Sample records for lymphocytosis

  1. Lymphocytosis (High Lymphocyte Count) (United States)

    ... com/test-catalog/Clinical+and+Interpretive/9109. Accessed May 19, 2016. Kaushansky K, et al. Lymphocytosis and lymphocytopenia. In: Williams Hematology. 9th ed. New York, N.Y.: The McGraw-Hill ...

  2. Histopathology of Marine and Freshwater Fish Lymphocytosis Disease Virus (LCDV)

    International Nuclear Information System (INIS)

    Hossain, M.; Myung-Joo, Oh


    Lymphocytosis disease (LCD) in fishes is caused by the agent called lymphocytosis disease virus (LCDV). LCDV is a chronic and benign virus. The disease affects 96 species of marine and fresh water fishes ranged among 34 families in the world. Affected fish with LCD has a typical external symptom with clusters consisted of enormously hypertrophied dermal cells on the skin and fins. The hypertrophied cells, generally named lymphocytosis cells, have a thick hyaline capsule, an enlarged nucleus and prominent basophilic cytoplasmic inclusions. Among the four species of fishes, olive flounder Paralichthys olivaceus, and rockfish Sebastes schlegeli were marine cultured fish, and gourami Trichogaster leeri and painted glass fish Channa baculis were freshwater ornamental fish. Although LCD causes low mortality, the disfigurement of infected fish can make them unsellable. Thus LCD has resulted in an important economic loss in the aquaculture industry. This study of histopathology may be adequate for a presumptive diagnosis of lymphocytosis diseases both in marine and freshwater fish species. (author)

  3. Lymphocytosis after treatment with dasatinib in chronic myeloid leukemia: Effects on response and toxicity. (United States)

    Schiffer, Charles A; Cortes, Jorge E; Hochhaus, Andreas; Saglio, Giuseppe; le Coutre, Philipp; Porkka, Kimmo; Mustjoki, Satu; Mohamed, Hesham; Shah, Neil P


    The proliferation of clonal cytotoxic T-cells or natural killer cells has been observed after dasatinib treatment in small studies of patients with chronic myeloid leukemia (CML). The incidence of lymphocytosis and its association with response, survival, and side effects were assessed in patients from 3 large clinical trials. Overall, 1402 dasatinib-treated patients with newly diagnosed CML in chronic phase (CML-CP), CML-CP refractory/intolerant to imatinib, or with CML in accelerated or myeloid-blast phase were analyzed. Lymphocytosis developed in 32% to 35% of patients and persisted for >12 months. This was not observed in the patients who received treatment with imatinib. Dasatinib-treated patients in all stages of CML who developed lymphocytosis were more likely to achieve a complete cytogenetic response, and patients who had CML-CP with lymphocytosis were more likely to achieve major and deep molecular responses. Progression-free and overall survival rates were significantly longer in patients with CML-CP who were refractory to or intolerant of imatinib and had lymphocytosis. Pleural effusions developed more commonly in patients with lymphocytosis. Overall, lymphocytosis occurred and persisted in many dasatinib-treated patients in all phases of CML. Its presence was associated with higher response rates, significantly longer response durations, and increased overall survival, suggesting an immunomodulatory effect. Prospective studies are warranted to characterize the functional activity of these cells and to assess whether an immunologic effect against CML is detectable. Cancer 2016;122:1398-1407. © 2016 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society. © 2016 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society.

  4. Functional properties of T cells in patients with chronic T gamma lymphocytosis and chronic T cell neoplasia

    NARCIS (Netherlands)

    Rümke, H. C.; Miedema, F.; ten Berge, I. J.; Terpstra, F.; van der Reijden, H. J.; van de Griend, R. J.; de Bruin, H. G.; von dem Borne, A. E.; Smit, J. W.; Zeijlemaker, W. P.; Melief, C. J.


    The expanded T cell populations of 10 patients with either T gamma lymphocytosis (five patients) or proven chronic T cell malignancy (five patients) were analyzed with respect to functional activity in vitro, including proliferative responses to mitogens, cytotoxic activity (killer [K] and natural

  5. Telomere length analysis in monoclonal B-cell lymphocytosis and chronic lymphocytic leukemia Binet A

    Directory of Open Access Journals (Sweden)

    F.M. Furtado

    Full Text Available Monoclonal B-cell lymphocytosis (MBL is an asymptomatic clinical entity characterized by the proliferation of monoclonal B cells not meeting the diagnosis criteria for chronic lymphocytic leukemia (CLL. MBL may precede the development of CLL, but the molecular mechanisms responsible for disease progression and evolution are not completely known. Telomeres are usually short in CLL and their attrition may contribute to disease evolution. Here, we determined the telomere lengths of CD5+CD19+ cells in MBL, CLL, and healthy volunteers. Twenty-one CLL patients, 11 subjects with high-count MBL, and 6 with low-count MBL were enrolled. Two hundred and sixty-one healthy volunteers aged 0 to 88 years were studied as controls. After diagnosis confirmation, a flow cytometry CD19+CD5+-based cell sorting was performed for the study groups. Telomere length was determined by qPCR. Telomere length was similar in the 3 study groups but shorter in these groups compared to normal age-matched subjects that had been enrolled in a previous study from our group. These findings suggest that telomere shortening is an early event in CLL leukemogenesis.

  6. Abnormal MRI in a patient with 'headache with neurological deficits and CSF lymphocytosis (HaNDL)'. (United States)

    Yilmaz, A; Kaleagasi, H; Dogu, O; Kara, E; Ozge, A


    A 27-year-old woman was admitted to the Emergency Department with right upper-extremity numbness and mild weakness followed by a bifrontal throbbing headache for 30 min, which was similar to a headache lasting for 12 h that had occurred 3 days ago. Laboratory tests were unremarkable except for cerebrospinal fluid (CSF) lymphocytic pleocytosis. On the following day, a headache episode with left hemiparesis and hemihypoaesthesia, left hemifield visio-spatial inattention, anosagnosia and confusion recurred. The headache was diagnosed as headache and neurological deficits with cerebrospinal fluid lymphocytosis (HaNDL) syndrome according to the criteria of the second edition of the International Classification of Headache Disorders. Simultaneously performed magnetic resonance imaging (MRI) revealed swelling of the grey matter, CSF enhancement in the sulci of the right temporal and occipital regions and hypoperfusion of the same brain regions. During the following 10 days two more similar episodes recurred and during the ensuing 12 months the patient remained headache free. Neuroimaging findings of the HaNDL syndrome are always thought as virtually normal. MRI abnormalities in our patient have not been reported in HaNDL syndrome previously, although they have been reported in hemiplegic migraine patients before. The findings in our case suggest that hemiplegic migraine and HaNDL syndrome may share a common pathophysiological pathway resulting in similar imaging findings and neurological symptoms.

  7. Natural History Study of Monoclonal B Cell Lymphocytosis (MBL), Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL), Lymphoplasmacytic Lymphoma (LPL)/Waldenstrom Macroglobulinemia (WM), and Splenic Marginal Zone Lymphoma (SMZL) (United States)


    B-Cell Chronic Lymphocytic Leukemia; Monoclonal B-Cell Lymphocytosis; Lymhoma, Small Lymphocytic; Chronic Lymphocytic Leukemia; Lymphoplasmacytic Lymphoma; Waldenstrom Macroglobulinemia; Splenic Marginal Zone Lymphoma

  8. Isometric Thumb Exertion Induces B Cell and T Cell Lymphocytosis in Trained and Untrained Males: Physical Aptitude Determines Response Profiles

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    Adam Michael Szlezak


    Full Text Available Purpose: The present study examined the effect of low-dose thumb exertion on lymphocyte subpopulation trafficking. The potential role of blood lactate in mediating lymphocyte redistribution was also investigated. Methods: 27 male participants (18 weightlifting-trained; 9 untrained were separated into 3 groups of 9 (Weightlifting and Untrained Experimental: WLEXP, UTEXP; Weightlifting Placebo: WLPLA. WLEXP and UTEXP performed 4x60 second isometric thumb intervals separated by 60 second rest intervals in a single-blinded placebo-controlled study.  Participants were assessed over a 60 minute post-intervention recovery period for pain, blood lactate and lymphocyte subpopulation counts. Results: WLPLA did not change for any measured variable (p>0.05. The two experimentalgroups increased significantly (p0.05. No differences in cell count were seen for CD56+/CD16+ lymphocytes across time for any group (p>0.05. UTEXP showed an early significant increase (20 min post-intervention in CD4+CD3+ (20.78%, p0.05. Conversely, WLEXP group showed no early increase followed by a delayed increase in cell count evident at the final time-point; CD4+CD3+ (19.06%, p<0.01, CD8+CD3+ (11.46%, p=0.033 and CD19+ (28.87%, p<0.01. Blood lactate was not correlated with lymphocyte counts. Conclusions: Physical aptitude and not cellular energy demand influences the lymphocyte response to resistance-exercise. Keywords: B-Lymphocytes; Exercise; Lactic Acid; Lymphocytosis; Resistance Training; T-Lymphocytes

  9. Translocation of the B cell receptor to lipid rafts is inhibited in B cells from BLV-infected, persistent lymphocytosis cattle

    International Nuclear Information System (INIS)

    Hamilton, Valerie T.; Stone, Diana M.; Cantor, Glenn H.


    Bovine leukemia virus (BLV) infection causes a significant polyclonal expansion of CD5 + , IgM+ B lymphocytes known as persistent lymphocytosis (PL) in approximately 30% of infected cattle. There is evidence that this expanded B cell population has altered signaling, and resistance to apoptosis has been proposed as one mechanism of B cell expansion. In human and murine B cells, antigen binding initiates movement of the B cell receptor (BCR) into membrane microdomains enriched in sphingolipids and cholesterol, termed lipid rafts. Lipid rafts include members of the Src-family kinases and exclude certain phosphatases. Inclusion of the BCR into lipid rafts plays an important role in regulation of early signaling events and subsequent antigen internalization. Viral proteins may also influence signaling events in lipid rafts. Here we demonstrate that the largely CD5 + B cell population in PL cattle has different mobilization and internalization of the BCR when compared to the largely CD5-negative B cells in BLV-negative cattle. Unlike B cells from BLV-negative cattle, the BCR in B cells of BLV-infected, PL cattle resists movement into lipid rafts upon stimulation and is only weakly internalized. Expression of viral proteins as determined by detection of the BLV transmembrane (TM) envelope glycoprotein gp30 did not alter these events in cells from PL cattle. This exclusion of the BCR from lipid rafts may, in part, explain signaling differences seen between B cells of BLV-infected, PL, and BLV-negative cattle and the resistance to apoptosis speculated to contribute to persistent lymphocytosis

  10. Intrinsic renal cells induce lymphocytosis of Th22 cells from IgA nephropathy patients through B7-CTLA-4 and CCL-CCR pathways. (United States)

    Gan, Lu; Zhou, Qiaoling; Li, Xiaozhao; Chen, Chen; Meng, Ting; Pu, Jiaxi; Zhu, Mengyuan; Xiao, Chenggen


    IgA nephropathy (IgAN), the most common glomerulonephritis, has an unclear pathogenesis. The role of Th22 cells, which are intimately related to proteinuria and progression in IgAN, in mediating infection-related IgAN is unclear. This study aimed to characterize the association between intrinsic renal cells (tubular epithelial cells and mesangial cells) and Th22 cells in immune regulation of infection-related IgAN and to elucidate the impact of Th22 lymphocytosis; the proinflammatory cytokines IL-1, IL-6, and TNF-α; and CCL chemokines on kidney fibrosis. Hemolytic streptococcus infection induced an increase in IL-1, IL-6, and TNF-α, resulting in Th22 cell differentiation from T lymphocytes obtained from patients with IgAN, and the CCL20-CCR6, CCL22-CCR4, and/or CCL27-CCR10 axes facilitated Th22 cell chemotaxis. The increased amount of Th22 cells caused an increase in TGF-β1 levels, and anti-CD80, anti-CD86, and CTLA-4Ig treatment reduced TGF-β1 levels by inhibiting Th22 lymphocytosis and secretion of cytokines and chemokines, thus potentially relieving kidney fibrosis. Our data suggest that Th22 cells might be recruited into the kidneys via the CCL20-CCR6, CCL22-CCR4, and/or CCL27-CCR10 axes by mesangial cells and tubular epithelial cells in infection-related IgAN. Th22 cell overrepresentation was attributed to stimulation of the B7-CTLA-4Ig antigen-presenting pathway and IL-1, IL-6, and TNF-α.

