tbuckley/cabot-search huggingface dataset:
Binding and repair of 2-acetylaminofluorene adducts in distinct liver cell populations
Authors: J. G. Westra, A. Visser, A. Tulp
Journal: Environmental Health Perspectives (1983)

The study of the binding of the liver carcinogen, N-acetyl-2-aminofluorene, to the DNA of the target organ—as the probable initial step in the process of carcinogenesis—has shown that three modes of interaction occur. N-Acetyl-2-aminofluorene is covalently bound with the nitrogen to the carbon 8 of guanine (I) and with the 3-position to the free NH2-group of guanine (II). The third mode of interaction is formed by a covalent bond between the nitrogen of 2-aminofluorene and the carbon 8 of guanine (III). In this study the different modes of interaction were measured separately in stromal and parenchymal cells of the rat liver, after a single intraperitoneal dose. The DNA was isolated from nuclei that had been separated by 1g sedimentation. In parenchymal DNA the types of interaction I and III occur in the same amounts one day after application. In stromal cells the amount of interaction I is relatively small and interaction III predominates (ratio III:I = 5). The amount of interaction III in tetraploid hepatocytes (the largest cell population in the studied rats) per mg DNA is about two times higher than in the stromal cells. While the removal of the total amount of DNA-bound carcinogen takes place at the same rate in the two cell types, a difference in rate and efficiency of repair is observed for the different types of interaction. In tetraploid hepatocytes, interaction I is almost completely removed from the DNA 2 weeks after application, while interaction III diminishes to about 1/3 during the first week but the remaining part disappears very slowly. As shown in earlier studies, interaction II remains in the DNA at a constant level.
Niche-construction, co-evolution, and domain-specificity
Authors: James R. Hurford
Journal: Behavioral and Brain Sciences (2008)

Abstract That language is shaped to fit the human brain is close to the Chomskyan position. The target article by Christiansen &amp; Chater (C&amp;C) assumes an entity, “(the) language,” outside individual heads. What is the nature of this entity? Linguistic niche-construction and co-evolution of language and genes are possible, with some of what evolved being language-specific. Recent generative theory postulates much less than the old Universal Grammar (UG).
Patterns and distribution of tobacco consumption in India: Study should be interpreted cautiously
Authors: Preeti Singh, Umesh Kapil
Journal: BMJ (2004)

Future of Kerala depends on its willingness to learn from pastEditor-The Kerala model in health, cited by Bhutta et al in the theme issue on health in South Asia as replicable for South Asian countries, 1 is facing serious threats.The state has a triple burden of communicable, non-communicable, and traumatic diseases.Stupendous growth of the private sector has resulted in skyrocketing healthcare costs.Lured by the hi tech sophistication of the private sector, people are abandoning basic principles of primary health care.Even poor people prefer private hospitals, and a major reason for sustaining poverty is healthcare cost. 2 The government is reducing its investments in health and education due to fiscal crises and pressure from funding and lending agencies.The opening up of the medical education sector to private entrepreneurs, lack of guidelines for the private practice of government doctors, and shortage of doctors for rural areas are all disturbing developments.Transfer of healthcare institutions under local self-governments is yet to show the desired benefits.The state is developing a long term plan, "Health Vision Kerala 2025," and a health policy.To equip the primary healthcare workforce to face the emerging challenges, 3 job responsibilities were redefined recently.Factors that determined the successful Kerala model, among others, include historically prevalent social justice, commitment of governments to health and education, land reforms, an organised public distribution system, streamlined primary health care, and an organised labour sector.Deterioration in these determinants is likely to have strong negative impact.Kerala should learn from its past to avoid the sad plight of some other Indian states.
Different genotypes are responsible for the normal Russell viper venom assays seen in some cases of congenital factor X deficiency
Authors: Antonio Girolami, Margherita Scapin, Pamela Scarparo, Silvia Vettore
Journal: American Journal of Hematology (2008)

We read with great interest the letter by Ludwig et al. [1] that raised important concerns about the reliability of our published data concerning the negative impact of erythropoiesis-stimulating agents (ESA) on myeloma patients' survival [2].As we have commented in the discussion of our article [2], it is correct that the lack of balance of strong predictors of outcome between the ESA and the non-ESA group is the major limitation of our study.This drawback was also nicely addressed by David Steensma in the excellent Editorial that accompanies our publication [3].The two accompanying tables to this response, however, allow us to present some additional data which support our findings.As shown in Table I, ESA maintained its detrimental impact on overall survival (OS) in paired groups with accepted prognostic factors for survival in myeloma, such as age, b2 microglobulin (b2M), serum albumin, and hemoglobin (Hb), which were compara-
Charities lobby EU over access to generic drugs
Authors: A. Gulland
Journal: BMJ (2012)

Campaigners are waiting to find out whether talks on free trade between India and the European Union will spell an end to the supply of cheap generic drugs to poor countries.

