tbuckley/cabot-search huggingface dataset:
Risk for Venous Thromboembolism in Carriers of the Factor V Leiden Mutation
Authors: Rebecca L. Orwoll
Journal: Annals of Internal Medicine (2003)

Letters7 January 2003Risk for Venous Thromboembolism in Carriers of the Factor V Leiden MutationRebecca L. Orwoll, MDRebecca L. Orwoll, MDPortland, OR 97213 (Orwoll)Author, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-138-1-200301070-00021 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:I was surprised at the conclusion drawn by Middeldorp and colleagues in their article on venous thromboembolism in asymptomatic carriers of the factor V Leiden mutation (1). After relatively short follow-up in carriers discovered by family screening, the authors determined that the absolute risk for spontaneous venous thromboembolism was extremely low and that routine screening was not justified. I found it interesting that 61 of the 534 carriers identified were excluded because they had already had a venous thromboembolic event. What this means is that approximately 11% of the relatives of patients with symptomatic venous thromboembolism who ...Reference1. Middeldorp S, Meinardi JR, Koopman MM, van Pampus EC, Hamulyk K, van Der Meer J, . A prospective study of asymptomatic carriers of the factor V Leiden mutation to determine the incidence of venous thromboembolism. Ann Intern Med. 2001;135:322-7. [PMID: 11529695] LinkGoogle Scholar Author, Article, and Disclosure InformationAffiliations: Portland, OR 97213 (Orwoll) PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoA Prospective Study of Asymptomatic Carriers of the Factor V Leiden Mutation To Determine the Incidence of Venous Thromboembolism Saskia Middeldorp , Johan R. Meinardi , Maria M.W. Koopman , Elisabeth C.M. van Pampus , Karly Hamulyák , Jan van der Meer , Martin H. Prins , and Harry R. Büller Risk for Venous Thromboembolism in Carriers of the Factor V Leiden Mutation Saskia Middeldorp , Harry R. Bller , and Martin H. Prins Metrics 7 January 2003Volume 138, Issue 1Page: 76KeywordsFactor V LeidenPreventive medicineThromboembolismVenous thromboembolism ePublished: 7 January 2003 Issue Published: 7 January 2003 Copyright & PermissionsCopyright © 2003 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Mechanism of Anterior ST Segment Depression During Acute Inferior Myocardial Infarction
Authors: WILLIAM C. LITTLE
Journal: Annals of Internal Medicine (1984)

Anterior ST segment depression, found in 13 of 17 patients with acute inferior myocardial infarctions, resolved promptly in all 11 patients whose occluded right coronary arteries were opened with an infusion of streptokinase. Failure of streptokinase to open the artery produced no change in the electrocardiogram. Five of the patients with anterior ST segment depression had normal left anterior descending coronary arteries. In the other patients opening the right coronary artery normalized the anterior ST segments without resulting in collateral flow to the anterior wall, or changing blood pressure or heart rate. Anterior ST depression was a manifestation of the inferior infarction and was not due to anterior ischemia.
999 LOW-DOSE PEGINTERFERON ALFA-2A (40KD) (PEGASYS®) TO TREAT HEPATITIS C-INFECTED, END-STAGE RENAL DISEASE PATIENTS UNDERGOING HAEMODIALYSIS: FINAL STUDY RESULTS
Authors: M. Peck-Radosavljevic, J. Boletis, F. Besisik, M. Lucia Ferraz, L. Alric, D. Samuel, D. Messinger, H. Cheinquer
Journal: Journal of Hepatology (2008)
PTU-085 Did The 2010 Nice Guidelines Impact On Biologics Prescription?: Abstract PTU-085 Table 1
Authors: H Steed, A Townsend, A Rowlinson, F Leslie
Journal: Gut (2014)

