Bacterial cholangitis causing secondary sclerosing cholangitis: A case report

Background  

Although bacterial cholangitis is frequently mentioned as a cause of secondary sclerosing cholangitis, it appears to be extremely rare, with only one documented case ever reported.     

Human interleukin-5 (IL-5) regulates the production of eosinophils in human bone marrow cultures: comparison and interaction with IL-1, IL-3, IL-6, and GMCSF

Recombinant human interleukin-5 (rhIL-5), in either liquid or semi- solid cultures, selectively induced eosinophil production from normal human bone marrow, with no activity on other cell lineages. The time course of eosinophil production induced by murine IL-5, rhIL-3, and rh granulocyte-macrophage colony stimulating factor (GMCSF) was similar to rhIL-5. The rate of eosinophil maturation in vitro was independent of the stimulating cytokine, mature eosinophils being produced after 4 to 5 weeks in liquid culture with each of these cytokines. The eosinophils produced in response to each cytokine were morphologically indistinguishable, and had the ultrastructural features of maturity except that the electron-dense material in the granules had not formed into crystalline cores. Neither rhIL-1 nor rhIL-6 alone, or in combination with rhIL-5 or rhIL-3, induced eosinophil differentiation or proliferation under the conditions used. rhIL-3 and rhGMCSF induced more eosinophil colonies than rhIL-5, rhIL-5 had an additive, not synergistic, effect on eosinophil colony production when combined with either rhIL-3 or rhGMCSF, suggesting that rhIL-5 stimulates a smaller and possibly different population of eosinophil progenitors. However, rhIL-5 induced the greatest eosinophil production in liquid cultures, suggesting that although it may act on a smaller population of precursors, it is able to stimulate more proliferative steps than either rhIL-3 or rhGMCSF.     

The diagnostic value of the fibrinogen/fibrin fragment E antigen assay in clinically suspected deep vein thrombosis

We have evaluated the fibrinogen/fibrin fragment E antigen assay as a diagnostic test in patients with clinically suspected venous thrombosis by comparing the results of this assay with venography in 272 patients. The result of the fragment E antigen assay was elevated in 79 of 80 patients with positive venograms for recent venous thrombosis (sensitivity 99%) and within the normal range in 161 of 192 patients with normal venograms (specificity 84%). The fragment E assay was also evaluated in 130 medical and surgical controls without evidence of venous thrombosis by leg scanning and the test was found to be relatively nonspecific. However, in the patient group under study, a correct clinical diagnosis of no thrombosis, based on a normal fragment E result, was made in 161 of 162 cases (negative predictive value of 99%). Therefore, a normal test result effectively excludes a diagnosis of venous thrombosis in clinically symptomatic patients. The assay, as currently performed, is technically demanding and takes 24 hr to complete. Therefore, it will have to be simplified before it can be applied to clinical practice.     

System for Rapid Assessment of Pneumonia and Influenza-Related Mortality—Ohio, 2009–2010

Rapid mortality surveillance is critical for state emergency preparedness. To enhance timeliness during the 2009–2010 influenza A H1N1 pandemic, the Ohio Department of Health activated a drop-down menu within Ohio’s Electronic Death Registration System for reporting of pneumonia- or influenza-related deaths approximately 5 days postmortem. We used International Classification of Diseases—Tenth Revision (ICD-10) codes, available 2–3 months postmortem as the standard, and assessed their agreement with drop-down-menu codes for pneumonia- or influenza-related deaths. Among 56 660 Ohio deaths during September 2009–March 2010, agreement was 97.9% for pneumonia (κ = 0.85) and 99.9% for influenza (κ = 0.79). Sensitivity was 80.2% for pneumonia and 73.9% for influenza. Drop-down menu coding enhanced timeliness while maintaining high agreement with ICD-10 codes.     

