tbuckley/cabot-search huggingface dataset:
Immunogenicity and Tolerability of Recombinant Serogroup B Meningococcal Vaccine Administered With or Without Routine Infant Vaccinations According to Different Immunization Schedules
Authors: Nicoletta Gossger, Matthew D. Snape, Ly-Mee Yu, Adam Finn, Gianni Bona, Susanna Esposito, Nicola Principi, Javier Diez-Domingo, Etienne Sokal, Birgitta Becker, Dorothee Kieninger, Roman Prymula, Peter Dull, Ellen Ypma, Daniela Toneatto, Alan Kimura, Andrew J. Pollard, for the European MenB Vaccine Study Group
Journal: JAMA (2012)

<h3>Context</h3>In the absence of an effective vaccine, serogroup B Neisseria meningitidis (MenB) remains a major cause of invasive disease in early childhood in developed countries.<h3>Objective</h3>To determine the immunogenicity and reactogenicity of a multicomponent MenB vaccine (4CMenB) and routine infant vaccines when given either concomitantly or separately.<h3>Design, Setting, and Participants</h3>Phase 2b, multicenter, open-label, parallel-group, randomized controlled study of 1885 infants enrolled at age 2 months from August 2008 to July 2010 in Europe.<h3>Intervention</h3>Participants were randomized 2:2:1:1 to receive (1) 4CMenB at 2, 4, and 6 months with routine vaccines (7-valent pneumococcal and combined diphtheria, tetanus, acellular pertussis, inactivated polio, hepatitis B, Haemophilus influenzae type b vaccines); (2) 4CMenB at 2, 4, and 6 months and routine vaccines at 3, 5, and 7 months; (3) 4CMenB with routine vaccines at 2, 3, and 4 months; or (4) routine vaccines alone at 2, 3, and 4 months.<h3>Main Outcome Measures</h3>Percentage of participants with human complement serum bactericidal activity (hSBA) titer of 1:5 or greater against 3 MenB strains specific for vaccine antigens (NZ98/254, 44/76-SL, and 5/99).<h3>Results</h3>After three 4CMenB vaccinations, 99% or more of infants developed hSBA titers of 1:5 or greater against strains 44/76-SL and 5/99. For NZ98/254, this proportion was 79% (95% CI, 75.2%-82.4%) for vaccination at 2, 4, and 6 months with routine vaccines, 86.1% (95% CI, 82.9%-89.0%) for vaccination at 2, 4, and 6 months without routine vaccines, and 81.7% (95% CI, 76.6%-86.2%) for vaccination at 2, 3, and 4 months with routine vaccines. Responses to routine vaccines given with 4CMenB were noninferior to routine vaccines alone for all antigens, except for the responses to pertactin and serotype 6B pneumococcal polysaccharide. Fever was seen following 26% (158/602) to 41% (247/607) of 4CMenB doses when administered alone, compared with 23% (69/304) to 36% (109/306) after routine vaccines given alone and 51% (306/605) to 61% (380/624) after 4CMenB and routine vaccines administered together.<h3>Conclusion</h3>A 4CMenB vaccine is immunogenic against reference strains when administered with routine vaccines at 2, 4, and 6 or at 2, 3, and 4 months of age, producing minimal interference with the response to routine infant vaccinations.<h3>Trial Registration</h3>clinicaltrials.gov Identifier: NCT00721396
Global clinical trials are burdened by excessive bureaucracy, conference hears
Authors: S. Ginn
Journal: BMJ (2011)

Large multinational randomised clinical trials are under threat because of the burden of regulation imposed in high income countries, a conference has heard.

Ian Roberts, director of the clinical trials unit at the London School of Hygiene and Tropical Medicine, said that ethical requirements for trials are sometimes impractical and even “silly.” He was speaking at the Global Health 2011 conference at BMA House on 29 September.

