tbuckley/cabot-search huggingface dataset:
Clinical prediction model to aid emergency doctors managing febrile children at risk of serious bacterial infections: diagnostic study
Authors: R. G. Nijman, Y. Vergouwe, M. Thompson, M. van Veen, A. H. J. van Meurs, J. van der Lei, E. W. Steyerberg, H. A. Moll, R. Oostenbrink
Journal: BMJ (2013)

<b>Objective</b> To derive, cross validate, and externally validate a clinical prediction model that assesses the risks of different serious bacterial infections in children with fever at the emergency department. <b>Design</b> Prospective observational diagnostic study. <b>Setting</b> Three paediatric emergency care units: two in the Netherlands and one in the United Kingdom. <b>Participants</b> Children with fever, aged 1 month to 15 years, at three paediatric emergency care units: Rotterdam (n=1750) and the Hague (n=967), the Netherlands, and Coventry (n=487), United Kingdom. A prediction model was constructed using multivariable polytomous logistic regression analysis and included the predefined predictor variables age, duration of fever, tachycardia, temperature, tachypnoea, ill appearance, chest wall retractions, prolonged capillary refill time (&gt;3 seconds), oxygen saturation &lt;94%, and C reactive protein. <b>Main outcome measures</b> Pneumonia, other serious bacterial infections (SBIs, including septicaemia/meningitis, urinary tract infections, and others), and no SBIs. <b>Results</b> Oxygen saturation &lt;94% and presence of tachypnoea were important predictors of pneumonia. A raised C reactive protein level predicted the presence of both pneumonia and other SBIs, whereas chest wall retractions and oxygen saturation &lt;94% were useful to rule out the presence of other SBIs. Discriminative ability (C statistic) to predict pneumonia was 0.81 (95% confidence interval 0.73 to 0.88); for other SBIs this was even better: 0.86 (0.79 to 0.92). Risk thresholds of 10% or more were useful to identify children with serious bacterial infections; risk thresholds less than 2.5% were useful to rule out the presence of serious bacterial infections. External validation showed good discrimination for the prediction of pneumonia (0.81, 0.69 to 0.93); discriminative ability for the prediction of other SBIs was lower (0.69, 0.53 to 0.86). <b>Conclusion</b> A validated prediction model, including clinical signs, symptoms, and C reactive protein level, was useful for estimating the likelihood of pneumonia and other SBIs in children with fever, such as septicaemia/meningitis and urinary tract infections.
A new conus peptide ligand for mammalian presynaptic Ca2+ channels
Authors: David R. Hillyard, Virginia D. Monje, Isabelle M. Mintz, Bruce P. Bean, Laszlo Nadasdi, J. Ramachandran, G. Miljanich, Aryan Azimi-Zoonooz, J.Michael McIntosh, Lourdes J. Cruz, Julita S. Imperial, Baldomero M. Olivera
Journal: Neuron (1992)
Induction of TFF1 gene expression in pancreas overexpressing transforming growth factor alpha
Authors: M P A Ebert, J Hoffmann, C Haeckel, K Rutkowski, R M Schmid, M Wagner, G Adler, H U Schulz, A Roessner, W Hoffmann, P Malfertheiner
Journal: Gut (1999)

<h3>BACKGROUND/AIMS</h3> Chronic pancreatitis is an inflammatory disease of the exocrine pancreas associated with extensive fibrosis, enlarged pancreatic ducts, acinar cell degeneration, and the formation of tubular complexes. The molecular and biochemical alterations associated with these histological changes are not kown. Generally, the new family of TFF peptides (formerly known as P-domain peptides or trefoil factors) is aberrantly expressed during chronic inflammatory diseases of the gastrointestinal tract. <h3>METHODS</h3> Using human pancreatic tissues obtained from patients with chronic pancreatitis and murine pancreatic tissues obtained from transgenic mice overexpressing transforming growth factor α (TGF-α), the expression and cellular distribution of TFF1 was analysed using northern blot analysis, polymerase chain reaction (PCR), and immunohistochemistry. <h3>RESULTS</h3> In the normal human pancreas, TFF1 was scarce, with only a few ducts exhibiting cytoplasmic TFF1 immunoreactivity. In contrast, human chronic pancreatitis tissue specimens exhibited strong TFF1 immunoreactivity in ductal cells, areas of ductal hyperplasia, and tubular complexes. Semiquantitative PCR analysis of TFF1 mRNA levels showed enhanced expression of TFF1 in the pancreas of patients with chronic pancreatitis. Furthermore, TFF1 mRNA levels were detectable in the pancreas in four of five transgenic mice overexpressing TGF-α. In contrast, four of five wild type mice did not exhibit a TFF1 mRNA transcript. In addition, while no specific TFF1 immunoreactivity was present in the pancreas of the wild type mice, ductal epithelial cells and duct-like tubular complexes in the pancreas of the transgenic mice overexpressing TGF-α exhibited pronounced TFF1 immunoreactivity. <h3>CONCLUSIONS</h3> Ductal cells and tubular complexes in pancreatic fibrosis express TFF1. As the 5′-flanking region of TFF1 contains an epidermal growth factor responsive enhancer region and the expression of epidermal growth factor and TGF-α is enhanced in pancreatic fibrosis, the enhanced expression of TFF1 in pancreatic fibrosis may be mediated by TGF-α.
CASE OF PITYRIASIS RUBRA PILARIS (DEVERGIE) IN CHILD OF FOUR YEARS
Authors: ARTHUR HALL
Journal: British Journal of Dermatology (1903)

