tbuckley/cabot-search huggingface dataset:
Bacteremia among Children Admitted to a Rural Hospital in Kenya
Authors: James A. Berkley, Brett S. Lowe, Isaiah Mwangi, Thomas Williams, Evasius Bauni, Saleem Mwarumba, Caroline Ngetsa, Mary P.E. Slack, Sally Njenga, C. Anthony Hart, Kathryn Maitland, Mike English, Kevin Marsh, J. Anthony G. Scott
Journal: New England Journal of Medicine (2005)

There are few epidemiologic data on invasive bacterial infections among children in sub-Saharan Africa. We studied every acute pediatric admission to a rural district hospital in Kenya to examine the prevalence, incidence, types, and outcome of community-acquired bacteremia.Between August 1998 and July 2002, we cultured blood on admission from 19,339 inpatients and calculated the incidence of bacteremia on the basis of the population served by the hospital.Of a total of 1783 infants who were under 60 days old, 228 had bacteremia (12.8 percent), as did 866 of 14,787 children who were 60 or more days of age (5.9 percent). Among infants who were under 60 days old, Escherichia coli and group B streptococci predominated among a broad range of isolates (14 percent and 11 percent, respectively). Among infants who were 60 or more days of age, Streptococcus pneumoniae, nontyphoidal salmonella species, Haemophilus influenzae, and E. coli accounted for more than 70 percent of isolates. The minimal annual incidence of community-acquired bacteremia was estimated at 1457 cases per 100,000 children among infants under a year old, 1080 among children under 2 years, and 505 among children under 5 years. Of all in-hospital deaths, 26 percent were in children with community-acquired bacteremia. Of 308 deaths in children with bacteremia, 103 (33.4 percent) occurred on the day of admission and 217 (70.5 percent) within two days.Community-acquired bacteremia is a major cause of death among children at a rural sub-Saharan district hospital, a finding that highlights the need for prevention and for overcoming the political and financial barriers to widespread use of existing vaccines for bacterial diseases.
Relationship between Overnight Rostral Fluid Shift and Obstructive Sleep Apnea in Nonobese Men
Authors: Stefania Redolfi, Dai Yumino, Pimon Ruttanaumpawan, Brian Yau, Mao-Chang Su, Jennifer Lam, T. Douglas Bradley
Journal: American Journal of Respiratory and Critical Care Medicine (2008)

The cause of increased pharyngeal collapsibility in patients with obstructive sleep apnea is incompletely understood. In awake healthy subjects, we showed that fluid displacement from the legs into the neck induced by lower body positive pressure reduces upper airway size and increases its collapsibility. Prolonged sitting leads to dependent fluid accumulation in the legs.To test the hypotheses that the apnea-hypopnea index (AHI) during sleep will be related to the amount of fluid spontaneously displaced from the legs overnight, and that this will, in turn, be related to the time spent sitting the previous day.In 23 nonobese healthy men referred for sleep studies for suspected obstructive sleep apnea, we assessed the changes in leg fluid volume and in neck circumference from the beginning to the end of the night, and the time spent sitting during the previous day.The overnight change in leg fluid volume correlated strongly with the AHI (r = -0.773, P < 0.001), the change in neck circumference (r = -0.792, P < 0.001), and the time spent sitting (r = -0.588, P = 0.003). Multivariate analysis showed that the only significant independent correlates of the AHI were the overnight changes in leg fluid volume and neck circumference, which together explained 68% of the variability in the AHI among subjects.These novel findings suggest that overnight rostral fluid displacement from the legs, related to prolonged sitting, may play a previously unrecognized role in the pathogenesis of obstructive sleep apnea in nonobese men that is independent of body weight.
Global Burden of Disease estimates of depression – how reliable is the epidemiological evidence?
Authors: Petra Brhlikova, Allyson M Pollock, Rachel Manners
Journal: Journal of the Royal Society of Medicine (2011)

