tbuckley/cabot-search huggingface dataset:
Foundation hospitals: a new direction for NHS reform?
Authors: K. Walshe
Journal: Journal of the Royal Society of Medicine (2003)

The Government's proposals to create new ‘foundation hospitals’ are moving forward rapidly, despite considerable political opposition not least within the Labour Party itself, and deep scepticism about the ideas in many quarters of the National Health Service and the professions. Advocates claim they will lead the way to a new understanding of public services and public ownership, ‘set the NHS free’ from the iron grip of Whitehall control, and make health services more accountable to and responsive to patients and local communities1. Critics argue that the ideas are, at best, a half-baked, reheated version of NHS trusts launched in the early 1990s2. At worst, they assert, foundation hospitals are the start of the break-up of the NHS, a creeping form of privatization that will undermine the fundamental values of social solidarity, care according to clinical need rather than ability to pay, and equity in healthcare provision on which the NHS was founded. Although the necessary legislation has yet to be passed, the Government has already issued a prospectus for potential applicants for foundation status, and set out a timetable that would see the first foundation hospital identified this year and coming into being in April 20043.

This paper examines the case for foundation hospitals, and tries to set it in the wider context of health policy development and NHS reform over the past two decades. It argues that there is a need for a fundamental change in the systems for governance and accountability in the NHS and examines how the creation of foundation hospitals might help to meet that need.
Medical Management of the Acute Radiation Syndrome: Recommendations of the Strategic National Stockpile Radiation Working Group
Authors: Jamie K. Waselenko
Journal: Annals of Internal Medicine (2004)

Physicians, hospitals, and other health care facilities will assume the responsibility for aiding individuals injured by a terrorist act involving radioactive material. Scenarios have been developed for such acts that include a range of exposures resulting in few to many casualties. This consensus document was developed by the Strategic National Stockpile Radiation Working Group to provide a framework for physicians in internal medicine and the medical subspecialties to evaluate and manage large-scale radiation injuries. Individual radiation dose is assessed by determining the time to onset and severity of nausea and vomiting, decline in absolute lymphocyte count over several hours or days after exposure, and appearance of chromosome aberrations (including dicentrics and ring forms) in peripheral blood lymphocytes. Documentation of clinical signs and symptoms (affecting the hematopoietic, gastrointestinal, cerebrovascular, and cutaneous systems) over time is essential for triage of victims, selection of therapy, and assignment of prognosis. Recommendations based on radiation dose and physiologic response are made for treatment of the hematopoietic syndrome. Therapy includes treatment with hematopoietic cytokines; blood transfusion; and, in selected cases, stem-cell transplantation. Additional medical management based on the evolution of clinical signs and symptoms includes the use of antimicrobial agents (quinolones, antiviral therapy, and antifungal agents), antiemetic agents, and analgesic agents. Because of the strong psychological impact of a possible radiation exposure, psychosocial support will be required for those exposed, regardless of the dose, as well as for family and friends. Treatment of pregnant women must account for risk to the fetus. For terrorist or accidental events involving exposure to radioiodines, prophylaxis against malignant disease of the thyroid is also recommended, particularly for children and adolescents.
Molecular basis of complement activation in ischemic myocardium: identification of specific molecules of mitochondrial origin that bind human C1q and fix complement.
Authors: A Kagiyama, H E Savage, L H Michael, G Hanson, M L Entman, R D Rossen
Journal: Circulation Research (1989)

Mitochondria may be a source of molecules that activate complement during ischemic injury to myocardium, providing therewith a stimulus for infiltration of polymorphonuclear leukocytes. To identify specific molecules that activate the classical complement pathway, detergent lysates of canine cardiac mitochondria were fractionated by polyacrylamide gel electrophoresis and transferred electrophoretically to nitrocellulose paper (NCP). The NCP replicas of the gels were incubated with isolated C1q and fresh sera as a source of complement, washed briefly, and overlaid with sensitized sheep erythrocytes (RBC) in agarose. A cluster of four to six molecules between 45 and 53 kDa as well as four others, 34, 30, 26, and 23 kDa, consumed complement thereby preventing complement-mediated lysis of sensitized sheep RBC in the agarose overlay. Additional molecules reactive with C1 were identified by their ability to bind isolated human C1q and to serve as assembly sites for later acting complement components. Sites of localization of complement were demonstrated by incubating NCP replicas of fractionated mitochondria with antisera specific for C1q, C3, C5, and C9, followed by peroxidase-conjugated anti-immunoglobulin and substrate. A total of 12 C1q binding molecules ranging in size from 67 kDa to 23 kDa, which can fix later acting complement components, were identified. At least two of these reacted with antisera prepared against canine cardiac lymph collected in the first 3-4 hours after a 45-minute coronary artery occlusion. These studies present direct evidence that specific molecules, released from subcellular fractions of myocardial cells rich in mitochondria, can activate the complement cascade.
The arrest of intestinal epithelial `turnover' by the use of x-irradiation
Authors: G. Wiernik, R. G. Shorter, B. Creamer
Journal: Gut (1962)

