Hypercalcemia after transplant nephrectomy in a hemodialysis patient: a case report

<p>Abstract</p> <p>Introduction</p> <p>Hypercalcemia is a complication often seen in chronic hemodialysis patients. A rare cause of this condition is sarcoidosis. Its highly variable clinical presentation is challenging. Especially in patients suffering chronic kidney graft failure the nonspecific constitutional symptoms of sarcoidosis like fever, weight loss, arthralgia and fatigue may be easily misleading.</p> <p>Case presentation</p> <p>A 51 year old male developed hypercalcemia, arthralgia and B-symptoms after explantation of his kidney graft because of suspected acute rejection. The removed kidney showed vasculopathy and tubulointerstitial nephritis, which had not been overt in the biopsy taken half a year earlier. Despite explantation and withdrawal of the immunosuppression the patient's general condition deteriorated progressively. A rapid rise in serum calcium finally provoked us to check for sarcoidosis. CT scans of the lungs, broncho-alveolar-lavage and further lab tests confirmed the diagnosis.</p> <p>Conclusion</p> <p>This case demonstrates that withdrawal of immunosuppressive drugs sometimes unmasks sarcoidosis. It should be considered as differential diagnosis even in hemodialysis patients, in whom other reasons for hypercalcemia are much more common.</p

Investigating organizational quality improvement systems, patient empowerment, organizational culture, professional involvement and the quality of care in European hospitals: the 'Deepening our Understanding of Quality Improvement in Europe (DUQuE)' project

BACKGROUND: Hospitals in European countries apply a wide range of quality improvement strategies. Knowledge of the effectiveness of these strategies, implemented as part of an overall hospital quality improvement system, is limited. METHODS/DESIGN: We propose to study the relationships among organisational quality improvement systems, patient empowerment, organisational culture, professionals' involvement with the quality of hospital care, including clinical effectiveness, patient safety and patient involvement. We will employ a cross-sectional, multi-level study design in which patient-level measurements are nested in hospital departments, which are in turn nested in hospitals in different EU countries. Mixed methods will be used for data collection, measurement and analysis. Hospital/care pathway level constructs that will be assessed include external pressure, hospital governance, quality improvement system, patient empowerment in quality improvement, organisational culture and professional involvement. These constructs will be assessed using questionnaires. Patient-level constructs include clinical effectiveness, patient safety and patient involvement, and will be assessed using audit of patient records, routine data and patient surveys. For the assessment of hospital and pathway level constructs we will collect data from randomly selected hospitals in eight countries. For a sample of hospitals in each country we will carry out additional data collection at patient-level related to four conditions (stroke, acute myocardial infarction, hip fracture and delivery). In addition, structural components of quality improvement systems will be assessed using visits by experienced external assessors. Data analysis will include descriptive statistics and graphical representations and methods for data reduction, classification techniques and psychometric analysis, before moving to bi-variate and multivariate analysis. The latter will be conducted at hospital and multilevel. In addition, we will apply sophisticated methodological elements such as the use of causal diagrams, outcome modelling, double robust estimation and detailed sensitivity analysis or multiple bias analyses to assess the impact of the various sources of bias. DISCUSSION: Products of the project will include a catalogue of instruments and tools that can be used to build departmental or hospital quality and safety programme and an appraisal scheme to assess the maturity of the quality improvement system for use by hospitals and by purchasers to contract hospitals

Development of a novel small antibody that retains specificity for tumor targeting

<p>Abstract</p> <p>Background</p> <p>For the targeted therapy of solid tumor mediated by monoclonal antibody (mAb), there have different models of rebuilding small antibodies originated from native ones. Almost all natural antibody molecules have the similar structure and conformation, but those rebuilt small antibodies cannot completely keep the original traits of parental antibodies, especially the reduced specificity, which gravely influences the efficacy of small antibodies.</p> <p>Methods</p> <p>In this study, authors developed a novel mimetic in the form of V_HFR1_C-10-V_HCDR1-V_HFR2-V_LCDR3-V_LFR4_N-10for a parental mAb induced with human breast cancer, and the mimetic moiety was conjugated to the C-terminal of toxicin colicin Ia. The novel fusion peptide, named protomimecin (PMN), was administered to MCF-7 breast cancer cells to demonstrate its killing competency <it>in vitro </it>and <it>in vivo</it>.</p> <p>Results</p> <p>Compared with original antibody-colicin Ia (Fab-Ia) and single-chain antibody-colicin Ia (Sc-Ia) fusion proteins, PMN retained the targeting specificity of parental antibody and could specifically kill MCF-7 cells <it>in vitro</it>. By injecting intraperitoneally into BALB/c athymic mice bearing MCF-7 tumors, with reduced affinity, PMN significantly suppressed the growth of tumors compared with control mice treated by toxicin protein, Fab-Ia protein, Sc-Ia protein or by PBS (<it>p </it>< 0.05).</p> <p>Conclusion</p> <p>This novel mimetic antibody retained original specificity of parental antibody, and could effectively guide killer moiety to suppress the growth of breast cancer by targeted cell death.</p

