tbuckley/cabot-search huggingface dataset:
Teenager carrying anencephalic fetus is granted right to travel to UK for abortion
Authors: Clare Dyer
Journal: BMJ (2007)

An influential group of MPs has claimed that widespread financial incompetence is adding to the cost of the United Kingdom's controversial private finance initiative (PFI).The House of Commons Committee of Public Accounts made its new attack on the PFI after it discovered that the government had clawed back £100m (€145m; $200m) less than was predicted from the new private-public profit sharing schemes.The committee's chairman, the Conservative MP Edward Leigh, blamed the loss on the failure of Treasury officials to oversee key refinancing arrangements.In 2002 ministers introduced changes so that public sector bodies could share in some of the financial gains when big PFI loans were rearranged.Typically, these loans were renegotiated on a more favourable basis once PFI projects had been completed and the risks involved were lower.However, left to their own devices, officials in local hospitals had been out of their depth negotiating with their counterparts in the private sector, the committee says.In 2003 the Office of Government Commerce, which then had responsibility for PFI policy, told the public accounts committee that it expected the public sector to receive between £175m and £200m from the voluntary sharing arrangements in early PFI deals.However, up to December 2006 the government had secured the right to gains of only £93m."Proceeds gained by the public sector from PFI debt refinancing under the voluntary code for the sharing of gains are currently well short of expectations" said Mr Leigh.
Leukotriene C4 binds to human glomerular epithelial cells and promotes their proliferation in vitro.
Authors: L Baud, J Sraer, J Perez, M P Nivez, R Ardaillou
Journal: Journal of Clinical Investigation (1985)

In human and experimental glomerulonephritis, glomerular hypercellularity results both from accumulation of macrophages and proliferation of resident glomerular cells. The recent identification of macrophage-derived factors that stimulate mesangial and epithelial cell proliferation suggests that these factors might contribute to the hypercellularity. To determine the identity of such macrophage-derived growth factors, we studied the effect of leukotrienes (LTs), products that are released from macrophages and leukocytes, on proliferation of human glomerular epithelial cells in culture. Dose-dependent (1-100 nM) stimulation of [3H]thymidine incorporation, an index of cell proliferation, was observed in cells incubated with the sulfidopeptide LTs, LTC4 and LTD4, but not with LTB4. The response was 248 and 172% of control values at 100 nM LTC4 and LTD4, respectively. This effect of LTC4 was abolished by FPL 55712. Subsequent binding studies demonstrated that glomerular epithelial cells possess specific receptors for LTC4. [3H]LTC4 bound rapidly at 8 degrees C to the cells. There was a plateau after 40 min incubation. Maximum specific binding was 70-90% of total binding. Specific binding was totally reversible with addition of an excess of unlabeled LTC4. Analysis of time-course association slopes at two concentrations of [3H]LTC4 and of the competition between a single concentration of [3H]LTC4 and increasing concentrations of unlabelled LTC4 allowed calculation of dissociation constants (Kd) of 220 and 217 nM, respectively. Both LTD4 and LTE4 exhibited ED50 values that were at least one order of magnitude higher than for LTC4. Thus, our findings suggest that LTC4 binds to specific receptors of glomerular epithelial cells, promotes proliferation of these cells, and could contribute to epithelial hypercellularity found in glomerulonephritis.
STUDIES ON THE PATHOGENESIS OF STAPHYLOCOCCAL INFECTION
Authors: Keiichi Goshi, Leighton E. Cluff, Joseph E. Johnson
Journal: The Journal of Experimental Medicine (1961)