Mitotic activity and hence cell turnover has been abolished by x-irradiation with 1,000 r. in segments of the rat's gut. The whole stomach, the ascending colon, and 5 cm. of jejunum and ileum were irradiated and the changes observed histologically up to three days. Cessation of cell turnover in the small intestine is followed by cell death and desquamation within 24 hours, leading to denudation of the epithelium and collapse of villous structure. The pylorus and colon showed similar but less marked changes. In contrast the fundus and body of the stomach were unaffected by the absence of mitosis over a period of three days. It is concluded that cell turnover is, in part, necessary to maintain the mucosal structure, particularly the villous pattern in the small intestine.
Low-Density Lipoprotein Cholesterol–Lowering Effects of AMG 145, a Monoclonal Antibody to Proprotein Convertase Subtilisin/Kexin Type 9 Serine Protease in Patients With Heterozygous Familial Hypercholesterolemia
Authors: Frederick Raal, Rob Scott, Ransi Somaratne, Ian Bridges, Gang Li, Scott M. Wasserman, Evan A. Stein
Journal: Circulation (2012)

Background— Despite statin treatment, many patients with heterozygous familial hypercholesterolemia do not reach desired low-density lipoprotein cholesterol (LDL-C) targets. AMG 145, a fully human monoclonal antibody against proprotein convertase subtilisin/kexin type 9 (PCSK9) serine protease, demonstrated significant reductions in LDL-C in phase 1 studies. This phase 2, multicenter, double-blind, randomized, placebo-controlled, dose-ranging study evaluated the efficacy and safety of AMG 145 in heterozygous familial hypercholesterolemia patients. Methods and Results— Patients with heterozygous familial hypercholesterolemia diagnosed by Simon Broome criteria with LDL-C ≥2.6 mmol/L (100 mg/dL) despite statin therapy with or without ezetimibe were randomized 1:1:1 to AMG 145 350 mg, AMG 145 420 mg, or placebo-administered subcutaneously every 4 weeks. The primary end point was percentage change from baseline in LDL-C at week 12. Of 168 patients randomized, 167 received investigational product and were included in the full analysis set (mean [SD] age, 50 [13] years; 47% female; 89% white; mean [SD] baseline LDL-C, 4.0 [1.1] mmol/L (156 [42] mg/dL)). At week 12, LDL-C reduction measured by preparative ultracentrifugation (least squares mean [standard error (SE)]) was 43 (3)% and 55 (3)% with AMG 145 350 mg and 420 mg, respectively, compared with 1 (3)% increase with placebo ( P &lt;0.001 for both dose groups). Serious adverse events (not considered treatment-related) occurred in 2 patients on AMG 145. Conclusions— AMG 145 administered every 4 weeks yielded rapid and substantial reductions in LDL-C in heterozygous familial hypercholesterolemia patients despite intensive statin use, with or without ezetimibe, with minimal adverse events and good tolerability. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT01375751.
A Method of Draining the Septic Uterus
Authors: A. R. Hobbs
Journal: BMJ (1927)

To those who are much engaged in the treatment of puerperal sepsis there is one.form of treatment, at any rate, which is rapidly passing out of favour,-and that is leaving the septic uterus to take care of itself.This opinioni was definiitely reached in this hospital when it was found that in over half the cases of puerperal sepsis admitted there was pent-up pus.
DNA Topoisomerases: Essential Enzymes and Lethal Targets
Authors: A Y Chen, L F Liu
Journal: The Annual Review of Pharmacology and Toxicology (1994)

