferase isoenzymes were identified both with an approximate molecular weight of 130,000. Bile salt sulfotransferase I eluted with 0.05 M NaCl, had an isoelectric point at pH 6.8, was stimulated by estrogen, and was responsible for 90% of total bile salt sulfotransferase activity in the mature female. Bile salt sulfotransferase II eluted with 0.14 Af NaCl, had an isoelectric point at pH 5.3, was unresponsive to estrogen, and accounted for 75 to 80% of bile salt sulfotransferase activity in the mature male. Bile salt sulfotransferase I was 3.8-fold more active toward 3/3-hydroxy-5-cholenoate as glycolith-ocholate, and its activity for glycolithocholate was completely inhibited by 3-ketolithocholate. Conversely, bile salt sulfotransferase II had very little detectable activity towards 3β-hydroxy-5-cholenoate, and its activity toward glycolithocholate was only marginally (13%) inhibited by 3-ketolithocholate. The activity of both bile salt sulfotransferase isoenzymes with various bile acids was: monohydroxylated &gt; dihydroxylated &gt; trihydroxylated. Hepatic bile salt sulfation in the mature rat is catalyzed by two isoenzymes that had the same approximate molecular weight, but differ in sex distribution, substrate activities, regulation by gonadal hormones and inhibition of activity for glycolithocholate by keto bile acids.
Macrophage Migration Inhibitory Factor in Cardiovascular Disease
Authors: Alma Zernecke, Jürgen Bernhagen, Christian Weber
Journal: Circulation (2008)

The highly conserved and archetypical yet atypical cytokine macrophage migration inhibitory factor (MIF) fulfills pleiotropic immune functions in many acute and chronic inflammatory diseases. Recent evidence has emerged from both expression and functional studies to implicate MIF in various aspects of cardiovascular disease. The present review is aimed at providing a synopsis of the involvement of MIF in the inflammatory pathogenesis of atherosclerosis and its consequences, namely unstable plaque formation, remodeling after arterial injury, aneurysm formation, myocardial infarction, or ischemia-reperfusion injury. In addition, other forms of myocardial dysfunction and inflammation and the role of MIF in angiogenesis are reviewed. The functional data are reconciled with recent progress in the identification of heptahelical (CXC chemokine) receptors for MIF, its prototypic role as their noncanonical ligand, and its signal transduction profile operative in atherogenic and inflammatory recruitment of mononuclear cells and in the oxidative damage and apoptosis of cardiomyocytes. Its unique features and functions clearly distinguish MIF from other cytokines implicated in atherogenesis and make it a prime target for achieving therapeutic regression of atherosclerosis. The potential of targeting or exploiting MIF for therapeutic strategies or as a diagnostic marker in the management of cardiovascular diseases or disorders is scrutinized.
Targeted <i>In vivo</i> Imaging of Integrin αvβ6 with an Improved Radiotracer and Its Relevance in a Pancreatic Tumor Model
Authors: Sven H. Hausner, Craig K. Abbey, Richard J. Bold, M. Karen Gagnon, Jan Marik, John F. Marshall, Cathy E. Stanecki, Julie L. Sutcliffe
Journal: Cancer Research (2009)

Abstract The cell surface receptor αvβ6 is epithelial specific, and its expression is tightly regulated; it is low or undetectable in adult tissues but has been shown to be increased in many different cancers, including pancreatic, cervical, lung, and colon cancers. Studies have described αvβ6 as a prognostic biomarker linked to poor survival. We have recently shown the feasibility of imaging αvβ6 in vivo by positron emission tomography (PET) using the peptide [18F]FBA-A20FMDV2. Here, we describe improved αvβ6 imaging agents and test their efficacy in a mouse model with endogenous αvβ6 expression. The modified compounds maintained high affinity for αvβ6 and &amp;gt;1,000-fold selectivity over related integrins (by ELISA) and showed significantly improved αvβ6-dependent binding in cell-based assays (&amp;gt;60% binding versus &amp;lt;10% for [18F]FBA-A20FMDV2). In vivo studies using either a melanoma cell line (transduced αvβ6 expression) or the BxPC-3 human pancreatic carcinoma cell line (endogenous αvβ6 expression) revealed that the modified compounds showed significantly improved tumor retention. This, along with good clearance of nonspecifically bound activity, particularly for the new radiotracer [18F]FBA-PEG28-A20FMDV2, resulted in improved PET imaging. Tumor/pancreas and tumor/blood biodistribution ratios of &amp;gt;23:1 and &amp;gt;47:1, respectively, were achieved at 4 hours. Significantly, [18F]FBA-PEG28-A20FMDV2 was superior to 2-[18F]fluoro-2-deoxy-d-glucose ([18F]FDG) in imaging the BxPC-3 tumors. Pancreatic ductal adenocarcinoma is highly metastatic and current preoperative evaluation of resectability using noninvasive imaging has limited success, with most patients having metastases at time of surgery. The fact that these tumors express αvβ6 suggests that this probe has significant potential for the in vivo detection of this malignancy, thus having important implications for patient care and therapy. [Cancer Res 2009;69(14):5843–50]
A retrospective study of ampullary adenocarcinomas: overall survival and responsiveness to fluoropyrimidine-based chemotherapy
Authors: Z.-Q. Jiang, G. Varadhachary, X. Wang, S. Kopetz, J.E. Lee, H. Wang, R. Shroff, M. Katz, R.A. Wolff, J. Fleming, M.J. Overman
Journal: Annals of Oncology (2013)
Comparative genomics of the core and accessory genomes of 48 Sinorhizobium strains comprising five genospecies
Authors: Masayuki Sugawara, Brendan Epstein, Brian D Badgley, Tatsuya Unno, Lei Xu, Jennifer Reese, Prasad Gyaneshwar, Roxanne Denny, Joann Mudge, Arvind K Bharti, Andrew D Farmer, Gregory D May, Jimmy E Woodward, Claudine Médigue, David Vallenet, Aurélie Lajus, Zoé Rouy, Betsy Martinez-Vaz, Peter Tiffin, Nevin D Young, Michael J Sadowsky
Journal: Genome biology (2013)

