tbuckley/cabot-search huggingface dataset:
Incidence of seroconversion to positivity for hepatitis C antibody in repeat blood donors in England, 1993-5
Authors: K Soldan, J A J Barbara, J Heptonstall
Journal: BMJ (1998)

<h3>Abstract</h3> <b>Objective:</b> To estimate the rate of seroconversion to positivity for hepatitis C antibody in repeat blood donors in England and to describe the probable routes of infection in these donors. <b>Design:</b> Retrospective survey of blood donors becoming positive for hepatitis C antibody and of the results of donation testing. <b>Setting:</b> The 14 blood centres in England. <b>Subjects:</b> All repeat donors giving blood between January 1993 and December 1995. <b>Main outcome measures:</b> Number of donors developing hepatitis C between donations during the three years of testing for hepatitis C antibody at English blood centres and the rate of seroconversion among repeat blood donors. Probable routes of infection. <b>Results:</b> 14 donors during 1993-5 fulfilled the case definition for seroconversion to positivity for hepatitis C antibody. The estimated seroconversion rate for infection with hepatitis C in repeat donors was 0.26 per 100 000 person years (95% confidence interval 0.15 to 0.43). Counselling after diagnosis found that four of these donors had risk factors specified in the criteria excluding people from giving blood but these factors had not come to light before donation. Another of the donors who seroconverted had a risk factor that has since been included in the exclusion criteria. Heterosexual intercourse was considered to be the most likely route of infection for five of the 14 donors. <b>Conclusions:</b> The rate of seroconversion for positivity to hepatitis C antibody in repeat blood donors in England was extremely low. During 1993-5 fewer than 1 in 450 000 donations were estimated to have come from repeat donors who had become positive for hepatitis C antibody since the previous donation. <h3>Key messages</h3> The rate of seroconversion for positivity to hepatitis C antibody in English blood donors is low—0.26 per 100 000 person years during 1993-5 (95% confidence interval 0.15 to 0.43) The probable route of infection was unknown in a third of the blood donors who seroconverted during 1993-5 and who provided information on risk factors The exclusion of blood donors with a history of probable exposure to hepatitis C remains an important strategy to help keep the blood supply free of infection
Allelic dilution obscures detection of a biologically significant resistance mutation in EGFR-amplified lung cancer
Authors: J. A. Engelman, T. Mukohara, K. Zejnullahu, E. Lifshits, A. M. Borras, C.-M. Gale, G. N. Naumov, B. Y. Yeap, E. Jarrell, J. Sun, S. Tracy, X. Zhao, J. V. Heymach, B. E. Johnson, L. C. Cantley, P. A. Janne
Journal: Journal of Clinical Investigation (2006)

EGFR is frequently mutated and amplified in lung adenocarcinomas sensitive to EGFR inhibitors gefitinib and erlotinib. A secondary mutation, T790M, has been associated with acquired resistance but has not been shown to be sufficient to render EGFR mutant/amplified lung cancers resistant to EGFR inhibitors. We created a model for studying acquired resistance to gefitinib by prolonged exposure of a gefitinib-sensitive lung carcinoma cell line (H3255; EGFR mutated and amplified) to gefitinib in vitro. The resulting resistant cell line acquired a T790M mutation in a small fraction of the amplified alleles that was undetected by direct sequencing and identified only by a highly sensitive HPLC-based technique. In gefitinib-sensitive lung cancer cells with EGFR mutations and amplifications, exogenous introduction of EGFR T790M effectively conferred resistance to gefitinib and continued ErbB-3/PI3K/Akt signaling when in cis to an activating mutation. Moreover, continued activation of PI3K signaling by the PIK3CA oncogenic mutant, p110alpha E545K, was sufficient to abrogate gefitinib-induced apoptosis. These findings suggest that allelic dilution of biologically significant resistance mutations may go undetected by direct sequencing in cancers with amplified oncogenes and that restoration of PI3K activation via either a T790M mutation or other mechanisms can provide resistance to gefitinib.
The Synaptic Vesicle Protein CSPα Prevents Presynaptic Degeneration
Authors: Rafael Fernández-Chacón, Markus Wölfel, Hiroshi Nishimune, Lucia Tabares, Frank Schmitz, Manuel Castellano-Muñoz, Christian Rosenmund, Maria L Montesinos, Joshua R Sanes, Ralf Schneggenburger, Thomas C Südhof
Journal: Neuron (2004)
The Difficulty of Diagnosis between Disease Symptoms and Drug Symptoms
Authors: A. Carpenter
Journal: BMJ (1888)