Professor Roberts was the lead investigator of the CRASH-2 trial that examined the benefits of tranexamic acid in trauma and was conducted in 40 …
Ulcerative Colitis–Associated Colorectal Cancer Arises in a Field of Short Telomeres, Senescence, and Inflammation
Authors: Rosa Ana Risques, Lisa A. Lai, Cigdem Himmetoglu, Anoosheh Ebaee, Lin Li, Ziding Feng, Mary P. Bronner, Bassel Al-Lahham, Kris V. Kowdley, Keith D. Lindor, Peter S. Rabinovitch, Teresa A. Brentnall
Journal: Cancer Research (2011)

Abstract Inflammation plays a role in the progression to cancer and it is linked to the presence of senescent cells. Ulcerative colitis (UC) is a chronic inflammatory disease that predisposes to colorectal cancer. Tumorigenesis in this setting is associated with telomere shortening that can be observed in the nondysplastic epithelium of UC patients with high-grade dysplasia (HGD) or cancer (UC progressors). We hypothesized that a preneoplastic field of inflammation, telomere shortening, and senescence underlies tumor progression in UC progressors. Multiple biopsies of varying histologic grade were collected along the colon of nine UC progressors and analyzed for telomere length, DNA damage, senescence, p53, p16, and chronic and acute inflammation. Twenty biopsies from four UC nonprogressors and twenty-one biopsies from control individuals without UC were also analyzed. Short telomeres and increased DNA damage, senescence, and infiltrating leukocytes were observed in biopsies located less than 10 cm from HGD or cancer. Low-grade dysplasia (LGD) had the shortest telomeres along with the highest levels of senescence and infiltrating leukocytes, whereas HGD biopsies showed the opposite pattern. The expression of p16 and p53 was low in nondysplastic biopsies but progressively increased in LGD and HGD. In addition, high levels of infiltrating leukocytes were associated with telomere shortening, senescence, and reduced p53 expression. These results suggest that dysplasia arises in a preneoplastic field of chronic inflammation, which leads to telomere shortening, DNA damage, and senescence. Our findings argue that senescence acts as a tumor suppressor mechanism that is abrogated during the transition from LGD to HGD in UC. Cancer Res; 71(5); 1669–79. ©2011 AACR.
Evidence based mergers?
Authors: P. Garside
Journal: BMJ (1999)

The NHS seems to be in the grips of “merger mania.” Why is this happening and why now? More importantly, on what basis do we judge whether the merger of two or more NHS organisations is successful and is there an evidence base on how to manage them?

Seventeen mergers of NHS trusts took place in England in 1991-7.1 The cycle of trust establishment and merger activity follows the NHS financial year. Twenty three mergers came into effect from 1 April 1998, and ministers are considering further proposals for April 1999. In Scotland's current “reconfiguration” the number of trusts is planned to reduce from 47 to 26, and in Wales 26 trusts will be reconfigured into 16 by April 1999. The government sees these mergers as “evidence of a new cooperative culture developing inside the NHS.” Laudably the key test that will be applied in judging the merits of merger proposals will be whether they improve patient care. All will also have to lead to proved reductions in bureaucracy.2

Mergers occur in mature industries because of trends such as globalisation, increased competitiveness, and government deregulation policies: thus many examples …
γ-Secretase Inhibitor Prevents Notch3 Activation and Reduces Proliferation in Human Lung Cancers
Authors: Jun Konishi, Keiko S. Kawaguchi, Huan Vo, Nobuhiro Haruki, Adriana Gonzalez, David P. Carbone, Thao P. Dang
Journal: Cancer Research (2007)

Abstract Notch receptors are key regulators of development by controlling cell-fate determination in many multicellular organisms. Genes that are important for normal differentiation play a role in cancer when their normal functions became dysregulated. Notch signaling has been shown to promote and maintain survival of many types of cancers, and we previously have shown that Notch3 plays an important role in lung cancer. In this study, we showed that a high percentage of lung cancer lines expressed Jagged1, Notch receptors, and their transcriptional target genes (HES1, Hey1), suggesting that the Notch pathway plays an important role in lung cancer biology. Thus, inhibition of Notch receptor activation represents a compelling treatment strategy. Notch activation requires proteolytic cleavage of the receptor by γ-secretase protein complex. In this study, we determined the ability of MRK-003, a γ-secretase inhibitor, to inhibit Notch3 signaling, growth, and apoptosis of lung cancer cell lines in vitro and in vivo using mouse xenograft models. We also found that MRK-003 inhibited Notch3 signaling, reduced tumor cell proliferation, inhibited serum independence, and induced apoptosis. This drug had no effect when Notch3 expression was knocked down using small interfering RNA (siRNA), suggesting that the observed effects were mediated by specific action on this receptor. In conclusion, these results support the hypothesis that inhibition of Notch activation using a γ-secretase inhibitor represents a potential new approach for the targeted therapy of lung cancer. [Cancer Res 2007;67(17):8051–7]
Trisomy 8 in Philadelphia‐negative cells during imatinib therapy
Authors: P. Bernardeschi, G. Fiorentini, S. Rossi, P. Dentico, P. Simi, S. Guidi
Journal: American Journal of Hematology (2004)

