tbuckley/cabot-search huggingface dataset:
Interferon-gamma release assays for tuberculosis screening of healthcare workers: a systematic review
Authors: Alice Zwerling, Susan van den Hof, Jerod Scholten, Frank Cobelens, Dick Menzies, Madhukar Pai
Journal: Thorax (2011)

Healthcare workers (HCWs) are at increased risk of exposure to tuberculosis (TB). Traditionally, screening for latent TB infection (LTBI) is done using the tuberculin skin test (TST). Interferon-gamma release assays (IGRAs) are now increasingly being used for diagnosis of LTBI, but their role in HCW screening is unclear. A systematic review was conducted of all IGRA studies in HCWs to summarise their performance in cross-sectional and serial testing settings. By searching four electronic databases and other sources, all available studies using any one of the commercial IGRA assays in HCWs were retrieved and screened. 50 unique studies were identified which met the inclusion criteria including five from high TB incidence settings. Among 24 cross-sectional studies in low TB incidence settings, the pooled prevalence of positive IGRA using either test was significantly lower than for a positive TST. However, in high-incidence settings (n=2) there were no consistent differences in the prevalence of positive tests. IGRAs showed good correlation with occupational risk factors for TB exposure in low-incidence settings. Only 10 studies assessed use of IGRA for serial testing and all showed large variation in the rates of conversions and reversions, with no data suggesting that IGRAs are better at identifying the incidence of new TB infection than the TST. The use of IGRAs instead of TST for one-time screening may result in a lower prevalence of positive tests and fewer HCWs who require LTBI treatment, particularly in low TB incidence settings. However, the use of IGRAs for serial testing is complicated by lack of data on optimum cut-offs for serial testing and unclear interpretation and prognosis of conversions and reversions. Further longitudinal research will be required to inform guidelines on serial testing using IGRAs.
Treatment of systemic sclerosis.
Authors: T A Medsger
Journal: Annals of the Rheumatic Diseases (1991)

Proper classification of patients into diffuse cutaneous and limited cutaneous subsets and the anticipation of complications are the keys to the management of subjects with systemic sclerosis (scleroderma). Patients with early diffuse disease and rapidly progressive skin thickening are at highest risk of developing serious disease of the internal organs (intestine, lung, heart, kidney) and should be considered for disease modifying treatment. The targets of the disease and sites of possible intervention are vascular endothelium (vasoprotective agents), mononuclear cell subsets (immunosuppressive agents), and fibroblasts (colchicine, D-penicillamine). A number of new agents with sound scientific rationale are currently undergoing therapeutic trials. Much can be done to improve the lifestyle of those with scleroderma. The most dramatic recent development is the ability to reverse kidney disease by the prompt use of angiotensin converting enzyme inhibitors and modern methods of renal dialysis and transplantation. Scleroderma is not a hopeless disease.
Lessons from the central Hampshire electronic health record pilot project:evaluation of the electronic health record for supporting patient care and secondary analysis
Authors: Hugh Sanderson, Trina Adams, Martin Budden, Chris Hoare
Journal: BMJ (2004)

The central Hampshire electronic health record (CHEHR) was constructed by linking several electronic patient records.1 Its two main objectives were to test the clinical usefulness of the electronic record in supporting emergency and out of hours care and to determine whether clinical data could be extracted and used to assess patient care.

A clinical committee was established to determine access protocols for staff. All stakeholders were represented. Access to the central Hampshire electronic health record, training in its use, and consent conditions applied to several staff (box 1).

The pilot ran from January to March 2003. Staff who used the system were asked to complete an evaluation form at the end of their shift. Overall, 148 forms were returned, mainly from eight staff (two senior house officers, two nurse advisers, two practice managers, and two general practitioners) who between them had accessed the system on more than 260 occasions. The senior house officers used the system most often. They had been partially funded by the project for the purpose of evaluation so they became expert, and fellow clinicians used them to access patient details.