  11. Persistent Intraepithelial Lymphocytosis in Celiac Patients Adhering to Gluten-Free Diet Is Not Abolished Despite a Gluten Contamination Elimination Diet

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    Barbara Zanini


    Full Text Available The gluten-free diet (GFD is the only validated treatment for celiac disease (CD, but despite strict adherence, complete mucosal recovery is rarely obtained. The aim of our study was to assess whether complete restitutio ad integrum could be achieved by adopting a restrictive diet (Gluten Contamination Elimination Diet, GCED or may depend on time of exposure to GFD. Two cohorts of CD patients, with persisting Marsh II/Grade A lesion at duodenal biopsy after 12–18 months of GFD (early control were identified. Patients in Cohort A were re-biopsied after a three-month GCED (GCED control and patients in Cohort B were re-biopsied after a minimum of two years on a standard GFD subsequent to early control (late control. Ten patients in Cohort A and 19 in Cohort B completed the study protocol. There was no change in the classification of duodenal biopsies in both cohorts. The number of intraepithelial lymphocytes, TCRγδ+ (T-Cell Receptor gamma delta T cell and eosinophils significantly decreased at GCED control (Cohort A and at late control (Cohort B, compared to early control. Duodenal intraepithelial lymphocytosis persisting in CD patients during GFD is not eliminated by a GCED and is independent of the length of GFD. [NCT 02711696

  12. Distinction between asymptomatic monoclonal B-cell lymphocytosis with cyclin D1 overexpression and mantle cell lymphoma: from molecular profiling to flow cytometry. (United States)

    Espinet, Blanca; Ferrer, Ana; Bellosillo, Beatriz; Nonell, Lara; Salar, Antonio; Fernández-Rodríguez, Concepción; Puigdecanet, Eulàlia; Gimeno, Javier; Garcia-Garcia, Mar; Vela, Maria Carmen; Luño, Elisa; Collado, Rosa; Navarro, José Tomás; de la Banda, Esmeralda; Abrisqueta, Pau; Arenillas, Leonor; Serrano, Cristina; Lloreta, Josep; Miñana, Belén; Cerutti, Andrea; Florensa, Lourdes; Orfao, Alberto; Sanz, Ferran; Solé, Francesc; Dominguez-Sola, David; Serrano, Sergio


    According to current diagnostic criteria, mantle cell lymphoma (MCL) encompasses the usual, aggressive variants and rare, nonnodal cases with monoclonal asymptomatic lymphocytosis, cyclin D1-positive (MALD1). We aimed to understand the biology behind this clinical heterogeneity and to identify markers for adequate identification of MALD1 cases. We compared 17 typical MCL cases with a homogeneous group of 13 untreated MALD1 cases (median follow-up, 71 months). We conducted gene expression profiling with functional analysis in five MCL and five MALD1. Results were validated in 12 MCL and 8 MALD1 additional cases by quantitative reverse transcription polymerase chain reaction (qRT-PCR) and in 24 MCL and 13 MALD1 cases by flow cytometry. Classification and regression trees strategy was used to generate an algorithm based on CD38 and CD200 expression by flow cytometry. We found 171 differentially expressed genes with enrichment of neoplastic behavior and cell proliferation signatures in MCL. Conversely, MALD1 was enriched in gene sets related to immune activation and inflammatory responses. CD38 and CD200 were differentially expressed between MCL and MALD1 and confirmed by flow cytometry (median CD38, 89% vs. 14%; median CD200, 0% vs. 24%, respectively). Assessment of both proteins allowed classifying 85% (11 of 13) of MALD1 cases whereas 15% remained unclassified. SOX11 expression by qRT-PCR was significantly different between MCL and MALD1 groups but did not improve the classification. We show for the first time that MALD1, in contrast to MCL, is characterized by immune activation and driven by inflammatory cues. Assessment of CD38/CD200 by flow cytometry is useful to distinguish most cases of MALD1 from MCL in the clinical setting. MALD1 should be identified and segregated from the current MCL category to avoid overdiagnosis and unnecessary treatment. ©2013 AACR

  13. Diffuse Infiltrative Lymphocytosis Syndrome (DILS)

    African Journals Online (AJOL)

    their HIV clinical stage with longer survival.2,7 Some authors however report that up to 37% of their patients met the Centers for Disease. Control and Prevention case definition of AIDS.3 There has been no published literature on the CD8+ cell counts in patients with DILS. Our own experience suggests that most of our ...

  14. Syndrome of transient headache and neurological deficits with cerebrospinal fluid lymphocytosis (HaNDL) in a patient with confusional symptoms, diffuse EEG abnormalities, and bilateral vasospasm in transcranial Doppler ultrasound: A case report and literature review. (United States)

    Hidalgo de la Cruz, M; Domínguez Rubio, R; Luque Buzo, E; Díaz Otero, F; Vázquez Alén, P; Orcajo Rincón, J; Prieto Montalvo, J; Contreras Chicote, A; Grandas Pérez, F


    HaNDL syndrome (transient headache and neurological deficits with cerebrospinal fluid lymphocytosis) is characterised by one or more episodes of headache and transient neurological deficits associated with cerebrospinal fluid lymphocytosis. To date, few cases of HaNDL manifesting with confusional symptoms have been described. Likewise, very few patients with HaNDL and confusional symptoms have been evaluated with transcranial Doppler ultrasound (TCD). TCD data from patients with focal involvement reveal changes consistent with vasomotor alterations. We present the case of a 42-year-old man who experienced headache and confusional symptoms and displayed pleocytosis, diffuse slow activity on EEG, increased blood flow velocity in both middle cerebral arteries on TCD, and single-photon emission computed tomography (SPECT) findings suggestive of diffuse involvement, especially in the left hemisphere. To our knowledge, this is the first description of a patient with HaNDL, confusional symptoms, diffuse slow activity on EEG, and increased blood flow velocity in TCD. Our findings suggest a relationship between cerebral vasomotor changes and the pathophysiology of HaNDL. TCD may be a useful tool for early diagnosis of HaNDL. Copyright © 2017 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

  15. Papel da imunofenotipagem por citometria de fluxo no diagnóstico diferencial das pancitopenias e das linfocitoses The role of flow cytometer-based immunophenotyping in the differential diagnosis of pancytopenia and of lymphocytosis

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    Eduardo M. Rego


    Full Text Available A imunofenotipagem por citometria de fluxo (CMF é atualmente uma ferramenta indispensável para o diagnóstico hematopatológico. Nos últimos anos muitos progressos foram alcançados em instrumentação, novos anticorpos e fluorocromos e programas de análise. Consequentemente, houve um grande avanço no conhecimento da patogênese das neoplasias hematológicas e novos marcadores diagnósticos e prognósticos foram descritos. Revisamos aqui a contribuição destas novas técnicas no diagnóstico diferencial de pacientes com bi- ou pancitopenia e linfocitose. São apresentados os achados mais frequentes e as dificuldades na interpretação dos resultados. Além disto, a importância do uso concomitante de um conjunto de outras técnicas diagnósticas é demonstrada.The use of flow cytometry for immunophenotyping is currently an essential tool in the diagnosis of hematological abnormalities. In recent years, new equipment, antibodies, fluorochromes and computer programs have become available. As a result, a better understanding of the pathogeneses of hematological malignancies has emerged and new markers with diagnostic and prognostic relevance have been described. Here we review how this new technology may contribute to the differential diagnosis of patients with bi- or pancytopenia and of lymphocytosis. The common findings as well as the difficulties in interpreting the results obtained by flow cytometry will be discussed. The importance of the concomitant analyses by different methods is also demonstrated.

  16. Atypical lymphocytosis in leptospirosis: a cohort of hospitalized cases between 1996 and 2009 in State of Rio de Janeiro, Brazil Linfócitos atípicos na leptospirose: coorte de pacientes hospitalizados entre 1996 e 2009, Estado do Rio de Janeiro

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    Paulo Vieira Damasco


    Full Text Available INTRODUCTION: Leptospirosis is a zoonotic disease found in tropical and temperate countries, and its clinical diagnostic confusion with arboviruses (dengue fever, oropouche fever and yellow fever, Brazilian spotted fever, viral hepatitis and hantaviruses has been an ongoing public health concern. The aim of this observational study was to demonstrate an association between findings of atypical lymphocytosis and the progression of endemic leptospirosis. METHODS: A retrospective analysis was performed on the demographic, epidemiological, clinical and laboratory aspects of 27 human leptospirosis cases that occurred over a period of 13 years (1996-2009 with no reported epidemic outbreaks in Rio de Janeiro, Brazil. RESULTS: The overall mortality rate was 11.1% in our cohort of hospitalized cases. However, there was no mortality among patients with atypical lymphocytosis (OR = 11.1; 95% CI = 1.12-110.9; p = 0.04. Two patients who were in the septicemic phase showed signs of expansion of γδ T cell responses in peripheral blood. CONCLUSIONS: Atypical lymphocytosis may be observed in patients with leptospirosis. Our observations suggest that these atypical leukocyte subsets are associated with partial protection during the disease course of leptospirosis.INTRODUÇÃO: Leptospirose é uma zoonose que permanece endêmica em regiões tropicais e temperadas. A dificuldade no diagnóstico clínico diferencial entre os quadros de leptospirose humana e as várias arboviroses (dengue, febre amarela, febre de oropouche, febre maculosa brasileira, hepatite viral e hantavirose permanece um problema na Saúde Pública. MÉTODOS: No presente estudo, foi realizada análise retrospectiva de características demográficas, epidemiológicas, clínicas e laboratoriais de 27 casos de leptospirose humana que ocorrerem durante um período de 13 anos sem ocorrência de notificação de surtos epidêmicos no Rio de Janeiro, Brasil (1996-2009. RESULTADOS: A mortalidade da

  17. Ibrutinib-induced lymphocytosis in patients with chronic lymphocytic leukemia

    DEFF Research Database (Denmark)

    Herman, S E M; Niemann, C U; Farooqui, M


    Ibrutinib and other targeted inhibitors of B-cell receptor signaling achieve impressive clinical results for patients with chronic lymphocytic leukemia (CLL). A treatment-induced rise in absolute lymphocyte count (ALC) has emerged as a class effect of kinase inhibitors in CLL and warrants further...... investigation. Here we report correlative studies in 64 patients with CLL treated with ibrutinib. We quantified tumor burden in blood, lymph nodes (LNs), spleen and bone marrow, assessed phenotypic changes of circulating cells and measured whole-blood viscosity. With just one dose of ibrutinib, the average...

  18. Large granular lymphocytosis in a patient infected with HTLV-II. (United States)

    Martin, M P; Biggar, R J; Hamlin-Green, G; Staal, S; Mann, D


    HTLV-II has been associated with a variety of lymphoproliferative disorders, including atypical hairy cell leukemia, chronic T cell leukemia, T prolymphocytic leukemia, and large granular lymphocytic leukemia. However, a direct or indirect role for HTLV-II in these disorders is not yet firmly established. We studied a patient diagnosed as having leukemia of the large granular lymphocyte (LGL) type who was HTLV-II seropositive, to determine if the expanded cell population was infected. Two populations of CD3-CD16+ LGL were identified; one was CD8+, the other CD8-. Populations of cells with these surface markers as well as normal CD3+CD4+ and CD3+CD8+ cells were separated by flow cytometric methods, DNA extracted, and gene regions of HTLV-II pol and tax amplified, using the polymerase chain reaction, and probed after Southern blotting. HTLV-II was detected in the CD3+CD8+ population, and not in the CD3-CD16+ large granular lymphocyte population. This finding indicates that the role of HTLV-II, if any, in LGL proliferation is indirect.

  19. When is the last time you looked for diffuse infiltrative lymphocytosis ...

    African Journals Online (AJOL)

    Data synthesis: Pathologically, under light microscopy, DILS resembles the focal sialadenitis seen with Sjogren's syndrome, although it tends to be less destructive of the glandular architecture than in Sjogren's syndrome. Most of the inflammatory infiltrate is composed of CD8+ lymphocytes unlike Sjogren's which are CD4+.

  20. Elevated expression of NEU1 sialidase in idiopathic pulmonary fibrosis provokes pulmonary collagen deposition, lymphocytosis, and fibrosis. (United States)

    Luzina, Irina G; Lockatell, Virginia; Hyun, Sang W; Kopach, Pavel; Kang, Phillip H; Noor, Zahid; Liu, Anguo; Lillehoj, Erik P; Lee, Chunsik; Miranda-Ribera, Alba; Todd, Nevins W; Goldblum, Simeon E; Atamas, Sergei P


    Idiopathic pulmonary fibrosis (IPF) poses challenges to understanding its underlying cellular and molecular mechanisms and the development of better therapies. Previous studies suggest a pathophysiological role for neuraminidase 1 (NEU1), an enzyme that removes terminal sialic acid from glycoproteins. We observed increased NEU1 expression in epithelial and endothelial cells, as well as fibroblasts, in the lungs of patients with IPF compared with healthy control lungs. Recombinant adenovirus-mediated gene delivery of NEU1 to cultured primary human cells elicited profound changes in cellular phenotypes. Small airway epithelial cell migration was impaired in wounding assays, whereas, in pulmonary microvascular endothelial cells, NEU1 overexpression strongly impacted global gene expression, increased T cell adhesion to endothelial monolayers, and disrupted endothelial capillary-like tube formation. NEU1 overexpression in fibroblasts provoked increased levels of collagen types I and III, substantial changes in global gene expression, and accelerated degradation of matrix metalloproteinase-14. Intratracheal instillation of NEU1 encoding, but not control adenovirus, induced lymphocyte accumulation in bronchoalveolar lavage samples and lung tissues and elevations of pulmonary transforming growth factor-β and collagen. The lymphocytes were predominantly T cells, with CD8(+) cells exceeding CD4(+) cells by nearly twofold. These combined data indicate that elevated NEU1 expression alters functional activities of distinct lung cell types in vitro and recapitulates lymphocytic infiltration and collagen accumulation in vivo, consistent with mechanisms implicated in lung fibrosis.

  1. B-Cell Hematologic Malignancy Vaccination Registry (United States)


    Monoclonal Gammopathy of Undetermined Significance; Multiple Myeloma; Waldenstrom Macroglobulinemia; Lymphocytosis; Lymphoma, Non-Hodgkin; B-Cell Chronic Lymphocytic Leukemia; Hematological Malignancies

  2. Practice Research: Is the serological diagnosis of infectious mononucleosis always necessary? (United States)

    Ho-Yen, D O


    Clinical and serological data from 100 patients who had a Downey lymphocytosis of ≥ 40% of all white cells were assessed over three years. All had clinical evidence of infectious mononucleosis, suggesting that Downey lymphocytosis of ≥ 40% is specific for the illness. PMID:6414623

  3. Immunogenic Properties of Ricinus Communis Var Minor Seed on ...

    African Journals Online (AJOL)

    Prof. Ogunji

    1College of Health Technology, Zawan, Plateau State.2Department of ... Ricinus communis var minor seed included in their feed (5g/100g body weight). ... White Blood cell Count (WBC) count and lymphocytosis in the differential count.