Abstract Targeted therapy with imatinib selectively suppresses Philadelphia‐positive cells in chronic myeloid leukemia cells, with reappearance of apparently normal hemopoiesis in a considerable number of patients. Recently, clonal abnormalities have been observed in Philadelphia‐negative cells during imatinib therapy, the biologic and prognostic significance of which is actually unknown. A case of trisomy 8 occurring in Philadelphia‐negative cells, which was treated by bone marrow transplantation, is reported. Chromosomal abnormalities in Philadelphia‐negative cells do not seem to herald disease transformation, but the long‐term prognosis may be influenced by an increased incidence of myelodysplasia in younger patients. Am. J. Hematol. 77:88–89, 2004. © 2004 Wiley‐Liss, Inc.
Hong Kong's murky skyline is linked with excess deaths
Authors: J. Parry
Journal: BMJ (2011)

Hong Kong’s air pollution is associated with 1200 excess deaths a year in the city, say researchers at the University of Hong Kong. For every 6.5 km reduction in visibility from a clear horizon of 30 km there is a 1.13% rise in all non-accidental causes of death, they say.

Anthony Hedley, the study’s principal researcher and honorary professor of the university’s School of Public Health and its Li Ka Shing Faculty of Medicine, said, “Visibility is now the most dominant feature of Hong Kong’s environmental air quality problem, with serious implications for health, economic activities, and the overall …
Neither pre-transplant rituximab nor splenectomy affects de novo HLA antibody production after renal transplantation
Authors: Satoshi Ashimine, Yoshihiko Watarai, Takayuki Yamamoto, Takahisa Hiramitsu, Makoto Tsujita, Koji Nanmoku, Norihiko Goto, Asami Takeda, Akio Katayama, Kazuharu Uchida, Takaaki Kobayashi
Journal: Kidney International (2013)
The Gap between the Current Dyslipidemia Guidelines and the Physicians’ Treatment Targets in Patients with Type 2 Diabetes
Authors: Nihan Kahya Eren, Ece Harman, Devrim Dolek, Sadık Volkan Emren, Aliye Pelin Tütüncüoğlu, Cem Nazlı, Oktay Ergene
Journal: Journal of the American College of Cardiology (2013)
1040. Towards Gene Correction Therapy for Wiskott-Aldrich Syndrome Using Designed Zinc Finger Endonucleases
Authors: Brian R. Davis, Nicole L. Prokopishyn, Jonathan Rosenberg, Michael DiCola, Jennifer Brosius, R. Michael Blaese, Richard A. Metz, Lei Zhang, Danny Xia, Jeffrey C. Miller, Kenneth Kim, Fyodor D. Urnov, Philip D. Gregory, Michael C. Holmes
Journal: Molecular Therapy (2006)

Wiskott-Aldrich Syndrome (WAS) is a severe X-linked primary immunodeficiency resulting from mutations in a hematopoietic- specific and developmentally-regulated gene. WAS is a prime candidate for treatment by autologous hematopoietic stem cell (HSC) gene editing since this disorder is caused by a single gene defect and corrected cells should have a strong selective advantage in vivo, especially at the level of T lymphocyte precursors and perhaps even at the level of HSCs. Based on the efficient gene editing demonstrated by chimeric Zinc Finger Nucleases (ZFNs) at the IL2Rg locus (Urnov et al., 2005), ZFNs engineered to target exon 10 of the human WASP gene were similarly developed. These ZFNs were shown to efficiently bind and cleave the intended target sequences in vitro. In order to assess the efficiency of the WAS-ZFNs to bind their intended target site and mediate double strand DNA break formation in cells, we generated an integrated reporter system in HEK-293 cells. These cells contain a single integrated copy of a defective GFP reporter gene, disrupted by a portion of the WAS exon 10 sequence (GFP- WAS). We observed efficient repair ( 1%) of the GFP-WAS reporter by co-delivering the ZFN/donor constructs by lipofection. Examination of potential factors that influence the efficiency of gene correction revealed that delivery method and cell cycle status are key factors. Direct nuclear microinjection of the ZFNs/donor constructs into the GFP-WAS cells increased the repair rate by several fold (6%). We have subsequently delivered ZFNs/donors to normal human dermal fibroblasts (NHDFs) and primary hematopoietic CD34+ cells via microinjection. We are currently analyzing gene editing at the endogenous WAS locus in these cells. We have also developed an optimized reversible cell cycle synchronization procedure to allow for increased gene editing and improved cell expansion. Administration of either Vinblastine or Nocodazole (G2/M arrest agents) to the GFP-WAS cells significantly increased the gene correction efficiency (5-10 fold), but only Nocodazole treatment was fully reversible. We have also confirmed the reversible Nocodazole cell cycle synchronization in primary NHDFs. We now have available for these studies T (HTLV-I transformed) and B (EBV transformed) cell lines derived from a WAS patient. Experiments examining the efficiency of gene correction in these two patient lines are in progress. Authors B.R. Davis (Presenter), N.L. Prokopishyn, J. Rosenberg, M. DiCola, J. Brosius, R.M. Blaese, R.A. Metz have no financial affiliation with Sangamo BioSciences. Authors L. Zhang, J.C. Miller, K. Kim, F.D. Urnov, P.D. Gregory, M.C. Holmes are employees of Sangamo BioSciences, Inc.
Syncope after running.
Authors: E Tsutsumi, H Hara
Journal: BMJ (1979)