Necrosis of rabbit skin produced by thermal injury was found to result in a striking increase in local infectivity of staphylococci that were coagulase-positive and hemolytic, but no local increase in the infectivity of non-pathogenic staphylococci. Infection produced in necrotic burns extended beyond the area of burn and was characterized by hemorrhage, edema, and necrosis of contiguous normal skin. Such infections, however, never resulted in bacteriemia or metastatic abscesses, and there was no effect of the necrotic burn upon the infectivity of staphylococci injected into normal skin of the burned animal. Recovery of rabbits from severe burn infections was associated with the development of high titers of serum antibody to the alpha hemolysin or dermonecrotoxin of the staphylococcus. Thirty to 100 days after the initial burn infection, it was found that rabbits could no longer be infected in a necrotic burn, although infection induced in normal skin of these resistant animals was no different from that in normal rabbits. Immunity to infection by pathogenic staphylococci in necrotic burns could be induced by vaccination with potent alpha hemolysin toxoid, and this immunity was passively transferable with rabbit antiserum. No strain specificity was detected for this immunity in that immunization with toxoid prepared from bacteriophage type 52/42B/80/81 staphylococci protected animals against infection in a necrotic burn by other typable and non-typable staphylococci. Histopathological study of infected necrotic burns in normal rabbits showed extensive necrosis, hemorrhage, edema, and many masses of bacteria but leucocytic infiltration was observed only at the margin of the infection. In contrast, the infected necrotic burns in animals immunized with alpha hemolysin toxoid showed few bacteria and marked leucocytic infiltration throughout the burn. These experiments have, therefore, demonstrated a significant immunity to infection by pathogenic staphylococci in necrotic tissue but not in normal skin, associated with serum antibody to the alpha hemolysin or dermonecrotoxin of the bacteria. The implications of these findings are discussed.
Travel and tiredness
Authors: T. Smith
Journal: BMJ (1995)

We all enjoy laughing at the pompous, arrogant assertions made by doctors in the 19th century: they would prescribe complex diets, regulate the patient's intake of coffee and tea as well as alcohol, forbid or encourage exertion, recommend radical surgery--and all this with no research based evidence at all. When the first passenger trains came into operation physicians warned that travel at 30 miles per hour was hazardous to the cardiovascular and nervous systems. Indeed travel was clearly an important factor in the medical assessment of lifestyle; on the one hand victims of tuberculosis and bronchitis were sent on …
Comparisons of care provided by specialists vs. generalists in the medical ICU/CCU
Authors: Kim A. Eagle, Albert G. Mulley, Terry Fields, Steven Skates, George Bero, Chester C. Clark, Jayne O. Sexton, Victoria A. Reder, Gretchen Berrigan, Joyce Procaccini, George E. Thibault
Journal: Journal of the American College of Cardiology (1990)
Heat-shock protein induction in rat hearts. A direct correlation between the amount of heat-shock protein induced and the degree of myocardial protection.
Authors: M M Hutter, R E Sievers, V Barbosa, C L Wolfe
Journal: Circulation (1994)

BACKGROUND Previous studies have demonstrated that heat-shock treatment results in the induction of 72-kD heat-shock protein (HSP72) and a reduction of infarct size after subsequent ischemia and reperfusion. METHODS AND RESULTS To test the hypothesis that the degree of protection from ischemic injury in heat-shocked rats correlates with the degree of prior HSP72 induction, rats pretreated with 40 degrees C, 41 degrees C, or 42 degrees C of whole-body hyperthermia followed by 24 hours of recovery and control rats (n = 6 in each group) were quantitatively assessed for the presence of myocardial HPS72 by optical densitometry of Western blots and a primary antibody that is specific for HSP72 and a tertiary antibody labeled with 125I. Although rats heat-shocked to 40 degrees C had no significant induction of myocardial HSP72, rats heat-shocked to 41 degrees C and 42 degrees C demonstrated progressively increased amounts of myocardial HSP72 compared with controls. Separate groups of rats heat-shocked to 40 degrees C (n = 16), 41 degrees C (n = 37), and 42 degrees C (n = 36) with 24 hours of recovery and controls (n = 26) were subjected to 35 minutes of left coronary artery occlusion and 120 minutes of reperfusion. Compared with control and 40 degrees C rats, there was progressive infarct size reduction, assessed by triphenyltetrazolium chloride staining, in rats that were heat-shocked to 41 degrees C and 42 degrees C. Furthermore, there was a direct correlation between the amount of HSP72 induced and the reduction in infarct size (r = .97, P = .037). CONCLUSIONS These results suggest that the improved salvage after heat-shock pretreatment may be related to the amount of HSP72 induced before prolonged ischemia and reperfusion.
From a cancer drug fund to value based pricing of drugs
Authors: M. Duerden
Journal: BMJ (2010)

