Safety and Phosphate-Binding Capacity of Oxylanthanum Carbonate in Healthy Volunteers.

Despite the widespread use of currently available serum phosphate management options, elevated serum phosphate is common in patients with end-stage kidney disease on dialysis. Characteristics of currently available phosphate binders that lead to poor patient experiences such as large drug volume size of required daily medication (e.g.

Laboratory Workup of Lymphoma in Adults.

Objectives: The diagnostic workup of lymphoma continues to evolve rapidly as experience and discovery lead to the addition of new clinicopathologic entities and techniques to differentiate them. The optimal clinically effective, efficient, and cost-effective approach to diagnosis that is safe for patients can be elusive, in both community-based and academic practice. Studies suggest that there is variation in practice in both settings.

Laboratory Workup of Lymphoma in Adults: Guideline From the American Society for Clinical Pathology and the College of American Pathologists.

Context.—: The diagnostic workup of lymphoma continues to evolve rapidly as experience and discovery led to the addition of new clinicopathologic entities and techniques to differentiate them. The optimal clinically effective, efficient, and cost-effective approach to diagnosis that is safe for patients can be elusive, in both community-based and academic practice.

Detection of Polyclonal Increases in Immunoglobulin G4 Subclass by Distinct Patterns on Capillary Serum Protein Electrophoresis: Diagnostic Pitfalls and Clinical Observations in a Study of 303 Cases.

Objectives: Autoimmunity, hypersensitivity, and the recently recognized set of syndromes collectively termed immunoglobulin G4-related disease (IgG4-RD) may be associated with increased serum IgG4 levels. We reviewed our experience detecting increased IgG4 by distinct serum protein electrophoresis (SPEP) patterns.

Methods: We studied 303 capillary SPEP cases with dome-like anodal γ changes and increased measured serum IgG4.

Building a laboratory workforce to meet the future: ASCP Task Force on the Laboratory Professionals Workforce.

Objectives: To analyze the demand for services from the nation's medical laboratories, which is predicted to dramatically increase as our citizens age and millions receive insurance coverage through the Affordable Care Act.

Methods: A systematic review of relevant publications and databases was conducted to assess the current state of the nation's medical laboratory workforce and to examine the impact of population demographics and health reform on workforce development to address the future demand for laboratory services.

Results: Building a Laboratory Workforce to Meet the Future, a new report from the American Society for Clinical Pathology (ASCP), provides a comprehensive strategy to address the future workforce needs of the nation's medical laboratories to meet this demand to provide timely, accurate, and safe patient care and to fully realize the benefits of personalized medicine.

Immunophenotypic signatures of benign and dysplastic granulopoiesis by cytomic profiling.

Background: The role of flow cytometry (FCM) in diagnosing myelodysplastic syndromes (MDS) remains controversial, because analysis of myeloid maturation may involve subjective interpretation of sometimes subtle patterns on multiparameter FCM.

Methods: Using six-parameter marker combinations known to be useful in evaluating the myeloid compartment in MDS, we measured objective immunophenotypic differences between non-neoplastic (n = 25) and dysplastic (n = 17) granulopoiesis using a novel method, called Fisher information nonparametric embedding (FINE), that measures information distances among FCM datasets modeled as individual high-dimensional probability density functions, rather than as sets of two-dimensional histograms. Information-preserving component analysis (IPCA) was used to create information-optimized "rotated" two-dimensional histograms for visualizing myelopoietic immunophenotypes for each individual sample.

Statistical file matching of flow cytometry data.

Flow cytometry is a technology that rapidly measures antigen-based markers associated to cells in a cell population. Although analysis of flow cytometry data has traditionally considered one or two markers at a time, there has been increasing interest in multidimensional analysis. However, flow cytometers are limited in the number of markers they can jointly observe, which is typically a fraction of the number of markers of interest.

The phosphate binder equivalent dose.

