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1.
Am J Clin Pathol ; 137(1): 20-5, 2012 Jan.
Article in English | MEDLINE | ID: mdl-22180474

ABSTRACT

A long-standing practice in clinical laboratories has been to automatically repeat laboratory tests when values trigger automated "repeat rules" in the laboratory information system such as a critical test result. We examined 25,553 repeated laboratory values for 30 common chemistry tests from December 1, 2010, to February 28, 2011, to determine whether this practice is necessary and whether it may be possible to reduce repeat testing to improve efficiency and turnaround time for reporting critical values. An "error" was defined to occur when the difference between the initial and verified values exceeded the College of American Pathologists/Clinical Laboratory Improvement Amendments allowable error limit. The initial values from 2.6% of all repeated tests (668) were errors. Of these 668 errors, only 102 occurred for values within the analytic measurement range. Median delays in reporting critical values owing to repeated testing ranged from 5 (blood gases) to 17 (glucose) minutes.


Subject(s)
Clinical Chemistry Tests/standards , Diagnostic Errors/prevention & control , Laboratories, Hospital/organization & administration , Pathology, Clinical/organization & administration , Clinical Chemistry Tests/statistics & numerical data , Diagnostic Errors/statistics & numerical data , Humans , Laboratories, Hospital/standards , Pathology, Clinical/standards , Quality Control , Reference Values , Reproducibility of Results
2.
Am J Dermatopathol ; 33(8): e99-102, 2011 Dec.
Article in English | MEDLINE | ID: mdl-22024573

ABSTRACT

Although most cases of intravascular large cell lymphoma exhibit a B-cell phenotype, less than 50 cases in the literature describe a T-cell or natural killer cell phenotype and, of these, the majority are CD3+, CD4-, CD5-, CD30-, CD56+, TIA-1+, and EBER+. We present a case of a rare intravascular large T-cell lymphoma in a 59-year-old man with an unusual CD3+, CD4+, CD5-, CD30+, CD56-, TIA-1-negative and EBER-negative phenotype. This T helper or CD30 phenotype is particularly uncommon. To our knowledge, it has only been described once before and never in the absence of the cytotoxic marker TIA-1. This case exemplifies the particular diagnostic challenges raised by intravascular large cell lymphomas generally and should encourage the use of endothelial immunohistochemical staining in questionable cases. While evaluating skin punch biopsies, it is critical to keep this rare entity on the differential diagnosis along with the relatively more common intravascular large B-cell lymphoma and epithelial malignancies. Additionally, our understanding of intravascular large natural killer/T-cell lymphoma as a heterogeneous phenotypic entity continues to evolve. This case demonstrates that the degree of this phenotypic heterogeneity may be even greater than previously thought.


Subject(s)
Biomarkers, Tumor/analysis , Endothelial Cells/immunology , Lymphoma, T-Cell/immunology , T-Lymphocytes, Helper-Inducer/immunology , Vascular Neoplasms/immunology , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Biopsy , Diagnosis, Differential , Endothelial Cells/pathology , Humans , Immunohistochemistry , Lymphoma, T-Cell/drug therapy , Lymphoma, T-Cell/pathology , Male , Middle Aged , Phenotype , Predictive Value of Tests , T-Lymphocytes, Helper-Inducer/pathology , Treatment Outcome , Vascular Neoplasms/drug therapy , Vascular Neoplasms/pathology
3.
Hum Immunol ; 71(10): 968-75, 2010 Oct.
Article in English | MEDLINE | ID: mdl-20600446

