tbuckley/cabot-search huggingface dataset:
Wood's Light Fluorescence and Pseudomonas Burn Wound Infection
Authors: C. Gillon Ward
Journal: JAMA (1967)

Invasive infection, usually arising from the burn wound itself, remains the primary danger to the seriously burned man (Table). The offending organism is most often<i>Pseudomonas aeruginosa</i>, although the frequency of and mortality from such sepsis has recently been reduced by effective surface antibacterial agents.<sup>1,2</sup> The onset of<i>Pseudomonas</i>burn sepsis is often insidious, perhaps even more so when the patient is treated with 0.5% aqueous silver nitrate. The organism is notoriously resistant to tolerable anti-bacterial agents, whether administered locally or systemically. Delayed diagnosis and the low therapeutic index of presently available antibiotics are very likely responsible for the high mortality associated with<i>Pseudomonas</i>burn wound sepsis. However, dilute solutions of silver nitrate, when optimally applied, uniformly control the bacteria at the site of invasion, the burn wound itself. Furthermore, every strain isolated from our patients has remained sensitive in vitro to 0.5% aqueous silver nitrate. The delay in
Prognostic Value of Growth-Differentiation Factor-15 in Patients With Non–ST-Elevation Acute Coronary Syndrome
Authors: Kai C. Wollert, Tibor Kempf, Timo Peter, Sylvia Olofsson, Stefan James, Nina Johnston, Bertil Lindahl, Rüdiger Horn-Wichmann, Georg Brabant, Maarten L. Simoons, Paul W. Armstrong, Robert M. Califf, Helmut Drexler, Lars Wallentin
Journal: Circulation (2007)

Growth-differentiation factor-15 (GDF-15) is a member of the transforming growth factor-beta cytokine superfamily that is induced in the heart after ischemia-and-reperfusion injury. Circulating levels of GDF-15 may provide prognostic information in patients with non-ST-elevation acute coronary syndrome.Blood samples were obtained on admission from 2081 patients with acute chest pain and either ST-segment depression or troponin elevation who were included in the Global Utilization of Strategies to Open Occluded Arteries (GUSTO)-IV Non-ST-Elevation Acute Coronary Syndrome trial and from a matching cohort of 429 apparently healthy individuals. GDF-15 levels were determined by immunoradiometric assay. Approximately two thirds of patients presented with GDF-15 levels above the upper limit of normal in healthy controls (1200 ng/L); one third presented with levels >1800 ng/L. Increasing tertiles of GDF-15 were associated with an enhanced risk of death at 1 year (1.5%, 5.0%, and 14.1%; P<0.001). By multiple Cox regression analysis, only the levels of GDF-15 and N-terminal pro-B-type natriuretic peptide, together with age and a history of previous myocardial infarction, contributed independently to 1-year mortality risk. Receiver operating characteristic curve analyses further illustrated that GDF-15 is a strong marker of 1-year mortality risk (area under the curve, 0.757; best cutoff, 1808 ng/L). At this cutoff value, GDF-15 added significant prognostic information in patient subgroups defined by age; gender; time from symptom onset to admission; cardiovascular risk factors; previous cardiovascular disease; and the risk markers ST-segment depression, troponin T, N-terminal pro-B-type natriuretic peptide, C-reactive protein, and creatinine clearance.GDF-15 is a new biomarker of the risk for death in patients with non-ST-elevation acute coronary syndrome that provides prognostic information beyond that provided by established clinical and biochemical markers.
A review of family donor constructs: Current research and future directions
Authors: Olga van den Akker
Journal: Human Reproduction Update (2005)