Journal Article CASE OF PITYRIASIS RUBRA PILARIS (DEVERGIE) IN CHILD OF FOUR YEARS Get access ARTHUR HALL, MA., M.B.Cantab., M.R.C.P. ARTHUR HALL, MA., M.B.Cantab., M.R.C.P. Physician, Sheffield Royal Hospital; Professor of Pathology, University College, Sheffield Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 15, Issue 11, 1 November 1903, Pages 403–407, https://doi.org/10.1111/j.1365-2133.1903.tb16472.x Published: 01 November 1903
Red Blood Cells Induce Necroptosis of Lung Endothelial Cells and Increase Susceptibility to Lung Inflammation
Authors: Danielle Y. Qing, David Conegliano, Michael G. S. Shashaty, Jeongyun Seo, John P. Reilly, G. Scott Worthen, Dongeun Huh, Nuala J. Meyer, Nilam S. Mangalmurti
Journal: American Journal of Respiratory and Critical Care Medicine (2014)

Red blood cell (RBC) transfusions are associated with increased risk of acute respiratory distress syndrome (ARDS) in the critically ill, yet the mechanisms for enhanced susceptibility to ARDS conferred by RBC transfusions remain unknown.To determine the mechanisms of lung endothelial cell (EC) High Mobility Group Box 1 (HMGB1) release following exposure to RBCs and to determine whether RBC transfusion increases susceptibility to lung inflammation in vivo through release of the danger signal HMGB1.In vitro studies examining human lung EC viability and HMGB1 release following exposure to allogenic RBCs were conducted under static conditions and using a microengineered model of RBC perfusion. The plasma from transfused and nontransfused patients with severe sepsis was examined for markers of cellular injury. A murine model of RBC transfusion followed by LPS administration was used to determine the effects of RBC transfusion and HMGB1 release on LPS-induced lung inflammation.After incubation with RBCs, lung ECs underwent regulated necrotic cell death (necroptosis) and released the essential mediator of necroptosis, receptor-interacting serine/threonine-protein kinase 3 (RIP3), and HMGB1. RIP3 was detectable in the plasma of patients with severe sepsis, and was increased with blood transfusion and among nonsurvivors of sepsis. RBC transfusion sensitized mice to LPS-induced lung inflammation through release of the danger signal HMGB1.RBC transfusion enhances susceptibility to lung inflammation through release of HMGB1 and induces necroptosis of lung EC. Necroptosis and subsequent danger signal release is a novel mechanism of injury following transfusion that may account for the increased risk of ARDS in critically ill transfused patients.
Rituximab: Expanding Role in Therapy for Lymphomas and Autoimmune Diseases
Authors: William Rastetter, Arturo Molina, Christine A. White
Journal: Annual Review of Medicine (2004)