<h3>Introduction</h3> In 2010 NICE updated their guidelines on the prescription of anti-tumour necrosis factor alpha (a-TNF) for Crohn’s disease (CD) to include Adalimumab as a treatment for patients with severe active CD. As a therapeutic option it provided an attractive alternative, both to units, struggling for infusion capacity and limited specialist nurse input, and to patients, as a time-saving, home delivered and administered option. <h3>Methods</h3> A retrospective review of inflammatory bowel disease patients at University Hospital North Staffordshire up until December 2012. <h3>Results</h3> Of 3600 inflammatory bowel disease 117 patients are on a-TNF. A further 47 patients have had, but are no longer on, a-TNF. 37 patients had their original a-TNF switched during their disease course (21%). 25 patients (68% of all switches) had their a-TNF switched for non-clinical reasons (*including patient choice and unit preference). All of these were from infliximab to adalimumab, 8 had to be switched back to infliximab. Prior to switching 23 of the 25 patients were in clinical remission with the other 2 being partial responders. After switching 11 remained in clinical remission, 13 did not have clinical remission and the data was unavailable in 1 patient. <h3>Conclusion</h3> The revision of NICE guidelines to include adalimumab was associated with a significant percentage of *non-clinical switches. There was a 52% loss of efficacy in non-clinical switches. Loss of efficacy when switching has been confirmed in prospective trials.<sup>1,2</sup> <h3>References</h3> Hoentjen F, Haarhuis BJ, Drenth JP, de Jong DJ. Elective switching from infliximab to adalimumab in stable Crohn’s disease.<i> Inflamm Bowel Dis</i> 2013:19:761–6 Van Assche G, Vermeire S, Ballet V, Gabriels F, Noman M, D’Haens G, Claessens C, Humlet E, Vande Casteele N, Gils A, Rutgeerts P. Switch to adalimumab in patients with Crohn’s disease controlled by maintenance infliximab: prospective randomised SWITCH trial.<i> Gut</i> 2012:61:229–34 <h3>Disclosure of Interest</h3> None Declared.
Letter: Outbreak of giardiasis.
Authors: P A Shave, B T Thom
Journal: BMJ (1974)

Outbreak of Giardiasis SIR,-In April 1971 a group of Swedish students visited Leningrad and subsequently 90% were found to be suffering from Giardia lamblia infestation with associated symptoms in the majority.This outbreak was reported by Andersson et al.,1 who referred to pre- vious outbreaks in similar circumstances.Recently, in November and December 1973, 227 people went on two four-day trips from the Brighton area to Leningrad.A considerable number have suffered from protracted diarrhoea, abdominal pain, nausea, or vomiting since their return.Investigations are proceeding.To date G. lamblia cysts, often in large numbers, have been found in specimens from 27 out of 47 people ex- amined, all of whom have had symptoms sufficient to take them to their family practitioner.We are making this preliminary report in view of the fact that G. lamblia infestation is often regarded as being innocuous in adults and because we are beginning to learn of cases in persons who were not involved in either of these trips, though a visit to Leningrad has remained a common factor.We should like to a-knowledge the interest shown by
Abstract 3851: Killing of Kras mutant colon cancer cells by the αGBP cytokine, a physiological PI3K inhibitor therapeutically effective <i>in vivo</i>
Authors: Livio Mallucci, Lavinia V. Lotti, Renato Mariani-Costantini, Valerie Wells, Daniel Zicha
Journal: Cancer Research (2012)

Abstract Activating Kras mutations are the most frequent oncogenic mutations in human cancer. Numerous downstream pathways responsible for cell proliferation and cell survival have been shown to be deregulated by oncogenic Kras but there are no effective targeted therapies to date for Kras driven oncogenesis. Mutant-activated Kras defines a subset of patients for whom prognosis is poor and therapeutic options are limited. We demonstrate that αGBP, a cytokine produced by CD4+ and CD8+ activated T cells, which operates by inhibiting class IA and class IB PI3K, is a potent activator of apoptosis in Kras-mutant colorectal cancer cells, even when co-harboring mutant-activated PIK3CA. Mechanics initiate with inhibition of PI3K activity and Rac-independent actin reorganisation assignable to phosphoinositide changes at the plasma membrane. Cyclin E deregulation, arrest of DNA synthesis and Chk2 activation underscore events critical to the activation of intrinsic apoptosis. Clustering of CD95/Fas death receptors underscores events critical to the activation of extrinsic apoptosis. In nude mice we present the first evidence that tumor development is strongly inhibited. This first demonstration of therapeutic efficacy against Kras-mutant colon cancer suggests that Hu-r-αGBP may be therapeutically effective against other cancers harbouring activating Ras mutations. Wells, V. and Mallucci, L. (2009). Phosphoinositide 3-kinase targeting by the β-galactoside binding protein cytokine negates akt gene expression and leads aggressive breast cancer cells to apoptotic death. Breast Cancer Research 11, R2, 1-10. Wells, V., Downward, D. and Mallucci, L. (2007). Functional inhibition of PI3K by the αGBP molecule suppresses Ras-MAPK signalling to block cell proliferation. Oncogene 26, 7709-7714. Mallucci, L. and Wells, V. (2007). Alternative use of signaling by the αGBP cytokine in cell growth modulation and cancer control. From surveillance to therapy. In: Apoptosis, Cell Signaling and Human Diseases. Ed. R. Srivastava. The Humana Press Inc. Vol. I, 203-216. Patents US patent no. 7,994,113 granted August 9th 2011 PCT WO 2008/152392: Europe, Canada, Australia, Japan, published Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3851. doi:1538-7445.AM2012-3851
Transplantation of Autologous Serum-Derived Cultivated Corneal Epithelial Equivalents for the Treatment of Severe Ocular Surface Disease
Authors: Takahiro Nakamura, Tsutomu Inatomi, Chie Sotozono, Leonard P. K. Ang, Noriko Koizumi, Norihiko Yokoi, Shigeru Kinoshita
Journal: Ophthalmology (2006)
Human cytomegalovirus induces stage-specific embryonic antigen 1 in differentiating human teratocarcinoma cells and fibroblasts.
Authors: P W Andrews, E Gönczöl, B A Fenderson, E H Holmes, G O'Malley, S Hakomori, S Plotkin
Journal: The Journal of Experimental Medicine (1989)