Phosphate binders include calcium acetate or carbonate, sevelamer hydrochloride or carbonate, magnesium and lanthanum carbonate, and aluminum carbonate or hydroxide. Their relative phosphate-binding capacity has been assessed in human, in vivo studies that have measured phosphate recovery from stool and/or changes in urinary phosphate excretion or that have compared pairs of different binders where dose of binder in each group was titrated to a target level of serum phosphate. The relative phosphate-binding coefficient (RPBC) based on weight of each binder can be estimated relative to calcium carbonate, the latter being set to 1.

Interleukin-33 contributes to both M1 and M2 chemokine marker expression in human macrophages.

Background: Interleukin-33 is a member of the IL-1 cytokine family whose functions are mediated and modulated by the ST2 receptor. IL-33-ST2 expression and interactions have been explored in mouse macrophages but little is known about the effect of IL-33 on human macrophages. The expression of ST2 transcript and protein levels, and IL-33-mediated effects on M1 (i.

Immunomodulator agent-related lymphoproliferative disorders.

The recent development of inhibitors of key immune response proteins has revolutionized the therapy of autoimmune diseases; these immunomodulator agents include monoclonal antibodies and receptor antagonists. However, as with all therapies, these new agents are not without side effects and complications. In particular, anti-tumor necrosis factor alpha (TNFalpha) agents have been reported to be associated with an increased incidence of lymphoproliferative disorders, infections, and vasculitis.

FINE: fisher information nonparametric embedding.

We consider the problems of clustering, classification, and visualization of high-dimensional data when no straightforward euclidean representation exists. In this paper, we propose using the properties of information geometry and statistical manifolds in order to define similarities between data sets using the Fisher information distance. We will show that this metric can be approximated using entirely nonparametric methods, as the parameterization and geometry of the manifold is generally unknown.

Lanthanum carbonate reduces phosphorus burden in patients with CKD stages 3 and 4: a randomized trial.

Background And Objectives: Lanthanum carbonate (FOSRENOL, Shire Pharmaceuticals) is an effective noncalcium, nonresin phosphate binder for the control of hyperphosphatemia in chronic kidney disease (CKD) stage 5 patients undergoing dialysis.

Design, Setting, Participants And Measurements: A Phase 2, randomized, double-blind, placebo-controlled trial evaluating the efficacy and safety of lanthanum carbonate in CKD stage 3 and 4 patients. Of 281 patients screened, 121 were randomized (2:1) to lanthanum carbonate or placebo (80 versus 41).

Differences in germinal centre and non-germinal center phenotype in gastric and intestinal diffuse large B-cell lymphomas.

The gastrointestinal tract is the most common extranodal site of lymphoma, and the most common gastrointestinal lymphoma is diffuse large B-cell type (DLBCL). DLBCL can be separated into germinal centre (GCP) and non-germinal centre phenotypes (non-GCP) using CD10, BCL-6 and MUM1 immunohistochemistry, but primary gastrointestinal DLBCL has not been extensively studied. We investigated 48 cases of primary gastrointestinal DLBCL (33% involving the small intestine, 50% the stomach, 13% the large intestine and 4% the ileocecal junction) and found that most (88%) DLBCL in the intestines were of GCP, while only 58% of gastric DLBCL were of GCP.

Analysis of clinical flow cytometric immunophenotyping data by clustering on statistical manifolds: treating flow cytometry data as high-dimensional objects.

Background: Clinical flow cytometry typically involves the sequential interpretation of two-dimensional histograms, usually culled from six or more cellular characteristics, following initial selection (gating) of cell populations based on a different subset of these characteristics. We examined the feasibility of instead treating gated n-parameter clinical flow cytometry data as objects embedded in n-dimensional space using principles of information geometry via a recently described method known as Fisher Information Non-parametric Embedding (FINE).

Methods: After initial selection of relevant cell populations through an iterative gating strategy, we converted four color (six-parameter) clinical flow cytometry datasets into six-dimensional probability density functions, and calculated differences among these distributions using the Kullback-Leibler divergence (a measurement of relative distributional entropy shown to be an appropriate approximation of Fisher information distance in certain types of statistical manifolds).