For social services access was restricted to patients' personal details, their registered general practitioner, and the social service record. Health service staff were allowed more access to the social services record and could access details of patients and residential or non-residential care. The social care plan is not held electronically and was therefore not available for the pilot.

As only three practices participated in the pilot there were numerous occasions when there was no general practice record available for a patient in hospital. Patient records were found on only 47% of attempts. Even when records were found, they did not always contain useful information. Only 20% of forms reported finding the information being sought, but …
Arterial Hypertension Determined by Ambulatory Blood Pressure Profiles
Authors: Axel Dost, Christoph Klinkert, Thomas Kapellen, Andreas Lemmer, Andrea Naeke, Matthias Grabert, Joachim Kreuder, Reinhard W. Holl
Journal: Diabetes Care (2008)

OBJECTIVE—Arterial hypertension is a key player in the development of diabetes complications. We used a nationwide database to study risk factors for abnormal 24-h blood pressure regulation and microalbuminuria in children and adolescents with type 1 diabetes. RESEARCH DESIGN AND METHODS—Ambulatory blood pressure monitoring was performed in 2,105 children and adolescents from 195 pediatric diabetes centers in Germany and Austria. Individual least median squares (LMS)-SD scores were calculated for diurnal and nocturnal systolic (SBP), diastolic (DBP), and mean arterial (MAP) blood pressure according to normalized values of a reference population of 949 healthy German children. The nocturnal blood pressure reduction (dipping) was calculated for SBP as well as DBP. RESULTS—In diabetic children, nocturnal blood pressure in particular was significantly elevated (SBP +0.51, DBP +0.58, MAP +0.80 LMS-SD) and dipping of SBP DBP, and MAP was significantly reduced (P &amp;lt; 0.0001). Age, diabetes duration, sex BMI, A1C, and insulin dose were related to altered blood pressure profiles; dipping, however, was only affected by age, female sex, and A1C. The presence of microalbuminuria was associated with nocturnal DBP (P &amp;lt; 0.0001) and diastolic dipping (P &amp;lt; 0.01). CONCLUSIONS—Our observations revealed a clear link between the quality of metabolic control and altered blood pressure regulation even in pediatric patients with short diabetes duration. Nocturnal blood pressure in particular seems to mainly contribute to diabetes complications such as microalbuminuria.
Ontogeny of the Thy-1-, Lyt-2+ murine intestinal intraepithelial lymphocyte. Characterization of a unique population of thymus-independent cytotoxic effector cells in the intestinal mucosa.
Authors: J R Klein
Journal: The Journal of Experimental Medicine (1986)

Murine intestinal intraepithelial lymphocytes (IEL) from unprimed thymus-bearing and athymic nude mice were characterized according to the expression of murine lymphocyte antigenic markers and cytotoxic activity. The majority of IEL from thymus-bearing mice were Lyt-2+, L3T4- lymphocytes, over half of which did not express Thy-1 surface antigens. Nude IEL and spleen cells were void of Thy-1+ cells; however, Lyt-2 antigens were expressed on a significant proportion of IEL, but not splenic lymphocytes. Overall, 40-70% of IEL from either thymus-bearing or athymic mice expressed the cytotoxic activation antigen, CT-1, and the J11d lymphocyte marker, both of which were associated with a population of Thy-1-, Lyt-2+ cytotoxic IEL. These data are taken to mean that the intestinal epithelium is a site uniquely enriched for activated cytotoxic cells, a significant proportion of which originate as non-thymus-derived lymphocytes with acquired lytic activity.
Effects of Selective Coronary Embolization on Coronary Blood Flow and Coronary Sinus Venous Blood Oxygen Saturation in Dogs
Authors: James W. West, Tachio Kobayashi, Fred S. Anderson
Journal: Circulation Research (1962)