To re-assess the quality of the epidemiological studies used to estimate the global burden of depression 2000, as published in the GBDep study.Primary and secondary data sources used in the global burden of depression estimate were identified and assigned to country of origin. Each source was assessed with respect to completeness and representativeness for national/regional estimates and against the inclusion criteria used by the scientific team estimating GBDep.Not applicable.Not applicable.Not applicable.First, National estimates: The 28 scientific sources cited in the GBDep study related to 40 of the 191 WHO member countries. The EURO region had studies relating to 15 of 52 countries whereas AFRO region had studies for only three of 46 countries. Only six of the 40 countries had data drawn from a nationally representative population: the three AFRO country studies were based on a single village or town and, likewise, SEARO region had no nationally representative data; second, GBDep criteria: GBDep inclusion criteria required study sample size of more than 1000 people; 19 (45%) of the 42 studies did not meet this criterion. Sixteen (44%) of 36 studies did not meet the requirement that studies show a clear sample frame and method. GBD estimates rely on estimates of incidence; only two of the 42 country studies provided incidence data (Canada and Norway), the remaining 34 studies were prevalence studies. Duration of depression is based on three studies conducted in the USA and Holland.Most studies exhibit significant shortcomings and limitations with respect to study design and analysis and compliance with GBDep inclusion criteria. Poor quality data limit the interpretation and validity of global burden of depression estimates. The uncritical application of these estimates to international healthcare policy-making could divert scarce resources from other public healthcare priorities.
Determinants of management errors in acute severe asthma
Authors: J. Kolbe, M. Vamos, W. Fergusson, G. Elkind
Journal: Thorax (1998)

It is hypothesised that, despite recent initiatives to improve asthma self-management including asthma education, detailed investigation of the sequence of events culminating in hospital admission will lead to the identification of important management errors and thus the likelihood that the majority of severe asthma attacks are preventable by currently available strategies, and that psychological, health care and socioeconomic factors are risk factors for such management errors.A cross sectional study was undertaken of 138 patients aged 15-50 years admitted to hospital (general ward or intensive care unit) with acute severe asthma who were assessed within 24-72 hours of admission using a number of previously validated instruments. A detailed history of events of the attack was assessed against predetermined criteria for non or delayed use of oral corticosteroids and non or delayed use of emergency ambulance services.Subjects had evidence of severe chronic asthma and had acute severe asthma at presentation (n = 90, pH = 7.3 (0.2), PaCO2 = 7.2 (5.0) kPa) but duration of hospital stay was short (3.7 (2.6) days). Serious management errors occurred very frequently and most were deemed to have been made by the patient. Forward stepwise regression revealed that delayed or non-use of oral corticosteroids was predicted independently by lack of paying job (p = 0.02), high total use of inhaled beta agonists in the 24 hours before index admission (p = 0.04), loss of a job in the last year (p = 0.04), low frequency of use of oral corticosteroids in the last year (p = 0.06), concerns during the index attack about medical expenses (p = 0.07), and delay in the use of ambulance services (p = 0.05)--the model being responsible for 23% of the variance. Delayed or non-summoning of emergency ambulance services was predicted independently by total life events (p = 0.03), having something stolen in the last year (p = 0.003), panic during the index attack (p = 0.01), and concerns during the index attack about taking time off work (p = 0.07)--the model being responsible for 21% of the variance.The results of this study show that, despite recent educational advances, serious management errors are common in those admitted to hospital with acute severe asthma and that most management errors relate to patient self-management behaviour. Serious management errors are predicted by a variety of socio-economic and psychological factors. While the results of this study are consistent with the widely held view that most acute severe attacks are theoretically preventable, the challenge for the future is to change patients' behaviour in the face of considerable adverse socioeconomic and psychological factors.
Firstborn Status, Early Day Care Use and Allergen-Specific IgE, Hay Fever, and Asthma in Young Adults
Authors: C.C. Johnson, G.R. Wegienka, S.L. Havstad, K.J. Woodcroft, L.K. Williams, C.L.M. Joseph, D.R. Ownby, E.M. Zoratti
Journal: Journal of Allergy and Clinical Immunology (2007)
Calciphylaxis in a patient without renal failure or elevated parathyroid hormone: possible aetiological role of chemotherapy
Authors: S. Goyal, K.M. Huhn, T.T. Provost
Journal: British Journal of Dermatology (2000)