  4. Neutrophil recruitment and barrier impairment in celiac disease : A genomic study

    NARCIS (Netherlands)

    Diosdado, Begona; Van Bakel, Harm; Strengman, Eric; Franke, Lude; Van Oort, Erica; Mulder, Chris J.; Wijmenga, Cisca; Wapenaar, Martin C.

    Background & Aims: Celiac disease is an enteropathy featuring villous atrophy, crypt hyperplasia, and lymphocytosis. Tissue remodeling is driven by an inflammatory reaction to gluten in genetically susceptible individuals. The adaptive pathway is considered the major immune response but recent

  5. Hairy B-cell lymphoproliferative disorder and its differential diagnosis: a case with long-term follow-up

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    Kensuke Matsuda


    Full Text Available Hairy B-cell lymphoproliferative disorder (HBLD is one of chronic polyclonal B-cell lymphocytosis. We report a 47-year-old female Japanese patient diagnosed as having HBLD based on lymphocytosis with hairy cell appearance and characteristic phenotypes including CD11c+, and without B-cell monoclonalities. She was a non-smoker, and possessed HLA-DR4. She has been closely followed up without treatment and lymphoma development for over five years. Although this disease is quite rare and has been reported, to our knowledge, in only 13 Japanese cases, an accurate diagnosis, particularly differential diagnosis from persistent polyclonal B-cell lymphocytosis or hairy cell leukemia-Japanese variant is essential for the prevention of unnecessary treatments.

  6. Effects of bovine leukemia virus infection on crossbred and purebred dairy cattle productive performance in Brazil

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    Daniela Souza Rajão


    Full Text Available The aim of this study was to evaluate the effects of bovine leukemia virus (BLV infection on productive performance of dairy cattle in Brazil. A total of 158 blood samples from lactating adult cows, purebred Holstein and crossbred Holstein X Zebu, were analyzed by Agar Gel Immunodifusion Test (AGID and leukogram. According to AGID and leukogram results, animals were grouped into three categories: seronegative, seropositive without persistent lymphocytosis, and seropositive with persistent lymphocytosis. Milk production data were compared between groups, according to breed. BLV infected females showed lower milk yield than uninfected ones, both purebred and crossbred ones. There was no difference between milk yield of seropositive cows with or without persistent lymphocytosis. These results indicate an association between BLV infection and reduction of milk production, and this study is the first one to show these effects in crossbred Holstein X Zebu cows.

  7. 81 - 88_Salim et al.,,

    African Journals Online (AJOL)



    Jun 1, 2017 ... conventional drugs in terms of how they functi. This enables herbal medicines ... oderate sinusoidal lymphocytosis with prominent kupfer cells and fo he test groups. ... decoction of the chopped stem barks and leaf of ..... cells being stable cells heal by regeneration and mild ... Internal Medicine: 19(1):40-45.

  8. HIV/HTLV-1 co-infection

    African Journals Online (AJOL)

    result of a lymphoproliferative disorder. In the context of HIV co-infection, lympho- cytosis has been described during early sero- conversion associated with CMV, as well as in HIV/HTLV-1 co-infection where CD4+ lymphocytosis can be caused by both a reactive or clonal expansion. Consequently, patients with untreated ...

  9. CD34+ (Non-Malignant) Stem Cell Selection for Patients Receiving Allogeneic Stem Cell Transplantation (United States)


    Bone Marrow Failure Syndrome; Severe Aplastic Anemia; Severe Congenital Neutropenia; Amegakaryocytic Thrombocytopenia; Diamond-Blackfan Anemia; Schwachman Diamond Syndrome; Primary Immunodeficiency Syndromes; Acquired Immunodeficiency Syndromes; Histiocytic Syndrome; Familial Hemophagocytic Lymphocytosis; Lymphohistiocytosis; Macrophage Activation Syndrome; Langerhans Cell Histiocytosis (LCH); Hemoglobinopathies; Sickle Cell Disease; Sickle Cell-beta-thalassemia

  10. The composition of T cell subtypes in duodenal biopsies are altered in coeliac disease patients

    DEFF Research Database (Denmark)

    Vagner Steenholt, Janni; Nielsen, Christian; Baudewijn, Leen


    One of the hallmarks of Celiac disease (CD) is intraepithelial lymphocytosis in the small intestine. Until now, investigations to characterize the T cell subpopulations within the epithelial layer have not discriminated between the heterodimeric co-receptor molecule, CD8αβ, and the possibly...

  11. Chronic Lymphocytic Leukemia (CLL) as an Unusual Cause of Rapid Airway Compromise (United States)


    obstruction is even more uncommon. We describe a case of a patient with known history of CLL and stable lymphocytosis that developed an enlarging...lymphoid base of tongue (BOT) mass which was identified as non- transformed CLL. Case Presentation: A 62-year-old woman with untreated Rai stage II

  12. Acute effects of high- and low-intensity exercise bouts on leukocyte counts

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    Pedro Rogério Da Silva Neves


    Conclusion: When the same participants were submitted to different exercise intensities, the acute and short-term effects of exercise on white blood cells were intensity-dependent immediately after exercise (i.e., lymphocytosis and monocytosis and 2 hours after passive recovery (i.e., neutrophilia.

  13. T-lymphocyte subset dynamics in well-treated HIV-infected men during a bout of exhausting exercise

    DEFF Research Database (Denmark)

    Dirksen, Carsten; Hansen, Birgitte R; Kolte, Lilian


    In healthy individuals the substantial lymphocytosis during a bout of exhausting exercise constitutes primarily mature T cells from the peripheral lymphoid organs but naïve T cells are also recruited. This study investigated whether the defective CD4 + T-lymphocyte count in peripheral blood during...

  14. Disseminated intravascular coagulation as an unusual presentation of an Epstein-Barr virus infection

    NARCIS (Netherlands)

    van Steijn, JHM; van Tol, KM; van Essen, LH; Gans, ROB


    Epstein-Barr viral (EBV)-infection usually presents as fever, sore throat, fatigue, lymphadenopathy and atypical lymphocytosis. We describe a patient with disseminated intravascular coagulation as the presenting symptom caused by a primary EBV infection. (C) 2000 Elsevier Science B.V. All rights

  15. Optimization and testing of dried antibody tube: The EuroFlow LST and PIDOT tubes as examples

    NARCIS (Netherlands)

    V.H.J. van der Velden (Vincent); J. Flores-Montero (Juan); M. Perez-Andres; M. Martin-Ayuso (M.); Crespo, O. (Oliver); Blanco, E. (Elena); T. Kalina (Tomas); J. Philippé (Jan); Bonroy, C. (Carolien); M. de Bie (Maaike); J.G. te Marvelde (Jeroen); C. Teodosio (Cristina); Corral Mateos, A. (Alba); V. Kanderová (V.); M. van der Burg (Mirjam); Van Hoof, D. (Dennis); J.J.M. van Dongen (Jacques); A. Orfao (Alberto)


    textabstractWithin EuroFlow, we recently developed screening tubes for hematological malignancies and immune deficiencies. Pipetting of antibodies for such 8-color 12-marker tubes however is time-consuming and prone to operational mistakes. We therefore evaluated dried formats of the lymphocytosis

  16. Rapid and simple immunophenotypic characterization of lymphocytes using a new test. (United States)

    Bellido, M; Rubiol, E; Ubeda, J; Estivill, C; López, O; Manteiga, R; Nomdedéu, J F


    In this paper, we report our experience of lymphocyte phenotyping of a series of 108 consecutive samples using a simple flow cytometry test (Lymphogram). The kit consists of a combination of 5 different markers conjugated with three fluorochromes (CD8-FITC, CD19-FITC, CD56-PE, CD3-PE, CD4-PECy5) in the same tube. This allows identification of different T-cells, NK subpopulations and B lymphocytes. The samples were divided into three groups: samples with absolute lymphocytosis (> 5 x 10(9)/L) (n = 50), samples with relative lymphocytosis (> 50%) (n = 24) and other categories for which a lymphocyte immunophenotype was required (T-cell lymphoma and estimation of blood involvement in chronic lymphoproliferative disorders (CLPD) (n = 34). When CD19+ cells exceeded the normal range or there was a suspicion of CLPD without B-cell lymphopenia, clonality was investigated by means of light chain restriction analysis. In the first group, 29 samples were abnormal (10 CLPD, 3 polyclonal B-cell lymphocytosis, 13 inversions of the CD4/CD8 ratio and 3 cases with CD4 lymphocytosis) and 21 samples were regarded as normal. In the second group 7 samples showed abnormalities (2 CLPD, 3 inverted CD4/CD8 ratios and 2 with a relative increase in CD4 cells). In one sample from the third group B-cell clonality without lymphocytosis was detected whereas in 18 samples a polyclonal pattern was observed. The presence of B-cell lymphopenia precluded further clonality study in 13 samples. Lymphogram associated with clonality analysis is a rapid, easy and cheap method of assessing lymphocyte phenotypes in the majority of clinically relevant situations.

  17. Lymphocytic gastritis is not associated with active Helicobacter pylori infection. (United States)

    Nielsen, Jennifer A; Roberts, Cory A; Lager, Donna J; Putcha, Rajesh V; Jain, Rajeev; Lewin, Matthew


    Lymphocytic gastritis (LG), characterized by marked intra-epithelial lymphocytosis in the gastric mucosa, has been frequently associated with both celiac disease (CD) and H. pylori gastritis. The aim of this study was to review and correlate the morphology of LG with the presence of CD and H. pylori. Gastric biopsies diagnosed with LG from 1/1/2006 to 8/1/2013 at our institution and corresponding small bowel biopsies, when available, were reviewed for verification of the diagnosis and to assess for the presence of H. pylori and CD. Immunohistochemical (IHC) staining for H. pylori was performed on all gastric biopsies. Demographic, clinical, and laboratory data were obtained from the medical record. Fifty-four of the 56 cases that met inclusion criteria demonstrated significant intra-epithelial lymphocytosis as the predominant histologic abnormality; however, none were associated with H. pylori infection by IHC staining. Two cases that also showed a prominent intra-epithelial and lamina propria neutrophilic infiltrate were both positive for H. pylori and were excluded from further study. Of the 36 small bowel biopsies available, 19 (53%) showed changes in CD. LG is not a distinct clinicopathologic entity, but a morphologic pattern of gastric injury that can be secondary to a variety of underlying etiologies. When restricted to cases with lymphocytosis alone, LG is strongly associated with CD and not with active H. pylori infection. However, cases that also show significant neutrophilic infiltrate should be regarded as "active chronic gastritis" and are often associated with H. pylori infection. A morphologic diagnosis of LG should prompt clinical and serologic workup to exclude underlying CD. © 2014 John Wiley & Sons Ltd.

  18. Clinical forms of canine visceral Leishmaniasis in naturally Leishmania infantum-infected dogs and related myelogram and hemogram changes.

    Directory of Open Access Journals (Sweden)

    Roney de Carvalho Nicolato

    Full Text Available Hematological analysis has limited applications for disease diagnosis in Leishmania infantum-infected dogs, but it can be very important in evaluating the clinical forms of the disease and in understanding the evolution of canine visceral leishmaniasis (CVL pathogenesis. Recently, we demonstrated that alterations in leucopoiesis and erythropoiesis are related to clinical status and bone marrow parasite density in dogs naturally infected by L. infantum. To further characterize these alterations, we evaluated the association between the hematological parameters in bone marrow and peripheral blood alterations in groups of L. infantum-infected dogs: asymptomatic I (AD-I: serum negative/PCR+, asymptomatic II (AD-II: serum positive, oligosymptomatic (OD, and symptomatic (SD. Results were compared with those from noninfected dogs (NID. The SD group was found to present a decrease in erythropoietic lineage with concomitant reductions in erythrocytes, hemoglobin, and hematocrit parameters, resulting in anemia. The SD group also had increased neutrophils and precursors and decreased band eosinophils and eosinophils, leading to peripheral blood leucopenia. In the AD-II group, lymphocytosis occurred in both the peripheral blood and the bone marrow compartments. The SD group exhibited lymphocytosis in the bone marrow, with lymphopenia in the peripheral blood. In contrast, the AD-I group, showed no significant changes suggestive of CVL, presenting normal counts in bone marrow and peripheral blood. Our results showed for the first time that important changes in hematopoiesis and hematological parameters occur during ongoing CVL in naturally infected dogs, mainly in symptomatic disease. Taken together, our results based on myelogram and hemogram parameters enable better understanding of the pathogenesis of the anemia, lymphocytosis, and lymphopenia, as well as the leucopenia (eosinopenia and monocytopenia, that contribute to CVL prognosis.

  19. Evidence for the replication of bovine leukemia virus in the B lymphocytes

    International Nuclear Information System (INIS)

    Paul, P.S.; Pomeroy, K.A.; Johnson, D.W.; Muscoplat, C.C.; Handwerger, B.S.; Soper, F.F.; Sorensen, D.K.


    Bovine peripheral blood lymphocytes from a cow with persistent lymphocytosis were separated on nylon wool columns into nylon-adherent and nonadherent populations. Nylon-adherent cells were highly enriched for surface immunoglobulin (SIg) bearing B lymphocytes (95.5%) and nonadherent cells for SIg negative non-B cells, presumably T lymphocytes (96.3%). The B lymphocytes were found to be the major producers for bovine leukemia virus. A total of 39% of the B-enriched cells, surviving after 72 hours in culture, produced bovine leukemia virus as compared with 0.5% of the non-B cells

  20. Hypercalcaemia associated with chronic lymphocytic leukaemia in a Giant Schnauzer. (United States)

    Kleiter, M; Hirt, R; Kirtz, G; Day, M J


    A 7-year-old male Giant Schnauzer was referred with a history of severe vomiting, lethargy, weight loss, polydipsia and polyuria. Detailed investigations revealed leucocytosis with a marked lymphocytosis, mild non-regenerative anaemia, thrombocytopenia, hypercalcaemia and azotaemia. Circulating lymphocytes were small and well-differentiated, and the same lymphoid population was present in bone marrow. Chronic lymphocyctic leukaemia with associated paraneoplastic hypercalcaemia was diagnosed. Immunohistochemical staining of a bone marrow biopsy revealed a neoplastic B-cell line expressing CD79. The dog responded to therapy with prednisolone and chlorambucil for a period of 8 months.