Rituximab (Rituxan®) is a human-mouse chimeric monoclonal antibody that targets the B-cell CD20 antigen and causes rapid and specific B-cell depletion. Rituximab was approved in the United States in 1997 to treat low-grade or follicular, relapsed or refractory, CD20-positive B-cell non-Hodgkin's lymphoma (NHL). Since then, further clinical experience with rituximab has been incorporated into the prescribing information, which now stipulates an extended eight-week schedule, treatment of patients with refractory or relapsed bulky disease measuring &gt;10 cm, and retreatment of patients who responded to rituximab previously. In 1998, the European Union approved rituximab (MabThera®) to treat stage III/IV, follicular, chemotherapy-resistant, or relapsed NHL. Recently, the European Union also approved the use of rituximab in combination with standard chemotherapy for aggressive NHL. Many clinical trials have evaluated rituximab, alone or with other therapies, in indolent and aggressive NHL as well as other B-cell lymphoproliferative disorders. New studies are evaluating rituximab's role in first-line therapy, maintenance therapy, and stem-cell transplantation procedures. The use of rituximab against autoimmune disorders, such as rheumatoid arthritis, immune thrombocytopenic purpura, autoimmune hemolytic anemia, systemic lupus erythematosus, and multiple sclerosis, is also under investigation.
Sunitinib-Induced Myeloid Lineage Redistribution in Renal Cell Cancer Patients: CD1c+ Dendritic Cell Frequency Predicts Progression-Free Survival
Authors: Hester van Cruijsen, Astrid A.M. van der Veldt, Laura Vroling, Dinja Oosterhoff, Henk J. Broxterman, Rik J. Scheper, Giuseppe Giaccone, John B.A.G. Haanen, Alfons J.M. van den Eertwegh, Epie Boven, Klaas Hoekman, Tanja D. de Gruijl
Journal: Clinical Cancer Research (2008)

Abstract Purpose: A disturbed myeloid lineage development with abnormally abundant neutrophils and impaired dendritic cell (DC) differentiation may contribute to tumor immune escape. We investigated the effect of sunitinib, a tyrosine kinase inhibitor of fms-like tyrosine kinase-3, KIT, and vascular endothelial growth factor receptors, on myeloid differentiation in renal cell cancer (RCC) patients. Experimental Design: Twenty-six advanced RCC patients were treated with sunitinib in a 4-week on/2-week off schedule. Enumeration and extensive phenotyping of myeloid subsets in the blood was done at baseline and at weeks 4 and 6 of the first treatment cycle. Baseline patient data were compared with sex- and age-matched healthy donor data. Results: Baseline frequencies of DC subsets were lower in RCC patients than in healthy donors. After 4 weeks of sunitinib treatment, a generalized decrease in myeloid frequencies was observed. Whereas neutrophils and monocytes, which were both abnormally high at baseline, remained low during the 2-week off period, DC rates recovered, resulting in a normalized myeloid lineage distribution. Subsequent to sunitinib treatment, an increase to high levels of myeloid DC (MDC) subset frequencies relative to other myeloid subsets, was specifically observed in patients experiencing tumor regression. Moreover, high CD1c/BDCA-1+ MDC frequencies were predictive for tumor regression and improved progression-free survival. Conclusion: The sunitinib-induced myeloid lineage redistribution observed in advanced RCC patients is consistent with an improved immune status. Immunologic recovery may contribute to clinical efficacy as suggested by the finding of highly increased MDC frequencies relative to other myeloid subsets in patients with tumor regression.
Clinical classification criteria for knee osteoarthritis: performance in the general population and primary care
Authors: G Peat
Journal: Annals of the Rheumatic Diseases (2006)

<b>Background:</b> Doubts have been expressed about the performance of the American College of Rheumatology (ACR) clinical classification criteria for osteoarthritis when applied in the general population. <b>Objective:</b> To investigate whether the distribution of population subgroups and underlying disease severity might explain the performance of these criteria in the population setting. <b>Methods:</b> Population-based cross-sectional study. 819 adults aged ⩾50 years reporting knee pain in the last 12 months were clinically assessed by research therapists using standardised protocols and blinded to radiographic status. All participants underwent plain radiography of the knees, scored by a single reader blinded to clinical status. The relationship between fulfilling the ACR clinical classification criteria for knee osteoarthritis and the presence of symptomatic radiographic knee osteoarthritis was summarised for the sample as a whole and within subgroups. <b>Results:</b> Radiographic osteoarthritis was present in 539 participants (68%) and symptomatic radiographic knee osteoarthritis in 259 (33%). 238 participants (30%) fulfilled the ACR clinical criteria for knee osteoarthritis. Agreement between the ACR clinical criteria and symptomatic radiographic knee osteoarthritis was low (sensitivity 41%; specificity 75%; positive predictive value 44%; negative predictive value 72%). Sensitivity and specificity did not vary markedly between population subgroups, although they were influenced by the underlying severity of radiographic osteoarthritis. <b>Conclusion:</b> The ACR clinical criteria seem to reflect later signs in advanced disease. Other approaches may be needed to identify early, mild osteoarthritis in the general population and primary care.
THE RHYTHMIC RANGE OF THE WHITE BLOOD CELLS IN HUMAN, PATHOLOGICAL LEUCOPENIC AND LEUCOCYTIC STATES, WITH A STUDY OF THIRTY-TWO HUMAN BONE MARROWS
Authors: Charles A. Doan, Leon G. Zerfas
Journal: The Journal of Experimental Medicine (1927)