ally.' Enterotoxin, detected by its cytopathic effect on Hep2 cells in tissue culture and neutralisable by Cl sordellii antitoxin (Wellcome Foundation Research Laboratories), was found in the stool in high titre (table ).Treatnent was instituted with oral metronidazole 400 mg thrice daily and continued for 10 days.Within 36 hours the stool no longer contained visible blood and within three days was well formed.Sigmoidoscopy one week after beginning metronidazole showed a normal mucosa.After treatment the patient remained asymptomatic with no demonstrable Cl difficile organisms or toxin in the stool. Stool cultures forClostridium difficile and neutralisable Cl difficile toxin titres throughout metronidazole treatment Neutralisable Duration of Stool culture for Cl difficile toxin metronidazole treatment Cl difficile titre in stool* Pretreatment .Positive 1/1000 2 days .Positive 1/500 4 days .Negative Nil 10 days Negative Nil 2 weeks after treatment .Negative Nil *One gram wet-weight stool extracted in 5 ml physiological saline.
Heal Thyself: The Health of Health Care Professionals
Authors: Ronald L. Martin
Journal: JAMA (1986)

Health care professionals attend to the health of others. What about their own health? Are they more or less likely to suffer the same ills that afflict those they treat? Are they at risk for any additional health problems? What effect does their health status have on the care they provide? These important questions are receiving increasing attention, as documented in this book. These concerns are not new. The inspiration for the title, "Physician, heal thyself' (Luke 4:23), traces such inquiry at least to the time of the New Testament. Self-scrutiny by the health care profession is not new either. Tradition holds that St Luke was himself a physician. Indeed, the 29 contributors to the current text are health care providers and include physicians, nurses, and dentists. Health care providers are certainly not immune to health problems. The prevailing tone of the 20 chapters of this book is that the
Role of naive-derived T memory stem cells in T-cell reconstitution following allogeneic transplantation
Authors: Alessandra Roberto, Luca Castagna, Veronica Zanon, Stefania Bramanti, Roberto Crocchiolo, James E. McLaren, Sara Gandolfi, Paolo Tentorio, Barbara Sarina, Inna Timofeeva, Armando Santoro, Carmelo Carlo-Stella, Benedetto Bruno, Cristiana Carniti, Paolo Corradini, Emma Gostick, Kristin Ladell, David A. Price, Mario Roederer, Domenico Mavilio, Enrico Lugli
Journal: Blood (2015)
Enzyme release into the interstitial space of the isolated rat heart induced by changes in contractile performance
Authors: W. Wienen, E. Jungling, H. Kammermeier
Journal: Cardiovascular Research (1994)