In all there is emotional depression; downcast, despondent, grieved, some of them are in tears.In very nearly all are suicidal ideas, and in many these are carried out in suicidal attempts.The emotional state is not always merely onie of de- pression, with or without weepinig, moniniilg, and a lugubrious aspect; indefinite fear or (lrea(l may posse'ss the patient; he may be afraid to go to sleel), or l)erlhlass, vaguely, of somethiing about to happen.Some are extremely suspiciouis, or are timid, anLxious, careworn, or are listless, or very obstiiate, irritable, uinsociable, sullen, sulky, slovenly, neglectful, forgetful.Halluciniationts andI illusions exist in all, if we inclu(le those few cases taking the form of a melancholia curn.stupore,where, ex- tremely probable as is their existence, it cannot be definitely ascertained.Relatively prelominating are the lhalluciniations of hearing, next most frequent are those of smell, and nearly as many have liallucinations of taste or of sight.At one period or another, or at several, refusal of food is a marked symptom in about two-thir(ds, and some disinclination for foo(d or anorexia is noted in a few others.Insomniia is a frequleiit symptoin.Some exhibit general apathy, at letast at times.A few show marked mental confusion or excitement; and some are iniattentive, or mis- take the identity of their attendants, taking them for relatives; others wander aimlessly aboout.Although onily slight an(d transitory in one case, uisually of melancholia sirplex, delusions are found in all, except in the "tlunderstruck "or stuporose, where, too, they doubtless exist.In some they concern the religiouis feelings nid idleas; the patient fancies that he has done some wrong, or is force(d to (do it by his
Postlaparoscopic Abdominal Port-Site Metastasis: F-18 FDG PET/CT Demonstration
Authors: Ba D. Nguyen, Michael C. Roarke
Journal: Clinical Nuclear Medicine (2007)

Laparoscopic surgery has expanded its applications to treatment of malignant neoplasms with lower morbidity and mortality compared with the ones carried by conventional procedures. With the increasing volume of this minimally invasive technique, complications such as port-site tumor seeding may have a higher occurrence. Abdominal wall metastasis has been reported with conventional cross-sectional imaging. The authors present 2 cases of early detection of port-site tumor implantation by PET/CT.
Evolution of Antigen-specific T Cell Receptors In Vivo: Preimmune and Antigen-driven Selection of Preferred Complementarity-determining Region 3 (CDR3) Motifs
Authors: Louise J. McHeyzer-Williams, Joanne Fanelli Panus, John A. Mikszta, Michael G. McHeyzer-Williams
Journal: The Journal of Experimental Medicine (1999)

Antigen (Ag)-driven selection of helper T cells (Th) in normal animals has been difficult to study and remains poorly understood. Using the major histocompatibility complex class II– restricted murine response to pigeon cytochrome c (PCC), we provide evidence for both preimmune and Ag-driven selection in the evolution of Ag-specific immunity in vivo. Before antigenic challenge, most Vα11+Vβ3+ Th (70%) express a critical complementarity-determining region 3 (CDR3) residue (glutamic acid at TCR-α93) associated with PCC peptide contact. Over the first 5 d of the primary response, PCC-responsive Vα11+Vβ3+ Th expressing eight preferred CDR3 features are rapidly selected in vivo. Clonal dominance is further propagated through selective expansion of the PCC-specific cells with T cell receptor (TCR) of the “best fit.” Ag-driven selection is complete before significant emergence of the germinal center reaction. These data argue that thymic selection shapes TCR-α V region bias in the preimmune repertoire; however, Ag itself and the nongerminal center microenvironment drive the selective expansion of clones with preferred TCR that dominate the response to Ag in vivo.
A prospective study of the prevalence of heparin‐induced antibodies and other associated thromboembolic risk factors in pediatric patients undergoing hemodialysis
Authors: Hadef Skouri, Raoudha Gandouz, Saoussen Abroug, Imen Kraiem, Henda Euch, Jalel Gargouri, Abdelaziz Harbi
Journal: American Journal of Hematology (2006)

