Thrombopoietin stimulates colony-forming unit-megakaryocyte proliferation and megakaryocyte maturation independently of cytokines that signal through the gp130 receptor subunit

Thrombopoietin (Tpo), the ligand for the c-Mpl receptor, is a major regulator of megakaryopoiesis. Treatment of mice with Tpo raises the platelet count fourfold within a few days. Conversely, c-mpl knock-out mice have platelet counts that are 15% that of normal. The subunit structure of the c-Mpl receptor is not fully understood. Some cytokines that stimulate megakaryopoiesis (IL-6, IL-11, leukemia inhibitory factor, and oncostatin M) bind to receptors that use gp130 as a signal transduction subunit. For these reasons, we determined whether gp130 function was required for Tpo-induced signal transduction. Murine marrow cells were cultured in semi-solid media in the presence of Tpo or IL-3, with or without a neutralizing anti-gp130 monoclonal antibody (RX187) or a soluble form of c-Mpl receptor (soluble Mpl) that blocks Tpo bioactivity, and the numbers of colony-forming unit-megakaryocyte (CFU-Meg) colonies were counted on day 5. Murine marrow cells were also cultured in suspension under serum-free conditions for 5 days, and megakaryocyte DNA content was measured by flow cytometry, as an index of nuclear maturation. The addition of RX187 did not block Tpo-induced CFU-Meg colony growth nor CFU-Meg nuclear maturation in suspension culture. However, IL-3-induced CFU-Meg colony growth and megakaryocyte nuclear maturation decreased in the presence of RX187. Soluble Mpl completely ablated Tpo-induced CFU-Meg growth, and partially blocked IL- 3-stimulated CFU-Meg growth. Thus the effects of Tpo on megakaryopoiesis in vitro do not depend on cytokines that signal through gp130. Furthermore, it is unlikely that gp 130 serves as a beta chain for the c-Mpl receptor, as Tpo signalling is unimpaired in the presence of RX187. In contrast, the effects of IL-3 on CFU-Meg growth are mediated in part through Tpo and through gp130-signalling cytokines.     

Reduced susceptibility to penicillin among pneumococci causing invasive infection in children - Canada, 1991 to 1998.

OBJECTIVE: To determine, over time, the rate and serotypes of pneumococci with reduced penicillin susceptibility obtained from children with invasive infection. DESIGN: Active, hospital-based, multicentre surveillance spanning from 1991 to 1998. SETTING: Eleven Canadian tertiary care paediatric facilities located from coast to coast. POPULATION STUDIED: 1847 children with invasive pneumococcal infection whose isolates (from a normally sterile site) were available for serotyping and standardized testing for penicillin susceptibility at the National Centre for Streptococcus. MAIN RESULTS: The prevalence of reduced penicillin susceptibility increased from 2.5% of 197 cases in 1991 to 13.0% of 276 cases in 1998. In the latter year, 8.7% of isolates had intermediate level resistance, and 4.3% had high level resistance. Since they were first detected in 1992, strains with high level resistance have been encountered only sporadically at most centres, but by 1998, all centres but two had encountered examples. Of 40 isolates with high level resistance and 101 isolates with intermediate level resistance, serotypes matched those included in new seven-valent conjugate vaccines for children in 97.5% and 79.2% of cases, respectively. CONCLUSIONS: Pneumococci with reduced susceptibility to penicillin are increasing in frequency across Canada among children with invasive infection. The Immunization Monitoring Program, Active data indicate that new conjugate vaccines could help to curb infections due to pneumococci with reduced susceptibility to penicillin but are unlikely to control completely the problem of antibiotic resistance.     

Tumours and pseudotumours of the region of the ampulla of Vater: an endoscopic, clinical and pathological study.

From a large series of patients referred for endoscopic retrograde cholangiopancreatography to one endoscopist, 49 patients had the duodenoscopic appearance of a periampullary tumour. Thirty eight of these lesions were neoplastic, but the remaining 11 patients had inflammatory non-neoplastic lesions (pseudotumours). These could not be distinguished from the neoplasms on endoscopic appearances. The cholangiopancreatograms were similar except that the diameter of the pancreatic duct tended to be higher in the tumour group and gall stones were present significantly more often in the patients with pseudotumour. Endoscopic biopsy correctly diagnosed 28 of 34 ampullary carcinomas. Two of the 11 pseudotumour patients were subjected to surgical excision biopsy because of suspicious histological features of endoscopic biopsy. In the neoplastic group 19 patients underwent Whipple's procedure, seven surgical bypass, seven endoscopic sphincterotomy only and five died without successful biliary drainage. The overall one year survival was 44.7%. By contrast, the patients with pseudotumours were clinically well at a median follow up 24 months (range 12-41 months), after endoscopic sphincterotomy except for one 89 year old patient who died 22 months later from unrelated causes.     

The National Cancer Informatics Program (NCIP) Annotation and Image Markup (AIM) Foundation Model

Knowledge contained within in vivo imaging annotated by human experts or computer programs is typically stored as unstructured text and separated from other associated information. The National Cancer Informatics Program (NCIP) Annotation and Image Markup (AIM) Foundation information model is an evolution of the National Institute of Health’s (NIH) National Cancer Institute’s (NCI) Cancer Bioinformatics Grid (caBIG®) AIM model. The model applies to various image types created by various techniques and disciplines. It has evolved in response to the feedback and changing demands from the imaging community at NCI. The foundation model serves as a base for other imaging disciplines that want to extend the type of information the model collects. The model captures physical entities and their characteristics, imaging observation entities and their characteristics, markups (two- and three-dimensional), AIM statements, calculations, image source, inferences, annotation role, task context or workflow, audit trail, AIM creator details, equipment used to create AIM instances, subject demographics, and adjudication observations. An AIM instance can be stored as a Digital Imaging and Communications in Medicine (DICOM) structured reporting (SR) object or Extensible Markup Language (XML) document for further processing and analysis. An AIM instance consists of one or more annotations and associated markups of a single finding along with other ancillary information in the AIM model. An annotation describes information about the meaning of pixel data in an image. A markup is a graphical drawing placed on the image that depicts a region of interest. This paper describes fundamental AIM concepts and how to use and extend AIM for various imaging disciplines.     

Accessory muscles around the foot and ankle presenting as chronic undiagnosed pain. An illustrative case report and review of the literature

The differential diagnosis of ankle pain is extensive. Pathology may be classified as intra- or extra-articular. Additionally, ankle pain may be traumatic or non-traumatic. One of the unusual differential diagnoses for pain in the ankle is an accessory muscle. Magnetic resonance imaging is the radiological investigation of choice. However, this is invariably reported as normal unless one specifically looks for an accessory muscle. The purpose of this report is to highlight important features of these muscles and to draw attention to this uncommonly reported condition.