Such pricing may be hard to implement and may not add value 

In late May 2010, the National Institute for Health and Clinical Excellence (NICE) decided not to support sorafenib (Nexavar) for use in hepatocellular cancer in England and Wales. NICE advised that the drug was not cost effective; it costs around £27 000 (€32 400; $42 500) for each course of treatment and improves median survival by 2.8 months in people dying of cancer (50% of people might be expected not to get this benefit, and 50% might get this benefit or more).1 The media response was mostly an outcry, “Fury as new cancer drug is banned.”2

Various patient groups and experts were also not happy with this decision. Professor Karol Sikora representing CancerPartnersUK said, “It is devastating that NICE has failed to use this opportunity to properly consider the very strong recommendations from UK oncologists who only want the best for their patients.”3 It is noteworthy that none of these emotive responses suggested or recognised that the drug may cost too much in relation to its limited benefit and that this money might be better spent elsewhere in the NHS—for example, on palliative care services, where arguably it might give better value for money.

NICE’s most favourable analysis of the incremental cost per quality adjusted life year (QALY) for sorafenib versus best supportive care was £52 000, even with the drug company reducing the cost paid by the NHS by 25% as part of a patient access scheme.1 Even using controversial “end of life” criteria, …
SURGERY OF TUMORS OF THE BLADDER FROM A MODERN ASPECT.
Authors: G. KOLISCHER
Journal: JAMA (1907)

Operative interference in tumors of the bladder is not at the present time conducted in a uniform manner, nor is it based on any generally accepted rules, as is the case in other domains of surgery. Each operator has notions and fancies of his own and operates accordingly, employing in many instances methods which, if applied in other branches of akiurgy, would bring ridicule on his head. Therefore, the possibility of approaching this subject in a more orderly and systematic manner, as well as the great scientific advantage to be derived therefrom, has induced us to attempt, by taking into consideration the work that we had observed in various genitourinary clinics, by availing ourselves of the pertinent literature, and by analyzing our own experiences, to establish certain basic principles on which, as a foundation, might eventually be built up a rational and consistent surgery of tumors of the bladder. From the
Separable Learning Systems in the Macaque Brain and the Role of Orbitofrontal Cortex in Contingent Learning
Authors: Mark E. Walton, Timothy E.J. Behrens, Mark J. Buckley, Peter H. Rudebeck, Matthew F.S. Rushworth
Journal: Neuron (2010)

Orbitofrontal cortex (OFC) is widely held to be critical for flexibility in decision-making when established choice values change. OFC's role in such decision making was investigated in macaques performing dynamically changing three-armed bandit tasks. After selective OFC lesions, animals were impaired at discovering the identity of the highest value stimulus following reversals. However, this was not caused either by diminished behavioral flexibility or by insensitivity to reinforcement changes, but instead by paradoxical increases in switching between all stimuli. This pattern of choice behavior could be explained by a causal role for OFC in appropriate contingent learning, the process by which causal responsibility for a particular reward is assigned to a particular choice. After OFC lesions, animals' choice behavior no longer reflected the history of precise conjoint relationships between particular choices and particular rewards. Nonetheless, OFC-lesioned animals could still approximate choice-outcome associations using a recency-weighted history of choices and rewards.
The Compassionate Patient
Authors: Samuel Vaisrub
Journal: JAMA (1980)

