tbuckley/cabot-search huggingface dataset:
Severe necrotising leucocytoclastic vasculitis in a patient taking bosentan
Authors: Stefan Gasser, Max Kuhn, Rudolf Speich
Journal: BMJ (2004)

A 47 year old woman had had severe idiopathic pulmonary arterial hypertension since 1988.The patient declined treatment with prostanoids or lung transplantation.Her clinical course was extraordinarily stable with merely acenocoumarol and metolazone.In June 2002 right heart catheterisation was performed (mean pulmonary arterial pressure 68 mm Hg, cardiac index 2.0 l/min/m 2 , mixed venous oxygen saturation 51%, no vasoreactivity).Treatment with bosentan 62.5 mg twice daily was started, and spironolactone was added.Four weeks later, the patient could walk a distance of 380 metres in six minutes, compared with 338 metres before treatment.The bosentan dosage was increased to 125 mg twice daily.Four days later the patient experienced itching of both legs.Within another three days typical vasculitic skin lesions appeared on both legs (figure).A skin biopsy showed leucocytoclastic vasculitis and negative immune complex staining.Haematology, blood chemistry, and immunological variables were unremarkable.Bosentan was stopped immediately.Diuretics and acenocoumarol were continued.The vasculitic skin lesions improved slowly over the following weeks.Bosentan is an endothelin receptor antagonist approved for the treatment of pulmonary arterial hypertension. 1 2On the basis of a review of the data from the World Health Organization and the manufacturer's safety database we found that vasculitis has not been reported so far. 3 4 Known side effects of the drug include liver toxicity, which was not present in this case.Vasculitis is well described as an adverse drug reaction to metolazone.This drug, however, had been used by our patient for years, and the vasculitis improved despite the continuation of metolazone.History and immunology evaluation showed no other causes of the vasculitis, and the skin changes improved after discontinuation of bosentan (positive de-challenge).A re-challenge to corroborate coherency was not considered feasible because of the severity of the skin disorder.The vasculitic skin lesions in our patient are most probably attributable to bosentan treatment alone or to some hitherto unknown interaction.We recommend that clinicians be alert in patients complaining about pruritus and discontinue the drug if a skin rash appears.
The 67-kD elastin/laminin-binding protein is related to an enzymatically inactive, alternatively spliced form of beta-galactosidase.
Authors: A Hinek, M Rabinovitch, F Keeley, Y Okamura-Oho, J Callahan
Journal: Journal of Clinical Investigation (1993)

We and others have previously shown that a 67-kD cell surface elastin/laminin-binding protein (EBP) is responsible for cell adhesion to elastin and laminin and for mediating the process of elastin fiber assembly, but the nature of this protein was unknown. In this report we provide evidence that a 67-kD catalytically inactive form of beta-galactosidase produced by alternative splicing demonstrates immunological and functional similarity and sequence homology to the 67-kD EBP, suggesting that the two might be the same. Antibody prepared to a synthetic peptide, N-Ac-GSPSAQDEASPL, corresponding to a frame-shift-generated sequence unique to the alternatively spliced form of human beta-galactosidase, also recognized sheep EBP both on Western blotting and in aortic tissue. Furthermore, this synthetic peptide (S-GAL) binds to elastin and laminin, but not to fibronectin, collagen I, or collagen III. Moreover, both tropoelastin and laminin which bind to S-GAL peptide affinity columns can be specifically eluted from them with an excess of free S-GAL peptides. In addition, sequence homology among this splice variant of human beta-galactosidase, sheep EBP, and NH2-terminal sequences of some elastases suggests that these proteins share a common ligand-binding motif that has not been previously recognized.
TCT-641 The effect of balloon angioplasty compared with drug-eluting stent (DES) implantation for the treatment of DES in-stent restenosis
Authors: taku ichihashi, Yasushi Asakura, Maoto Habara, Syuichi ishiduka, Tsuyoshi Ito, Masashi Kimura, Yoshihisa Kinoshita, Atsuko kodama, Tairo Kurita, Tetsuo Matsubara, Kenya Nasu, Takahiko Suzuki, Tomohiko Teramoto, Mitsuyasu Terashima, Etsuo Tsuchikane, Daisuke Yokota
Journal: Journal of the American College of Cardiology (2012)
652 RECOMBINANT MAMMALIAN CELL DERIVED HEPATITIS C VIRUS LIKE PARTICLES INDUCE NEUTRALISING ANTIBODY AND B CELL RESPONSES TO HEPATITIS C VIRUS
Authors: D.F. Johnson, B. Chua, R. Chin, L. Earnest-Silveira, H. Zentgraf, C.-T. Bock, W. Zeng, D.C. Jacskon, J. Torresi
Journal: Journal of Hepatology (2010)
Yet More, Yet Older, Snakes
Authors: Louis C. Johnston
Journal: JAMA (1986)