Cell surface expression of stage specific embryonic antigen 1 (SSEA-1), or Lex (III3 FucnLC4), was induced in differentiated human teratocarcinoma cells and in human diploid fibroblasts 3-6 d after infection with human cytomegalovirus (HCMV). In parallel, fucosylated lactoseries glycolipids bearing the SSEA-1/Lex epitope were readily detected in the infected cells but not in the uninfected cells. HCMV infection also results in altered expression of several glycosyltransferases. SSEA-1/Lex induction is probably a consequence of both increased expression of beta 1----3N-acetylglucosaminyltransferase, which catalyzes the rate-limiting step in lactoseries core chain synthesis, and subtle alterations in the relative competition for common precursor structures at key points in the biosynthetic pathway. Since SSEA-1 has been suggested to play a role in some morphogenetic cell-cell interactions during embryonic development, the induction of this antigen at inappropriate times might provide one mechanism whereby intrauterine infection with HCMV can damage the developing fetal nervous system.
Porcine Aortic Smooth Muscle Cells Secrete a Serine Protease for Insulin-like Growth Factor Binding Protein-2
Authors: Amy Gockerman, David R. Clemmons
Journal: Circulation Research (1995)

Abstract Porcine aortic smooth muscle cells secrete two forms of insulin-like growth factor (IGF) binding proteins (IGFBP-2 and -4), and both forms have been shown to modulate IGF-I actions in this cell type. Recently, we showed that IGFBP-4 inhibited IGF-I action and that the cells produced a protease that cleaved IGFBP-4 into non-IGF binding fragments. After the cleavage of IGFBP-4, the cellular DNA synthesis response to IGF-I was enhanced. This study reports that these cells also secrete a protease for IGFBP-2. Like the IGFBP-4 protease, this protease is also secreted constitutively, but unlike the IGFBP-4 protease, its secretion is enhanced if the cells are serum-deprived for 24 hours before the collection of conditioned medium. The protease cleaved IGFBP-2 into 25- and 16-kD fragments, which had reduced IGF-I binding activity. Protease activity was enhanced by coincubation with IGF-I or IGF-II, and IGF-II was more potent than IGF-I. The protease is a serine protease, since its activity can be inhibited by 3,4-dichloroisocoumarin and aprotinin. It is also inhibited by EDTA, and its activity can be restored with calcium but not zinc. The heparin-binding serpins, specifically, heparin cofactor II and antithrombin III, are inhibitory. Heparin alone also had activity, and the combination of antithrombin III plus heparin caused complete inhibition. The conditioned medium also contained proteolytic activities for IGFBP-4 and -5 but it did not cleave IGFBP-1 and -3. Chromatography of the conditioned medium on heparin-sepharose indicated that the IGFBP-2 protease bound very weakly to heparin, since it was eluted with 0.2 mol/L NaCl. This contrasts with the IGFBP-5 protease activity, which required 2.0 mol/L NaCl to elute most of the activity. α 1 -Antichymotrypsin inhibited the IGFBP-2 protease, but it had no effect on the IGFBP-5 protease. Exposure to other growth factors such as transforming growth factor-β, fibroblast growth factor, or platelet-derived growth factor did not alter protease activity. In summary, porcine aortic smooth muscle cells secrete a serine protease for IGFBP-2. This protease cleaves IGFBP-2 into two fragments that have reduced IGF binding, and its activity is enhanced by prior serum deprivation of the cells. The protease has the potential to significantly modify IGF actions in this cell type.
Adenine Arabinoside 5′–Monophosphate Treatment of Chronic Type B Hepatitis
Authors: Jay H. Hoofnagle, Gerald Y. Minuk, Geoffrey M. Dusheiko, Daniel F. Schafer, Rodney Johnson, Stephen Straus, Anthony E. Jones, John L. Gerin, Kamal Ishak
Journal: Hepatology (1982)