In a study of twenty clinical cases with a wide range of diagnoses, repeated total counts of the white cells at 15 minute intervals reveal a large fluctuation at various levels comparable to that found for the normal (1, 2). The granulocytes seem to follow a more or less hourly rhythm, the most marked shift to the left in the Ameth pattern and the moment of greatest percentage of motility coinciding with the peaks. The independence found existing between the peripheral blood concentrations of individual strains of white cells and the red cells, as determined by total and differential counts, their differential response to pathological and pharmacological stimuli, and their normal relative relations, all indicate some separate physiological mechanism of control for each type of cell, either working through, or independently of, their sources of origin. The many factors to which the circulation of the blood, as such, is subject, the complexity of the influences on origin, maturation, delivery, longevity, and destruction of each cell group, the limitations inherent in the present involved, indirect technics of counting, combine to make any single observation subject to grave misinterpretation. The value to the clinician must come in repeated observations, at times when the diagnosis or a therapeutic procedure is in doubt, at frequent intervals, at other times over longer or shorter periods, but always with the relation between consecutive counts, rather than the absolute values, the important point for consideration. Both the red and the white cells probably change their relative concentrations in the peripheral blood from time to time over a considerable range that is quite within normal physiological limits, so that, in theoretical considerations and in practical functional estimations, a zonal concept with adequate individual extremes should always be kept in mind for both physiological and pathological states. A cytological analysis of thirty-two bone marrows from human biopsy and autopsy material shows the striking reciprocity found to exist between the myelocytes and the mature polymorphonuclear leucocytes. This, together with the observed focal uniformity of maturation found in bone marrow, and the periodicity of the fluctuations of the neutrophils in the peripheral blood, leads to the formulation of the hypothesis of a constant functional withdrawal of granulocytes from the peripheral blood with a periodic delivery of new cells from the marrow, which in leucopenia and in leucocytosis represents a depression or a stimulation, respectively, of the normal mechanism. The nature and degree of the response are an approximate index of the cellular factor in the complex of the "resistance" of the particular individual.
Allergen-induced IL-6 trans-signaling activates γδ T cells to promote type 2 and type 17 airway inflammation
Authors: Md Ashik Ullah, Joana A. Revez, Zhixuan Loh, Jennifer Simpson, Vivian Zhang, Lisa Bain, Antiopi Varelias, Stefan Rose-John, Antje Blumenthal, Mark J. Smyth, Geoffrey R. Hill, Maria B. Sukkar, Manuel A.R. Ferreira, Simon Phipps
Journal: Journal of Allergy and Clinical Immunology (2015)
Prevalence of extracranial venous narrowing on catheter venography in people with multiple sclerosis, their siblings, and unrelated healthy controls: a blinded, case-control study
Authors: Anthony L Traboulsee, Katherine B Knox, Lindsay Machan, Yinshan Zhao, Irene Yee, Alexander Rauscher, Darren Klass, Peter Szkup, Robert Otani, David Kopriva, Shanti Lala, David K Li, Dessa Sadovnick
Journal: The Lancet (2013)
Once-daily ciclesonide is as effective as twice-daily budesonide in maintaining lung function and asthma control in patients with asthma
Authors: D.A. Gadgil, P. Niphadkar, K.T. Jagannath, J.M. Joshi, N. Awad, S.K. Chhabra, S. Hellbardt, R. Engelstätter
Journal: Journal of Allergy and Clinical Immunology (2005)
Re: Gene Therapy Strategies for Tumor Antiangiogenesis
Authors: H L Kong, R G Crystal
Journal: JNCI Journal of the National Cancer Institute (1998)

Based on the concept that solid tumors cannot grow without the generation of new blood vessels, there is growing interest in the use of antiangiogenesis agents to inhibit tumor growth. This review summarizes the concepts of using gene transfer vectors to provide high concentration of antiangiogenic proteins within an organ. While there are many challenges that must be met before antiangiogenesis can be used to effectively treat human tumors, gene transfer strategies have the potential to provide sustained, high, local concentrations of antiangiogenic mediators specifically targeted to organs containing tumors, minimizing systemic toxicity. Antiangiogenesis gene therapy strategies will most likely be effective in a state of low tumor burden, where this "genetic tourniquet" can provide trans (i.e., acting in the extracellular milieu as opposed to within tumor cells) suppression of the growth of endothelial cells in the milieu of micrometastases.
THE PATHOGENESIS OF DEFERRED CANCER
Authors: William F. Friedewald, Peyton Rous
Journal: The Journal of Experimental Medicine (1950)