This review addresses research on gamete donors, recipients, and offspring and demonstrates that the foci on all three within the triad are largely directed at disclosure or anonymity; and each in turn centers on the perceived importance of the genetic link. The importance attached to genetics has led some countries to review the ethics of anonymous gamete donation (e.g. New Zealand's 'open system' of information sharing) and has led other countries (Sweden, Austria, Victoria, Australia; the Netherlands, the UK) to change their laws allowing donor gamete offspring the right to obtain identifying information about their genetic parent. This review demonstrates that genealogical inconsistencies between and within members of the triad are common regardless of legislation. A discussion of future trends and concerns, relating to the use of gamete donation and the effects legislation is likely to have on the donor triads in the UK following 2005, is provided. The review also addresses the importance of testing theoretical models within future research, and argues this would lead to a better understanding of the underlying problems encountered at a psychosocial level, such as continued preference for anonymity in donors and denial in large numbers of users of the involvement of a donor in conception. Lack of disclosure effectively prevents true implementation of legislation; if a child is not informed, it is the result of donated gametes, it cannot take up the legally available option of finding out identifiable information about their genetic parent(s).
Plasma Epstein–Barr viral DNA load at midpoint of radiotherapy course predicts outcome in advanced-stage nasopharyngeal carcinoma
Authors: S.F. Leung, K.C.A. Chan, B.B. Ma, E.P. Hui, F. Mo, K.C.K. Chow, L. Leung, K.W. Chu, B. Zee, Y.M.D. Lo, A.T.C. Chan
Journal: Annals of Oncology (2014)
Combined Zidovudine and Interferon-α Therapy in Patients with Kaposi Sarcoma and the Acquired Immunodeficiency Syndrome (AIDS)
Authors: Joseph A. Kovacs
Journal: Annals of Internal Medicine (1989)

To evaluate the toxicity and potential clinical efficacy of combined therapy with zidovudine and interferon-alpha for patients with Kaposi sarcoma and the acquired immunodeficiency syndrome (AIDS).Nonrandomized, open trial study.Outpatient clinic of a government referral-based research hospital.Volunteer sample of 39 patients with human immunodeficiency virus (HIV) infection and Kaposi sarcoma.Patients received zidovudine, 250, 100, or 50 mg orally every 4 hours; 6 weeks after interferon-alpha was begun at a dose of 5 million U/d, and the dose was increased every 2 weeks until a maximum tolerated dose was determined. Patients then received the maximum tolerated dose of the combination for a minimum of 12 weeks before formal efficacy evaluations.In the dose-escalation phase, the ability to tolerate interferon-alpha was clearly related to the zidovudine dose. Of the 13 patients receiving 250 mg of zidovudine, only 1 patient was able to tolerate at least 10 million U/d of interferon-alpha. Of the 12 patients receiving 100 mg of zidovudine, 8 tolerated 10 million U/d, 5 tolerated 15 million U/d, and none tolerated higher doses. Of the 12 patients receiving 50 mg of zidovudine, 8 tolerated 10 million U/d, 7 tolerated 15 million U/d, and 6 tolerated 20 million U/d or more. Dose-limiting toxicities included neutropenia (57%), fatigue (16%), thrombocytopenia (14%), and hepatic dysfunction (10%). Of the 22 patients who received a stable dose of both drugs for 12 weeks, 11 patients had a complete or partial tumor response and 8 showed an anti-HIV effect. Peak serum levels of interferon-alpha (32 to 250 U/mL) and zidovudine (0.40 to 3.85 microM) were in the ranges previously shown to be synergistic against HIV.Combination therapy with zidovudine and interferon-alpha can be administered to patients with HIV infection and Kaposi sarcoma in doses that effect antiviral and antitumor responses; it appears to have a potential role in managing such patients.
On the Correlation Between Composition and Site-Specific Evolutionary Rate: Implications for Phylogenetic Inference
Authors: Vivek Gowri-Shankar, Magnus Rattray
Journal: Molecular Biology and Evolution (2005)