The cardiovascular effects of selective coronary embolization were studied with improved techniques in an attempt to obtain evidence for the existence of intercoronary reflexes and their role in potentiating myocardial ischemia. These studies demonstrated that embolization of the coronary arterial bed by lycopodium spores produced an initial marked decrease in coronary blood flow followed by a maintained (approximately 10 minutes) increase which was accompanied by an increase in coronary sinus venous oxygen saturation. Supporting evidence was obtained from selective coronary angiograms and from changes in coronary vascular resistance. Attempts at eliminating these responses by certain autonomic blocking agents (atropine, hydralazine, tetraethylammonium chloride, hexamethonium, and dibozane), surgical denervation of the heart, and adrenalectomy were all ineffective. Experimental evidence obtained by comparing the initial effect of embolization with pitressin vasoconstriction and coronary occlusion all led to the conclusion that reflex coronary spasm does not occur during coronary occlusion. The cause of the initial decrease in coronary blood flow during embolization (lycopodium spores) is, therefore, mechanical block within the distribution of the vessel by the emboli.
Proinflammatory cytokine signaling required for the generation of natural killer cell memory
Authors: Joseph C. Sun, Sharline Madera, Natalie A. Bezman, Joshua N. Beilke, Mark H. Kaplan, Lewis L. Lanier
Journal: The Journal of Experimental Medicine (2012)

Although natural killer (NK) cells are classified as innate immune cells, recent studies demonstrate that NK cells can become long-lived memory cells and contribute to secondary immune responses. The precise signals that promote generation of long-lived memory NK cells are unknown. Using cytokine receptor-deficient mice, we show that interleukin-12 (IL-12) is indispensible for mouse cytomegalovirus (MCMV)-specific NK cell expansion and generation of memory NK cells. In contrast to wild-type NK cells that proliferated robustly and resided in lymphoid and nonlymphoid tissues for months after MCMV infection, IL-12 receptor–deficient NK cells failed to expand and were unable to mediate protection after MCMV challenge. We further demonstrate that a STAT4-dependent IFN-γ–independent mechanism contributes toward the generation of memory NK cells during MCMV infection. Understanding the full contribution of inflammatory cytokine signaling to the NK cell response against viral infection will be of interest for the development of vaccines and therapeutics.
STUDIES ON A PARATYPHOID INFECTION IN GUINEA PIGS
Authors: John B. Nelson
Journal: The Journal of Experimental Medicine (1928)

The course is considered of a second type of Salmonella infection naturally appearing in a guinea pig population during the endemic stage of an earlier outbreak. After a quiescent period of 5 months the percentage mortality increased abruptly; fluctuated, with a second rise during the 9th month; and then declined. With the exception of a high rate during the 2nd month the percentage mortality from the initial infection tended to remain on a low level. The spread of infection in the cages of the breeding stock is recorded from the time of the first fatal case. There was a slow but general dissemination of the second organism through the group. Fatal cases were confirmed solely to the sows. It is suggested that a lowered individual resistance occuring during pregnancy might be associated with the regular cage spread and with the apparent difference in susceptibility of the sexes. Natural host resistance, virulence of the organisms and acquired host resistance are discussed from the standpoint of their bearing on the unequal distribution of deaths from the two infections.
The best is yet to come: The promise of models of developmental disorders
Authors: Yuko Munakata, Jamie O. Edgin, Jennifer Merva Stedron
Journal: Behavioral and Brain Sciences (2002)

The developmental modeling approach to investigating developmental disorders appears highly promising. In this commentary, we question the untapped potential of this approach for supporting insights into particular developmental disorders, developmental processes across the life span, and the viability of traditional theories of developmental disorders.
Reviewer's recommendations predict impact: why you have to send us your very best work
Authors: T Opthof
Journal: Cardiovascular Research (2000)

Six months ago we acknowledged the help of many thousands of our reviewers who helped us with the editorial decision process over the last 5 years [1]. The aim of editors is two-fold: they wish to make fair decisions, but they also want to select the best work from the submitted material in order to increase the esteem of their journal which is to a large extent reflected by its impact factor. Moreover, editors have to deal with page limitations. The task of editors is therefore not easy, also because reviewers in fact relatively seldomly recommend to reject a paper [2]. Reviewer's reports are in general constructive and aim at improvement of a manuscript and not at its rejection. Therefore the high rejection rates of leading journals are primarily based on priority considerations [2–4].