Objective: The aim was to investigate changes in interstitial concentration and release of creatine kinase in isolated perfused rat hearts after an experimental inotropic stimulation or after recovery from a negative inotropic intervention (low Ca2+ or high K+ buffer). Methods: Interstitial transudate emerging at the surface of the heart and venous effluent were analysed for creatine kinase. Results: The interstitial concentration of creatine kinase was always higher, by a factor of 25 to 100 (range from 10 to 580 mU·ml−1), than the concentration in the venous effluent (close to or below the limit of detection: 0.4 mU·ml−1). Continuous stimulation with a submaximal effective concentration (8 nM) of isoprenaline for 30 min resulted in an initial transient increase in the interstitial release of creatine kinase to about 160% of the control (p < 0.05). Similarly, in a second series, three repeated (5 min) periods of inotropic stimulation also caused a significant and transient increase in the interstitial release of creatine kinase to a maximum of 180%. Change to a buffer containing 2.0 mM Ca2+ after a 60 min period of low Ca2+ perfusion (0.25 mM) led to restoration of contractile function and an immediate and transient increase in the interstitial release of creatine kinase to about 900%. After a period of cardiac arrest (16 mM K+ for 60 min), perfusion with 4 mM K+ also immediately restored cardiac function, and led to an increase in creatine kinase release of 2500%. In additional experiments dilatation of the left ventricle by inflating an intraventricular balloon during cardioplegic perfusion induced a significant fivefold increase in the interstitial release of creatine kinase, which was further enhanced 3.5-fold during the subsequent recovery period. Conclusions: The coincidence of an increase in or a restoration of cardiac contractile function and an increase in the interstitial enzyme release suggests that myocardial enzyme release may occur in response to physiological stimuli during different episodes of metabolic or mechanical stress, as well as under pathophysiological conditions. Cardiovascular Research 1994;28:1292-1298
Assessment of the prevalence of kyphosis disorders in students
Authors: L Ghorbani, A H Daneshjoo, A B Nazarian, A M Mohammadi Domieh
Journal: British Journal of Sports Medicine (2010)

The aim of this study was to assess the prevalence of kyphosis disorders in students. Total of 502 students in three levels including primary (99 girls, 99 boys), guidance (47 girls, 57 boys) and high schools (100 girls, 100 boys) participated in this study. Frontal Cobb angle was measured by flexi curve ruler. Data were analysed by χ 2 test. After collecting, subjects were classified in four categories including flat back, normal, kyphosis and hyperkyphosis. Of 256 boys, 2% had flat back, 76.6% were normal and 21.4% had kyphosis and of 256 girls 4.5% showed flat back, 80% showed flat back normal and 15% showed kyphosis, but there were significant differences between their disorders (p &gt; 0.05). There was significant difference between boys and girls in elementary school (p &lt; 0.05). In guidance and high school boy and girls, there were significant differences between their spinal deformities (flat back, normal and kyphosis). We concluded that reducing improper habits and familiarising the children with the proper way of carrying their bags and performing proper activities such as sitting and sleeping and also participating in regular training can reduce the risk of spinal deformities.
Intoxication and psychiatric disorders
Authors: F. Pochard, J. J. Lanore, M. Belghith, J. P. Mira, B. Renaud, F. Bellivier, I. Hamy, J. F. Vaxalaire, F. Brunet, J. F. Dhainaut, F. Pochards, N. Gerogianni, V. Tsiora, N. Kapravelos, E. Mouloudi, K. Katsanoulas, S. Gayol, A. Jaeger, S. Nogué, L. Marruecos, J. Nolla, J. Montels, A. Ferrer, E. Civeira, M. L. Sonnet, D. Perrot, D. Floret, B. Delafosse, Y. Bouffard, C. Dereymez, J. Motin
Journal: Intensive Care Medicine (1992)
Whipple Endocarditis without Overt Gastrointestinal Disease: Report of Four Cases
Authors: Jacques G.H. Gubler, Marcel Kuster, Fabrizio Dutly, Fridolin Bannwart, Martin Krause, Hans Peter Vögelin, Gianni Garzoli, Martin Altwegg
Journal: Annals of Internal Medicine (1999)

Background: Cardiac manifestations of Whipple disease are rarely diagnosed before death. Objective: To describe four patients with endocarditis caused by Tropheryma whippelii who did not have overt gastrointestinal disease. Design: Case series. Setting: Five hospitals in eastern Switzerland. Patients: Three men and one woman undergoing replacement of insufficient heart valves. Measurements: Histologic characteristics of heart valves and intestinal biopsy; broad-range and specific polymerase chain reaction for T. whippelii. Results: Tropheryma whippelii was found in the heart valves (three aortic valves and one mitral valve) of four patients with culture-negative endocarditis necessitating valve replacement. All patients had arthralgia for different lengths of time. Only one patient had mild gastrointestinal symptoms. Histologic characteristics of intestinal mucosa were normal in all patients, and polymerase chain reaction on intestinal biopsy was positive for T. whippelii in only one patient, who did not have diarrhea. In all patients, arthralgia resolved promptly after institution of antibiotic therapy. Disease did not recur in any patient after prolonged antibiotic therapy with cotrimoxazole. Conclusion: In patients with culture-negative endocarditis, the absence of clinical, microscopic, or microbiological evidence of gastrointestinal disease did not rule out T. whippelii.