Charities such as Oxfam and Medecins Sans Frontieres have highlighted the issue on the eve of high level talks between the EU’s president, Jose Manuel Barroso, and India’s prime minister, Manmohan Singh, in New Delhi on 10 February.

The talks ended without any firm agreement but had, said Mr Barroso, moved a “significant step forward” and should be finalised this autumn. Charities are worried that as part …
TCT-131 Cerebral Ischemia After Thoracic Endovascular Aortic Repair: A Diffusion-Weighted Magnetic Resonance Imaging Study
Authors: Philipp Kahlert, Holger Eggebrecht, Thomas Konorza, Rolf Alexander Janosi, Konstantinos Tsagakis, Heinz Jakob, Raimund Erbel, Marc Schlamann
Journal: Journal of the American College of Cardiology (2012)
A case of peripheral gangrene and osteomyelitis secondary to terlipressin therapy in advanced liver disease
Authors: Heon Ju Lee, Myung Jin Oh
Journal: Clinical and Molecular Hepatology (2013)

Variceal bleeding and hepatorenal syndrome (HRS) are serious and life-threatening complications of advanced liver disease. Terlipressin is widely used to manage both acute variceal bleeding and HRS due to its potency and long duration of action. The most severe (though rare) adverse event is ischemia. The present report describes the case of a patient with gangrene and osteomyelitis secondary to terlipressin therapy. A 71-year-old male with alcoholic liver cirrhosis (Child-Pugh B) and chronic hepatitis C was admitted due to a drowsy mental status. The patient had several experiences of orthopedic surgery. His creatinine level had gradually elevated to 4.02 mg/dL, and his urine output decreased to 500 mL/24 hr. The patient was diagnosed as having grade III hepatic encephalopathy (HE) and type II HRS. Terlipressin and albumin were administered intravenously to treat the HRS over 11 days. Although he recovered from the HE and HRS, the patient developed peripheral gangrene and osteomyelitis in both feet. His right toes were cured with the aid of rescue therapy, but his left three toes had to be amputated. Peripheral gangrene and osteomyelitis secondary to terlipressin therapy occur only rarely, and there is no specific rescue therapy for these conditions. Thus, attention should be paid to the possibility of ischemia of the skin and bone during or after terlipressin therapy. Keywords: Liver cirrhosis; Hepatorenal syndrome; Terlipressin; Gangrene; Osteomyelitis
Augmenting Cryoprecipitate Factor VIII Activity
Authors: F. Nour-Eldin
Journal: JAMA (1975)

To the Editor.—  Recently, there has been an outcry in the medical journals as well as in some daily newspapers regarding the astronomical cost of treating hemophilic patients with cryoprecipitate factor VIII. This, as stated by many physicians, has resulted in the chronic undertreatment of these unfortunate patients. Since most of the commercial preparations are imported from the United States, I thought you might be kind enough to include my letter in your column.  The basic scientific problem is a well-known and accepted fact, namely, that the benefit derived from transfused factor VIII is far below that expected from in vitro activity. Various methods for improving the therapeutic effect of factor VIII in hemophilia have been tried. A peanut extract was claimed to diminish hemorrhagic episodes, but a controlled trial showed that this could not be substantiated and its beneficial effect, if any, was most probably due to an antifibrinolytic
The G protein-coupled receptor G2A: Involvement in hepatic lipid metabolism and gallstone formation in mice
Authors: Laura E. Johnson, Marc S. Elias, David T. Bolick, Marcus D. Skaflen, Richard M. Green, Catherine C. Hedrick
Journal: Hepatology (2008)