  1. Latent Lymphocytic Enterocolitis Associated with Celiac Disease Manifesting after Resection for Colon Cancer: Case Report and Review of the Literature

    Directory of Open Access Journals (Sweden)

    Vikram Tangri


    Full Text Available Lymphocytic colitis, a cause of chronic watery diarrhea, is histologically characterized by increased intraepithelial lymphocytosis. Studies have associated this disorder with celiac disease, although there are no reports of patients with both lymphocytic colitis and colon cancer. The present case report describes a patient with lymphocytic colitis, which manifested five years after he presented with a cecal adenocarcinoma, and three years following a diagnosis of celiac disease. Pathological review of his initial resection specimen demonstrated lymphocytic enterocolitis, indicating a five-year latency in the presentation of this disease.

  2. Rare Cause of Seizures, Renal Failure, and Gangrene in an 83-Year-Old Diabetic Male

    Directory of Open Access Journals (Sweden)

    Stalin Viswanathan


    Full Text Available We report an 83-year-old diabetic male who presented with acute-onset renal failure, seizures, psychosis, pneumonia, and right foot gangrene. Investigations revealed thrombocytopenia, CSF lymphocytosis, ANA and dsDNA positivity, hypocomplementemia, and pneumonitis following which he was treated with pulse methylprednisolone. He was treated for Pseudomonas-related ventilator-associated pneumonia, candiduria, and E. coli-related bedsore infection prior to discharge. He was discharged at request and died 17 days later due to a respiratory infection.

  3. No evidence of transmission of chronic lymphocytic leukemia through blood transfusion

    DEFF Research Database (Denmark)

    Hjalgrim, Henrik; Rostgaard, Klaus; Vasan, Senthil K


    Monoclonal B-cell lymphocytosis (MBL) is a precursor of chronic lymphocytic leukemia (CLL). Observations of MBL in blood donors raise concern that transmitted MBL may cause recipient CLL. Using a database with health information on 1.5 million donors and 2.1 million recipients, we compared CLL...... of 0.94 (95% confidence interval, 0.52-1.71). Analyses using the entire database showed no evidence of CLL clustering among recipients of blood from individual donors. In conclusion, when donor MBL was approximated by subsequent donor CLL diagnosis, data from 2 countries' entire computerized...

  4. Chronic Lymphocytic Leukemia as an Unusual Cause of Rapid Airway Compromise

    Directory of Open Access Journals (Sweden)

    Adrian R. Bersabe


    Full Text Available Chronic Lymphocytic Leukemia (CLL is the most prevalent form of non-Hodgkin’s lymphoma (NHL in Western countries predominantly affecting adults over the age of 65. CLL is commonly indolent in nature but can present locally and aggressively at extranodal sites. Although CLL may commonly present with cervical lymphadenopathy, manifestation in nonlymphoid regions of the head and neck is not well described. CLL causing upper airway obstruction is even more uncommon. We describe a case of a patient with known history of CLL and stable lymphocytosis that developed an enlarging lymphoid base of tongue (BOT mass resulting in rapid airway compromise.

  5. Changes in haemogram of pulmonary TB patients during positive clinical and radiology improvement

    Directory of Open Access Journals (Sweden)

    N. A. Matsegora


    In the haemogram of patients with infiltrative tuberculosis, there was a greater severity of inflammation events, and in disseminated form – of allergic and autoimmune processes. In favourable cases, quantity and quality of blood cells become normal, reflecting the cessation of bacterial excretion, toxicity, and discussion of foci and areas of infiltration. Allergenic or toxic effects of different antibacterial medicines on haematopoiesis cannot be excluded. They often caused eosinophilia, in some cases - leukocytosis, band left shift, lymphocytosis, rarely leukopenia, which may stimulate the lymphoid and reticular reaction. The results indicate the feasibility to add TB chemotherapy with cytoprotective medicines. Key words: haemogram of patients with tuberculosis.

  6. Phenotypical and functional characterization of double-negative (CD4-CD8-) alpha beta T-cell receptor positive cells from an immunodeficient patient

    DEFF Research Database (Denmark)

    Illum, N; Ralfkiaer, E; Pallesen, G


    We have characterized CD4-CD8- double-negative (DN) alpha beta TCR+ T cells from a patient with immunodeficiency, lymphocytosis, lymphadenopathy, and hepatosplenomegaly. The majority of peripheral blood lymphocytes were DN alpha beta TCR+ T cells as evaluated by FACS and biochemical analysis...... (MoAbs) indicated a polyclonal T-cell expansion. Thymic biopsy showed normal histology, whereas lymph node biopsy samples showed altered histological and immunohistological patterns with markedly expanded paracortical areas containing the DN T cells of the same phenotype as found in peripheral blood T...

  7. Unusual infectious mononucleosis complicated by vasculitis

    Directory of Open Access Journals (Sweden)

    Srimanta Kumar Sahu


    Full Text Available Infectious mononucleosis (IM is a clinical syndrome caused by Epstein-Barr virus (EBV. It manifests as fever, pharyngitis, malaise, adenopathy, and atypical lymphocytosis. Cardiovascular complications are thought to be rare in IM. There are very few case reports of EBV-associated vasculitides, like Kawasaki disease and systemic polyarteritis nodosa, however, involvement of the large caliber arteries like the aorta and its branches have been reported only scarcely. Myocarditis also is rare as an early manifestation of EBV infection. We present here a rare case of IM, presented initially with acute myocarditis and later with large-vessels arteritis.

  8. Osseous pseudo-myelomatose compromise, in leukemia chronic lymphoid

    International Nuclear Information System (INIS)

    Martinez Betancur, Octavio; Lopez de Goenaga, Maria Ines


    It was described a case of chronic lymphocytic leukemia in a 75 year old man, with pseudomyelomatosis osteolytic lesions in the skull, excluding other potential causes of osteolytic lesions in the clinical context of malignant lymphoproliferative neoplasm. The real frequency of osseous compromise in chronic lymphocytic leukemia is 10%. Lesions are defined as generalized osteoporosis and osteolysis with lacunar aspect, similar to myeloma lesions. Because histopathology in lymphoproliferative neoplasms may be similar, it might be difficult to diagnose chronic lymphocytic leukemia certainly, if the clinical manifestations are not considered. Differential diagnosis with other lymphoproliferative neoplasm is based basically in absolute lymphocytosis greater than 10 X 109/L, with lymphocytes with mature appearance

  9. Bronchoalveolar lavage, serum angiotensin-converting enzyme, and 67Ga scanning in extrathoracic sarcoidosis

    International Nuclear Information System (INIS)

    Wallaert, B.; Ramon, P.; Fournier, E.; Tonnel, A.B.; Voisin, C.


    Results of bronchoalveolar lavage (BAL), 67Ga scanning, and serum angiotensin-converting enzyme (SACE) assay are compared in the assessment of pulmonary involvement in ten cases of extrathoracic sarcoidosis. Standard clinical, radiologic, and pulmonary function tests detected no pulmonary changes in these patients, but BAL demonstrated an increased alveolar lymphocytosis in eight of ten cases. SACE levels were increased in two cases, and the thoracic gallium uptake was normal in all cases. BAL appears to be the best technique for diagnosing latent pulmonary involvement in extrathoracic sarcoidosis

  10. HaNDL Syndrome Presenting During Pregnancy: A Case Report and Review of the Literature

    Directory of Open Access Journals (Sweden)

    Yüksel Kaplan


    Full Text Available Headache associated with neurological deficits and cerebrospinal fluid lymphocytosis (HaNDL is a self-limited syndrome characterized by sudden-onset headache with a temporary neurological deficit and cerebrospinal fluid (CSF lymphocytosis. We aimed to disscus a case of HaNDL syndrome presenting during pregnancy with relevant literature. A 20-year-old female presented with a 5-day history of severe, bilateral throbbing headache accompanied by nausea, vomiting, and phonophobia. Approximately 2 days after the pain developed, she became acutely confused for less than 90 minutes. 2 days after this episode, she experienced again confusional state and left hemiparesis. There were no symptoms consistent with meningoencephalitis. She was pregnant and at 11 weeks gestation. A neurologic examination showed confusional state, bilateral papilledema, and mild left hemiparesis. The neuroradiological examination was normal. The cerebrospinal fluid revealed lymphocytic pleocytosis, mildly elevated protein, and increased opening pressure. She recovered completely after 8 days. The precise etiology of HaNDL is unknown, although an inflammatory or infectious origin and autoimmune factors have been proposed. Moreover, the risk factors and medical conditions associated with HaNDL are unknown. It is obviously difficult to determine whether the pregnancy was coincidental or associated in this case. We believe that comprehensive studies are needed to clarify the risk factors and medical conditions associated with HaNDL

  11. Analysis Of Clinical, Haematological And Biochemical Parameters In Patients With Infectious Mononucleosis

    Directory of Open Access Journals (Sweden)

    Canović Petar


    Full Text Available Primary infection with Epstein-Barr virus (EBV usually occurs in early childhood and often does not present clinical symptoms. More than 90% of adults are infected with this virus. A primary infection that occurs in adolescence or adulthood is usually clinically presented as infectious mononucleosis with a triad of symptoms: fever, lymphadenopathy and pharyngitis. Our retrospective study included 51 patients with a median age of 17 (9-23 years and serologically confirmed infectious mononucleosis. All patients with infectious mononucleosis were treated at the Clinic for Infectious Diseases at the Clinical Center in Kragujevac during 2013. We analysed the clinical, haematological and laboratory parameters of patients. The aspartate-aminotransferase levels were increased in 40 patients, with a mean value of 116.24 (±93.22; the alanine-aminotransferase levels were increased in 44 patients, with a mean value of 189.24 (±196.69. Lymphadenopathy was the most common clinical feature upon admission in 49 patients (96%; 38 patients (74.5% had splenomegaly, and 20 (39% had hepatomegaly. Twenty-six patients (51% had leukocytosis with lymphocytosis, while 15 (75% of the 20 who had a normal leukocyte count also had lymphocytosis. In the present study, we updated the clinical, haematological and laboratory parameters, which may lead to the establishment of an accurate diagnosis and promote further treatment of the patients.

  12. What are the clinical implications of nodular gastritis? Clues from histopathology. (United States)

    Sokmensuer, Cenk; Onal, Ibrahim Koral; Yeniova, Ozgur; Ersoy, Osman; Aydinli, Musa; Yonem, Ozlem; Harmanci, Ozgur; Onal, Eda Demir; Altinok, Gulcin; Batman, Figen; Bayraktar, Yusuf


    There is no widely accepted histopathological definition for nodular gastritis. In this study we aim to uncover the pathologic entity responsible for the nodular appearance and to find clues about the clinical implications of nodular gastritis. Antral biopsy specimens of 160 patients with nodular gastritis and 133 patients without nodular gastritis were examined by an experienced pathologist for dysplasia, foveolar hyperplasia, inflammatory activity, intraepithelial lymphocytosis, intestinal metaplasia, and lymphoid follicle/aggregate formation, and comparative analysis was performed between the two groups of patients. The presence of intraepithelial lymphocytosis was more frequent in patients with nodular gastritis (P < 0.05). There was no difference between the two groups regarding the other pathological features such as presence of dysplasia, inflammatory activity, intestinal metaplasia, lymphoid hyperplasia, and Helicobacter pylori (H. pylori) infection. Increase of intraepithelial lymphocytes may contribute to formation of macroscopical nodules in this peculiar type of gastritis. Nodular gastritis would not indicate a new therapeutic approach in addition to the current measures for Helicobacter pylori infection.