Model-based phylogenetic reconstruction methods traditionally assume homogeneity of nucleotide frequencies among sequence sites and lineages. Yet, heterogeneity in base composition is a characteristic shared by most biological sequences. Compositional variation in time, reflected in the compositional biases among contemporary sequences, has already been extensively studied, and its detrimental effects on phylogenetic estimates are known. However, fewer studies have focused on the effects of spatial compositional heterogeneity within genes. We show here that different sites in an alignment do not always share a unique compositional pattern, and we provide examples where nucleotide frequency trends are correlated with the site-specific rate of evolution in RNA genes. Spatial compositional heterogeneity is shown to affect the estimation of evolutionary parameters. With standard phylogenetic methods, estimates of equilibrium frequencies are found to be biased towards the composition observed at fast-evolving sites. Conversely, the ancestral composition estimates of some time-heterogeneous but spatially homogeneous methods are found to be biased towards frequencies observed at invariant and slow-evolving sites. The latter finding challenges the result of a previous study arguing against a hyperthermophilic last universal ancestor from the low apparent G + C content of its rRNA sequences. We propose a new model to account for compositional variation across sites. A Gaussian process prior is used to allow for a smooth change in composition with evolutionary rate. The model has been implemented in the phylogenetic inference software PHASE, and Bayesian methods can be used to obtain the model parameters. The results suggest that this model can accurately capture the observed trends in present-day RNA sequences.
Effectiveness of Atypical Antipsychotic Drugs in Patients with Alzheimer's Disease
Authors: Lon S. Schneider, Pierre N. Tariot, Karen S. Dagerman, Sonia M. Davis, John K. Hsiao, M. Saleem Ismail, Barry D. Lebowitz, Constantine G. Lyketsos, J. Michael Ryan, T. Scott Stroup, David L. Sultzer, Daniel Weintraub, Jeffrey A. Lieberman
Journal: New England Journal of Medicine (2006)

Second-generation (atypical) antipsychotic drugs are widely used to treat psychosis, aggression, and agitation in patients with Alzheimer's disease, but their benefits are uncertain and concerns about safety have emerged. We assessed the effectiveness of atypical antipsychotic drugs in outpatients with Alzheimer's disease.In this 42-site, double-blind, placebo-controlled trial, 421 outpatients with Alzheimer's disease and psychosis, aggression, or agitation were randomly assigned to receive olanzapine (mean dose, 5.5 mg per day), quetiapine (mean dose, 56.5 mg per day), risperidone (mean dose, 1.0 mg per day), or placebo. Doses were adjusted as needed, and patients were followed for up to 36 weeks. The main outcomes were the time from initial treatment to the discontinuation of treatment for any reason and the number of patients with at least minimal improvement on the Clinical Global Impression of Change (CGIC) scale at 12 weeks.There were no significant differences among treatments with regard to the time to the discontinuation of treatment for any reason: olanzapine (median, 8.1 weeks), quetiapine (median, 5.3 weeks), risperidone (median, 7.4 weeks), and placebo (median, 8.0 weeks) (P=0.52). The median time to the discontinuation of treatment due to a lack of efficacy favored olanzapine (22.1 weeks) and risperidone (26.7 weeks) as compared with quetiapine (9.1 weeks) and placebo (9.0 weeks) (P=0.002). The time to the discontinuation of treatment due to adverse events or intolerability favored placebo. Overall, 24% of patients who received olanzapine, 16% of patients who received quetiapine, 18% of patients who received risperidone, and 5% of patients who received placebo discontinued their assigned treatment owing to intolerability (P=0.009). No significant differences were noted among the groups with regard to improvement on the CGIC scale. Improvement was observed in 32% of patients assigned to olanzapine, 26% of patients assigned to quetiapine, 29% of patients assigned to risperidone, and 21% of patients assigned to placebo (P=0.22).Adverse effects offset advantages in the efficacy of atypical antipsychotic drugs for the treatment of psychosis, aggression, or agitation in patients with Alzheimer's disease. (ClinicalTrials.gov number, NCT00015548 [ClinicalTrials.gov].).
Persistent Use of Evidence-Based Pharmacotherapy in Heart Failure Is Associated With Improved Outcomes
Authors: Gunnar H. Gislason, Jeppe N. Rasmussen, Steen Z. Abildstrom, Tina Ken Schramm, Morten Lock Hansen, Pernille Buch, Rikke Sørensen, Fredrik Folke, Niels Gadsbøll, Søren Rasmussen, Lars Køber, Mette Madsen, Christian Torp-Pedersen
Journal: Circulation (2007)