The G2A receptor is a member of the ovarian cancer G protein–coupled receptor 1 family of stress-inducible G protein–coupled receptors. In this study, we examined the hepatobiliary effects of loss of function of G2A in mice fed either a chow or lithogenic diet. G2A-deficient (G2A−/−) mice fed chow had a 25% reduction in biliary phosphatidylcholine content, reduced hepatic gene expression of the phosphatidylcholine transporter adenosine triphosphate–binding cassette B4, and an 8-fold increase in expression of the nuclear receptor liver X receptor (LXR). Despite the increased expression of LXR, transcription of several LXR target genes was reduced. G2A−/− mice fed a lithogenic diet had rapid gallstone formation, an increased cholesterol saturation index, a 2.5-fold increase in farnesoid X receptor expression, a 5-fold increase in LXR expression, and a 90% reduction in cholesterol 7α-hydroxylase expression in comparison with wild-type mice. There were no changes in gallbladder volume. Conclusion: These data demonstrate that the G2A receptor is important for hepatobiliary bile salt, cholesterol, and phospholipid homeostasis and for the pathogenesis of cholesterol gallstone formation. (HEPATOLOGY 2008;48:1138–1148.)
FATALITY FOLLOWING VARICOSE VEIN INJECTION
Authors: O. A. Olson
Journal: JAMA (1927)

A widow, aged 33, who had two children living and well, the youngest aged 2, and who had aborted the second month, in 1924, developed varicose veins in both legs during her first pregnancy. Rupture of the veins had not occurred. The Wassermann reaction was negative. The patient was treated by elastic stockings with complete relief until June 3, 1927, when she went to the university dispensary and received injections for varicose veins, with salt solution and calorose, June 3 and again June 8. She felt perfectly well until June 13, when at 5 p. m., while playing with her children, she fell dead. Autopsy revealed a well developed, well nourished white woman, 165 cm. in length and weighing about 140 pounds (63.5 Kg.). Rigor was present in the legs. There was purplish hypostasis; there was no edema, cyanosis or jaundice. The pupils were equal and regular. Varicose veins
Paracetamol plus ibuprofen for the treatment of fever in children (PITCH): economic evaluation of a randomised controlled trial
Authors: S. Hollinghurst, N. Redmond, C. Costelloe, A. Montgomery, M. Fletcher, T. J Peters, A. D Hay
Journal: BMJ (2008)

<b>Objective</b> To estimate the cost to the NHS and to parents and carers of treating febrile preschool children with paracetamol, ibuprofen, or both, and to compare these costs with the benefits of each treatment regimen. <b>Design</b> Cost consequences analysis and cost effectiveness analysis conducted as part of a three arm, randomised controlled trial. <b>Participants</b> Children between the ages of 6 months and 6 years recruited from primary care and the community with axillary temperatures ≥37.8°C and ≤41°C. <b>Interventions</b> Paracetamol, ibuprofen, or both drugs. <b>Main outcome measures</b> Costs to the NHS and to parents and carers. Cost consequences analysis at 48 hours and 5 days comparing cost with children’s temperature, discomfort, activity, appetite, and sleep; cost effectiveness analysis at 48 hours comparing cost with percentage of children “recovered.” <b>Results</b> Difficulties in recruiting children to the trial lowered the precision of the estimates of cost and some outcomes. At 48 hours, cost to the NHS was £11.33 for paracetamol, £8.49 for ibuprofen, and £8.16 for both drugs. By day 5 these costs rose to £19.63, £18.36, and £13.92 respectively. For parents and carers, the 48 hour costs were £23.86 for paracetamol, £20.60 for ibuprofen, and £25.07 for both, and the day 5 costs were £26.35, £29.90, and £24.02 respectively. Outcomes measured at 48 hours and 5 days were inconclusive because of lack of power; the cost effectiveness analysis at 48 hours provided little evidence that one treatment choice was significantly more cost effective than another. At 4 hours ibuprofen and the combined treatment were superior to paracetamol in terms of the trial primary outcome of time without fever; at 24 hours the combined treatment performed best on this outcome. <b>Conclusions</b> There is no strong evidence of a difference in cost between the treatments, but clinical and cost data together indicate that using both drugs together may be most cost effective over the course of the illness. This treatment option performs best and is no more expensive because of less use of healthcare resources, resulting in lower costs to the NHS and to parents.
Coronary Heart Disease Incidence and Cardiovascular Mortality in Busselton with Reference to Glucose and Insulin Concentrations
Authors: T A Welborn, K Wearne
Journal: Diabetes Care (1979)