INTRODUCTION In 1971, Wang (1) discovered the first DNA topoisomerase in Escherichia coli. The enzyme (E. coli DNA topoisomerase I, or w protein) catalyzed relaxation of negatively supercoiled DNA in the absence of any energy cofactor (1). Wang proposed that this enzyme also catalyzed transient nicking of the DNA double helix and possessed both DNase and ligase activity in one polypeptide (1). The lack of any energy cofactor for the reaction also led Wang to the proposal that the enzyme may form a high-energy covalent bond between itself and the transiently broken DNA phosphodiester bond (1). Both of these predictions have turned out to be correct (2). Since the discovery of E. coli topoisomerase I, investigators have isolated many other DNA topoisomerases from both prokaryotes and eukaryotes. In 1972, Champoux & Dulbecco isolated an enzyme with activity similar to that of E. coli topoisomerase I from mouse embryo cells (3). In 1976, Gellert and his colleagues identified an enzyme activity opposing E. coli DNA topoisomerase I (4). They demonstrated that this enzyme (E. coli DNA topoisomerase II, or gyrase) catalyzed the conversion of relaxed DNA into negatively supercoiled DNA in a reaction requiring ATP hydrolysis (4). These two opposing activities are important for maintaining the super­ helical state of the chromosomal DNA during various DNA transactions (5-8). In 1979, Liu et al (9) isolated an enzyme from bacteriophage
Human CD271-Positive Melanoma Stem Cells Associated with Metastasis Establish Tumor Heterogeneity and Long-term Growth
Authors: Gianluca Civenni, Anne Walter, Nikita Kobert, Daniela Mihic-Probst, Marie Zipser, Benedetta Belloni, Burkhardt Seifert, Holger Moch, Reinhard Dummer, Maries van den Broek, Lukas Sommer
Journal: Cancer Research (2011)

Abstract Human melanoma is composed of distinct cell types reminiscent of neural crest derivatives and contains multipotent cells that express the neural crest stem cell markers CD271(p75NTR) and Sox10. When isolated from solid tumors by using a method that leaves intact cell surface epitopes, CD271-positive, but not CD271-negative, cells formed tumors on transplantation into nude or nonobese diabetic/severe combined immunodeficient (NOD/SCID) mice. These tumors fully mirrored the heterogeneity of the parental melanoma and could be passaged more than 5 times. In contrast, in more immunocompromised NOD/SCID/IL2rγnull mice, or in natural killer cell–depleted nude or NOD/SCID mice, both CD271-positive and CD271-negative tumor cell fractions established tumors. However, tumors resulting from either fraction did not phenocopy the parental tumors, and tumors derived from the CD271-negative cell fraction could not be passaged multiple times. Together, our findings identify CD271-positive cells as melanoma stem cells. Our observation that a relatively high frequency of CD271/Sox10-positive cells correlates with higher metastatic potential and worse prognosis further supports that CD271-positive cells within human melanoma represent genuine cancer stem cells. Cancer Res; 71(8); 3098–109. ©2011 AACR.
The Effect of Hypocapnia on Arterial Blood Pressure
Authors: J. F. BURNUM, J. B. HICKAM, H. D. MCINTOSH
Journal: Circulation (1954)

In man, hypocapnia induced by hyperventilation causes a drop in arterial pressure. The calculated peripheral resistance is decreased, indicating a net vasodilatation. The forearm blood flow is markedly increased, and the vascular resistance of the forearm is much reduced. Persons with impaired function of the sympathetic nervous system continue to show these effects. The increase in forearm flow is not prevented by brachial block. These results suggest that hypocapnia acts directly on blood vessels to produce a net over-all vasodilatation and fall in blood pressure, and that this effect is not mediated through the nervous system, as usually supposed.
Embolisation in Behcet's disease
Authors: A K Bozkurt
Journal: Thorax (2002)