Journal Article Calciphylaxis in a patient without renal failure or elevated parathyroid hormone: possible aetiological role of chemotherapy Get access S. Goyal, S. Goyal Department of Dermatology, The Johns Hopkins University, School of Medicine, 601 North Caroline Street, Baltimore, MD 21287‐0900, U.S.A. Search for other works by this author on: Oxford Academic Google Scholar K.M. Huhn, K.M. Huhn Department of Dermatology, The Johns Hopkins University, School of Medicine, 601 North Caroline Street, Baltimore, MD 21287‐0900, U.S.A. Search for other works by this author on: Oxford Academic Google Scholar T.T. Provost T.T. Provost Department of Dermatology, The Johns Hopkins University, School of Medicine, 601 North Caroline Street, Baltimore, MD 21287‐0900, U.S.A. Thomas T.Provost, 7401 Osler Drive, Suite 107, Towson, Maryland 21204, USA. Tel: +1 410 321 5900; fax +1 410 821 6052. Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 143, Issue 5, 1 November 2000, Pages 1087–1090, https://doi.org/10.1046/j.1365-2133.2000.03853.x Published: 01 November 2000
Cleavage of protein S by a platelet membrane protease.
Authors: C A Mitchell, H H Salem
Journal: Journal of Clinical Investigation (1987)

Protein S is a vitamin K-dependent glycoprotein cofactor to the serine protease, activated protein C. In this study we demonstrate that 125I-protein S bound to unstimulated platelets in a time- and calcium-dependent saturable reaction. Half-maximal binding occurred at a protein S concentration of 10 nM, with approximately 1,100 binding sites per platelet. The binding of protein S to platelets was followed by rapid cleavage of the protein mediated by a protease confined to the platelet membrane. The membrane protease was Ca++-dependent, inhibited by high concentrations of diisopropyl fluorophosphate, but was resistant to a variety of other protease inhibitors. Functional studies demonstrated that the cleavage of protein S was associated with complete loss of cofactor anticoagulant activity. We conclude that protein S binds to platelets and is inactivated by a novel Ca++-dependent membrane protease. This may represent a physiological reaction that regulates the activity of protein S.
Acquisition of direct antiviral effector functions by CMV-specific CD4+ T lymphocytes with cellular maturation
Authors: Joseph P. Casazza, Michael R. Betts, David A. Price, Melissa L. Precopio, Laura E. Ruff, Jason M. Brenchley, Brenna J. Hill, Mario Roederer, Daniel C. Douek, Richard A. Koup
Journal: The Journal of Experimental Medicine (2006)

The role of CD4+ T cells in the control of persistent viral infections beyond the provision of cognate help remains unclear. We used polychromatic flow cytometry to evaluate the production of the cytokines interferon (IFN)-γ, tumor necrosis factor (TNF)-α, and interleukin (IL)-2, the chemokine macrophage inflammatory protein (MIP)-1β, and surface mobilization of the degranulation marker CD107a by CD4+ T cells in response to stimulation with cytomegalovirus (CMV)-specific major histocompatibility complex class II peptide epitopes. Surface expression of CD45RO, CD27, and CD57 on responding cells was used to classify CD4+ T cell maturation. The functional profile of virus-specific CD4+ T cells in chronic CMV infection was unique compared with that observed in other viral infections. Salient features of this profile were: (a) the simultaneous production of MIP-1β, TNF-α, and IFN-γ in the absence of IL-2; and (b) direct cytolytic activity associated with surface mobilization of CD107a and intracellular expression of perforin and granzymes. This polyfunctional profile was associated with a terminally differentiated phenotype that was not characterized by a distinct clonotypic composition. Thus, mature CMV-specific CD4+ T cells exhibit distinct functional properties reminiscent of antiviral CD8+ T lymphocytes.
Immunologic effects of prophylactic donor lymphocyte infusion after allogeneic marrow transplantation for multiple myeloma
Authors: Roberto Bellucci, Edwin P. Alyea, Edie Weller, Antoinette Chillemi, Ephraim Hochberg, Catherine J. Wu, Christine Canning, Robert Schlossman, Robert J. Soiffer, Kenneth C. Anderson, Jerome Ritz
Journal: Blood (2002)
The Influence of Tone upon Responses of Small and Large Vessels to Serotonin
Authors: F. J. HADDY, P. GORDON, D. A. EMANUEL
Journal: Circulation Research (1959)