Abstract Heparin, which is used at high doses in hemodialysis patients, may induce antibodies favoring thromboembolic complications. We prospectively investigated the prevalence of heparin‐induced platelet‐reactive antibodies in a cohort of 38 pediatric hemodialysis patients, by means of heparin/platelet factor 4 (H/PF4) ELISA and heparin‐induced platelet activation assay (HIPA). We also assessed other acquired and congenital hypercoagulable states. Heparin‐induced antibodies were detected in 13 and 21% of patients with HIPA and ELISA, respectively. Anti‐H/PF4 antibodies were negatively correlated with the number of hemodialysis sessions. These antibodies disappeared after a median time of 6 months despite continuing heparin treatment. The prevalence of antiphospholipid antibodies was 21% (anticardiolipin 10.5%, anti‐β2GPI 13%, and lupus anticoagulant 5%). Blood levels of homocysteine, factor VIII, and fibrinogen were significantly higher and factor II levels were significantly lower in hemodialysis patients than in controls, whereas factor VII, factor IX, and natural coagulation inhibitor levels were similar in patients and controls. Overall, 26 of 38 patients had at least one biomarker of hypercoagulability, but only 1 patient, without anti‐H/PF4 antibodies, presented with thrombosis. In conclusion, heparin induces the transient production of anti‐H/PF4 antibodies in children undergoing hemodialysis, but other abnormalities probably contribute to hypercoagulability. These findings may help to improve the diagnosis and management of thrombotic events in hemodialysis patients. Am. J. Hematol. 81:328–334, 2006. © 2006 Wiley‐Liss, Inc.
Five year follow up of patients at high cardiovascular risk who took part in randomised controlled trial of health promotion
Authors: M E Cupples, A McKnight
Journal: BMJ (1999)

Health promotion programmes for patients with coronary heart disease are valuable,1 2 but there is little evidence on their lasting effect.3 A randomised controlled trial in which patients who received personalised health promotion for two years showed significant benefits in lifestyle and quality of life.2 4 We investigated whether the differences in lifestyle, quality of life, and risk factors persisted between the two groups five years after enrolment.

Patients aged under 75 who had had angina (all grades included) for at least six months and no other concurrent serious illness were identified by 18 general practices in Belfast. Their diagnosis was confirmed at interview, and they were randomly allocated to receive either usual NHS care and personal health promotion from a trained nurse every four months for two years or usual NHS care alone. Sealed envelopes opened at interview showed group allocations. Both groups were reviewed …
Migration and geographic variations in blood pressure in Britain.
Authors: J Elford, A Phillips, A G Thomson, A G Shaper
Journal: BMJ (1990)

OBJECTIVE--To evaluate the relative contributions of factors acting at different stages in life to regional differences in adult blood pressure. DESIGN--Prospective cohort study (British regional heart study). SETTING--One general practice in each of 24 towns in Britain. SUBJECTS--7735 Men aged 40-59 years when screened in 1978-80 whose geographic zone of birth and zone of examination were classified as south of England, midlands and Wales, north of England, and Scotland. Non-migrants (n = 3144) were born in the town where they were examined; internal migrants (n = 4147) were born in Great Britain but not in the town where they were examined; and international migrants (n = 422) were born outside Great Britain. MAIN OUTCOME MEASURES--Systolic and diastolic blood pressures and height. RESULTS--Regardless of where they were born, men living in the south of England had lower mean blood pressures than men living in Scotland (142.5/80.1 v 148.1/85.2 mm Hg). The effects of the place of birth and place of examination on adult blood pressure were examined in a multiple regression model. For internal migrants the modelled increase in mean systolic blood pressure across adjacent zones of examination was 2.1 mm Hg (95% confidence interval 1.3 to 2.9); for adjacent zones of birth the corresponding increase was 0.1 mm Hg (-0.7 to 0.7). The place of examination seemed to be a far more important determinant of mean adult blood pressure than the place of birth. Height is an accepted marker of genetic and early life influences. Regional differences in height were therefore analysed to test whether the multiple regression model could correctly distinguish between the influence of place of birth and place of examination. As expected, men born in Scotland were shorter on average than men born in the south of England irrespective of where they lived in Britain (172.6 cm v 175.1 cm for internal migrants). CONCLUSION--Regional variations in blood pressure were strongly influenced by where the men had lived for most of their adult lives rather than by where they were born and brought up. Among middle aged men, factors acting in adult life seemed to be more important determinants of regional differences in blood pressure than those acting early in life such as genetic inheritance, intrauterine environment, and childhood experience.
A re-assessment of the epidemiology and patient characteristics of hepatitis D virus infection in inner city London
Authors: C.Y. William Tong, Radha Asher, Martina Toby, Siew L. Ngui, Kate Tettmar, Samreen Ijaz, Richard Tedder, Ranjababu Kulasegaram, Mark Wilkinson, Terry Wong
Journal: Journal of Infection (2013)
Genetic control of radiation leukemia virus-induced tumorigenesis II. Influence of Srlv-1, a locus not linked to H-2.
Authors: D Meruelo, M Lieberman, B Deak, H O McDevitt
Journal: The Journal of Experimental Medicine (1977)