  13. Functional and clinical relevance of VLA-4 (CD49d/CD29) in ibrutinib-treated chronic lymphocytic leukemia (United States)

    Tissino, Erika; Benedetti, Dania; Herman, Sarah E.M.; ten Hacken, Elisa; Rossi, Francesca Maria; Dal Bo, Michele; Bulian, Pietro; Bomben, Riccardo; Bayer, Elisabeth; Härzschel, Andrea; Gutjahr, Julia Christine; Postorino, Massimiliano; Santinelli, Enrico; Zaja, Francesco; Pozzato, Gabriele; Chigaev, Alexandre; Sklar, Larry A.; Burger, Jan A.; Ferrajoli, Alessandra; Shanafelt, Tait D.; Wiestner, Adrian; Del Poeta, Giovanni; Hartmann, Tanja Nicole


    The Bruton’s tyrosine kinase (BTK) inhibitor ibrutinib, which antagonizes B cell receptor (BCR) signals, demonstrates remarkable clinical activity in chronic lymphocytic leukemia (CLL). The lymphocytosis experienced by most patients under ibrutinib has previously been attributed to inhibition of BTK-dependent integrin and chemokine cues operating to retain the tumor cells in nodal compartments. Here, we show that the VLA-4 integrin, as expressed by CD49d-positive CLL, can be inside-out activated upon BCR triggering, thus reinforcing the adhesive capacities of CLL cells. In vitro and in vivo ibrutinib treatment, although reducing the constitutive VLA-4 activation and cell adhesion, can be overcome by exogenous BCR triggering in a BTK-independent manner involving PI3K. Clinically, in three independent ibrutinib-treated CLL cohorts, CD49d expression identifies cases with reduced lymphocytosis and inferior nodal response and behaves as independent predictor of shorter progression-free survival, suggesting the retention of CD49d-expressing CLL cells in tissue sites via activated VLA-4. Evaluation of CD49d expression should be incorporated in the characterization of CLL undergoing therapy with BCR inhibitors. PMID:29301866

  14. Imbalance of tumor necrosis factor receptors during progression in bovine leukemia virus infection

    International Nuclear Information System (INIS)

    Konnai, Satoru; Usui, Tatsufumi; Ikeda, Manabu; Kohara, Junko; Hirata, Toh-ichi; Okada, Kosuke; Ohashi, Kazuhiko; Onuma, Misao


    Previously, we found an up-regulation of tumor necrosis factor alpha (TNF)-α and an imbalance of TNF receptors in sheep experimentally infected with bovine leukemia virus (BLV). In order to investigate the different TNF-α-induced responses, in this study we examined the TNF-α-induced proliferative response and the expression levels of two distinct TNF receptors on peripheral blood mononuclear cells (PBMC) derived from BLV-uninfected cattle and BLV-infected cattle that were aleukemic (AL) or had persistent lymphocytosis (PL). The proliferative response of PBMC isolated from those cattle with PL in the presence of recombinant bovine TNF-α (rTNF-α) was significantly higher than those from AL cattle and uninfected cattle and the cells from PL cattle expressed significantly higher mRNA levels of TNF receptor type II (TNF-RII) than those from AL and BLV-uninfected cattle. No difference was found in TNF-RI mRNA levels. Most cells expressing TNF-RII in PL cattle were CD5 + or sIgM + cells and these cells showed resistance to TNF-α-induced apoptosis. Additionally, there were significant positive correlations between the changes in provirus load and TNF-RII mRNA levels, and TNF-α-induced proliferation and TNF-RII mRNA levels. These data suggest that imbalance in the expression of TNF receptors could at least in part contribute to the progression of lymphocytosis in BLV infection

  15. Analysis of Efficacy and Tolerability of Bruton Tyrosine Kinase Inhibitor Ibrutinib in Various B-cell Malignancies in the General Community: A Single-center Experience. (United States)

    Ali, Naveed; Malik, Faizan; Jafri, Syed Imran Mustafa; Naglak, Mary; Sundermeyer, Mark; Pickens, Peter V


    Ibrutinib, an irreversible inhibitor of Bruton tyrosine kinase (BTK), is a novel drug that has shown significant efficacy and survival benefit for treatment of various B-cell malignancies. The primary objective of the present study was to investigate the efficacy of ibrutinib therapy in various B-cell malignancies in the general community. The secondary objectives included studying the adverse effects, ibrutinib-induced peripheral lymphocytosis, and effect on immunoglobulin levels. The present study was a retrospective observational cohort analysis conducted at Abington Jefferson Health. The clinical response was determined from the hematologist's assessment and evaluated independently using the response criteria for each B-cell malignancy. Adverse effects were graded according to the Common Terminology Criteria for Adverse Events, version 4.0. The Wilcoxon signed-rank test was used to compare immunoglobulin levels before and after ibrutinib. Forty five patients with B-cell malignancies and receiving ibrutinib therapy were eligible. The median age was 73 years (range, 49-96 years), and 84.4% of the patients had received ≥ 1 previous therapy. The best overall response rate of all cohorts combined was 63.8%. The greatest overall response rate was observed in patients with chronic lymphocytic leukemia or small lymphocytic lymphoma (76.1%), followed by those with Waldenström macroglobulinemia (75%). Of the 45 patients, 88.9% experienced adverse effects. Antiplatelet activity of ibrutinib was most commonly observed (30.5%). Of note, 5 patients (11%) developed new-onset atrial fibrillation after drug initiation. Peripheral lymphocytosis after drug initiation was observed in most patients, with a peak level at 1 month (median lymphocyte count, 2.7 × 10 3 cells/μL). Although the IgG levels at 3, 6, and 12 months had decreased (P = .01 for all) compared with the levels before ibrutinib, the IgA levels had not increased at 3, 6, 12, and 24 months (P = .6, P = .5

  16. The clinical safety of ibrutinib in chronic lymphocytic leukemia. (United States)

    Molica, Stefano


    Ibrutinib , a targeted inhibitor of B-cell receptor signaling, achieved impressive clinical results for patients with chronic lymphocytic leukemia (CLL). These results allowed the approval of ibrutinib for the treatment of patients with CLL who have received at least one prior therapy and those with a 17p deletion regardless of line of therapy. Comprehensive data from either Phase I-II or randomized Phase III studies are analyzed in this article. In addition, we reviewed data on the prevalence and the clinical management of some peculiar toxicities ibrutinib related such as lymphocytosis, major bleeding and atrial fibrillation. Ibrutinib has radically changed the scenery of relapsed/refractory CLL treatment and established an important paradigm in the molecularly targeted approach of this disease. Discontinuation of ibrutinib is rarely due to adverse events related to the drug. Patients who discontinue treatment represent a challenge to the physicians because treatment options are very limited.

  17. Ibrutinib (PCI-32765), the first BTK (Bruton's tyrosine kinase) inhibitor in clinical trials. (United States)

    Brown, Jennifer R


    Ibrutinib is a potent covalent kinase inhibitor that targets BTK. BTK, or Bruton's tyrosine kinase, is an obvious target for therapy of B cell diseases because inactivating mutations lead to B cell aplasia in humans and the disease X-linked agammaglobulinemia. Ibrutinib has modest cytotoxicity against CLL cells in vitro but also blocks trophic stimuli from the microenvironment. As with other inhibitors of the BCR pathway, ibrutinib causes rapid nodal reduction and response associated with rapid increase in lymphocytosis, which then returns to baseline over time. The ORR of ibrutinib in relapsed refractory CLL is 67 % with PFS 88 % at 15 months. In a cohort of untreated patients 65 years and over, the estimated 15 month PFS is 96 %. Registration trials have been initiated, and the difficult task that remains is to determine where in the course of CLL therapy this drug will have the greatest impact and benefit for patients.

  18. B cell receptor inhibition as a target for CLL therapy. (United States)

    Jeyakumar, Deepa; O'Brien, Susan


    Inhibitors of the B cell receptor (BCR) represent an attractive therapeutic option for patients with chronic lymphocytic leukemia. Recently approved inhibitors of Bruton's tyrosine kinase (ibrutinib) and phosphatidylinositol 3-kinase (idelalisib), are promising agents because they are generally well tolerated and highly effective. These agents may be particularly important in the treatment of older patients who are less able to tolerate the myelosuppression (and infections) associated with chemoimmunotherapy. As a class of medications, BCR inhibitors have some unique side effects including redistribution lymphocytosis. Ibrutinib has specific toxicities including increased risk for bleeding and atrial fibrillation. Idelalisib also has some unique toxicities consisting of transaminitis, diarrhea and pneumonitis. Ongoing clinical trials are evaluating these agents in combination with antibodies, chemotherapy and other small molecules. Copyright © 2016 Elsevier Ltd. All rights reserved.

  19. From the “old NEC” to the “new NECs”

    Directory of Open Access Journals (Sweden)

    Melania Puddu


    Full Text Available Necrotizing enterocolitis (NEC is an acute inflammatory disease of the neonatal intestine that strikes in 1 of 1,000 live births. Its etiology is unknown.  This review describes in detail the new NECs especially those which affect preterm infants: contagion or lymphocytosis associated, transfusion associated and cow’s milk allergy associated. A wide repertory of images are presented, together with algorithms for differential diagnosis. Proceedings of the International Course on Perinatal Pathology (part of the 10th International Workshop on Neonatology · October 22nd-25th, 2014 · Cagliari (Italy · October 25th, 2014 · The role of the clinical pathological dialogue in problem solving Guest Editors: Gavino Faa, Vassilios Fanos, Peter Van Eyken

  20. Coeliac disease

    DEFF Research Database (Denmark)

    Reilly, Norelle R; Husby, Steffen; Sanders, David S


    Coeliac disease is increasingly recognized as a global problem in both children and adults. Traditionally, the findings of characteristic changes of villous atrophy and increased intraepithelial lymphocytosis identified in duodenal biopsy samples taken during upper gastrointestinal endoscopy have...... been required for diagnosis. Although biopsies remain advised as necessary for the diagnosis of coeliac disease in adults, European guidelines for children provide a biopsy-sparing diagnostic pathway. This approach has been enabled by the high specificity and sensitivity of serological testing. However......, these guidelines are not universally accepted. In this Perspective, we discuss the pros and cons of a biopsy-avoiding pathway for the diagnosis of coeliac disease, especially in this current era of the call for more biopsies, even from the duodenal bulb, in the diagnosis of coeliac disease. In addition, a contrast...

  1. T-cell receptor gene rearrangement in Epstein-Barr virus infectious mononucleosis. (United States)

    Marbello, L; Riva, M; Veronese, S; Nosari, A M; Ravano, E; Colosimo, A; Paris, L; Morra, E


    This report describes the case of a previously healthy young man who presented with fever, pharyngitis, cervical lymphadenopathy, lymphocytosis, and severe thrombocytopenia. Serological tests for Epstein-Barr virus were diagnostic of a primary Epstein-Barr virus infectious mononucleosis but severe thrombocytopenia aroused the suspicion of a lymphoproliferative disease. T-cell receptor gene analysis performed on peripheral and bone marrow blood revealed a T-cell receptor γ-chain rearrangement without the evidence of malignancy using standard histologic and immunophenotype studies. Signs and symptoms of the infectious disease, blood count, and T-cell receptor gene rearrangement resolved with observation without the evidence of emergence of a lymphoproliferative disease. In the contest of a suspected lymphoproliferative disease, molecular results should be integrated with all available data for an appropriate diagnosis.

  2. Acute Kidney Injury Complicated Epstein-Barr Virus Infection in Infancy

    Directory of Open Access Journals (Sweden)

    Gamze Ozgurhan


    Full Text Available Infectious mononucleosis is an acute lymphoproliferative disorder caused by the Epstein-Barr virus (EBV and seen most commonly in children and young adults. Clinical presentation of the disease is characterized by fever, tonsillopharyngitis, lymphadenopathy, and hepatosplenomegaly, whereas serological findings of this benign disorder include positive heterophilic antibody formation (transient increase in heterophilic antibodies and prominence of hematological lymphocytosis of more than 10% of atypical lymphocytes. An EBV infection is usually asymptomatic in childhood, but acute kidney injury can be a rare complication during its course. Most cases recover from the disease completely. Early recognition of EBV infection and estimation of its complication are important for its prognosis. In light of previous literature, we discuss the case evaluated as an EBV infection complicated by acute kidney injury in early childhood and results of tubulointerstitial nephritis shown on a renal biopsy that was later diagnosed as an EBV infection by serological examination.

  3. Infectious mononucleosis hepatitis in young adults: two case reports. (United States)

    Kang, Min-Jung; Kim, Tae-Hun; Shim, Ki-Nam; Jung, Sung-Ae; Cho, Min-Sun; Yoo, Kwon; Chung, Kyu Won


    Infectious mononucleosis due to Epstein-Barr virus (EBV) infection sometimes causes acute hepatitis, which is usually self-limiting with mildly elevated transaminases, but rarely with jaundice. Primary EBV infection in children is usually asymptomatic, but in a small number of healthy individuals, typically young adults, EBV infection results in a clinical syndrome of infectious mononucleosis with hepatitis, with typical symptoms of fever, pharyngitis, lymphadenopathy, and hepatosplenomegaly. EBV is rather uncommonly confirmed as an etiologic agent of acute hepatitis in adults. Here, we report two cases: the first case with acute hepatitis secondary to infectious mononucleosis and a second case, with acute hepatitis secondary to infectious mononucleosis concomitantly infected with hepatitis A. Both cases involved young adults presenting with fever, pharyngitis, lymphadenopathy, hepatosplenomegaly, and atypical lymphocytosis confirmed by serologic tests, liver biopsy and electron microscopic study.

  4. Epstein-Barr virus, cytomegalovirus, and infectious mononucleosis. (United States)

    Bravender, Terrill


    Infectious mononucleosis (IM) is a clinical syndrome that is common in adolescents and young adults and is characterized by fever, lymphadenopathy, pharyngitis, and fatigue. IM is most commonly associated with Epstein-Barr virus (EBV) infection in which case laboratory findings include a lymphocytosis with an elevated number of atypical lymphocytes seen on peripheral smear and a heterophile or EBV-specific antibody response. Approximately 10% of those with IM will not be acutely infected with EBV. Many of these individuals will have their symptoms attributed to cytomegalovirus (CMV) infection. This chapter reviews the history, diagnosis, clinical management, and potential complications of both EBV- and CMV-associated IM in adolescents and young adults.

  5. Alice in Wonderland Syndrome, Burning Mouth Syndrome, Cold Stimulus Headache, and HaNDL: Narrative Review. (United States)

    Valença, Marcelo M; de Oliveira, Daniella A; Martins, Hugo André de L


    Unusual headache syndromes are not as infrequent in clinical practice as was generally believed. About three fourths of the classified headache disorders found in the ICHD-II can be considered rare. The aim of this narrative review was to perform a literature review of the pathophysiology, clinical presentation, diagnostic criteria, and treatment of the following unusual headache disorders: Alice in Wonderland syndrome, burning mouth syndrome, cold stimulus headache, and the syndrome of transient headache and neurologic deficits with cerebrospinal fluid lymphocytosis. A literature review was performed using PubMed for each of the abovementioned headache disorders. The unusual headache syndromes as a distinct group of disorders are not as infrequent in clinical practice as was generally believed. Some of them, albeit considered as unusual, may occur with relative frequency, such as cold stimulus headache and burning mouth syndrome. © 2015 American Headache Society.