Undertreatment with recommended pharmacotherapy is a common problem in heart failure and may influence prognosis. We studied initiation and persistence of evidence-based pharmacotherapy in 107,092 patients discharged after first hospitalization for heart failure in Denmark from 1995 to 2004.Prescriptions of dispensed medication and mortality were identified by an individual-level linkage of nationwide registers. Inclusion was irrespective of left ventricular function. Treatment with renin-angiotensin inhibitors (eg, angiotensin-converting enzyme inhibitors and angiotensin-2 receptor blockers), beta-blockers, spironolactone, and statins was initiated in 43%, 27%, 19%, and 19% of patients, respectively. Patients who did not initiate treatment within 90 days of discharge had a low probability of later treatment initiation. Treatment dosages were in general only 50% of target dosages and were not increased during long-term treatment. Short breaks in therapy were common, but most patients reinitiated treatment. Five years after initiation of treatment, 79% patients were still on renin-angiotensin inhibitors, 65% on beta-blockers, 56% on spironolactone, and 83% on statins. Notably, multiple drug treatment and increased severity of heart failure was associated with persistence of treatment. Nonpersistence with renin-angiotensin inhibitors, beta-blockers, and statins was associated with increased mortality with hazard ratios for death of 1.37 (95% CI, 1.31 to 1.42), 1.25 (95% CI, 1.19 to 1.32), 1.88 (95% CI, 1.67 to 2.12), respectively.Persistence of treatment was high once medication was started, but treatment dosages were below recommended dosages. Increased severity of heart failure or increased number of concomitant medications did not worsen persistence, but nonpersistence identified a high-risk population of patients who required special attention. A focused effort on early treatment initiation, appropriate dosages, and persistence with the regimen is likely to provide long-term benefit.
Docetaxel versus active symptom control for refractory oesophagogastric adenocarcinoma (COUGAR-02): an open-label, phase 3 randomised controlled trial
Authors: Hugo E R Ford, Andrea Marshall, John A Bridgewater, Tobias Janowitz, Fareeda Y Coxon, Jonathan Wadsley, Wasat Mansoor, David Fyfe, Srinivasan Madhusudan, Gary W Middleton, Daniel Swinson, Stephen Falk, Ian Chau, David Cunningham, Paula Kareclas, Natalie Cook, Jane M Blazeby, Janet A Dunn
Journal: The Lancet Oncology (2013)

Community-based approaches to healthcare improvement are receiving increasing attention.Such approaches could offer an infrastructure for efficient knowledge-sharing and a potent means of influencing behaviours, but their potential is yet to be optimised.After briefly reviewing challenges to communitybased approaches, we describe in detail the clinical community model.Through exploring clinical communities in practice, we seek to identify practical lessons for optimising this community-based approach to healthcare improvement.Through comparative case studies based on secondary analysis, we examine two contrasting examples of clinical communities in practice e the USA-based Michigan Keystone ICU programme, and the UK-based Improving Lung Cancer Outcomes Project.We focus on three main issues.First, both cases were successful in mobilising diverse communities: favourable starting conditions, core teams with personal credibility, reputable institutional backing and embeddedness in wider networks were important.Second, top-down input to organise regular meetings, minimise conflict and empower those at risk of marginalisation helped establish a strong sense of community and reciprocal ties, while intervention components and measures common to the whole community strengthened peernorming effects.Third, to drive implementation, technical expertise and responsiveness from the core team were important, but so too were 'hard tactics' (e.g.strict limits on local customisation); these were more easily deployed where the intervention was standardised across the community and a strong evidence-base existed.Contrary to the idea of self-organising communities, our cases make clear that vertical and horizontal forces depend on each other synergistically for their effectiveness.We offer practical lessons for establishing an effective balance of horizontal and vertical influences, and for identifying the types of quality problems most amenable to community-based improvement.
Molecular cloning and characterization of the structural gene for the major iron-regulated protein expressed by Neisseria gonorrhoeae.
Authors: S A Berish, T A Mietzner, L W Mayer, C A Genco, B P Holloway, S A Morse
Journal: The Journal of Experimental Medicine (1990)