A single locus, tentatively denoted Srlv-1 (susceptibility to radiation leukemia virus [RadLV]-1), confers dominant susceptibility to RadLV-induced leukemogenesis. Srlv-1 is not linked to H-2, and appears to be distinct from Fv-1 and Fv-2. Preliminary data suggest that Srlv-1 affected virus proliferation. A striking feature of this system is that Srlv-1 overrides the protection afforded by the H2D-associated dominant resistance to RadLV-induced neoplasia.
Pharmacodynamics of Plasma Nitrate/Nitrite as an Indication of Nitric Oxide Formation in Conscious Dogs
Authors: Guillermo A. Zeballos, Robert D. Bernstein, Carl I. Thompson, Paul R. Forfia, Nahid Seyedi, Weiqun Shen, Pawel M. Kaminski, Michael S. Wolin, Thomas H. Hintze
Journal: Circulation (1995)

The present investigation was undertaken to better understand the production of nitric oxide (NO) in vivo as measured by alterations in plasma nitrite or nitrate in blood samples from studies in experimental animals or clinical studies in humans.Plasma samples were taken from the aorta, the coronary sinus, a peripheral vein in the leg (skeletal muscle), or the right ventricle (mixed venous) in chronically instrumented conscious dogs. Plasma nitrite was converted to NO gas in an argon environment by use of hydrochloric acid, and plasma nitrate was converted first to nitrite with nitrate reductase and then to NO gas with acid. Standard curves were constructed, and the amount of nitrite and nitrate in plasma was determined. The primary metabolite was nitrate, whereas nitrate was approximately 10% of the total and remained constant. In the resting dog, the only vascular bed with a positive arterial-venous nitrate difference, evidence for production of NO, was the heart. Nitrate infusion into quietly resting dogs resulted in increases in plasma nitrate up to 38 +/- 3.4 mmol/L, increases in systemic arterial pressure, and a marked diuresis. The plasma half-life was calculated as 3.8 hours. The volume of distribution was calculated as 0.215 L/kg, or equivalent to the extracellular volume.These studies indicate that nitrate is a reliable measure of NO metabolism in vivo but that because of the long half-life, nitrate will accumulate in plasma once it is produced. Because of the large volume of distribution (21% of body weight versus the 4% of body weight usually attributed to plasma volume, the compartment in which nitrate is measured), simple measures of plasma nitrate underestimate by a factor of 4 to 6 the actual production of nitrate or NO by the body. In disease states, such as heart failure, in which renal function and extracellular volume are altered, caution should be exercised when increases in nitrate in plasma as an index of NO formation are evaluated.
Provocations with perfume in the eyes induce airway symptoms in patients with sensory hyperreactivity
Authors: E Millqvist, U Bengtsson, O Löwhagen
Journal: Allergy (1999)

In earlier studies, we have shown that patients with a history of sensory hyperreactivity develop asthma-like symptoms when exposed to strong scents, even if they cannot smell any scent.For study of possible pathophysiologic mechanisms behind sensory hyperreactivity, the patients' airways and eyes were separately exposed to a common inducing factor, perfume. Eleven patients with a history of hyperreactivity to chemical trigger factors, such as perfume, were provoked single-blindly in a placebo-controlled, randomized study. During airway exposure, the eyes were covered and, during the eye exposure, the patients inhaled fresh air. A special face mask or a nose clip was used to avoid any smell.During the 30-min exposure to perfume, there was a gradual increase in three main symptoms; i.e., eye irritation, cough, and dyspnea, after both the airway and eye exposures. The increases were significant compared with placebo.Asthma-like and other symptoms, such as irritation of the eyes, may be induced by exposure of both the airways and the eyes in patients with sensory hyperreactivity. This points to the importance of studying the sensory nervous system, not only in the airways, but also in other organs.
Uveitis in a patient receiving rifabutin for Crohn's disease
Authors: O Awotesu, T Missotten, M C Pitcher, W A Lynn, S Lightman
Journal: Journal of the Royal Society of Medicine (2004)