<h3>To the Editor.—</h3> In their recent letters, Drs Rakel, Barbash, and Michael Pollack comment on the single- and twin-snaked caduceus, dating its source to the recording of the Grecian Aesculapian myth (or history?) of about 800 BC<sup>1</sup>and an earlier Biblical description in the Old Testament (Numbers 21:5-19),<sup>2</sup>the J-strand of which was written about as early as 950 BC.<sup>3</sup> I wish to bring to the attention of your readers a substantially earlier representation, Ningishzida, a major Babylonian god of healing, symbolized on a ceremonial beaker from about 2000 BC now in the Louvre, Paris, as twin snakes intertwined around a staff.<sup>4</sup>This is quite clearly shown on the 9-in-tall (actual size) replica before me now on my desk. He was deified for his power of periodically shedding his skin, thereby endlessly rejuvenating himself and symbolizing the cure of illness.
Autoantibodies in chronic arthritis of childhood: relations with each other and with histocompatibility antigens.
Authors: P.N Malleson, M.Y Fung, R.E Petty, M.J Mackinnon, M.L Schroeder
Journal: Annals of the Rheumatic Diseases (1992)

Studies have shown the presence of either antibodies to histone or anticardiolipin antibodies in some forms of childhood chronic arthritis. The relation between these autoantibodies has not been previously reported, however, and the immunogenetics of their association with childhood arthritis has not been studied. The interrelation of fluorescent antinuclear antibodies, antibodies to histone, and anticardiolipin antibodies and their associations with histocompatibility antigens (HLA) were studied in 114 children with chronic arthritis (45 children with pauciarticular onset juvenile chronic arthritis (JCA), 22 with polyarticular onset JCA, 13 with systemic onset JCA, and 34 with juvenile psoriatic arthritis (JPsA). Antibodies to histone and anticardiolipin antibodies were determined in 108 children. HLA antigens (A, B, C, and DR) were studied in the 83 white children. Antibodies to histone occurred in 0% (systemic onset JCA) to 42% (uveitis negative, pauciarticular onset JCA), and anticardiolipin antibodies in 26% (JPsA) to 55% (polyarticular onset JCA) of patients. Only 12 patients (11%) had both antibodies to histone and anticardiolipin antibodies. Neither antibodies to histone nor anticardiolipin antibodies associated with the type of arthritis. Neither of these antibodies alone associated with uveitis. Antibodies to histone were associated with HLA-A2, probably reflecting the known association of HLA-A2 with pauciarticular onset JCA. There was no other HLA association. Fluorescent antinuclear antibodies occurred most often in patients with uveitis; however, the occurrence of fluorescent antinuclear antibodies in patients with pauciarticular onset JCA (the group most at risk for uveitis) was not significantly greater in children with uveitis than in those without uveitis (100 and 88% respectively). Although antibodies to histone and anticardiolipin antibodies often occur in serum samples from patients with JCA and JPsA, they rarely occur together. Their presence does not associate with uveitis. This study did not show any strong evidence that production of either antibodies to histone or anticardiolipin antibodies in patients with JCA or JPsA is under the control of the histocompatibility locus.
AIDS: Principles, Practices, and Politics
Authors: Renslow Sherer
Journal: JAMA (1988)