We hear a great deal about the compassionate physician, but hardly a word about the compassionate patient. This oversight is totally undeserved. The compassionate patient is holistic. He views the physician as a whole person, replete with joys as well as anxieties that fluctuate with successes and failures of his therapy. He senses the physician's need for appreciation, gratitude, and approval. To satisfy this need, the compassionate patient praises the prescribed medication, even though it was never taken, or, worse still, it was ineffective. Such false feedbacks bolster the physician's self-confidence. Unfortunately, they also bolster the physician's confidence in what may be worthless drugs. The compassionate patient faces a serious dilemma when he becomes involved in a randomized, prospective, double-blind comparative trial of a drug and a placebo. Should he praise at the risk of praising a placebo or should he disparage at the risk of disparaging the real thing?
Limitation of the validity of the homeostasis model assessment as an index of insulin resistance in Korea
Authors: Eun Seok Kang, Yong Seok Yun, Seok Won Park, Hyeung Jin Kim, Chul Woo Ahn, Young Duk Song, Bong Soo Cha, Sung Kil Lim, Kyung Rae Kim, Hyun Chul Lee
Journal: Metabolism (2005)
Inflammatory T Cell Responses Rely on Amino Acid Transporter ASCT2 Facilitation of Glutamine Uptake and mTORC1 Kinase Activation
Authors: Mako Nakaya, Yichuan Xiao, Xiaofei Zhou, Jae-Hoon Chang, Mikyoung Chang, Xuhong Cheng, Marzenna Blonska, Xin Lin, Shao-Cong Sun
Journal: Immunity (2014)
No Statistical Refuge for the α1 Antitrypsin-Deficient Smoker
Authors: Kenneth M. Moser
Journal: JAMA (1975)

All would agree that the best solution to the near-epidemic problem of chronic obstructive pulmonary diseases is to learn how to prevent them. The great "antismoking wars" of the 1960s have proved inconclusive, and the combatants are obscured by an increasingly heavy layer of cigarette smoke. While the battle continues, the ultimate weapon— threat of death and disability—has been used; and without the decisive effect hoped for. To what weapons do we turn now? There are two of major potential. One is discovery of the causes of chronic obstructive lung diseases (COPD) (subtitle: how cigarette smoking does its deadly work). Such discovery may permit the institution of prophylactic alternatives acceptable to people bent on puffing away. The other weapon, less sweeping in impact, is the identification of persons in whom cigarette smoking will induce obstructive lung disease. A great refuge of the smoker is the statistical thicket. Since many smokers
Coxsackie and Adenovirus Receptor Is a Modifier of Cardiac Conduction and Arrhythmia Vulnerability in the Setting of Myocardial Ischemia
Authors: Roos F.J. Marsman, Connie R. Bezzina, Fabian Freiberg, Arie O. Verkerk, Michiel E. Adriaens, Svitlana Podliesna, Chen Chen, Bettina Purfürst, Bastian Spallek, Tamara T. Koopmann, Istvan Baczko, Cristobal G. dos Remedios, Alfred L. George, Nanette H. Bishopric, Elisabeth M. Lodder, Jacques M.T. de Bakker, Robert Fischer, Ruben Coronel, Arthur A.M. Wilde, Michael Gotthardt, Carol Ann Remme
Journal: Journal of the American College of Cardiology (2013)
Human leukocyte elastase is an endogenous ligand for the integrin CR3 (CD11b/CD18, Mac-1, alpha M beta 2) and modulates polymorphonuclear leukocyte adhesion.
Authors: T Q Cai, S D Wright
Journal: The Journal of Experimental Medicine (1996)

Integrin CR3 (CD11b/CD18, Mac-1, alpha M beta 2) mediates the transient adhesion of polymorphonuclear leukocytes (PMN) to surfaces coated with fibrinogen, C3bi, ICAM-1, and other ligands. Recent studies (Cai, T.-Q., and S.D. Wright 1995. J. Biol. Chem. 270:14358) suggest that adhesion may be favored by stimulus-dependent changes in the kinetics of ligand binding by CR3. Cell detachment, on the other hand, must occur by a different mechanism because binding kinetics cannot affect cell adhesion after binding of ligand has occurred. We have sought a mechanism that would reverse binding of ligand to CR3 and report here that lysates of PMN contain an endogenous ligand that binds CR3 and competes the binding of C3bi. Purification and sequence analysis identified the structurally homologous azurophilic granule proteins, elastase, protease 3, and azurocidin as candidates. Studies with purified elastase and azurocidin showed that each bound specifically to purified, immobilized CR3. Elastase may play a role in modulating integrin-mediated cell adhesion because it is expressed at the cell surface, and the expression level is inversely proportional to cell adhesivity. Furthermore, a monoclonal antibody against elastase prevented detachment of PMN from fibrinogen-coated surfaces and blocked chemotaxis, confirming a role for this protein in regulating integrin-mediated adhesion. These studies suggest a model for release of integrin-mediated cell adhesion in which endogenous ligands such as elastase may release adhesion by "'eluting" substrate-bound ligand. A role for the proteolytic activity of elastase appears likely but is not demonstrated in this study.
Exercise-Induced Late Asthmatic Reactions with Neutrophil Chemotactic Activity
Authors: Tak H. Lee, Toshikazu Nagakura, Niki Papageorgiou, Yoji Iikura, A. B. Kay
Journal: New England Journal of Medicine (1983)