Educating and Training a Workforce for Nutrition in a Post-2015 World

Nearly all countries in the world today are burdened with malnutrition, manifesting as undernutrition, micronutrient deficiencies, and/or overweight and obesity. Despite some progress, efforts to alleviate malnutrition are hampered by a shortage in number, skills, and geographic coverage, of a workforce for nutrition. Here, we report the findings of the Castel Gandolfo workshop, a convening of experts from diverse fields in March 2014 to consider how to develop the capacity of a global cadre of nutrition professionals for the post-2015 development era. Workshop participants identified several requirements for developing a workforce for nutrition, including an ability to work as part of a multisectoral team; communication, advocacy, and leadership skills to engage decision makers; and a set of technical skills to address future challenges for nutrition. Other opportunities were highlighted that could immediately contribute to capacity development, including the creation of a consortium to link global North and South universities, online training modules for middle managers, and practical, hands-on experiences for frontline nutrition workers. Institutional and organizational support is needed to enable workshop recommendations on education and training to be effectively implemented and sustained. The findings from the Castel Gandolfo workshop can contribute to the delivery of successful nutrition-relevant actions in the face of mounting external pressures and informing and attaining the forthcoming Sustainable Development Goals.     

A serological re-evaluation of acute non-A non-B hepatitis from the early 1970s

Background: The epidemiology and natural history of recently discovered viruses, which may be responsible for cases of seronegative infectious hepatitis, are currently being investigated. Retrospective studies of stored sera can provide a historical perspective of these infections. Aims: To re‐evaluate the serological, demographic and clinical characteristics of patients hospitalised in the early 1970s with acute hepatitis. Methods: The stored sera of 57 patients hospitalised between 1971 and 1974 with acute hepatitis, designated at that time as non‐A non‐B (NANB) hepatitis, were re‐tested using commercially available enzyme‐linked immunosorbent assays (ELISAs) for the presence of anti‐hepatitis A virus (HAV) IgM, hepatitis B surface antigen (HBsAg), anti‐hepatitis C virus (HCV) IgG, and anti‐hepatitis E virus (HEV) IgG. Stored sera from a group of 57 patients concurrently hospitalised for other conditions were also tested. Detailed records of the original epidemiological interviews were examined to compare patient demographics, risk factors for infectious hepatitis and clinical data for the NANB hepatitis group and an original control group of 604 hospitalised patients. Results: Serum from 15 of the 57 (26%) previously designated NANB hepatitis cases had elevated anti‐HAV IgM and are likely to represent missed cases of hepatitis A. Thirteen (23%) of cases previously designated as NANB hepatitis had positive hepatitis C antibody tests. These patients were younger and significantly more likely to have used intravenous drugs than control patients. Three NANB hepatitis and two hospital control patients were anti‐HEV IgG antibody positive. All of these individuals were born in, or had travelled to, developing countries. Serum from 27 (47%) of the NANB hepatitis patients were negative on all tests. These hepatitis non‐A‐E cases included children and elderly adults, but as a group were significantly more likely to have used intravenous drugs than hospitalised control patients.     

Discovery and characterization of a selective, nonpeptidyl thrombopoietin receptor agonist

OBJECTIVE: Peptide and other small molecule agonists have been described for several cytokines and growth factors. Hydrazone compounds described here as thrombopoietin receptor agonists were identified as activating STAT proteins in a Tpo responsive cell line. METHODS: STAT activation and analysis of signal transduction pathways in cell lines and normal human platelets was elucidated by Western blot and electrophoretic mobility shift assays. Proliferation assays in cell types responsive to other cytokines determined specificity for Tpo receptor. Flow cytometry quantified differentiation of CD34(+) cells into CD41(+) megakaryocytes and platelet production in vitro. RESULTS: Activation of STAT5, mitogen-activated protein kinase, p38, and early response genes by SB 394725 was similar to that induced by Tpo. SB 394725 induced a reporter gene response under a STAT activation promoter as well as the megakaryocyte-specific gpIIb promoter. The compound induced proliferation of Tpo responsive lines but demonstrated no activity in cell lines responding to other cytokines, i.e., erythropoietin, granulocyte-colony stimulating factor, interleukin-3, interferon-gamma. The response of normal human Tpo receptors was elucidated by measuring growth and differentiation of human bone marrow in vitro. Activation of endogenous Tpo receptors by SB 394725 was demonstrated in human and chimp platelets, but not in platelets of other species including mouse, dog, rabbit, or cynomolgus monkey. CONCLUSIONS: SB 394725, a small molecule with a molecular weight of 452 Da, is capable of activating Tpo-specific signal transduction, proliferation, and differentiation responses similar to the responses and functions of the protein growth factor, Tpo.