In the dog foreleg, serotonin antagonizes extremes of vascular tone induced by neurogenic means. It produces net dilatation when the bed is constricted and net constriction when the bed is dilated. This bidirectional response derives ultimately from the facts that changes in nervous activity change calibers of small vessels without greatly altering calibers of large vessels, and that serotonin produces small vessel dilatation at the same time that it constricts large vessels. When small vessels are already neurogenically dilated, serotonin cannot dilate them further, but continues to constrict large vessels. Thus, the net effect is constriction. When small vessels are highly constricted, serotonin dilates small vessels more than it constricts large vessels. The net effect is dilatation. The study also indicates why it is more difficult to demonstrate a similar antagonism when tone is varied by humoral means.
Spontaneous activity regulates Robo1 transcription to mediate a switch in thalamocortical axon growth
Authors: Erik Mire, Cecilia Mezzera, Eduardo Leyva-Díaz, Ana V Paternain, Paola Squarzoni, Lisa Bluy, Mar Castillo-Paterna, María José López, Sandra Peregrín, Marc Tessier-Lavigne, Sonia Garel, Joan Galcerán, Juan Lerma, Guillermina López-Bendito
Journal: Nature Neuroscience (2012)
Phased by Notch
Authors: Heather L. Van Epps
Journal: The Journal of Experimental Medicine (2005)

On page 157, Sarmento and colleagues show how the developmental regulator protein Notch1 advances the cell cycle. Activation of Notch1 induced the production of a protein that chops up cell cycle inhibitors, leading to a shortened G1 phase and a faster transition into S phase (but no overall increase in proliferation).

The Notch family of transmembrane receptors regulates both cell fate decisions and the maintenance of adult stem cells, processes that require precise control of the cell cycle. Although Notch1 activation had previously been shown to alter the cell cycle in hematopoietic progenitor cells and to delay their commitment to the myeloid lineage, a direct link between Notch1 and cell cycle control pathways had not been established in these cells.






Figure 

Notch1 promotes progression into the S phase of the cell cycle by inducing the expression of SKP2, a component of a ubiquitin ligase complex that degrades the CDK inhibitor p27kip1.




Sarmento et al. now find the link and show that constitutive Notch1 activation drives cell cycling by increasing the activity of cyclin-dependent kinase-2 (CDK2), a protein that promotes progression into the S phase of the cell cycle. CDK2 activation resulted from the degradation of the CDK inhibitor protein p27kip1, which was triggered by the Notch1-induced expression of a protein called SKP2—a component of a ubiquitin ligase complex that targets proteins for proteosomal degradation.

How Notch-induced changes in cell cycle kinetics influence differentiation programs is not completely clear. The authors suggest that a shortened G1 phase—during which cells are thought to be most responsive to fate-deciding differentiation signals—may minimize the window of differentiation opportunity and thus help maintain the progenitor cell pool.
Low-Density Lipoprotein Receptor Knockout Mice Exhibit Exaggerated Microvascular Responses to Inflammatory Stimuli
Authors: Dwight D. Henninger, Mary E. Gerritsen, D. Neil Granger
Journal: Circulation Research (1997)

Abstract The objective of this study was to determine whether genetically induced hypercholesterolemia affects leukocyte–endothelial cell interactions in postcapillary venules of the mouse cremaster muscle. Leukocyte adhesion, emigration, and other microvascular parameters were assessed in venules of normal (wild-type) and low-density lipoprotein receptor–deficient (LDLr −/ − ) mice maintained on either normal rodent chow or on a high cholesterol diet (HCD). Measurements were obtained under control conditions and after administration of either leukotriene B 4 (LTB 4 ), platelet-activating factor (PAF), or tumor necrosis factor-α (TNF-α). Elevated numbers of adherent and emigrated leukocytes were observed in venules of LDLr −/ − (compared with wild-type) mice on HCD, both under baseline conditions and after exposure to either LTB 4 , PAF, or TNF-α. Plasma TNF-α levels were also elevated in LDLr −/ − versus wild-type mice. Administration of blocking monoclonal antibodies demonstrated that intercellular adhesion molecule-1, but not vascular cell adhesion molecule-1, mediates the exaggerated leukocyte–endothelial cell adhesion observed in LDLr −/ − mice. The results of these studies indicate that chronic hypercholesterolemia predisposes the microvasculature to intense leukocyte–endothelial cell adhesion in response to different inflammatory stimuli.
Breast Cancer: Noninvasive and Special Situations
Authors: Robert W. Carlson, D. Craig Allred, Benjamin O. Anderson, Harold J. Burstein, W. Bradford Carter, Stephen B. Edge, John K. Erban, William B. Farrar, Andres Forero, Sharon Hermes Giordano, Lori J. Goldstein, William J. Gradishar, Daniel F. Hayes, Clifford A. Hudis, Britt-Marie Ljung, P. Kelly Marcom, Ingrid A. Mayer, Beryl McCormick, Lori J. Pierce, Elizabeth C. Reed, Mary Lou Smith, George Somlo, Neal S. Topham, John H. Ward, Eric P. Winer, Antonio C. Wolff
Journal: Journal of the National Comprehensive Cancer Network (2010)