Research of peer review is a young science with its own world congress [5–7] linked to the World Association of Medical Editors (WAME). The review process is in general anonymous and the pros and cons of this have been debated in the past in this journal [8,9] with comments from several experts [10]. The outcome of a survey amongst both authors and reviewers was that the majority of both groups voted for continuation of anonymity. One important other incentive for editors to follow such advice is that about half of the reviewers … 

* Corresponding author. Tel.: +31-30-253-8923; fax: +31-30-253-9036 t.opthof{at}med.uu.nl
Vascularization as a Potential Enemy in Valvular Heart Disease
Authors: Jun Yoshioka, Richard T. Lee
Journal: Circulation (2008)

V alvular heart disease remains a major problem world- wide and is responsible for Ͼ20 000 deaths each year in the United States, with an estimated 99 000 inpatient valve procedures performed annually. 1The mitral and tricuspid valve complexes comprise the valve leaflets, valvular annulus, papillary muscles, and chordae tendineae, which anchor the leaflets to the papillary muscles.As papillary muscles contract, chordae tendineae transmit tension to the valves, directing the valve leaflets to their correct position during the cardiac cycle.Rupture of the chordae tendineae occurs as a consequence of infective endocarditis, myxomatous degeneration, rheumatic fever, or rarely, osteogenesis imperfecta or relapsing polychondritis. 2In addition, ischemia-induced dysfunction of papillary muscles can cause stretching and ultimately rupture of the chordae tendineae, as well as release of chordal attachment at sites of papillary muscle necrosis.
Airborne dissemination of transmissible bacterial species in cystic fibrosis
Authors: Andrew M Jones
Journal: Thorax (2014)

Delivery of multidisciplinary care by experienced teams in specialist units has conferred considerable benefits in care for individuals with cystic fibrosis (CF), with significant improvements in clinical outcome and survival figures. However, one particular concern of congregating patients at specialist CF centres is the potential for cross-infection. Over the past decade, the emergence and spread of clonal (transmissible) Pseudomonas aeruginosa strains among patients with CF has become an international problem.1–⇓3 Case series suggest that initial infection with clonal P. aeruginosa strains may be more difficult to eradicate,4 and in cohort studies chronic infection is associated with worse clinical outcomes.1 ,5 ,6The mechanism of spread of P. aeruginosa between patients with CF is unresolved. Potential routes include direct or indirect contact, droplet spread of relatively large infectious particles that travel short distances or airborne spread of smaller particles containing microorganisms that travel further and remain suspended for longer periods. It has been shown that patients with CF infected with clonal P. aeruginosa can contaminate their hands and their immediate environment for brief periods.7 In addition, clonal P. aeruginosa have been isolated from CF clinics by room air sampling.7 ,8

Knibbs and coworkers present the findings of their recent work using equipment they developed with an aerobiological sampling system to measure the viability of P. aeruginosa in cough-generated aerosols from patients with CF.9 Their studies demonstrate that after a 5 min period of intense coughing by a patient with CF, viable P. aeruginosa can frequently be isolated from room air at a distance of at least 4 m from the source and can persist …
Induction of Murine Acquired Immunodeficiency Syndrome (MAIDS) in Allophenic Mice Generated from Strains Susceptible and Resistant to Disease
Authors: Joan M.G. Sechler, Ann Lawler, Janet W. Hartley, Herbert C. Morse, Thomas C. McCarty, Ruth Swofford, Amy S. Rosenberg
Journal: The Journal of Experimental Medicine (1996)