Six patients with chronic type B hepatitis were treated with adenine arabinoside 5'-monophosphate at a dosage of 10 to 15 mg per kg per day for 10 days. All demonstrated an immediate and marked decrease in serum hepatitis B virus DNA and DNA polymerase, and 5 of the 6 became negative for both markers by the end of the period of therapy. One patient remained negative for hepatitis B virus DNA and DNA polymerase when therapy was discontinued. This patient subsequently exhibited clinical, serum biochemical, and histological remission in disease activity concurrent with seroconversion from hepatitis B e antigen to antibody. In the remaining five patients, serum hepatitis B virus DNA and DNA polymerase returned to pretreatment values soon after therapy was stopped, and these patients demonstrated no significant changes in clinical, biochemical, serological, or histological features of the disease. Side effects of the therapy were mild and transient. These results suggest that a 10-day course of adenine arabinoside 5'-monophosphate is not adequate to induce permanent amelioration of infection and disease activity in the majority of patients with chronic type B hepatitis.
Absolute and relative risks
Authors: P. Sedgwick
Journal: BMJ (2012)

Researchers evaluated the effectiveness of a single application of topical chloramphenicol ointment in preventing wound infection after minor dermatological surgery. A randomised placebo controlled, double blind, multicentre trial was performed. Placebo was a single application of paraffin ointment. A total of 972 minor surgery patients with high risk sutured wounds were recruited and randomised to a single topical dose of chloramphenicol ointment (n=488) or placebo (n=484). The primary outcome measure was incidence of infection on the agreed day of removal of sutures or sooner if the patient re-presented with a perceived infection.1 The researchers reported that the percentage of participants with an infection was significantly lower in the chloramphenicol group than in the placebo group (6.6% versus 11%; P=0.01). The relative risk of wound infection for chloramphenicol compared with placebo was 0.6 (95% confidence interval 0.39 to 0.91). The number needed to treat was 22.8. Which of the following statements, if any, are true?
Length Dependence of Tension Generation in Rat Skinned Cardiac Muscle
Authors: Norio Fukuda, Daisuke Sasaki, Shin’ichi Ishiwata, Satoshi Kurihara
Journal: Circulation (2001)

At the basis of the Frank-Starling mechanism is the intrinsic ability of cardiac muscle to produce active tension in response to stretch. Titin, a giant filamentous molecule involved in passive tension development, is intimately associated with the thick filament in the sarcomere. Titin may therefore contribute to active tension development by modulating the thick filament structure when the muscle is elongated.Rat skinned right ventricular trabeculae were used. Passive tension at a sarcomere length (SL) of 2.0 to 2.4 micrometer was decreased after treatment of the preparation with trypsin (0.25 microgram/mL) for 13 minutes in the relaxed state at 20 degrees C. This mild trypsin treatment degraded titin without affecting other major contractile proteins. The sarcomere structure was little affected by brief contractions in the trypsin-treated preparations. When SL was adjusted to the slack SL (1.9 micrometer), active tension was unaffected by trypsin under partial (pCa 5.55) and maximal (pCa 4.8) activation. At longer SLs, however, active tension was significantly (P<0.01) decreased after trypsin treatment at either pCa. The increase in active tension on reduction of interfilament lattice spacing, produced by dextran T-500 (molecular weight approximately 500 000), was not influenced by trypsin (SL 1.9 micrometer). In trypsin-treated preparations, the increase in active tension as a function of muscle diameter was nearly the same for lengthening and osmotic compression at the slack SL.The length-dependent activation in cardiac muscle, an underlying mechanism of the Frank-Starling law of the heart, is at the myofilament level, predominantly modulated by titin and interfilament lattice spacing changes.
Absence of functional receptors for parathyroid hormone and parathyroid hormone-related peptide in Blomstrand chondrodysplasia.
Authors: A S Jobert, P Zhang, A Couvineau, J Bonaventure, J Roume, M Le Merrer, C Silve
Journal: Journal of Clinical Investigation (1998)