Overview The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Breast Cancer: Noninvasive and Special Situations presented here are the work of the NCCN Breast Cancer panel members. Categories of evidence and consensus were assessed and are noted in the algorithms and text. Although not explicitly stated at every decision point of the guidelines, patient participation in prospective clinical trials is the preferred option of treatment for all stages of breast cancer. These NCCN Guidelines foNCCN
HLA-DM Interactions with Intermediates in HLA-DR Maturation and a Role for HLA-DM in Stabilizing Empty HLA-DR Molecules
Authors: Lisa K. Denzin, Craig Hammond, Peter Cresswell
Journal: The Journal of Experimental Medicine (1996)

Major histocompatibility complex (MHC) class II–positive cell lines which lack HLA-DM expression accumulate class II molecules associated with residual invariant (I) chain fragments (class II–associated invariant chain peptides [CLIP]). In vitro, HLA-DM catalyzes CLIP dissociation from class II–CLIP complexes, promoting binding of antigenic peptides. Here the physical interaction of HLA-DM with HLA-DR molecules was investigated. HLA-DM complexes with class II molecules were detectable transiently in cells, peaking at the time when the class II molecules entered the MHC class II compartment. HLA-DR αβ dimers newly released from I chain, and those associated with I chain fragments, were found to associate with HLA-DM in vivo. Mature, peptide-loaded DR molecules also associated at a low level. These same species, but not DR-I chain complexes, were also shown to bind to purified HLA-DM molecules in vitro. HLA-DM interaction was quantitatively superior with DR molecules isolated in association with CLIP. DM-DR complexes generated by incubating HLA-DM with purified DR αβCLIP contained virtually no associated CLIP, suggesting that this superior interaction reflects a prolonged HLA-DM association with empty class II dimers after CLIP dissociation. Incubation of peptide-free αβ dimers in the presence of HLA-DM was found to prolong their ability to bind subsequently added antigenic peptides. Stabilization of empty class II molecules may be an important property of HLA-DM in facilitating antigen processing.
Treatment of young children with CNS-primitive neuroectodermal tumors/pineoblastomas in the prospective multicenter trial HIT 2000 using different chemotherapy regimens and radiotherapy
Authors: Carsten Friedrich, André O. von Bueren, Katja von Hoff, Nicolas U. Gerber, Holger Ottensmeier, Frank Deinlein, Martin Benesch, Robert Kwiecien, Torsten Pietsch, Monika Warmuth-Metz, Andreas Faldum, Joachim Kuehl, Rolf D. Kortmann, Stefan Rutkowski
Journal: Neuro-Oncology (2012)

Especially in young children, primitive neuroectodermal tumors of the central nervous system (CNS-PNET) and pineoblastomas are associated with an unfavorable outcome, and only a few prospective trials have been conducted thus far.From January 2001 through January 2005, 17 eligible children aged <4 years with CNS-PNET not otherwise specified (n = 8), ependymoblastoma (n = 1), or pineoblastoma (n = 8) confirmed by central review were prospectively treated in the trial HIT 2000. In nonmetastatic disease (n = 11), up to 5 postoperative cycles of HIT-SKK systemic multiagent chemotherapy (8 months duration), followed by craniospinal radiotherapy (CSI), were given. In metastatic disease (M1-M3, n = 6), treatment consisted of a shorter induction chemotherapy (2-3 months) with carboplatin and etoposide, followed by tandem high-dose chemotherapy (HDCT) in case of good response to induction. During induction and HDCT, patients received intraventricular methotrexate. CSI was applied to all patients with poor response to induction or residual disease after HDCT and was optional for patients with residual disease before HDCT.Five-year event-free survival and overall survival rates ± standard error for all eligible patients were 24% ± 10% and 40% ± 12%, respectively (median follow-up of survivors: 8.3 years). Only one patient with nonmetastatic disease remained free of relapse/progressive disease during induction. Three of 6 patients with metastatic disease responded to induction and received tandem-HDCT, followed by preventive CSI, and remain in continuous complete remission.Short intensive induction chemotherapy followed by tandem-HDCT in young children with CNS-PNET/pineoblastomas seems to be superior to the prolonged and less intensive induction regimen.