Site-specific morphologic differences in extranodal marginal zone B-cell lymphomas.

Context: Lymphoepithelial lesions (LELs) are a useful diagnostic feature of extranodal marginal zone B-cell lymphoma (EMZL); however, there is scant literature comparing their frequency and morphology at various sites.

Objective: To evaluate any diagnostically useful, site-specific, morphologic patterns in EMZLs.

Design: In this retrospective review, we evaluated 136 EMZLs from different sites for LEL pattern and other pathologic differences, including CD43 coexpression and plasma cell component features.

Diagnostic pathology and laboratory medicine in the age of "omics": a paper from the 2006 William Beaumont Hospital Symposium on Molecular Pathology.

Functional genomics and proteomics involve the simultaneous analysis of hundreds or thousands of expressed genes or proteins and have spawned the modern discipline of computational biology. Novel informatic applications, including sophisticated dimensionality reduction strategies and cancer outlier profile analysis, can distill clinically exploitable biomarkers from enormous experimental datasets. Diagnostic pathologists are now charged with translating the knowledge generated by the "omics" revolution into clinical practice.

Fascin expression in diffuse large B-cell lymphoma, anaplastic large cell lymphoma, and classical Hodgkin lymphoma.

Context: Fascin is an actin-bundling protein involved in the formation of dendritic processes. Fascin is a sensitive marker for classical Reed-Sternberg cells and has a high negative predictive value for diagnosis of classical Hodgkin lymphoma (CHL). Fascin has been used to distinguish CHL from non-Hodgkin lymphoma.

Cytochrome P450 3A5 expression in the kidneys of patients with calcineurin inhibitor nephrotoxicity.

Background: Nephrotoxicity secondary to calcineurin inhibitors is common in renal transplant recipients, occurring in 76-94% of patients. The role of drug transporters (P-glycoprotein) and drug metabolizing enzymes (cytochrome P450) as predisposing factors toward nephrotoxicity or its prevention has not been thoroughly examined.

Methods: The objective of this study was to analyse cytochrome P450 3A5 (CYP3A5) expression in kidneys of solid organ recipients by immunohistochemistry to determine if there is an association between expression of this enzyme and calcineurin inhibitor toxicity.

The clinical and renal consequences of contrast-induced nephropathy.

Contrast-induced nephropathy (CIN), an impairment of renal function following intravascular injection of contrast media, is commonly defined as an increase in the baseline serum creatinine concentration of >25% or 0.5 mg/dl (44 micromol/l). The incidence of CIN does not appear to have changed appreciably in the last three decades, and it continues to be the third leading cause of hospital-acquired acute renal failure (ARF).

Immunosuppression, hepatitis C infection, and acute renal failure in HIV-infected patients.

Background: Low CD4 cell counts predict HIV-related morbidity and mortality and may be associated with acute renal failure (ARF).

Objective: To estimate the effect of CD4 cell count on the incidence rate (IR) of ARF in ambulatory HIV-infected patients with access to highly active antiretroviral therapy.

Methods: Observational clinical cohort of HIV-infected patients recruited from a university-based infectious diseases clinic, between 2000 and 2002, and followed up until December 31, 2002.

Non-contrast-enhanced computerized tomography and analgesic-related kidney disease: report of the national analgesic nephropathy study.

Previous studies suggested that the non-contrast-enhanced computerized tomography (CT) scan is a highly reliable tool for the diagnosis of analgesic-associated renal disease. However, this issue has not been addressed in the US population. A total of 221 incident patients with ESRD from different regions of the United States underwent a helical CT scan and detailed questioning about drug history.

Unsupervised immunophenotypic profiling of chronic lymphocytic leukemia.

Background: Proteomics and functional genomics have revolutionized approaches to disease classification. Like proteomics, flow cytometry (FCM) assesses concurrent expression of many proteins, with the advantage of using intact cells that may be differentially selected during analysis. However, FCM has generally been used for incremental marker validation or construction of predictive models based on known patterns, rather than as a tool for unsupervised class discovery.