Abstract Background The sinorhizobia are amongst the most well studied members of nitrogen-fixing root nodule bacteria and contribute substantial amounts of fixed nitrogen to the biosphere. While the alfalfa symbiont Sinorhizobium meliloti RM 1021 was one of the first rhizobial strains to be completely sequenced, little information is available about the genomes of this large and diverse species group. Results Here we report the draft assembly and annotation of 48 strains of Sinorhizobium comprising five genospecies. While S. meliloti and S. medicae are taxonomically related, they displayed different nodulation patterns on diverse Medicago host plants, and have differences in gene content, including those involved in conjugation and organic sulfur utilization. Genes involved in Nod factor and polysaccharide biosynthesis, denitrification and type III, IV, and VI secretion systems also vary within and between species. Symbiotic phenotyping and mutational analyses indicated that some type IV secretion genes are symbiosis-related and involved in nitrogen fixation efficiency. Moreover, there is a correlation between the presence of type IV secretion systems, heme biosynthesis and microaerobic denitrification genes, and symbiotic efficiency. Conclusions Our results suggest that each Sinorhizobium strain uses a slightly different strategy to obtain maximum compatibility with a host plant. This large genome data set provides useful information to better understand the functional features of five Sinorhizobium species, especially compatibility in legume- Sinorhizobium interactions. The diversity of genes present in the accessory genomes of members of this genus indicates that each bacterium has adopted slightly different strategies to interact with diverse plant genera and soil environments.
Enhancement of Carboplatin-Mediated Lung Cancer Cell Killing by Simultaneous Disruption of Glutathione and Thioredoxin Metabolism
Authors: Melissa A. Fath, Iman M. Ahmad, Carmen J. Smith, Jacquelyn Spence, Douglas R. Spitz
Journal: Clinical Cancer Research (2011)

Cancer cells (relative to normal cells) show increased steady-state levels of hydroperoxides that are compensated by increased glucose and hydroperoxide metabolism. The current study determined whether inhibitors of glucose and hydroperoxide metabolism could induce chemoradiosensitization by enhancing oxidative stress in lung cancer cells.A549 and NCI-H292 human lung carcinoma cells were treated with 2-deoxy-d-glucose (2DG) combined with carboplatin + ionizing radiation (IR). Lung cancer cells were further sensitized with inhibitors of glutathione (GSH)- and thioredoxin (Trx)-dependent metabolism [buthionine sulfoximine (BSO) and auranofin, respectively] in vitro and in vivo.When 2DG was combined with carboplatin + IR, clonogenic cell killing was enhanced in A549 and NCI-H292 cells, and this combination was more effective than paclitaxel + carboplatin + IR. The thiol antioxidant (N-acetylcysteine, NAC) was capable of protecting cancer cells from 2DG + carboplatin -induced cell killing. Simultaneous treatment of cancer cells with BSO and auranofin, at doses that were not toxic as single agents, also enhanced lung cancer cell killing and sensitivity to 2DG + carboplatin. This treatment combination also increased oxidation of both GSH and Trx, which were inhibited by NAC. Mice treated with auranofin + BSO showed no alterations in circulating leukocytes or red blood cells. Xenograft lung tumor growth in mice was more effectively inhibited by treatment with auranofin + BSO + carboplatin than animals treated with carboplatin or auranofin + BSO alone.These results show in vitro and in vivo that simultaneous inhibition of GSH and Trx metabolism can effectively inhibit lung cancer cell growth and induce chemosensitization by a mechanism that involves thiol-mediated oxidative stress.
What is a non-randomised controlled trial?
Authors: P. Sedgwick
Journal: BMJ (2014)