Is the maturity of hospitals' quality improvement systems associated with measures of quality and patient safety?

UNLABELLED: ABSTRACT: BACKGROUND: Previous research addressed the development of a classification scheme for quality improvement systems in European hospitals. In this study we explore associations between the 'maturity' of the hospitals' quality improvement system and clinical outcomes. METHODS: The maturity classification scheme was developed based on survey results from 389 hospitals in eight European countries. We matched the hospitals from the Spanish sample (113 hospitals) with those hospitals participating in a nation-wide, voluntary hospital performance initiative. We then compared sample distributions and explored associations between the 'maturity' of the hospitals' quality improvement system and a range of composite outcomes measures, such as adjusted hospital-wide mortality, -readmission, -complication and -length of stay indices. Statistical analysis includes bivariate correlations for parametrically and non-parametrically distributed data, multiple robust regression models and bootstrapping techniques to obtain confidence-intervals for the correlation and regression estimates. RESULTS: Overall, 43 hospitals were included. Compared to the original sample of 113, this sample was characterized by a higher representation of university hospitals. Maturity of the quality improvement system was similar, although the matched sample showed less variability. Analysis of associations between the quality improvement system and hospital-wide outcomes suggests significant correlations for the indicator adjusted hospital complications, borderline significance for adjusted hospital readmissions and non-significance for the adjusted hospital mortality and length of stay indicators. These results are confirmed by the bootstrap estimates of the robust regression model after adjusting for hospital characteristics. CONCLUSIONS: We assessed associations between hospitals' quality improvement systems and clinical outcomes. From this data it seems that having a more developed quality improvement system is associated with lower rates of adjusted hospital complications. A number of methodological and logistic hurdles remain to link hospital quality improvement systems to outcomes. Further research should aim at identifying the latent dimensions of quality improvement systems that predict quality and safety outcomes. Such research would add pertinent knowledge regarding the implementation of organizational strategies related with quality of care outcomes

Crystal Structure of Reovirus Attachment Protein σ1 in Complex with Sialylated Oligosaccharides

Many viruses attach to target cells by binding to cell-surface glycans. To gain a better understanding of strategies used by viruses to engage carbohydrate receptors, we determined the crystal structures of reovirus attachment protein σ1 in complex with α-2,3-sialyllactose, α-2,6-sialyllactose, and α-2,8-di-siallylactose. All three oligosaccharides terminate in sialic acid, which serves as a receptor for the reovirus serotype studied here. The overall structure of σ1 resembles an elongated, filamentous trimer. It contains a globular head featuring a compact β-barrel, and a fibrous extension formed by seven repeating units of a triple β-spiral that is interrupted near its midpoint by a short α -helical coiled coil. The carbohydrate-binding site is located between β-spiral repeats two and three, distal from the head. In all three complexes, the terminal sialic acid forms almost all of the contacts with σ1 in an identical manner, while the remaining components of the oligosaccharides make little or no contacts. We used this structural information to guide mutagenesis studies to identify residues in σ1 that functionally engage sialic acid by assessing hemagglutination capacity and growth in murine erythroleukemia cells, which require sialic acid binding for productive infection. Our studies using σ1 mutant viruses reveal that residues 198, 202, 203, 204, and 205 are required for functional binding to sialic acid by reovirus. These findings provide insight into mechanisms of reovirus attachment to cell-surface glycans and contribute to an understanding of carbohydrate binding by viruses. They also establish a filamentous, trimeric carbohydrate-binding module that could potentially be used to endow other trimeric proteins with carbohydrate-binding properties

Post-Streptococcal Antibodies Are Associated with Metabolic Syndrome in a Population-Based Cohort