  6. Seronegative Intestinal Villous Atrophy: A Diagnostic Challenge

    Directory of Open Access Journals (Sweden)

    Cláudio Martins


    Full Text Available Celiac disease is the most important cause of intestinal villous atrophy. Seronegative intestinal villous atrophy, including those that are nonresponsive to a gluten-free diet, is a diagnostic challenge. In these cases, before establishing the diagnosis of seronegative celiac disease, alternative etiologies of atrophic enteropathy should be considered. Recently, a new clinical entity responsible for seronegative villous atrophy was described—olmesartan-induced sprue-like enteropathy. Herein, we report two uncommon cases of atrophic enteropathy in patients with arterial hypertension under olmesartan, who presented with severe chronic diarrhea and significant involuntary weight loss. Further investigation revealed intestinal villous atrophy and intraepithelial lymphocytosis. Celiac disease and other causes of villous atrophy were ruled out. Drug-induced enteropathy was suspected and clinical improvement and histologic recovery were verified after olmesartan withdrawal. These cases highlight the importance for clinicians to maintain a high index of suspicion for olmesartan as a precipitant of sprue-like enteropathy.

  7. A Case of Monoclonal Lymphoplasmacytosis of the Bone Marrow with IgM-Positive Russell Bodies

    Directory of Open Access Journals (Sweden)

    Hidekazu Kayano


    Full Text Available A 71-year-old Japanese male patient infected with HCV was diagnosed with thrombocytopenia. Histological examination of the bone marrow aspirate showed numerous lymphoid aggregates with Russell bodies. Immunohistochemistry and flow cytometric analysis demonstrated clonal expansion of CD5+ CD23+ B cells. Russell bodies were positive for IgM and lambda immunoglobulin light chain. The patient also underwent gastric biopsy, which revealed Helicobacter pylori (HP infection. Subsequent eradication of the bacteria resulted in improvement of his thrombocytopenia. The clinical course remained uneventful at 15-month follow-up, consistent with monoclonal B-cell lymphocytosis. The observed clonal expansion with plasmacytic differentiation may have occurred under the influence of HCV with HP infection.

  8. Compromiso óseo seudo-mielomatoso en leucemia linfoide crónica

    Directory of Open Access Journals (Sweden)

    Octavio Martínez Betancur


    Full Text Available It was described a case of chronic lymphocytic leukemia in a 75 year old man, with  pseudoyelomatous osteolytic lesions in the skull, excluding other potential causes of osteolytic lesions in the clinical context of malignant lymphoproliferative neoplasms. The real frecuency of osseous compromise in chronic lymphocytic leukemia is 10%. Lesions are defined as generalized osteoporosis and osteolisis with lacunar aspect, similar to myeloma lesions. Because histopathology in lymphoproliferative neoplasms may be similar, it might be difficult to diagnose chronic lymphocytic leukemia certainly, if the clinical manifestations are not considered. Difterential diagnosis with other lymphoproliferative neoplasms is based basically in absolute lymphocytosis greater than 10 X 109/L, with lymphocytes with mature appearance.

  9. Peripheral blood picture changes induced by chronic radone and silicon dioxide treatment (in combination or separately)

    International Nuclear Information System (INIS)

    Ivanov, Z.; Dermendzhiev, Kh.; Nikolova, M.


    Peripheral blood changes have been studied in rats after the following treatments: 4 hours daily for six months with a radon concentration of 1.10 -10 Ci/1 (group I), 1.10 -12 Ci/1 (group II) 50 mg pure silicon dioxide in 1 ml physiological solution (group III), and intratracheal incorporation of radon concentration in air of 1.10 -10 Ci/1 and silicon dioxide (group IV). Examinations during the third and sixth month after the start of experiment showed development of leukopenia in groups I, III and IV; lymphopenia was established in groups I and IV, and lymphocytosis in group III. Atypical morphological changes were observed in red blood cells. (A.B.)

  10. Lymphocytic reactions in persons occupationally exposed to ionizing radiation

    International Nuclear Information System (INIS)

    Bliznakov, V.; Nikolov, A.


    The most frequent reasons for deviations of hematological indicies in radiological and X-ray personnel are discussed. The dynamics of lymphocyte count in individuals working in the city of Sofia is tabulated for a period of 12 years. The data show that the number of deviations from the norm (accepted as 1.929±0.908 g/l) reduced in time, which is one of the features of radiation syndrome. 24.23% of the persons investigated have had lymphocytosis. The following most common reasons for this are mentioned: increased cummulative radiation dose, focal infections, alergie, neurosis, tyreotoxicosis, virus infections, leucosis. The second and third investigations of such persons before applying any therapy are proposed in order to precisize the diagnosting

  11. Collagenous sprue

    DEFF Research Database (Denmark)

    Soendergaard, Christoffer; Riis, Lene Buhl; Nielsen, Ole Haagen


    Collagenous sprue is a rare clinicopathological condition of the small bowel. It is characterised by abnormal subepithelial collagen deposition and is typically associated with malabsorption, diarrhoea and weight loss. The clinical features of collagenous sprue often resemble those of coeliac...... disease and together with frequent histological findings like mucosal thinning and intraepithelial lymphocytosis the diagnosis may be hard to reach without awareness of this condition. While coeliac disease is treated using gluten restriction, collagenous sprue is, however, not improved...... by this intervention. In cases of diet-refractory 'coeliac disease' it is therefore essential to consider collagenous sprue to initiate treatment at an early stage to prevent the fibrotic progression. Here, we report a case of a 78-year-old man with collagenous sprue and present the clinical and histological...

  12. Coeliac disease: to biopsy or not? (United States)

    Reilly, Norelle R; Husby, Steffen; Sanders, David S; Green, Peter H R


    Coeliac disease is increasingly recognized as a global problem in both children and adults. Traditionally, the findings of characteristic changes of villous atrophy and increased intraepithelial lymphocytosis identified in duodenal biopsy samples taken during upper gastrointestinal endoscopy have been required for diagnosis. Although biopsies remain advised as necessary for the diagnosis of coeliac disease in adults, European guidelines for children provide a biopsy-sparing diagnostic pathway. This approach has been enabled by the high specificity and sensitivity of serological testing. However, these guidelines are not universally accepted. In this Perspective, we discuss the pros and cons of a biopsy-avoiding pathway for the diagnosis of coeliac disease, especially in this current era of the call for more biopsies, even from the duodenal bulb, in the diagnosis of coeliac disease. In addition, a contrast between paediatric and adult guidelines is presented.

  13. Preleukemic state in atomic bomb survivors

    International Nuclear Information System (INIS)

    Mikami, Motoko


    Hematology data before onset of leukemia were available for 55 of the 1462 acute leukemia cases (as of the end of June 1976) collected by RERF. Among these, 8 showed preleukemic state and 2 were polycythemia. In content, preleukemic state comprised anemia, leukopenia and morphological abnormalities of RBC, platelets and WBC. Leukemia cases presenting preleukemic state were, by type, mostly erythroleukemia and monocytic leukemia. Preleukemic state was not necessarily frequent among cases of leukemia in A-bomb survivors exposed to high dose. The prevalence of the 5 items, prescribed as preleukemic state, i.e., anemia (female =50%), and relative monocytosis (>=10%), could not be said to be high in the survivors exposed to high dose. Anemia in males and leukopenia in males and females were increased significantly with age. Leukemia prevalence was significantly high especially in those cases that had presented leukopenia, relative neutropenia or relative lymphocytosis among the 5 items prescribed as preleukemic state. (author)

  14. Characteristics of patients presenting with erythema nodosum and sarcoidosis.

    LENUS (Irish Health Repository)

    O'Connor, T M


    We explored the relationship between erythema nodosum (EN) and sex, age, serum angiotensin converting enzyme (ACE), bronchoalveolar lavage lymphocytosis (BAL-I), interstitial granulomas and radiological stage in patients presenting with pulmonary sarcoidosis in Ireland. Sixty-nine patients diagnosed with sarcoidosis between 2003 and 2006 were studied. Forty one patients (59%) were male. Sixteen patients (23%) presented with EN. Forty one patients of 65 (63%) had transbronchial biopsies demonstrating non-caseating granulomas. Patients with sarcoidosis presenting with EN were more likely to be female (p=0.042), younger (p=0.012) and have earlier stage pulmonary disease (p=0.02). There were no correlations between serum ACE, interstitial granulomas and disease stage. BAL-I did however predict increasing disease radiological stage (p=0.042). In this study, one quarter of patients with sarcoidosis presented with EN among their presenting features. These patients were more likely to be young females with early stage radiological disease.

  15. Retention of urine and sacral paraesthesia in anogenital herpes simplex infection. (United States)

    Edis, R H


    Two definite and 2 probable cases of anogenital herpes simplex and sacral radiculitis are described. Symptoms were typical and consisted of paraesthesia and neuralgic pain in the perineum and legs, urinary retention and constipation occurring within several days to a week after an anogenital herpetic eruption. However, at presentation only 1 case had an obvious history of anogenital herpes simplex. Neurological signs were not striking and consisted of a reduced appreciation of light touch and pin prick over the sacral dermatomes and in 2 cases reduced anal sphincter tone. CSF examination in 3 patients showed a lymphocytosis. Bladder catheterisation was required for up to 2 weeks in 2 patients. The paraesthesia persisted for weeks to months. It should be more widely recognised that anogenital herpes simplex, with sacral radiculitis, is probably the commonest cause of acute retention of urine in young sexually active people.

  16. Sex-based differences in lymphocyte proliferation in the spleen after vanadium inhalation. (United States)

    Rodriguez-Lara, Vianey; Muñiz-Rivera Cambas, Angelica; González Villalva, Adriana; Fortoul, Teresa I


    Vanadium (V) is a transition metal often adhered to particulate matter and released into the atmosphere as vanadium pentoxide (V2O5) by the burning of fossil fuels. This air pollutant causes adverse effects in the immune system. Lymphocytosis and splenomegaly have been reported with increased white pulp in mice after V inhalation. The effect of V on the immune system as related to sex has been poorly investigated. This study sought to determine if V inhalation (a) produced lymphoproliferation that could explain the changes previously observed in the spleen and in peripheral blood lymphocyte counts and (b) whether any observed effects differed due to gender. Immunohistochemical analyses of Ki-67, a specific proliferation marker, was made in the spleens of CD-1 male and female mice exposed for 1 h, twice a week, over a 12-week period to V2O5 (at 1.4 mg V2O5/m(3)) by whole-body inhalation; similar analyses were performed on spleens of control mice exposed to vehicle (filtered air). The results showed that in male mice there was a significant increase in percentage of Ki-67 immunopositive lymphocytes starting from the second week and until the end of the exposure. The Ki-67 signal was cytoplasmic and nuclear in the exposed males, while in controls the signal was only nuclear. In female mice, V inhalation singificantly increased the percentage of proliferating lymphocytes only after 1 week of exposure. Ki-67 signal was observed only in the nucleus of lymphocytes from the control and exposed females. The results here help to explain the splenomegaly and lymphocytosis observed previously in male mice and support the lymphoproliferative effect induced by V. Lastly, the finding that there was a sex difference in the effect of vanadium on lymphocyte proliferation suggests a role for sex hormones in potential protection against V immunotoxicity; however, further studies are needed to support this hypothesis.

  17. Reactive gastropathy is associated with inflammatory conditions throughout the gastrointestinal tract. (United States)

    Maguilnik, I; Neumann, W L; Sonnenberg, A; Genta, R M


    The epidemiology of reactive gastropathy and its relationship with other conditions of the gastrointestinal tract associated with NSAID use have not been evaluated. To test the hypothesis that if reactive gastropathy shares common aetiological factors with these conditions, the analysis of a large cohort would unveil associations. We queried a national pathology database for subjects with a diagnosis of reactive gastropathy; controls were patients with normal gastric biopsies. We also extracted diagnoses of H. pylori infection, intestinal metaplasia, duodenal lymphocytosis, duodenitis, ileitis, microscopic colitis and focal colitis. Of 504 011 patients with gastric biopsies, 69 101 had oesophageal, 166 134 duodenal, 13 010 ileal and 83 334 colonic biopsies. Reactive gastropathy was diagnosed in 15.6% of patients, H. pylori infection in 10.3% and normal gastric mucosa in 16.3%. Reactive gastropathy was evenly distributed across the US and increased from 2.0% in the first decade of life to >20% in octogenarians. Compared with controls, reactive gastropathy was significantly associated with Barrett's mucosa (OR 1.21 95% CI 1.16-129); duodenitis (OR 1.36; 95% CI 1.28-1.44); duodenal intraepithelial lymphocytosis (OR 1.25; 95% CI 1.13-1.39); active ileitis (OR 1.88; 95% CI 1.47-2.40); focal active colitis (OR 1.57; 95% CI 1.33-1.86); and collagenous colitis (OR 1.50; 95% CI 1.12-2.03). Reactive gastropathy, a common histopathological feature of the stomach, shows an age-dependent rise and is associated with changes of the digestive tract believed to be caused by NSAID use or duodenogastric reflux. However, a large fraction of reactive gastropathy remains unexplained; its frequent occurrence merits further efforts at elucidating its aetiology. © 2012 Blackwell Publishing Ltd.