To examine whether a retroviral disease can be controlled in animals in which cells from a resistant strain coexist in a state of immunological tolerance with cells from a susceptible strain, allophenic mice were constructed and infected with LP-BM5 murine leukemia viruses which induce a fatal disorder, termed murine acquired immunodeficiency syndrome (MAIDS), characterized by lymphoproliferation and immunodeficiency in susceptible inbred strains of mice. We found that in two different strain combinations, resistance to MAIDS was contingent on the presence in individual animals of >50% of lymphocytes of resistant strain origin and correlated with reduction or elimination of retrovirus. In contrast, animals harboring substantial, but less than predominant, numbers of genetically resistant lymphocytes developed disease and died within the same time frame as susceptible control mice with uncontained proliferation of retrovirus.
Local Radiation Therapy Inhibits Tumor Growth through the Generation of Tumor-Specific CTL: Its Potentiation by Combination with Th1 Cell Therapy
Authors: Tsuguhide Takeshima, Kenji Chamoto, Daiko Wakita, Takayuki Ohkuri, Yuji Togashi, Hiroki Shirato, Hidemitsu Kitamura, Takashi Nishimura
Journal: Cancer Research (2010)

Radiation therapy is one of the primary treatment modalities for cancer along with chemotherapy and surgical therapy. The main mechanism of the tumor reduction after irradiation has been considered to be damage to the tumor DNA. However, we found that tumor-specific CTL, which were induced in the draining lymph nodes (DLN) and tumor tissue of tumor-bearing mice, play a crucial role in the inhibition of tumor growth by radiation. Indeed, the therapeutic effect of irradiation was almost completely abolished in tumor-bearing mice by depleting CD8(+) T cells through anti-CD8 monoclonal antibody administration. In mice whose DLN were surgically ablated or genetically defective (Aly/Aly mice), the generation of tetramer(+) tumor-specific CTL at the tumor site was greatly reduced in parallel with the attenuation of the radiation-induced therapeutic effect against the tumor. This indicates that DLN are essential for the activation and accumulation of radiation-induced CTL, which are essential for inhibition of the tumor. A combined therapy of local radiation with Th1 cell therapy augmented the generation of tumor-specific CTL at the tumor site and induced a complete regression of the tumor, although radiation therapy alone did not exhibit such a pronounced therapeutic effect. Thus, we conclude that the combination treatment of local radiation therapy and Th1 cell therapy is a rational strategy to augment antitumor activity mediated by tumor-specific CTL.
Dysregulation of Allergic Airway Inflammation in the Absence of Microbial Colonization
Authors: Tina Herbst, Anke Sichelstiel, Corinne Schär, Koshika Yadava, Kurt Bürki, Julia Cahenzli, Kathy McCoy, Benjamin J Marsland, Nicola L Harris
Journal: American Journal of Respiratory and Critical Care Medicine (2011)

Rationale: The incidence of allergic disorders is increasing in developed countries and has been associated with reduced exposure to microbes and alterations in the commensal bacterial flora.Objectives: To ascertain the relevance of commensal bacteria on the development of an allergic response, we used a model of allergic airway inflammation in germ-free (GF) mice that lack any exposure to pathogenic or nonpathogenic microorganisms.Methods: Allergic airway inflammation was induced in GF, specific pathogen–free (SPF), or recolonized mice by sensitization and challenge with ovalbumin. The resulting cellular infiltrate and cytokine production were measured.Measurements and Main Results: Our results show that the total number of infiltrating lymphocytes and eosinophils were elevated in the airways of allergic GF mice compared with control SPF mice, and that this increase could be reversed by recolonization of GF mice with the complex commensal flora of SPF mice. Exaggerated airway eosinophilia correlated with increased local production of Th2-associated cytokines, elevated IgE production, and an altered number and phenotype of conventional dendritic cells. Regulatory T-cell populations and regulatory cytokine levels were unaltered, but GF mice exhibited an increased number of basophils and decreased numbers of alveolar macrophages and plasmacytoid dendritic cells.Conclusions: These data demonstrate that the presence of commensal bacteria is critical for ensuring normal cellular maturation, recruitment, and control of allergic airway inflammation.