Background: Streptococcal infections are known to trigger autoimmune disorders, affecting millions worldwide. Recently, we found an association between post-streptococcal autoantibodies against Protein Disulphide Isomerase (PDI), an enzyme involved in insulin degradation and insulin resistance. This led us to evaluate associations between post-streptococcal antibodies and metabolic syndrome, as defined by the updated National Cholesterol Education Program definition, 2005. Methods and Findings: Metabolic data (HDL, triglycerides, fasting glucose, blood pressure, waist circumference, BMI, smoking), post-streptococcal antibodies (anti-Streptolysin O (ASO) and anti-PDI), and C-reactive protein (CRP, as a general inflammatory marker), were assessed in 1156 participants of the Wisconsin Sleep Cohort Study. Anti-PDI antibodies were found in 308 participants (26.6%), ASO$100 in 258 (22.3%), and 482 (41.7%) met diagnostic criteria for metabolic syndrome. Anti-PDI antibodies but not ASO were significantly associated with metabolic syndrome [n = 1156, OR 1.463 (95 % CI 1.114, 1.920), p = 0.0062; adjusted for age, gender, education, smoking]. Importantly, the anti-PDI- metabolic syndrome association remained significant after adjusting for CRP and fasting insulin. Conclusions: Post-streptococcal anti-PDI antibodies are associated with metabolic syndrome regardless of fasting insulin and CRP levels. Whereas these data are in line with a growing body of evidence linking infections, immunity an

Attenuated reovirus displays oncolysis with reduced host toxicity

Background: Although the naturally occurring reovirus causes only mild symptoms in humans, it shows considerable potential as an oncolytic agent because of its innate ability to target cancer cells. In immunocompromised hosts, however, wild-type reovirus can target healthy tissues, including heart, liver, pancreas and neural structures. Methods: We characterized an attenuated form of reovirus (AV) derived from a persistently infected cell line through sequence analysis, as well as western blot and in vitro transcription and translation techniques. To examine its pathogenesis and oncolytic potential, AV reovirus was tested on healthy embryonic stem cells, various non-transformed and transformed cell lines, and in severe combined immunodeficiency (SCID) mice with tumour xenografts. Results: Sequence analysis of AV reovirus revealed a premature STOP codon in its sigma 1 attachment protein. Western blot and in vitro translation confirmed the presence of a truncated ?1. In comparison to wild-type reovirus, AV reovirus did not kill healthy stem cells or induce black tail formation in SCID mice. However, it did retain its ability to target cancer cells and reduce tumour size. Conclusion: Despite containing a truncated attachment protein, AV reovirus still preferentially targets cancer cells, and compared with wild-type reovirus it shows reduced toxicity when administered to immunodeficient hosts, suggesting the potential use of AV reovirus in combination cancer therapy

Urban schools' teachers enacting project-based science

What teaching practices foster inquiry and promote students to learn challenging subject matter in urban schools? Inquiry-based instruction and successful inquiry learning and teaching in project-based science (PBS) were described in previous studies (Brown & Campione, 1990 ; Crawford, 1999 ; Krajcik, Blumenfeld, Marx, Bass, & Fredricks, 1998 ; Krajcik, Blumenfeld, Marx, & Solloway, 1994 ; Minstrell & van Zee, 2000 ). In this article, we describe the characteristics of inquiry teaching practices that promote student learning in urban schools. Teaching is a major factor that affects both achievement of and attitude of students toward science (Tamir, 1998 ). Our involvement in reform in a large urban district includes the development of suitable learning materials and providing continuous and practiced-based professional development (Fishman & Davis, in press; van Es, Reiser, Matese, & Gomez, 2002 ). Urban schools face particular challenges when enacting inquiry-based teaching practices like those espoused in PBS. In this article, we describe two case studies of urban teachers whose students achieved high gains on pre- and posttests and who demonstrated a great deal of preparedness and commitment to their students. Teachers' attempts to help their students to perform well are described and analyzed. The teachers we discuss work in a school district that strives to bring about reform in mathematics and science through systemic reform. The Center for Learning Technologies in Urban Schools (LeTUS) collaborates with the Detroit Public Schools to bring about reform in middle-school science. Through this collaboration, diverse populations of urban-school students learn science through inquiry-oriented projects and the use of various educational learning technologies. For inquiry-based science to succeed in urban schools, teachers must play an important role in enacting the curriculum while addressing the unique needs of students. The aim of this article is to describe patterns of good science teaching in urban school. © 2006 Wiley Periodicals, Inc. J Res Sci Teach 43: 722–745, 2006Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/55780/1/20102_ftp.pd