ABSTRACT

A major subset of human peripheral blood γδ T cells expresses the Vγ2Vδ2 T cell receptor and responds to malignant or infectious diseases. We noted significant differences in the numbers of Vγ2Vδ2 T cells in blood samples from healthy Caucasian CA or African American (AA) donors. On average, CA donors had 3.71% ± 4.37% Vδ2 cells (as a percentage of total lymphocytes) compared with 1.18% ± 2.14% Vδ2 cells for AA donors (p < 0.0001). Age and race had the greatest impact on Vδ2 cell levels; the effect of age was similar for both racial groups. The Vδ2 cell population was dominated, for both donor groups, by cells expressing the Vγ2-Jγ1.2 Vδ2 T cell receptor, an apparent result of strong positive selection and there was substantial overlap in the public Vγ2 clonotypes from both racial groups. Mechanisms for selection and amplification of Vδ2 cells are nearly identical for both groups, despite the significant difference in baseline levels. These data show that appropriate controls, matched for age and race, may be required for clinical studies of Vγ2Vδ2 T cells in infectious disease or cancer and raise important questions about the mechanisms regulating the levels of circulating Vδ2 cells.


Subject(s)
Receptors, Antigen, T-Cell, gamma-delta/metabolism , T-Lymphocyte Subsets/metabolism , T-Lymphocytes/metabolism , Adult , Black or African American , Age Factors , Cell Count , Cell Separation , Female , Flow Cytometry , Humans , Male , Middle Aged , Receptors, Antigen, T-Cell, gamma-delta/immunology , Sex Factors , T-Lymphocyte Subsets/immunology , T-Lymphocyte Subsets/pathology , T-Lymphocytes/immunology , T-Lymphocytes/pathology , White People
4.
J Infect Dis ; 195(1): 37-45, 2007 Jan 01.
Article in English | MEDLINE | ID: mdl-17152007

ABSTRACT

Vaccinia virus (VV) is an effective vaccine and vector but has evolved multiple mechanisms for evading host immunity. We characterized the interactions of VV (TianTan and New York City Board of Health strains) with human gammadelta T cells because of the role they play in immune control of this virus. Exposure to VV failed to trigger proliferative responses in gammadelta T cells from unprimed individuals, but it was an unexpected finding that VV blocked responses to model antigens by the Vgamma2Vdelta2 T cell subset. Infectious or ultraviolet light-inactivated VV inhibited proliferative Vgamma2Vdelta2 T cell responses to phosphoantigens and tumor cells, prevented cytolysis of Daudi B cells, and reduced cytokine production. Inhibiting Vgamma2Vdelta2 T cells may be a mechanism for evading host immunity and increasing VV virulence. Increased VV replication or expression in the absence of gammadelta T cell responses might contribute to its potency as a vaccine against poxvirus and recombinant antigens.


Subject(s)
Receptors, Antigen, T-Cell, gamma-delta/physiology , T-Lymphocyte Subsets/immunology , T-Lymphocytes, Cytotoxic/immunology , Vaccinia virus/immunology , Humans , Leukocytes, Mononuclear , Receptors, Antigen, T-Cell, gamma-delta/biosynthesis , Receptors, Antigen, T-Cell, gamma-delta/genetics , Receptors, Immunologic/genetics , T-Lymphocyte Subsets/virology , T-Lymphocytes, Cytotoxic/drug effects , Vaccinia/genetics , Vaccinia/immunology , Vaccinia/virology , Vaccinia virus/pathogenicity
5.
Infect Immun ; 74(8): 4505-11, 2006 Aug.
Article in English | MEDLINE | ID: mdl-16861636

ABSTRACT

Circulating Vgamma2Vdelta2 T-cell populations in healthy human beings are poised for rapid responses to bacterial or viral pathogens. We asked whether Vgamma2Vdelta2 T cells use the Toll-like receptor (TLR) family to recognize pathogen-associated molecular pattern molecules and to regulate cell functions. Analysis of expanded Vgamma2Vdelta2 T-cell lines showed the abundant presence of TLR2 mRNA, implying that these receptors are important for cell differentiation or function. However, multiple efforts to detect TLR2 protein on the cell surface or in cytoplasmic compartments gave inconsistent results. Functional assays confirmed that human Vgamma2Vdelta2 T cells could respond to the TLR2 agonist (S)-(2,3-bis(palmitoyloxy)-(2RS)-propyl)-N-palmitoyl-(R)-Cys-(S)-Ser(S)-Lys4-OH trihydrochloride (Pam3Cys), but the response required coincident stimulation through the gammadelta T-cell receptor (TCR). Dually stimulated cells produced higher levels of cytoplasmic or cell-free gamma interferon and showed increased expression of the lysosome-associated membrane protein CD107a on the cell surface. A functional TLR2 that requires coincident TCR stimulation may increase the initial potency of Vgamma2Vdelta2 T-cell responses at the site of infection and promote the rapid development of subsequent acquired antipathogen immunity.