In the 1966 study of the population of Busselton, Australia, blood sugar and serum insulin levels were measured one hour after an oral glucose load, in addition to the conventional cardiovascular risk factors. The six-year incidence of coronary heart disease (CHD) and the 12-yr mortality from CHD and from all cardiovascular diseases is described in relation to the initial baseline variables measured using the upper 20th percentile values (age-specific and sex-specific) to define the risk ratios. In younger subjects (ages less than 60 yr), elevated blood pressure levels for both sexes (risk ratios from 2.9 to 5.2) and elevated serum cholesterol concentrations for males (risk ratios from 3.0 to 3.3) were strong predictors of cardiovascular risk. In men aged 60 to 69 yr, those with upper range one-hour serum insulin concentrations showed marked associations with the six-year incidence of CHD, the 12-yr mortality from CHD, and the 12-yr mortality from all cardiovascular diseases (risk ratios were 2.0, 2.3, and 2.4, respectively). The relationship of elevated serum insulin and cardiovascular mortality persisted when males of all ages were analyzed, and it appeared to be independent of the other major risk factors. In females, no association between serum insulin and CHD or cardiovascular disease could be found. Although the age and sex specific upper 20th percentile values for one-hour blood sugar concentrations showed a low grade association in patients with subsequent cardiovascular disease end points, more noticeable risk ratios were demonstrated at the higher blood sugar level of 200 mg/100 ml or greater (in the age group 60 yr and over, risk ratios were 2.2 in males and 2.6 in females.
Sarcoidosis and Other Granulomatous Diseases
Authors: J. E. Kasik
Journal: JAMA (1981)

The published reports of proceedings of conferences are a difficult problem for a reviewer. These reports have the inherent problem of containing a large number of papers (in this case, more than 100) that are usually short and can vary in quality and in interest. The major advantages of this format are the timely nature of much of the material, often its diversity, and the fact that less-relevant portions of the volume can be ignored without significant loss of continuity to the reader. This volume represents the proceedings of the eighth international congress on Sarcoidosis and Other Granulomatous Diseases, convened in Cardiff, Wales, in 1978. It contains broad coverage of all the aspects of this fascinating disorder, including its pathology, etiology, immunologic aspects, diagnosis, and therapy. There is a complete chapter on the angiotensin-converting enzyme and its relevance to sarcoidosis and usefulness in the diagnosis. Since the papers included are
An important role of tumor necrosis factor receptor-2 on natural killer T cells on the development of dsRNA-enhanced Th2 cell response to inhaled allergens
Authors: J.-P. Choi, Y.-M. Kim, H.-I. Choi, S.-J. Choi, H. T. Park, W.-H. Lee, Y. S. Gho, Y.-K. Jee, S. G. Jeon, Y.-K. Kim
Journal: Allergy (2013)

Background Recent evidence indicates that TNF-α is a key mediator of the development of dsRNA-enhanced Th2 cell response to inhaled allergens. Natural killer T (NKT) cells may be a candidate source of Th2-polarizing cytokines. Objective The objective of this study was to evaluate the role of lung NKT cells on the development of TNF-α-mediated Th2 cell response. Methods A virus-associated asthma mouse model was generated by the administration of ovalbumin (OVA, 75 μg) and poly[I:C] (0.1 μg). Role of NKT and type I NKT cells was evaluated using CD1d- and Jα18-deficient mice. TNF-α receptors (TNFRs) were antagonized by using TNFR blocking peptides. Results The number of infiltrated NKT cells was increased in a virus-associated asthma mouse model. Increase in Th2 and Th17 cytokine levels in wild-type mice were abolished in both CD1d- and Jα18-deficient mice. In vitro co-culture experiments with alveolar macrophages and NKT cells showed that TNF-α produced by macrophages in the presence of poly[I:C] acts on NKT cells, inducing production of Th2-polarizing cytokines. Moreover, the induction of Th2-polarizing cytokines by poly[I:C] or recombinant TNF-α was impaired in both CD1d- and Jα18-deficient mice and that the above effect was reversed by a TNF-α receptor-2 (TNFR2) blocking peptide, but not by a TNFR1 blocker. Conclusions These findings suggest that NKT cells play a key role in the development of Th2 cell response to inhaled allergens and that TNF-α produced by alveolar macrophages induces Th2 cell response, via TNFR2 on NKT cells.
Semantic Problems Slow Progress of Family Practice
Authors: Leland B. Blanchard
Journal: JAMA (1973)