<b>Background:</b> Nitric oxide in exhaled air (FE<sub>NO</sub>) is a marker of eosinophilic airway inflammation. A study was undertaken to determine whether FE<sub>NO</sub> predicts asthma relapse in asymptomatic asthmatic children in whom inhaled corticosteroids are discontinued. <b>Methods:</b> Forty children (21 boys) of mean age 12.2 years on a median dose of 400 μg budesonide or equivalent (range 100–400) were included. FE<sub>NO</sub> was measured before and 2, 4, 12, and 24 weeks after withdrawal of steroids. A relapse was defined as more than one exacerbation per month, or need for β agonist treatment on 4 days per week for at least 2 weeks, or diurnal peak flow variability of &gt;20%. FE<sub>NO</sub> measurements were performed online with an expiratory flow of 50 ml/s. <b>Results:</b> Nine patients relapsed. Two and 4 weeks after withdrawal of steroids geometric mean FE<sub>NO</sub> in children who were about to relapse was higher than in those who did not relapse: 35.3 ppb <i>v</i> 15.7 ppb at 2 weeks (ratio 2.3; 95% CI 1.2 to 4.1; p = 0.01) and 40.8 ppb <i>v</i> 15.9 ppb at 4 weeks (ratio 2.6; 95% CI 1.3 to 5.1). An FE<sub>NO</sub> value of 49 ppb at 4 weeks after discontinuation of steroids had the best combination of sensitivity (71%) and specificity (93%) for asthma relapse. <b>Conclusion:</b> FE<sub>NO</sub> 2 and 4 weeks after discontinuation of steroids in asymptomatic asthmatic children may be an objective predictor of asthma relapse.
Dose-Intensive Therapy for Breast Cancer
Authors: Joyce A. O'Shaughnessy
Journal: JAMA (1993)

<h3>SELECTED CASE</h3> In 1988, a 38-year-old woman noticed progressive, symmetrical hardening of both breasts. Mammograms showed dense tissue bilaterally with no discrete masses and biopsies were unfortunately not recommended. In 1989, she developed lumbar back pain, and a complete blood cell count showed a hemoglobin level of 90 mg/L, a white blood cell count of 3.4×10<sup>9</sup>/L, and a platelet count of 90×10<sup>9</sup>/L. Her breast examination showed bilateral, diffuse denseness without skin involvement. Breast and bone marrow biopsies showed estrogen receptor-positive infiltrating ductal breast carcinoma metastatic to the bone marrow. She was treated with dose-intensive fluorouracil, leucovorin calcium, doxorubicin, and cyclophosphamide (FLAC) in combination with the hematopoietic growth factor, granulocyte-macrophage colony-stimulating factor (GMCSF). After two cycles of therapy, her back pain had disappeared and her blood cell counts normalized. After 10 cycles, her breast examination was normal, but repeat bone marrow examination showed a residual microscopic focus
Spontaneous spondylodiscitis caused by Klebsiella oxytoca
Authors: J M Sabio
Journal: Annals of the Rheumatic Diseases (2002)

The main objective of this work was the development of a skew-slit collimator for small-animal SPECT to replace the state-of-the-art multipinhole collimator. <b>Methods:</b> A pinhole forms a cone-beam imaging geometry. If the collimator rotates around the object in a circular orbit, the projection measurements acquired by the cone-beam imaging geometry are incomplete and not enough for artifact-free image reconstruction. The severity of the artifact is proportional to the cone angle of the pinhole in the direction of the axis of rotation. Multipinhole geometry can greatly reduce the data-insufficiency artifacts; however, image magnification is sacrificed. By transforming a pinhole into a pair of skewed slits, we are able to use a large cone angle in the transaxial direction to increase image magnification and a small cone angle in the direction of the axis of rotation to reduce data-insufficiency artifacts. This transformation is achieved by placing a vertical slit (i.e., the slit is parallel to the axis of rotation) close to the object and placing a horizontal slit farther out. Similar to the multipinhole collimator, we also propose a multiple–skew-slit collimator that has a single vertical slit and several horizontal slits. <b>Results:</b> Computer simulations were performed to verify the working principle of the skew-slit collimator. A prototype multiple–skew-slit collimator was fabricated, and phantom experiments were performed on a SPECT system. The smallest channels (of 0.75-mm diameter) in the phantom were clearly separated in the reconstructed image. <b>Conclusion:</b> This study suggests a novel technology in small-animal SPECT to replace the multipinhole collimator, resulting in significantly reduced image artifacts and increased transaxial resolution. A physical multiple–skew-slit system was built and tested. Compared with the multipinhole system, the multiple–skew-slit system has a larger image magnification in the transaxial direction and thus has better image resolution.
A double blind, randomised, parallel group study on the efficacy and safety of treating acute lateral ankle sprain with oral hydrolytic enzymes
Authors: G M M J Kerkhoffs, P A A Struijs, C de Wit, V W Rahlfs, H Zwipp, C N van Dijk
Journal: British Journal of Sports Medicine (2004)