Subject(s)
Antibodies/immunology , Dipeptides/immunology , Interferon-gamma/metabolism , Lipoproteins/immunology , Receptors, Antigen, T-Cell, gamma-delta/immunology , T-Lymphocytes/immunology , Toll-Like Receptor 2/agonists , Cell Line , Cells, Cultured , Dipeptides/pharmacology , Flow Cytometry , Humans , Lipoproteins/pharmacology , Lymphocyte Activation , Receptors, Antigen, T-Cell, gamma-delta/metabolism , Signal Transduction , T-Lymphocytes/drug effects , T-Lymphocytes/metabolism , Toll-Like Receptor 2/genetics , Toll-Like Receptor 2/metabolism
6.
Pediatr Infect Dis J ; 22(3): 216-24, 2003 Mar.
Article in English | MEDLINE | ID: mdl-12634581

ABSTRACT

BACKGROUND: Lopinavir/ritonavir has demonstrated antiviral activity in the HIV-infected adult. SUBJECTS: The objective of this study was to investigate a liquid coformulation of lopinavir/ritonavir, in combination with reverse transcriptase inhibitors, in HIV-infected children. METHODS: One hundred antiretroviral (ARV)-naive and ARV-experienced, nonnucleoside reverse transcriptase inhibitor-naive children between 6 months and 12 years of age participated in this Phase I/II, open label, multicenter trial. Subjects initially received either 230/57.5 mg/m(2) or 300/75 mg/m(2) lopinavir/ritonavir twice daily; ARV-naive subjects also received stavudine and lamivudine, whereas ARV-experienced subjects also received nevirapine and one or two nucleoside reverse transcriptase inhibitors. Lopinavir/ritonavir pharmacokinetics, safety and efficacy were evaluated. RESULTS: All subjects were escalated to the 300/75 mg/m(2) twice daily dose based on results from an interim pharmacokinetic and safety evaluation. The pharmacokinetics of lopinavir did not appear to be dependent on age when dosing was based on body surface area but were decreased on coadministration with nevirapine. Overall 79% of subjects had HIV RNA levels <400 copies/ml at Week 48 (intent-to-treat: missing = failure). Mean increases in absolute and relative (percent) CD4 counts from baseline to Week 48 were observed in both ARV-naive subjects (404 cells/mm(3); 10.3%) and ARV-experienced subjects (284 cells/mm(3); 5.9%). Only one subject prematurely discontinued the study because of a study drug-related adverse event. CONCLUSIONS: The liquid coformulation of lopinavir/ritonavir demonstrated durable antiviral activity and was safe and well-tolerated after 48 weeks of treatment in HIV-infected children.


Subject(s)
HIV Infections/drug therapy , Maximum Tolerated Dose , Pyrimidinones/administration & dosage , Reverse Transcriptase Inhibitors/administration & dosage , Ritonavir/administration & dosage , Administration, Oral , Biological Availability , Chemistry, Pharmaceutical , Child , Child, Preschool , Confidence Intervals , Dose-Response Relationship, Drug , Drug Administration Schedule , Drug Therapy, Combination , Female , Follow-Up Studies , HIV Infections/diagnosis , Humans , Infant , Lopinavir , Male , Multivariate Analysis , Pyrimidinones/pharmacokinetics , RNA, Viral/drug effects , Reverse Transcriptase Inhibitors/pharmacokinetics , Ritonavir/pharmacokinetics , Severity of Illness Index , Time Factors , Treatment Outcome , Viral Load
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