The ears of young adult rabbits were painted with methylcholanthrene (MC) long enough to call forth a few benign tumors (papillomas, frill horns), and the animals were followed throughout their later lives. Soon after the paintings were stopped the tumors began to dwindle and vanished, yet even while they were disappearing other growths of the same kinds arose, only to vanish later in their turn. For a long while more arose than disappeared, and in consequence the number of tumors increased throughout years. They accumulated at a constant rate despite concurrent changes in the supporting skin, which might have been supposed, on previous experience, to have prevented this from happening. Only in the old age of the animals did the number of tumors eventually fall off, and by this time the skin on which they had arisen, long since normal in the gross to all appearance, had become nearly so microscopically. Even then latent neoplastic potentialities still existed in the cutaneous tissue; where punch holes were healing new tumors arose. A great multitude of hidden neoplastic cells were present in the MCed skin, and from them many of the growths called forth by the stimulus of healing undoubtedly derived. Yet the facts make it difficult to suppose that the long accumulation, at a constant rate, of tumors visible in the gross was due wholly to the proliferation of cells rendered neoplastic during the period of exposure to MC, and lying hidden afterwards for periods determined by their differing, evenly graded capabilities. Nor can the accumulation be attributed to a sustained carcinogenesis resulting from the pathological state of the skin. As a whole the findings indicate that the linear increase in growths was due for the most part to a continual arrival at the neoplastic state and subsequent proliferation of cells, or the descendants of cells, that had been no more than started on the way toward becoming neoplastic by the carcinogen. There is clinical evidence for such a course of events. Now and again a carcinoma arose from the skin previously treated with MC, but they were few in all, as would follow from the presence of local conditions unfavorable to malignant change. Some appeared only after years,-in one instance more than 5 years after. The occurrence of deferred cancer in man can be understood in terms of the findings in rabbits.
Dietary fat intake and prevention of cardiovascular disease: systematic review
Authors: L. Hooper
Journal: BMJ (2001)

<h3>Abstract</h3> <b>Objective:</b> To assess the effect of reduction or modification of dietary fat intake on total and cardiovascular mortality and cardiovascular morbidity. <b>Design:</b> Systematic review. <b>Data sources:</b> Cochrane Library, Medline, Embase, CAB abstracts, SIGLE, CVRCT registry, and biographies were searched; trials known to experts were included. <b>Included studies:</b> Randomised controlled trials stating intention to reduce or modify fat or cholesterol intake in healthy adult participants over at least six months. Inclusion decisions, validity, and data extraction were duplicated. Meta-analysis (random effects methodology), meta-regression, and funnel plots were performed. <b>Results:</b> 27 studies (30 902 person years of observation) were included. Alteration of dietary fat intake had small effects on total mortality (rate ratio 0.98; 95% confidence interval 0.86 to 1.12). Cardiovascular mortality was reduced by 9% (0.91; 0.77 to 1.07) and cardiovascular events by 16% (0.84; 0.72 to 0.99), which was attenuated (0.86; 0.72 to 1.03) in a sensitivity analysis that excluded a trial using oily fish. Trials with at least two years9 follow up provided stronger evidence of protection from cardiovascular events (0.76; 0.65 to 0.90). <b>Conclusions:</b> There is a small but potentially important reduction in cardiovascular risk with reduction or modification of dietary fat intake, seen particularly in trials of longer duration. <h3>What is already known on this topic</h3> The epidemiological relation between dietary fat intake and cardiovascular disease is central in strategies aimed at risk reduction in populations and individuals Systematic review of randomised controlled trials supports manipulation of dietary fat to control serum lipid concentrations, though evidence of effect on one risk factor does not rule out an opposite or reinforced effect on another unstudied risk factor Randomised controlled trials of dietary fat reduction or modification have shown varying results on cardiovascular morbidity and mortality <h3>What this study adds</h3> Systematic review of trials of modified fat intake shows that reduction or modification of dietary fat intake results in reductions in cardiovascular events, but only in trials of at least two years9 duration There is little effect on total mortality Despite decades of effort and many thousands of people randomised, there is still only limited and inconclusive evidence of the effects of modification of total, saturated, monounsaturated, or polyunsaturated fats on cardiovascular morbidity and mortality