Objective: To compare the effectiveness and safety of the triple combination Phlogenzym (rutoside, bromelain, and trypsin) with double combinations, the single substances, and placebo. Design: Multinational, multicentre, double blind, randomised, parallel group design with eight groups structured according to a factorial design. Setting: Orthopaedic surgery and emergency departments in 27 European hospitals. Participants: A total of 721 patients aged 16–53 years presenting with acute unilateral sprain of the lateral ankle joint. Primary efficacy criteria: ( a ) Pain on walking one or two steps, as defined by the patient on a visual analogue scale. ( b ) The range of motion, as measured by the investigator and expressed as a sum of flexion and extension. ( c ) The volume of the injured ankle measured with a volometer. Results: At the primary end point at seven days, the greatest reduction in pain was in the bromelain/trypsin group (73.7%). The Phlogenzym group showed a median reduction of 60.3%, and the placebo group showed a median reduction of 73.3%. The largest increase in range of motion (median) was in the placebo group (60% change from baseline). The Phlogenzym group showed a median increase of 42.9%. The biggest decrease in swelling was in the trypsin group (3.9% change from baseline). The Phlogenzym group showed a −2.30% change from baseline and the placebo group a −2.90% change. In the subgroup analysis of patients who did not use a Caligamed brace, Phlogenzym was superior to placebo for the summarising directional test of the primary efficacy criteria (MW = 0.621; LB-CI 0.496; p = 0.029; one sided Wei-Lachin procedure). The vast majority of doctors and patients rated the tolerability of all treatments tested as very good or at least good. Conclusions: Phlogenzym was not found to be superior to the three two-drug combinations, the three single substances, or placebo for treatment of patients with acute unilateral sprain of the lateral ankle joint. The small subgroup of patients treated without the support of a Caligamed brace showed evidence of superiority of Phlogenzym over placebo. Further research is warranted to study this effect of Phlogenzym in patients treated without ankle support.
Pseudosclerosing cholangitis in extrahepatic portal venous obstruction.
Authors: J B Dilawari, Y K Chawla
Journal: Gut (1992)

Biliary changes secondary to portal hypertension have rarely been described in published reports. Twenty consecutive patients with extrahepatic portal venous obstruction, all of whom showed a variable degree of abnormalities in the biliary tract suggestive of sclerosing cholangitis, are described. These biliary abnormalities were: focal narrowing, dilatations, and cholangitic changes affecting the main bile ducts and hepatic ducts. The left hepatic duct and its branches were affected in all patients. Only one patient had clinical or biochemical evidence of cholestasis. The mechanism of these abnormalities in the biliary tract of these patients is perhaps the development of portal collaterals.
Weighted Neighbor Joining: A Likelihood-Based Approach to Distance-Based Phylogeny Reconstruction
Authors: William J. Bruno, Nicholas D. Socci, Aaron L. Halpern
Journal: Molecular Biology and Evolution (2000)

We introduce a distance-based phylogeny reconstruction method called “weighted neighbor joining,” or “Weighbor” for short. As in neighbor joining, two taxa are joined in each iteration; however, the Weighbor criterion for choosing a pair of taxa to join takes into account that errors in distance estimates are exponentially larger for longer distances. The criterion embodies a likelihood function on the distances, which are modeled as correlated Gaussian random variables with different means and variances, computed under a probabilistic model for sequence evolution. The Weighbor criterion consists of two terms, an additivity term and a positivity term, that quantify the implications of joining the pair. The first term evaluates deviations from additivity of the implied external branches, while the second term evaluates confidence that the implied internal branch has a positive branch length. Compared with maximum-likelihood phylogeny reconstruction, Weighbor is much faster, while building trees that are qualitatively and quantitatively similar. Weighbor appears to be relatively immune to the “long branches attract” and “long branch distracts” drawbacks observed with neighbor joining, BIONJ, and parsimony.