Two adults and 13 children with exercise-induced asthma had both immediate and late reductions in forced expiratory volume in one second (FEV1) after treadmill exercise. The late reactions developed 4 to 10 hours after exercise and in each instance were associated with wheezing or chest tightness (or both). Increases in neutrophil chemotactic activity, measured in the 2 adults and in 11 of the children, accompanied the reductions in FEV1 in all these subjects. In contrast, four other adults with only an immediate fall in FEV1 after exercise had only an initial elevation in neutrophil chemotactic activity, with no subsequent increase for the remaining 24-hour period. The agent responsible for the neutrophil chemotactic activity released during exercise-induced late reactions appeared to be identical to that released during immediate reactions. These observations suggest that some patients with exercise-induced asthma have late reactions that, as in the case of antigen-induced bronchoconstriction, are accompanied by the release of neutrophil chemotactic activity.
Age-Associated Increases in Pulmonary Artery Systolic Pressure in the General Population
Authors: Carolyn S.P. Lam, Barry A. Borlaug, Garvan C. Kane, Felicity T. Enders, Richard J. Rodeheffer, Margaret M. Redfield
Journal: Circulation (2009)

Background— In contrast to the wealth of data on isolated systolic hypertension involving the systemic circulation in the elderly, much less is known about age-related change in pulmonary artery systolic pressure (PASP) and its prognostic impact in the general population. We sought to define the relationship between PASP and age, to evaluate which factors influence PASP, and to determine whether PASP is independently predictive of mortality in the community. Methods and Results— A random sample of the Olmsted County, Minn, general population (n=2042) underwent echocardiography and spirometry and was followed up for a median of 9 years. PASP was measured from the tricuspid regurgitation velocity. Left ventricular diastolic pressure was estimated with Doppler echocardiography (E/e′ ratio), and arterial stiffening was assessed from the brachial artery pulse pressure. Among 1413 subjects (69%) with measurable PASP (age, 63±11 years; 43% male), median PASP was 26 mm Hg (25th to 75th percentile, 24 to 30 mm Hg) and increased with age ( r =0.31, P &lt;0.001). Independent predictors of PASP were age, pulse pressure, and mitral E/e′ (all P ≤0.003). Increasing PASP was associated with higher mortality (hazard ratio, 2.73 per 10 mm Hg; P &lt;0.001). In subjects without cardiopulmonary disease (any heart failure, coronary artery disease, hypertension, diabetes mellitus, or chronic obstructive lung disease), the age-adjusted hazard ratio was 2.74 per 10 mm Hg ( P =0.016). Conclusions— We provide the first population-based evidence of age-related increase in pulmonary artery pressure, its association with increasing left heart diastolic pressures and systemic vascular stiffening, and its negative impact on survival. Pulmonary artery pressure may serve as a novel cardiovascular risk factor and potential therapeutic target.
Natural History of Sickle Cell Anemia in Saudi Arabs
Authors: RICHARD P. PERRINE
Journal: Annals of Internal Medicine (1978)

We studied 270 Saudi Arabs with homozygous sickle cell anemia, using chart review, a register (since 1969), and home visiting in 42 cases. Average follow-up for the total group was 10 years. Seventy-four percent of those diagnosed by age 3 years presented on screening or with merely anemia; 26% presented with illness, abnormal physical findings, or pain. Compared with American or Jamaican blacks, serious complications occurred only 6% to 25% as frequently; leg ulcers did not occur at all; the mortality under age 15 years was 10% as great; mean levels of blood hemoglobin were higher (10 g/dl), reticulocyte count was lower (5% to 6%), and mean fetal hemoglobin (HbF), which was inversely correlated with reticulocytes, was higher (22% to 26.8%). The high HbF is believed to account for the very mild clinical manifestations.