  18. [Changes introduced into the recent International Classification of Headache Disorders: ICHD-III beta classification]. (United States)

    Belvis, Robert; Mas, Natàlia; Roig, Carles


    The International Headache Society (IHS) has published the third edition of the International Classification of Headache Disorders (ICHD-III beta), the most commonly used guide to diagnosing headaches in the world. To review the recent additions to the guide, to explain the new entities that appear in it and to compare the conditions that have had their criteria further clarified against the criteria in the previous edition. We have recorded a large number of clarifications in the criteria in practically all the headaches and neuralgias in the classification, but the conditions that have undergone the most significant clarifications are chronic migraine, primary headache associated with sexual activity, short-lasting unilateral neuralgiform headache attacks, new daily persistent headache, medication-overuse headache, syndrome of transient headache and neurological deficits with cerebrospinal fluid lymphocytosis. The most notable new entities that have been incorporated are external-compression headache, cold-stimulus headache, nummular headache, headache attributed to aeroplane travel and headache attributed to autonomic dysreflexia. Another point to be highlighted is the case of the new headaches (still not considered entities in their own right) included in the appendix, some of the most noteworthy being epicrania fugax, vestibular migraine and infantile colic. The IHS recommends no longer using the previous classification and changing over to the new classification (ICHD-III beta) in healthcare, teaching and research, in addition to making this new guide as widely known as possible.

  19. Drug reaction with eosinophilia and systemic symptoms syndrome in a patient taking phenytoin and levetiracetam: a case report

    Directory of Open Access Journals (Sweden)

    Hall David Jeffrey


    Full Text Available Abstract Introduction Drug reaction with eosinophilia and systemic symptoms syndrome is a potentially life-threatening hypersensitivity reaction with rash, fever, and internal organ involvement, often hepatitis, occurring most commonly two to eight weeks after initiation of a medication. The present case is an example of severe and potentially life-threatening hepatitis as a manifestation of drug reaction with eosinophilia and systemic symptoms syndrome. Case presentation We report a case of anti-epileptic-induced drug reaction with eosinophilia and systemic symptoms syndrome in an 18-year-old African-American man who presented with a five-day history of rash, periorbital and upper extremity edema, hepatitis and fever. Laboratory findings revealed an atypical lymphocytosis, eosinophilia, and elevated serum transaminases. No drug allergies were reported at the time of presentation, but phenytoin and levetiracetam therapy had been initiated five weeks prior to hospital admission for new-onset seizures. Both medications were discontinued on hospital admission, and after three days of high-dose corticosteroid therapy the patient experienced resolution of both his symptoms and laboratory markers of inflammation. Conclusion Given the significant mortality attributed to drug reaction with eosinophilia and systemic symptoms syndrome, medical personnel should be aware of the potential for this severe hypersensitivity reaction and should ensure close follow-up and offer anticipatory guidance when beginning any new medication, particularly anti-epileptic therapy. Early recognition of drug reaction with eosinophilia and systemic symptoms syndrome and initiation of appropriate therapy are imperative in limiting morbidity.

  20. Sub-acute occupational hypersensitivity pneumonitis due to low-level exposure to diisocyanates in a secretary. (United States)

    Schreiber, J; Knolle, J; Sennekamp, J; Schulz, K T; Hahn, J U; Hering, K G; Raulf-Heimsoth, M; Merget, R


    There is virtually no information in the literature about the exposure levels needed to induce hypersensitivity pneumonitis (HP) by diisocyanates. The present study reports a case of occupational HP due to diisocyanates after low-level exposure. A 53-yr-old female never-smoker developed progressive shortness of breath on exertion, cough, fatigue and flu-like symptoms shortly after she began work as a secretary of a car body repair shop. A diagnosis of HP was made 2 yrs later, based on a restrictive ventilatory defect, a reticulonodular and discrete ground-glass pattern on high-resolution computed tomography, lymphocytosis in bronchoalveolar lavage and specific immunoglobulin G antibodies to diisocyanate human serum albumin conjugates in the patient's serum. The diagnosis was confirmed by recovery after exposure cessation and deterioration after re-exposure. Ambient monitoring revealed air concentrations of different diisocyanate monomers below the detection limit in both the patient's work station and in front of the paint spray booths, with the exception of one measurement that showed 4,4-methylenediphenyl diisocyanate concentrations of 3 microg x m(-3) in front of one booth (corresponding to a total reactive isocyanate group concentration of 1 microg x m(-3)). The present authors conclude that concentrations of diisocyanates far below current exposure limits may induce hypersensitivity pneumonitis in susceptible subjects.

  1. Splenic marginal zone lymphoma. (United States)

    Piris, Miguel A; Onaindía, Arantza; Mollejo, Manuela

    Splenic marginal zone lymphoma (SMZL) is an indolent small B-cell lymphoma involving the spleen and bone marrow characterized by a micronodular tumoral infiltration that replaces the preexisting lymphoid follicles and shows marginal zone differentiation as a distinctive finding. SMZL cases are characterized by prominent splenomegaly and bone marrow and peripheral blood infiltration. Cells in peripheral blood show a villous cytology. Bone marrow and peripheral blood characteristic features usually allow a diagnosis of SMZL to be performed. Mutational spectrum of SMZL identifies specific findings, such as 7q loss and NOTCH2 and KLF2 mutations, both genes related with marginal zone differentiation. There is a striking clinical variability in SMZL cases, dependent of the tumoral load and performance status. Specific molecular markers such as 7q loss, p53 loss/mutation, NOTCH2 and KLF2 mutations have been found to be associated with the clinical variability. Distinction from Monoclonal B-cell lymphocytosis with marginal zone phenotype is still an open issue that requires identification of precise and specific thresholds with clinical meaning. Copyright © 2016 Elsevier Ltd. All rights reserved.

  2. Tuberculous meningitis in an immunocompetent male complicated by hydrocephalus. (United States)

    Dunphy, Louise; Shetty, Prashanth; Randhawa, Rabinder; Rani, Kharil Amir; Duodu, Yaw


    A 39-year-old man, born in India but resident in the UK for 10 years, was travelling in America when he became feverish with an altered mentation. He reported a 10-day history of fever, photophobia, headache and fatigue. His medical history included hypothyroidism and migraine. He was a non-smoker, did not consume alcohol and denied a history of drug use. He was transferred to the emergency department. Laboratory investigations confirmed hyponatraemia (sodium 128 mmol/L). A chest radiograph confirmed no focal consolidation. Further investigation with a CT brain was unremarkable. A lumbar puncture was suggestive of viral meningitis, with a raised white cell count, lymphocytosis, high protein and low glucose. His PCR was negative for enterovirus and herpes simplex virus. Further investigation with a CT thorax, abdomen and pelvis demonstrated bilateral upper-lobe infiltrations. A bronchoalveolar lavage was negative for acid alcohol fast bacilli (AAFB). A diagnosis of tuberculous meningitis was rendered following a repeat lumbar puncture. Gram stain revealed AAFB and PCR was also positive. He started antitubercular treatment and corticosteroids. A repeat CT brain demonstrated ventriculomegaly, suggestive of hydrocephalus and an MRI head revealed likely communicating hydrocephalus with basilar enhancement. He was repatriated to the UK. Eleven days post transfer, he became acutely confused and required external ventricular drain insertion. After surgical management of his hydrocephalus, there was no further neurological deterioration. He remains committed to his neurorehabilitation. 2016 BMJ Publishing Group Ltd.

  3. Clinical significance of acquired somatic mutations in aplastic anaemia. (United States)

    Marsh, J C W; Mufti, G J


    Aplastic anaemia (AA) is frequently associated with other disorders of clonal haemopoiesis such as paroxysmal nocturnal haemoglobinuria (PNH), myelodysplastic syndrome (MDS) and T-large granular lymphocytosis. Certain clones may escape the immune attack within the bone marrow environment and proliferate and attain a survival advantage over normal haemopoietic stem cells, such as trisomy 8, loss of heterozygosity of short arm of chromosome 6 and del13q clones. Recently acquired somatic mutations (SM), excluding PNH clones, have been reported in around 20-25 % of patients with AA, which predispose to a higher risk of later malignant transformation to MDS/acute myeloid leukaemia. Furthermore, certain SM, such as ASXL1 and DNMT3A are associated with poor survival following immunosuppressive therapy, whereas PIGA, BCOR/BCORL1 predict for good response and survival. Further detailed and serial analysis of the immune signature in AA is needed to understand the pathogenetic basis for the presence of clones with SM in a significant proportion of patients.

  4. Effects of neonatal thymic exposure to high doses of X-irradiation

    International Nuclear Information System (INIS)

    Bains, G.S.; Sundaram, K.


    The thymic region of neonatal Swiss mice was exposed to doses varying from 1000 R to 2000 R of X-irradiation. The animals did not show any signs of wasting syndrome up to 6 months after irradiation. At this time hyperplasia of the thymus with an associated lymphocytosis was evident in irradiated animals. Antibody production to sheep red blood cells (SRBC) was not affected. However, at 12 months post-irradiation the animals showed signs of wasting disease with a progressive increase in their numbers at 18 and 24 months of age. The percentage incidence of animals with wasting disease was dose dependent. At this stage in the majority of the animals with the disease the thymus showed varying degrees of atrophy along with splenomegaly. There were no significant differences in the number of lymphocytes but the number of granulocytes showed a substantial increase. This was more evident in animals exposed to 2000 R to the thymic region. Though one observed a lowered ability to form antibodies to bovine serum albumin (BSA) with advancing age, the thymic irradiation did not affect the immune response to BSA even in animals manifesting wasting disease. An interesting observation has been the development of a severe loss of muscle power and tone in the hind limbs in a large majority of animals. (author)

  5. [Histological features of celiac disease in south Tunisia: a study of 114 pediatric cases]. (United States)

    Kallel, Rim; Krichen-Makni, Saloua; Ellouze, Sameh; Châari, Chiraz; Charfi, Slim; Sellami, Ahmed; Tahri, Mohamed-Nabil; Hachicha, Mongia; Sellami-Boudawara, Tahya


    To report the histological features of celiac disease in a paediatric population originating from south Tunisia. A retrospective study of a series of duodenal biopsies from 114 children with celiac disease diagnosed over a period of 6 years (from January 1999 to December 2004). The diagnosis was confirmed by histological results, serological studies and clinical response to gluten free diet. The average age of patients was of 6.2 years (range 6 months-15 years). Sex ratio was 0.71. Symptoms were dominated by chronic diarrhea (48%), weight loss (50%) and anemia (20.1%). Histological findings showed an intraepithelial lymphocytosis (Marsh type 1) in 12.2% of cases, type 2 was present in 1.7% of cases and type 3 (villous atrophy) in 86% of cases. A treatment with a gluten-free diet was indicated for all patients, only the cases who haven't presented a clinical amelioration (11 cases) have beneficed a control biopsie; a villous atrophy was persistent in 80% of this patients. Histological features in duodenal biopsies for the diagnosis and the follow-up of patients with coeliac disease. This allows an appropriate treatment and prevents further complications.

  6. Selinexor is effective in acquired resistance to ibrutinib and synergizes with ibrutinib in chronic lymphocytic leukemia. (United States)

    Hing, Zachary A; Mantel, Rose; Beckwith, Kyle A; Guinn, Daphne; Williams, Erich; Smith, Lisa L; Williams, Katie; Johnson, Amy J; Lehman, Amy M; Byrd, John C; Woyach, Jennifer A; Lapalombella, Rosa


    Despite the therapeutic efficacy of ibrutinib in chronic lymphocytic leukemia (CLL), complete responses are infrequent, and acquired resistance to Bruton agammaglobulinemia tyrosine kinase (BTK) inhibition is being observed in an increasing number of patients. Combination regimens that increase frequency of complete remissions, accelerate time to remission, and overcome single agent resistance are of considerable interest. We previously showed that the XPO1 inhibitor selinexor is proapoptotic in CLL cells and disrupts B-cell receptor signaling via BTK depletion. Herein we show the combination of selinexor and ibrutinib elicits a synergistic cytotoxic effect in primary CLL cells and increases overall survival compared with ibrutinib alone in a mouse model of CLL. Selinexor is effective in cells isolated from patients with prolonged lymphocytosis following ibrutinib therapy. Finally, selinexor is effective in ibrutinib-refractory mice and in a cell line harboring the BTK C481S mutation. This is the first report describing the combined activity of ibrutinib and selinexor in CLL, which represents a new treatment paradigm and warrants further evaluation in clinical trials of CLL patients including those with acquired ibrutinib resistance. © 2015 by The American Society of Hematology.

  7. Bruton tyrosine kinase inhibitor ibrutinib (PCI-32765). (United States)

    Burger, Jan A; Buggy, Joseph J


    Over the past 3 years, ibrutinib (PCI-32765) has emerged as a breakthrough in targeted therapy for patients with certain types of B cell malignancies. Early stage clinical trials found ibrutinib to be particularly active in chronic lymphocytic leukemia (CLL) and mantle cell lymphoma (MCL), providing the rationale for ongoing phase 3 trials. In contrast to conventional chemo-immunotherapy, ibrutinib is not myelosuppressive, and responses are not affected by disease features that predict failure to respond to or short remission durations after chemo-immunotherapy, such as del17p. In CLL, ibrutinib characteristically causes an early redistribution of tissue-resident CLL cells into the blood, with rapid resolution of enlarged lymph nodes, along with a surge in lymphocytosis. Later, after weeks to months of continuous ibrutinib therapy, the growth- and survival-inhibitory activities of ibrutinib result in the normalization of lymphocyte counts and remissions in a majority of patients. This review discusses the discovery, preclinical and clinical development of ibrutinib, its pathophysiological basis, and outlines perspectives for future use of ibrutinib.