Researchers investigated whether a low cost public campaign by local health authorities reduced antibiotic prescribing for outpatients. A non-randomised controlled trial study design was used. The intervention was multifaceted and included posters, brochures, and advertisements on local media, plus a newsletter on local antibiotic resistance targeted at doctors and pharmacists. The campaign focused primarily on the prescription of antibiotics for upper respiratory tract infections. The trial was based in Emilia-Romagna in northern Italy. The provinces of Modena and Parma (about 1 150 000 residents) were chosen for implementation of the intervention between November 2011 and February 2012. The provinces where the campaign was not implemented, with no information provided to doctors and pharmacists, formed the control group (about 3 250 000 residents). The primary outcome was the change in prescribing rates of antibiotics for outpatients over five months.1 The researchers reported that a low cost community based public campaign targeted at residents, combined with a newsletter on local antibiotic resistance for doctors and pharmacists, was associated with a significantly decreased total rate of antibiotic prescribing. However, the campaign did not affect the participants' knowledge and attitudes about antibiotic resistance. Which of the following statements, if any, are true?
THE PHYSICAL WELFARE OF YOUTH
Authors: L. P. Lockhart
Journal: BMJ (1936)

tions and solutions in oil are apparently well absorbed in particles of this size in cats and dogs.If suitable conditions are found and absorption of drugs by the tracheo- bronchial mucous membrane is effected two great diffi- culties remain:1. To give a therapeuti.dose of a drug in an inhalation of moderate length.2. To measure exactly the dose given.
CCR2 is required for CD8-induced graft-versus-host disease
Authors: Theis H. Terwey, Theo D. Kim, Adam A. Kochman, Vanessa M. Hubbard, Sydney Lu, Johannes L. Zakrzewski, Teresa Ramirez-Montagut, Jeffrey M. Eng, Stephanie J. Muriglan, Glenn Heller, George F. Murphy, Chen Liu, Tulin Budak-Alpdogan, Onder Alpdogan, Marcel R. M. van den Brink
Journal: Blood (2005)
Radiation induced cytochrome c release causes loss of rat colonic fluid absorption by damage to crypts and pericryptal myofibroblasts
Authors: J R Thiagarajah, P Gourmelon, N M Griffiths, F Lebrun, R J Naftalin, K C Pedley
Journal: Gut (2000)

Therapeutic or accidental exposure to radiation commonly causes gastrointestinal disturbances, including diarrhoea. Rats subjected to whole body ionising radiation at a dose of 8 Gy lose their capacity to absorb fluid via the descending colon after four days. After seven days, fluid absorption recovers to control levels.To investigate the effect of ionising radiation on colonic permeability together with its effect on mitochondria dependent apoptotic signals and intercellular adhesion molecules.Rats were irradiated with doses of 0-12 Gy. Colonic permeability was measured by accumulation of fluorescein isothiocyanate (FITC) dextran in crypt lumens. Changes in levels of cytochrome c, caspase 3, E and OB cadherin, beta-catenin smooth muscle actin, and collagen IV were assessed using immunocytochemistry with confocal microscopy.Cytosolic cytochrome c increased after 8 Gy (t(1/2) 1.4 (0.6) hours) and peaked at approximately six hours. Caspase 3 increased more slowly, particularly in crypt epithelial cells (t(1/2) 57 (14.5) hours). Pericryptal myofibroblasts disintegrated within 24 hours as was evident from loss of OB cadherin and smooth muscle actin. This coincided with increased crypt permeability to dextran. Intercellular adhesion between crypt luminal cells was not lost until day 4 when both beta-catenin and E-cadherin were minimal. The half maximal dose-response for these effects was in the range 2-4 Gy. Recovery of colonic transport was concurrent with recovery of pericryptal smooth muscle actin and OB cadherin. The pan caspase inhibitor Z-Val-Ala-Asp.fluoromethylketone (1 mg/kg per day) had a small effect in conserving the pericryptal sheath myofibroblasts and sheath permeability but had no systemic therapeutic effects.These data suggest that radiation damage to the colon may be initiated by mitochondrial events. Loss of crypt fluid absorption and increased permeability coincided with decreased intercellular adhesion between crypt epithelial cells and loss of pericryptal sheath barrier function.
Cholangitis in the acquired immunodeficiency syndrome: report of two cases and review of the literature.
Authors: D Roulot, D Valla, F Brun-Vezinet, M A Rey, F Clavel, C Degott, J Guillan, J Verduron, B Rueff, J P Benhamou
Journal: Gut (1987)

We report the cases of one patient with the acquired immunodeficiency syndrome as a result of human immunodeficiency virus type 1/lymphadenopathy associated virus type 1/human T-cell lymphotrophic virus type III (HIV-1/LAV-1/HTLV-III) infection and of another patient with AIDS related complex caused by human immunodeficiency virus type 2/lymphadenopathy associated virus type 2 (HIV-2/LAV-2) infection, who were suffering from cholangitis. The manifestations and possible mechanisms for cholangitis in these patients and in 10 previously reported similar cases are reviewed.