One might wonder when a saturation point with the literature and public debate on policy concerning the acquired immunodeficiency syndrome (AIDS) will be reached. For example, now that we have seen premarital human immunodeficiency virus antibody testing identify four positives out of 12 000 persons tested in Illinois, at costs that could have purchased 160 million condoms, paid for zidovudine for one year for all persons with AIDS in Illinois, or quadrupled the state expenditure for AIDS education (<i>St Louis Post-Dispatch</i>, April 21, 1988, pp 1, 9), what more can this policy's advocates say? Or how many more times will the courts be called on to uphold the public health experts' authority on the issue of children with AIDS being allowed in school, before communities and/or the local school boards accept both the basis and the spirit of this policy? To date, every judgment has supported the child's right to
Spontaneous loss of HBsAg in children with chronic hepatitis B virus infection
Authors: Hong-Yuan Hsu, Mei-Hwei Chang, Chin-Yun Lee, Juei-San Chen, Hey-Chi Hsu, Ding-Shinn Chen
Journal: Hepatology (1992)

Spontaneous loss of HBsAg is infrequent in adult HBV carriers. Little is known about this serological change in children. In a prospective study of 420 hepatitis B virus-carrier children who were observed for 1 to 12 yr (mean = 4.3 yr), spontaneous loss of HBsAg occurred in 10 patients, with an average incidence of 0.6%/yr. The HBsAg clearance rate was significantly higher in children who had anti-HBe; children who were at an older age on entry; children whose mothers were HBsAg-; or children with severe liver histological changes detected while they were HBeAg+. Children who seroconverted from HBeAg to anti-HBe before the age of 6 or who had a peak serum ALT level above 100 IU/L were more likely to clear HBsAg. In all 10 patients who became HBsAg-, serum hepatitis B virus DNA became undetectable by both spot hybridization and the polymerase chain reaction, suggesting a complete clearance of the virus from serum. After the loss of HBsAg, the anti-HBs levels were higher in the children born to carrier mothers than in those born to noncarrier mothers. These findings suggest that chronic hepatitis B virus-carrier children rarely lose HBsAg, especially if they have been infected during the perinatal period and have mild histological changes. The poor humoral immune response to HBsAg may be a contributing factor in the establishment of carrier status during horizontal infection but may not be primarily involved in the establishment of carrier status during perinatal infection.
Antithrombotics for left-ventricular impairment?
Authors: Michael Ezekowitz
Journal: The Lancet (1998)

Use of any antithrombotic agent in patients with heart failure or reduced ventricular function has been the subject of considerable controversy because of the lack of definitive prospective studies to show conclusively the efficacy of this approach. The use of warfarin in patients with heart failure was first suggested in a report of the natural history of idiopathic dilated cardiomyopathy. 1 Fuster V Gersh B Giuliani E et al. The natural history of idiopathic dilated cardiomyopathy. Am J Cardiol. 1981; 47: 525-530 Summary Full Text PDF PubMed Scopus (796) Google Scholar In theory, antithrombotic agents may be of value in this group of patients because their low cardiac output may produce stasis in the left ventricle as well as in the left atrium, especially if there is atrial fibrillation. In addition, these patients tend to have venous stasis because of reduced activity. Coronary disease is the commonest cause of heart failure, and impaired ventricular function may also be improved by antithrombotic agents.
Common Polymorphism G(-248)A in the Promoter Region of the <i>bax</i> Gene Results in Significantly Shorter Survival in Patients With Chronic Lymphocytic Leukemia Once Treatment Is Initiated
Authors: Jane Starczynski, Chris Pepper, Guy Pratt, Laura Hooper, Alun Thomas, Donald Milligan, Paul Bentley, Christopher Fegan
Journal: Journal of Clinical Oncology (2005)

Chronic lymphocytic leukemia (CLL) is characterized by the development of drug resistance. The underlying biologic and genetic reasons for this resistance are complex, but the bcl-2 gene family seems to play a critical role. This retrospective study assessed the clinical impact of a common single nucleotide polymorphism of the pro-apoptotic bax gene in patients with chronic lymphocytic leukemia.The frequency of the novel polymorphism, G(-248)A, in the promoter region of the bax gene and bax protein expression was assessed in 203 CLL patients. The results were correlated with clinical outcome.The polymorphism was found in 23% of the CLL cohort and 15% of normal controls with no significant difference in allele frequency between the two groups (P = .15). It was associated with lower Bax protein expression and a shorter overall survival, especially in the treated patient group (P = .03). Furthermore, the adverse impact of the polymorphism was accentuated when comparing survival from the date of first treatment rather than diagnosis (P = .012). No significant difference in age at diagnosis, stage of disease at presentation, lymphocyte doubling time, time to first treatment, or progression-free survival were observed.The presence of this single nucleotide polymorphism in CLL critically influences the response to treatment and overall survival. Given the relatively high prevalence of this polymorphism in the normal population, further prospective studies in CLL and other human malignancies are indicated.
US lags behind most developed countries in use of electronic medical records but is set to change
Authors: B. Roehr
Journal: BMJ (2010)

The United States and Canada lag behind most other developed countries in their use of electronic medical records, a 2009 cross national survey of more than 10 000 primary care doctors has found. 