This report describes the cloning and sequencing of the major iron-regulated protein (termed Fbp) of Neisseria gonorrhoeae strain F62. Attempts to identify recombinants expressing the Fbp using specific antibody proved unsuccessful. Therefore, an alternative cloning strategy using oligonucleotide probes derived from NH2-terminal and tryptic fragments of this protein was used to identify short fragments of the gene. Using this methodology, the gene encoding the precursor of Fbp was cloned on three separate overlapping fragments and sequenced, and the amino acid sequence was deduced. These data were unambiguously confirmed by the known NH2-terminal amino acid sequence and were supported by the sequences from tryptic fragments that lie outside of this region. Using oligonucleotide probes, we were unable to obtain clones encoding the potential regulatory region of this protein. Therefore, the technique of inverse polymerase chain reaction was used to amplify a fragment containing an additional 200 bp. This fragment was cloned and sequenced and found to contain a consensus ribosome binding site and potential -10 and -35 sequences. Hybridization analysis of genomic DNA from gonococcal strain F62 indicated that only a single copy of the Fbp gene exists per genome. These results complement the biochemical characterization of the Fbp expressed by gonococci and further suggest that it has a role in iron-acquisition.
Health Care Delivery in the Community
Authors: B. Lionel Truscott
Journal: JAMA (1972)

Coordination and more effective use of available community health resources resulted in a more equitable access to better care for stroke patients in 19 predominantly rural counties in North Carolina. The almost 1 million people in these regions had access to community stroke programs involving 22 general hospitals (average bed capacity, 140), eight nursing homes, and one extended-care facility. The interdependent functions of existing health personnel and facilities form a health care delivery chain which offer the patient continuity of care. Evaluation of inhospital treatment of 178 prestroke program, and of 408 poststroke program cohorts illustrates that patterns of care can be improved promptly and economically. These concepts can be applied to the management of other disease categories in both urban and rural communities.
Cytotoxic T-Lymphocyte–Associated Antigen-4
Authors: April K.S. Salama, F. Stephen Hodi
Journal: Clinical Cancer Research (2011)

Cancer immunotherapy relies on the ability of the immune system to target tumor-specific antigens to generate an immune response. This initial response requires both binding of the MHC/antigen peptide to T-cell receptor complex, along with a second costimulatory signal created by the binding of CD28 on the T cell, with B7 located on the antigen-presenting cell. Regulatory checkpoints, such as cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4), serve to attenuate this signal, thereby preventing autoimmunity. Its key role in regulating the immune system has made CTLA-4 an attractive therapeutic target for cancer, with the development of fully human monoclonal antibodies that have successfully targeted CTLA-4 in clinical trials. Augmentation of the immune response via blockade of CTLA-4 represents a significant advance in the field of oncology and has shown an improvement in survival for patients with metastatic melanoma. An increased understanding of the components of this pathway and the identification of other methods to modulate the immune system hold great promise for future therapy.
Oral health of elite athletes and association with performance: a systematic review
Authors: P Ashley, A Di Iorio, E Cole, A Tanday, I Needleman
Journal: British Journal of Sports Medicine (2014)

Background We aimed to systematically review the epidemiology of oral disease and trauma in the elite athlete population and to investigate the impact of oral health on sporting performance. Methods Authors searched Ovid MEDLINE (1950 to October 2013), Ovid EMBASE (1980 to October 2013), EBSCO SPORTDiscus (up to October 2013) and OpenGrey ( http://www.opengrey.eu ). No date or language restrictions were applied. Papers were included if they evaluated the oral health of professional athletes. The methodological quality of papers was evaluated using a modification of the Newcastle-Ottawa scale. Results The literature search led to 9858 potentially relevant citations. Following a set of predefined exclusion criteria, 34 studies remained. Twenty-six studies reported on dental trauma, which ranged in prevalence from 14% to 47% varying by sport and country. Sixteen studies considered the oral health of athletes and reported high prevalence of oral diseases: dental caries 15–75%, dental erosion 36–85%, periodontal disease 15%. In four studies, a range between 5% and 18% of athletes reported negative impact of oral health or trauma on performance. The methodological quality of included studies was generally low. Conclusions Within the limits of the review, oral health of athletes is poor. We hypothesise that poor oral health associates with self-reported performance; however, this needs to be tested. Further studies on representative samples of athletes are needed to assess the size of the problem of poor oral health as well as to investigate the possible impact on performance using objective measures of performance.