Even though the Family Practice Movement appears to be gaining momentum, faster progress might be made were it not for at least two problems in semantics. One was described in an article 1 and an editorial 2 in a March 1971 issue ofThe Journal, the latter entitled General Practice vs Family Practice. If one had confidence that this issue had been resolved, he would be dismayed on reading a discussion published recently 3 during which the general practitioner on the panel maintained he cared for families in the same manner as the one who professed to be a family physician.  Most authorities agree that many general practitioners are now functioning well as family physicians in spite of not having been provided formal education specifically for this role. In a recent academic commentary, 4 I. R. McWhinney gives reasons for adopting the new terms but adds: The fact that we have
Amphetamine Poisoning Associated with Hyperpyrexia
Authors: S. C. Jordan, F. Hampson
Journal: BMJ (1960)

EYELIDSMEDICBALJOURNx high velocity, or where there is immediate damage to the central parts of the brain.None of the six patients in this series showed any immediate loss of consciousness or appeared much disturbed by their experience, and it is perhaps for this reason that the injuries were regarded as trivial and that in only one case was even the precaution of immediate x-ray examination deemed necessary.Yet the results were serious enough.One case sustained severe bilateral brain damage and four developed intracranial infections, with one fatality.There has been one established case of epilepsy and two more children are still at considerable risk.Three children needed multiple operations, and the total duration of their stay in hospital exceeded a year.
Menthol Hypersensitivity
Authors: Christopher M. Papa, Walter B. Shelley
Journal: JAMA (1964)

Investigation of urticaria in a young woman disclosed a hypersensitivity to menthol. Innocent systemic or percutaneous exposure to this very common substance had also elicited "hot flashes" over several years, but recognition of the symptom as an urticarial equivalent required hindsight. Production of these clinical manifestations and of a histamine headache followed different provocative tests. This was associated with a diagnostic drop in the number of circulating basophil leukocytes.
Phosphodiesterase inhibitors: Lily the Pink's medicinal compound for asthma?
Authors: G Dent, M A Giembycz
Journal: Thorax (1996)

The second messenger cyclic nucleotides, cyclic AMP and cyclic GMP, mediate relaxation of airways smooth muscle and suppression of multiple inflammatory cell functions. The intracellular concentrations of these cyclic nucleotides are regulated by a superfamily of phosphodiesterase (PDE) enzymes which break down cAMP and cGMP and, thereby, affect airway tone and inflammation. Theophylline and other drugs that act through inhibition of PDE are currently the subject of great research interest, since the uncovering of their anti-inflammatory actions suggests a possible additional mode of action in inflammatory diseases such as asthma. The characterisation of multiple families of PDE isoenzymes with distinct tissue distributions has encouraged hope that selective PDE inhibitors can be developed which act at specific targets without exhibiting the side effects of non-selective inhibitors like theophylline. The combination of bronchodilator and anti-inflammatory properties in a single drug by selective inhibition of specific PDE isoenzymes could produce agents most efficacious in every way for asthma therapy.
What to do with insolvent hospitals
Authors: Chris Ham
Journal: BMJ (2007)

The progress made by the NHS in England in converting a net deficit of £547m (€812m; $1121m) in 2005-6 into a net surplus of £510m in 2006-7 has given the government a breathing space. Yet behind the headline figures lies a picture that is more complex and promises to become more troubling as the programme of health reform gathers pace.

The net surplus in 2006-7 resulted from a gross deficit of £911m and a gross surplus of £1421m.1 Moreover, the gross deficit was concentrated in a small number of organisations, some of which face financial difficulties that cannot be easily resolved. To address these difficulties the Department of Health is working with strategic health authorities to identify long term solutions, focusing on 17 NHS trusts with the greatest challenges.

The experience of converting deficits into surpluses has shown that there are three main approaches to dealing with NHS providers in difficulty.2 The first is to develop recovery plans tailored to the circumstances of providers, often linked to the provision of loans.

In many cases, these recovery plans focus on reducing pay …