The survey results were presented on 29 October at a briefing for congressional staff in Washington, DC, by the charity the Commonwealth Fund.

Primary care doctors’ access to electronic medical records was “near universal” in the Netherlands (99%), New Zealand (97%), Norway (97%), the United Kingdom (96%), Australia (95%), and Sweden (94%), said Robin Osborn, director of international programmes in health policy and practice at the Commonwealth Fund. Germany (72%) and France (68%) were further down the list, while the US (46%) and Canada (37%) …
VEGF Blockade Enables Oncolytic Cancer Virotherapy in Part by Modulating Intratumoral Myeloid Cells
Authors: Mark A Currier, Francis K Eshun, Allyson Sholl, Artur Chernoguz, Kelly Crawford, Senad Divanovic, Louis Boon, William F Goins, Jason S Frischer, Margaret H Collins, Jennifer L Leddon, William H Baird, Amy Haseley, Keri A Streby, Pin-Yi Wang, Brett W Hendrickson, Rolf A Brekken, Balveen Kaur, David Hildeman, Timothy P Cripe
Journal: Molecular Therapy (2013)

Understanding the host response to oncolytic viruses is important to maximize their antitumor efficacy. Despite robust cytotoxicity and high virus production of an oncolytic herpes simplex virus (oHSV) in cultured human sarcoma cells, intratumoral (ITu) virus injection resulted in only mild antitumor effects in some xenograft models, prompting us to characterize the host inflammatory response. Virotherapy induced an acute neutrophilic infiltrate, a relative decrease of ITu macrophages, and a myeloid cell-dependent upregulation of host-derived vascular endothelial growth factor (VEGF). Anti-VEGF antibodies, bevacizumab and r84, the latter of which binds VEGF and selectively inhibits binding to VEGF receptor-2 (VEGFR2) but not VEGFR1, enhanced the antitumor effects of virotherapy, in part due to decreased angiogenesis but not increased virus production. Neither antibody affected neutrophilic infiltration but both partially mitigated virus-induced depletion of macrophages. Enhancement of virotherapy-mediated antitumor effects by anti-VEGF antibodies could largely be recapitulated by systemic depletion of CD11b(+) cells. These data suggest the combined effect of oHSV virotherapy and anti-VEGF antibodies is in part due to modulation of a host inflammatory reaction to virus. Our data provide strong preclinical support for combined oHSV and anti-VEGF antibody therapy and suggest that understanding and counteracting the innate host response may help enable the full antitumor potential of oncolytic virotherapy.
In vitro selection and extended culture of antigen-specific T lymphocytes. I. Description of selection culture procedure and initial characterization of selected cells.
Authors: S Z Ben-Sasson, W E Paul, E M Shevach, I Green
Journal: The Journal of Experimental Medicine (1975)

Specific selection of antigen-responsive guinea pig peritoneal exudate lymphocytes (PELs) was achieved by a selection culture procedure. This procedure involved the addition of PELs from immune donors to monolayers of antigen-pulsed adherent peritoneal exudate cells from nonprimed syngeneic donors. PELs which failed to adhere were discarded at 24 and 48 h; after 1 wk of culture, lymphocytes were obtained which were highly responsive to the antigen for which they were selected but which demonstrated little or no response to other antigens to which the original donor of the lymphocyte was immune. These selected cells were largely T lymphocytes and could be maintained in culture for 2-5 wk in an antigen-responsive state and, in 20-30% of cases, for 8-10 wk in an antigen-independent state.
The turning sky
Authors: K. Barraclough
Journal: BMJ (2000)