We report the absence of functional parathyroid hormone (PTH)/PTH-related peptide (PTHrP) receptors (PTH/PTHrP receptor) in Blomstrand chondrodysplasia, a genetic disorder characterized by advanced endochondral bone maturation. Analysis of PTH/PTHrP receptor genomic DNA from a patient with Blomstrand chondrodysplasia demonstrated that the patient was heterozygous for a point mutation (G--> A substitution at nucleotide 1176) inherited from the mother. Analysis of PTH/PTHrP receptor cDNA demonstrated that: (a) this point mutation caused the deletion of the first 11 amino acids of exon M5 (encoding the fifth transmembrane domain of the receptor), resulting from the use of a novel splice site created by the base substitution; (b) the mutant receptor was well expressed in COS-7 cells, but did not bind PTH or PTHrP, and failed to induce detectable stimulation of either cAMP or inositol phosphate production in response to these ligands; and (c) the paternal allele was not expressed. Thus, only the abnormal and nonfunctional PTH/PTHrP receptors encoded by the maternal allele were expressed by chondrocytes from this patient. In view of the known role played by the PTH/PTHrP receptor in bone and cartilage development, these results strongly support the conclusion that the absence of functional PTH/ PTHrP receptors is responsible for the skeletal abnormalities seen in Blomstrand chondrodysplasia, abnormalities that are the mirror image of those observed in Jansen's chondrodysplasia. These findings emphasize the importance of signaling through this receptor in human fetal skeletal development.
Mycoplasma pneumoniae and the aetiology of lobar pneumonia in northern Nigeria.
Authors: J T Macfarlane, D S Adegboye, M J Warrell
Journal: Thorax (1979)

Over a six-month period we studied 74 adult Nigerians who presented consecutively to Ahmadu Bello University Teaching Hospital, Zaria, with lobar or segmental pneumonia. Pneumococcal infection was diagnosed in 50% by the detection of pneumococcal polysaccharide antigen in serum or purulent sputum: 24% had pneumococcal antigenaemia. Twelve patients had evidence of Mycoplasma pneumoniae infection and half of these also had pneumococcal infection. The suggestion that M pneumoniae respiratory infection may predispose to serious bacterial pneumonia is discussed. The initial clinical and radiological features were similar in the pneumococcal and M pneumoniae groups. Raised cold agglutinin titres were not a reliable indication of M pneumoniae infection, perhaps due to altered autoantibody production in Nigerians. Pneumonia was commoner in the dry season, probably related to depressed nasopharyngeal defences caused by drying. Less common causes of lobar pneumonia that were found are also discussed and no cases of legionnaires' disease were identified.
Drug firms call for changes to German law that limits drug prices
Authors: A. Tuffs
Journal: BMJ (2012)

The new law in Germany that fixes the prices of drug according to cost-benefit comparisons with similar drugs is working, says the Institute for Quality and Efficiency in Health Care (IQWIG), the German equivalent of the UK National Institute for Health and Clinical Excellence, after evaluating 10 new drugs on the market. 

Three of the drugs offered substantial added value for certain indications and two offered a minor improvement. “This is a much better result than expected,” said Jurgen Windeler, head of IQWIG, in a public statement. Experts expect just one in 20 new drugs to be …
Relationship of Allergen‐Specific IgE Antibodies, Skin Prick Tests and Allergic Disorders in Unselected Adolescents
Authors: Tari Haahtela, Ilmari Jaakonmäki
Journal: Allergy (1981)

The relationship between serum levels of allergen‐specific IgE (RAST) and skin prick test reactivity and allergic disorders was evaluated in 137 subjects randomly selected from an adolescent population. AH subjects were prick tested with six common allergens, interviewed and physically examined. In addition, serum was collected for RAST analysis with three to six allergens. At least one positive RAST result (score 1–4) was observed in 40% and at least two positive RASTs in 22% of the subjects. Boys experienced more RAST reactions and generally with higher scores than girls. For instance, 26% of boys but only 11% of girls were RAST positive to timothy grass pollen. The correlation between prick test and RAST results was better with pollens than with house dust and animal epithelia. When the test results were discordant, the skin test was usually positive and RAST negative. Many of the small skin reactions (weal diameter 3–4 mm) were accompanied by a negative RAST. Respiratory allergy was closely connected with both positive skin test and RAST reactivity, while atopic dermatitis was less related. In 17% of the adolescents positive skin tests and in 14% positive RASTs occurred in the absence of any allergic symptom. We conclude that a positive RAST score 3–4 to inhaled allergens is a strong indicator of clinical allergy but low scores 1–2 are frequendy found in healthy young people.