Some clinicians are now treating Crohn's disease with rifabutin and a macrolide antibiotic1,2 because of evidence that Mycobacterium paratuberculosis contributes to the pathogenesis. In these circumstances, the development of uveitis may or may not be a rifabutin side-effect.
Abstract P3-08-14: Could the preoperative systemic therapy be a risk factor for breast cancer-related lymphedema in stage II/III breast cancer?
Authors: SY Jung, EJ Song, JY You, MH Lee, Y Kwon, KL Ko, IH Park, KS Lee, J Ro, S Lee, H-S Kang, E Lee, KH Shin
Journal: Cancer Research (2013)

Abstract Background: The breast cancer-related lymphedema (LE) has been known to be closely related to axillary lymph nodes dissection (ALND), chemotherapy, and radiation therapy. In this study, we evaluated whether the sequence of systemic chemotherapy and surgery could be a predictive factor in stage II/III breast cancer. Methods and Materials: A total of 867 patients with stage II/III breast cancer, who underwent curative surgery with adequate systemic therapy from 2004 to 2009, were retrospectively analyzed. Adjuvant chemotherapy (ACT) was performed in 571 patients (65.9%) and preoperative systemic chemotherapy (PSC) in 296 (34.1%). We evaluated the incidence of LE by clinicopathologic factors and treatments. Results: At a median follow-up of 5.1 years (range, 3.0-8.3 years), 360 patients (41.5%) had experienced LE, 244 patients have retained LE (permanent LE), and 116 patents were normalized. The overall 5-year cumulative incidence of LE was 17%. LE occurred in 188 patients (32.9%) in patients with ACT, 172 patients (58.1%) with PSC (P&amp;lt;0.001), permanent LE in 121 (21.2%) with ACT, 123 (41.6%) with PSC (P&amp;lt;0.001), respectively. Multivariate analysis showed that PSC (hazard ratio [HR], 1.65; P&amp;lt;.001), radiotherapy (HR, 2.24; P&amp;lt;0.01), ALND (HR, 1.41; P = 0.04), and nodal stage (HR, 1.93; P = 0.04) were independent risk factors for LE occurrence. For the permanent LE, PSC (HR, 1.44; P = 0.05), radiotherapy (HR, 2.79; P&amp;lt;0.01), ALND (HR, 1.77; P&amp;lt;0.01), and nodal stage (HR, 3.01; P = 0.02) showed the associations. Conclusions: The risk factors associated with LE were advanced stage, ALND and radiotherapy. PSC was one of predictors for transients LE. However, further evaluation should be done whether it is a risk factor for permanent LE. This research was supported by National Cancer Center Grant NCC-1210181-2 by the National Cancer Center, Republic of Korea. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P3-08-14.
Managing a Jehovah's Witness who agrees to blood transfusion
Authors: C Granger
Journal: BMJ (1994)

EDITOR, - The article by Simon Finger and colleagues1 and the ensuing correspondence2 illustrate the difficulties of treating Jehovah's Witnesses who refuse blood transfusions. I have been faced with the opposite problem, though a similar ethical dilemma.

A Previously fit Jehovah's Witness suffered multiple trauma after trying to commit suicide by jumping off a bridge. He was resuscitated and …
Malaria vaccine is partly effective in young children, study shows
Authors: S. Mayor
Journal: BMJ (2015)

The first malaria vaccine to reach phase III clinical testing is partly effective against clinical disease in young children in Africa, results reported in the Lancet have shown.1

The study included 6537 infants aged 6-12 weeks and 8922 children aged 5-17 months who were enrolled at 11 centres in seven countries across sub-Saharan Africa. They were randomly assigned to receive three doses of the malaria candidate vaccine RTS,S/AS01 at months 0, 1, and 2 and a booster dose at 20 months (booster group); three doses of the malaria vaccine and a dose of comparator vaccine at 20 months (no booster group); or a comparator vaccine at all time points (control group). …