Some years ago, in an age when I felt younger than I do now, I built myself an observatory. It stands there tonight, some 50 yards up the garden, a dark, domed, lonely place, throwing a circular shadow on to the moonlit grass. I built it in a spirit of optimism and rather, I think, of innocence. Time passes, and my responsibilities to those around me have grown, and with that the place stands empty, a haven for those insects …
PKCβ is essential for the development of chronic lymphocytic leukemia in the TCL1 transgenic mouse model: validation of PKCβ as a therapeutic target in chronic lymphocytic leukemia
Authors: Claudia Holler, Josefina D. Piñón, Ursula Denk, Christoph Heyder, Sebastian Hofbauer, Richard Greil, Alexander Egle
Journal: Blood (2009)
Primary care needs a new model of office practice
Authors: Joseph E Scherger
Journal: BMJ (2005)

Fewer in-person visits, more patient contacts 

P rimary care medical practice is well known for a brief office visit model of practice. However, this model no longer meets the needs and expectations of patients. Tools and methods are now available to revolutionize how primary care is delivered. New care models have the promise to be of higher quality, more efficient, and more satisfying for both patients and physicians. Now is the time to radically change how primary care is delivered throughout the world.

Until the last three decades, people generally went to their primary physicians only when they got sick. Respiratory infections, gastrointestinal maladies, and other common health problems were efficiently diagnosed and treated. Productivity in primary care has been defined by how many patients can be seen each day, and how many patients in a community the primary care physician can manage. While many primary care physicians do an amazing job seeing lots of patients every day, poor overall quality of care has been the dirty secret that has recently come to light.1–3

Today, primary care physicians are expected to provide comprehensive and continuing care to patients and families, including modern preventive care and chronic illness management. They must adhere to the latest clinical …
Psychological Aspects of Face Transplantation: Read the Small Print Carefully
Authors: Nichola Rumsey
Journal: The American Journal of Bioethics (2004)

As a member of the Working Party set up by the Royal
College of Surgeons (RCS) in England to consider the technical, psychological, medical, and ethical aspects of face transplantation in 2003, I welcome the chance to comment on the article by the prospective team in Louisville. This commentary is offered from the perspective of a psychologist specializing in appearance and disfigurement. My understanding of other aspects of facial transplantation is derived from the discussions and final report of the RCS Working Party (Royal College of Surgeons
2003). In addition to being an experimental surgical procedure, face transplantation is experimental from the psychological perspective. Previous research and current understanding indicate that the psychological risks are more
complex and extensive than the Louisville team suggest.
AN EXPERIMENTAL STUDY OF BLOOD GLYCOLYSIS. THE EFFECTS OF THYROID AND ADRENAL EXTRACTS AND PHLORHIZIN ON GLYCOLYSIS IN VITRO
Authors: George M. Mackenzie
Journal: The Journal of Experimental Medicine (1915)

1. Blood glycolysis in vitro during a period of three hours' incubation proceeds at practically the same rate under sterile conditions and when no effort is made to prevent contamination. 2. Fresh thyroid extract, adrenalin, and phlorhizin do not contain any substances which have a constant effect upon the rate of blood glycolysis outside of the body. No evidence of the presence of an antiferment was found.
Direct measurement of inner and outer wall thickening dynamics with epicardial echocardiography.
Authors: J H Myers, M C Stirling, M Choy, A J Buda, K P Gallagher
Journal: Circulation (1986)

Simple geometric models of the left ventricle and indirect experimental measurements suggest that the inner myocardial wall contributes the largest fraction to total wall thickening. We measured transmural differences in regional wall thickening directly, using an epicardial M mode echocardiographic transducer (6 mm diameter, 5 MHz) placed on the anterior free wall of the left ventricle. Wall thickness was partitioned into inner and outer regions by inserting a waxed, 3-0 suture at different depths within the wall. The suture was used as an intramural echo target that was imaged simultaneously with the endocardium to determine inner and outer fractional contribution to total wall thickness. Data were collected in open-chest dogs at rest, during inotropic stimulation with isoproterenol, and during right heart bypass, which was used to vary cardiac output and preload. Results obtained with this method demonstrated that systolic wall thickness was nonuniform at rest and during each intervention. The fractional contributions to total wall thickening of the inner, middle, and outer thirds of the myocardial wall were estimated from the data to be 58%, 25%, and 17%, respectively. The experimental findings corresponded closely to theoretical predictions, supporting the conclusion that a gradient of thickening exists across the myocardial wall, with the inner portion of the wall contributing the largest fraction to total systolic thickening.