  8. The Bruton tyrosine kinase inhibitor ibrutinib with chemoimmunotherapy in patients with chronic lymphocytic leukemia. (United States)

    Brown, Jennifer R; Barrientos, Jacqueline C; Barr, Paul M; Flinn, Ian W; Burger, Jan A; Tran, Anh; Clow, Fong; James, Danelle F; Graef, Thorsten; Friedberg, Jonathan W; Rai, Kanti; O'Brien, Susan


    The safety and efficacy of ibrutinib, an oral inhibitor of Bruton tyrosine kinase, were evaluated with chemoimmunotherapy (CIT) in a multicenter phase 1b study. Patients with relapsed/refractory chronic lymphocytic leukemia received bendamustine and rituximab (BR) or fludarabine, cyclophosphamide, and rituximab (FCR) for up to 6 cycles with daily ibrutinib (420 mg) until progressive disease or unacceptable toxicity. Enrollment to FCR-ibrutinib closed early due to a lack of fludarabine-naïve previously treated patients. No patients treated with BR-ibrutinib (n = 30) or FCR-ibrutinib (n = 3) experienced prolonged hematologic toxicity in cycle 1 (primary end point). Tolerability was as expected with either CIT or single-agent ibrutinib. The overall response rate (ORR) with BR-ibrutinib was 93.3%, including 16.7% complete responses (CRs) initially, which increased to 40% with the extension period. Including 1 patient with partial response with lymphocytosis, the best ORR was 96.7%. Sixteen of 21 patients with baseline cytopenias had sustained hematologic improvement. At 12 and 36 months, 86.3% and 70.3% remained progression-free, respectively. All 3 patients treated with ibrutinib-FCR achieved CR. Ibrutinib may enhance CIT efficacy without additive toxicities, providing the rationale for studying this combination in an ongoing phase 3 trial. The study is registered to as #NCT01292135. © 2015 by The American Society of Hematology.

  9. The Next Generation of Targeted Molecules for the Treatment of Chronic Lymphocytic Leukemia. (United States)

    Jeyakumar, Deepa; O'Brien, Susan


    With the recent approval of several new targeted therapies for chronic lymphocytic leukemia (CLL), there are now multiple options for its treatment. Inhibitors of Bruton tyrosine kinase (with ibrutinib being the first-in-class US Food and Drug Administration-approved agent) and phosphoinositide 3-kinase (with idelalisib as the first-in-class approved agent) are promising because they are generally well tolerated and highly effective against this malignancy. These agents may be particularly important in the treatment of older patients who are less able to tolerate the myelosuppression (and subsequent infections) associated with chemoimmunotherapy. As a class of medications, B-cell receptor inhibitors have some unique side effects, including redistribution lymphocytosis. Toxicities associated specifically with ibrutinib include increased risk for bleeding and atrial fibrillation. Idelalisib also has some unique toxicities: transaminitis, colitis, and pneumonitis. Targeted therapies recently approved for use in CLL include the novel anti-CD20 monoclonal antibodies obinutuzumab and ofatumumab, and the B-cell lymphoma 2 inhibitor venetoclax. This article describes the clinical data that led to approval of these B-cell receptor inhibitors for the treatment of CLL, and highlights newer agents in clinical development that target the same kinases as the currently available therapies.

  10. Three-year follow-up of treatment-naïve and previously treated patients with CLL and SLL receiving single-agent ibrutinib. (United States)

    Byrd, John C; Furman, Richard R; Coutre, Steven E; Burger, Jan A; Blum, Kristie A; Coleman, Morton; Wierda, William G; Jones, Jeffrey A; Zhao, Weiqiang; Heerema, Nyla A; Johnson, Amy J; Shaw, Yun; Bilotti, Elizabeth; Zhou, Cathy; James, Danelle F; O'Brien, Susan


    Ibrutinib is an orally administered inhibitor of Bruton tyrosine kinase that antagonizes B-cell receptor, chemokine, and integrin-mediated signaling. In early-phase studies, ibrutinib demonstrated high response rates and prolonged progression-free survival (PFS) in chronic lymphocytic leukemia (CLL). The durable responses observed with ibrutinib relate in part to a modest toxicity profile that allows the majority of patients to receive continuous therapy for an extended period. We report on median 3-year follow-up of 132 patients with symptomatic treatment-naïve and relapsed/refractory CLL or small lymphocytic lymphoma. Longer treatment with ibrutinib was associated with improvement in response quality over time and durable remissions. Toxicity with longer follow-up diminished with respect to occurrence of grade 3 or greater cytopenias, fatigue, and infections. Progression remains uncommon, occurring primarily in some patients with relapsed del(17)(p13.1) and/or del(11)(q22.3) disease. Treatment-related lymphocytosis remains largely asymptomatic even when persisting >1 year and does not appear to alter longer-term PFS and overall survival compared with patients with partial response or better. Collectively, these data provide evidence that ibrutinib controls CLL disease manifestations and is well tolerated for an extended period; this information can help direct potential treatment options for different subgroups to diminish the long-term risk of relapse. © 2015 by The American Society of Hematology.

  11. Haematological parameters in different african populations: an experience from united nations level 3 hospital

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    Iftikhar, R.; Khan, N.U.; Iqbal, Z.; Anwar, M.I.


    To evaluate hematological parameters in African population to estimate normal reference intervals for these tests. Study Design: Cross sectional observational study. Place and Duration of Study: Department of Pathology, United Nations level 3 hospital, Nyala, Darfur from 1st Mar to 30th Dec 2014. Material and Methods: There were 396 healthy African male and female volunteers selected between 18-65 years of age, belonging to different countries. Fresh whole blood was used to measure haemoglobin (Hb) concentration, haematocrit (Hct), total red blood cell (TRBC) count, mean corpuscular volume (MCV), mean corpuscular haemoglobin (MCH), mean corpuscular haemoglobin concentration (MCHC), platelet count, total leucocyte count (TLC) and differential white blood cells count. Data were analysed using SPSS version 19. Results: Mean Hb of study group was 13.81 +- 1.99 g/dl. Mean TLC was 5.50 +- 1.96 x 103/ul. Mean lymphocyte count was 2.58 +- 0.95. Mean platelet count was 234 +- 92 x103 /ul. Mean values for Hb Concentration, TRBC, Hct Ratio, MCV, MCH and MCHC were all higher for African Males than Females; this difference was statistically significant (p<0.05). Conclusion: This multi-national African population based study confirms the variations in haematological parameters previously described in single nation African studies. The commonly observed variations in normal adults are low RBC indices, relative neutropenia and lymphocytosis. (author)


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    Full Text Available The Bovine Leukosis Virus (BLV is the etiological agent of the Enzootic Bovine Leukemia (EBL, this disease is infectious, chronic and specifically cattle, presenting a low percentage of patients with clinical manifestations. Between 30-70% of infected animals can develop persistent lymphocytosis (LP and between 0,1-10% of cattle over three years of infection suffers some form of lymphosarcoma (LS. The aim of this work was serologically detection of BLV in milk samples from Holstein cows in three dairy herds in the department of Antioquia. Were taken 133 milk samples from Holstein cows three dairy herds located in the municipality of Medellin and Belmira, was conducted an indirect ELISA against gp51 envelope protein of the virus. The ELISA test showed a seroprevalence of 79,69% (106/133 for all samples tested. The herd was the largest herd seroprevalence 1 (82,86%, followed by the herd 2 (80% and finally the herd 3 (77,08%. The presence of the BLV has increased in recent years in Antioquia, so fast and efficient diagnosis through reliable methodologies allow control over the spread of the disease in dairy herds.

  13. Update on celiac disease – etiology, differential diagnosis, drug targets, and management advances

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    Scanlon SA


    Full Text Available Samantha A Scanlon1, Joseph A Murray1,21Department of Internal Medicine, 2Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USAAbstract: Celiac disease (CD is an immune-mediated enteropathy triggered by exposure to wheat gluten and similar proteins found in rye and barley that affects genetically susceptible persons. This immune-mediated enteropathy is characterized by villous atrophy, intraepithelial lymphocytosis, and crypt hyperplasia. Once thought a disease that largely presented with malnourished children, the wide spectrum of disease activity is now better recognized and this has resulted in a shift in the presenting symptoms of most patients with CD. New advances in testing, both serologic and endoscopic, have dramatically increased the detection and diagnosis of CD. While the gluten-free diet is still the only treatment for CD, recent investigations have explored alternative approaches, including the use of altered nonimmunogenic wheat variants, enzymatic degradation of gluten, tissue transglutaminase inhibitors, induction of tolerance, and peptides to restore integrity to intestinal tight junctions.Keywords: immune-mediated enteropathy, gliadin, gluten, epidemiology, CD diagnosis, therapy

  14. Pathogenetical Characterization of MHV-76: a Spontaneous 9.5-Kilobase-Deletion Mutant of Murine Lymphotropic Gammaherpesvirus 68

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    A. Chalupková


    Full Text Available Murid gammaherpesvirus 4 (MuHV-4 provides a small animal model for the study of animal gammaherpesviruses. MHV-76 is a spontaneous deletion mutant as compared to the prototype strain of MuHV-4 (MHV-68. The MHV-76 genome lacks at least 12 ORFs at the 5'-end including the M1, M2, M3 and M4 genes and the eight viral t-RNA-like genes. During 27 months of experimental infection of BALB/c mice we followed their pathogenesis, immunology and oncogenic properties. After intranasal infection with MHV-76, the infectious virus was detected in the blood, thymus, lungs, heart, liver, spleen, bone marrow, peritoneal macrophages, lymph nodes, kidneys, mammary glands, brain and small intestine. The acute phase of infection was attenuated, but the chronic phase of infection was accompanied with long persistence of virus not only in the lymphatic, but in the neural and glandular tissue, as well. In comparison with the prototype strain, splenomegaly and lymphocytosis was very low. Surprisingly, during 27 months the BALB/c mice infected with MHV-76 did not develop lymphoproliferative disorders like infectious mononucleosis, leukaemia or lymphomas. We hypothesize that the M4 gene, present in all oncogenic MHV isolates, might be related (directly or indirectly to their transforming properties.

  15. Clinical and laboratory characteristics of infectious mononucleosis by Epstein-Barr virus in Mexican children. (United States)

    González Saldaña, Napoleón; Monroy Colín, Victor Antonio; Piña Ruiz, Georgina; Juárez Olguín, Hugo


    Infectious mononucleosis (IM) or Mononucleosis syndrome is caused by an acute infection of Epstein-Barr virus. In Latin American countries, there are little information pertaining to the clinical manifestations and complications of this disease. For this reason, the purpose of this work was to describe the clinical and laboratory characteristics of infection by Epstein-Barr virus in Mexican children with infectious mononucleosis. A descriptive study was carried out by reviewing the clinical files of patients less than 18 years old with clinical and serological diagnosis of IM by Epstein-Barr virus from November, 1970 to July, 2011 in a third level pediatric hospital in Mexico City. One hundred and sixty three cases of IM were found. The most frequent clinical signs were lymphadenopathy (89.5%), fever (79.7%), general body pain (69.3%), pharyngitis (55.2%), hepatomegaly (47.2%). The laboratory findings were lymphocytosis (41.7%), atypic lymphocytes (24.5%), and increased transaminases (30.9%), there were no rupture of the spleen and no deaths among the 163 cases. Our results revealed that IM appeared in earlier ages compared with that reported in industrialized countries, where adolescents are the most affected group. Also, the order and frequency of the clinical manifestations were different in our country than in industrialized ones.

  16. Maximal exercise increases mucosal associated invariant T cell frequency and number in healthy young men. (United States)

    Hanson, Erik D; Danson, Eli; Nguyen-Robertson, Catriona V; Fyfe, Jackson J; Stepto, Nigel K; Bartlett, David B; Sakkal, Samy


    Mucosal associated invariant T (MAIT) cells have properties of the innate and acquired immune systems. While the response to vigorous exercise has been established for most leukocytes, MAIT cells have not been investigated. Therefore, the purpose was to determine if MAIT cell lymphocytosis occurs with acute maximal aerobic exercise and if this response is influenced by exercise duration, cardiovascular fitness, or body composition. Twenty healthy young males with moderate fitness levels performed an extended graded exercise test until volitional fatigue. Peripheral blood mononuclear cells were isolated from venous blood obtained prior and immediately after exercise and were labeled to identify specific T cell populations using flow cytometry. The percentage of MAIT cells relative to total T cells significantly increased from 3.0 to 3.8% and absolute MAIT cell counts increased by 2.2-fold following maximal exercise. MAIT cell subpopulation proportions were unchanged with exercise. Within cytotoxic T lymphocytes (CTL), MAIT cells consisted of 8% of these cells and this remained constant after exercise. MAIT cell counts and changes with exercise were not affected by body composition, VO 2peak , or exercise duration. Maximal exercise doubled MAIT cell numbers and showed preferential mobilization within total T cells but the response was not influenced by fitness levels, exercise duration, or body composition. These results suggest that acute exercise could be used to offset MAIT cell deficiencies observed with certain pathologies. MAIT cells also make up a substantial proportion of CTLs, which may have implications for cytotoxicity assays using these cells.

  17. Keto analogues and amino acids supplementation induces a decrease of white blood cell counts and a reduction of muscle damage during intense exercise under thermoneutral conditions. (United States)

    Lima, R C P; Camerino, S R A S; França, T C L; Rodrigues, D S A; Gouveia, M G S; Ximenes-da-Silva, A; Bassini, A; Prado, E S; Cameron, L C


    This study evaluated the acute effect of keto analogue and amino acid (AA-KAAA) supplementation on both white blood cell counts and the established biomarkers of muscle damage during exercise under thermoneutral conditions. Sixteen male cyclists received a ketogenic diet for two days and were divided into two equal groups: a group taking AA-KAAA (KA) or a control group (PL). The athletes performed a two hour cycling session followed by a maximum incremental test until voluntary exhaustion (VExh). Blood samples were obtained at rest and during exercise for further hematological and biochemical analyses. Exercise-induced ammonemia increased in the PL group at VExh (75%) but remained unchanged in the KA group. Both groups exhibited a significant increase in leukocyte and neutrophil counts of ∼85% (∼13 × 10 9 L -1 ), but the shape of the lymphocytes and the eosinophil counts suggest that AA-KAAA supplementation helps prevent lymphocytosis. AA-KAAA supplementation induced a decrease in creatine kinase and aspartate aminotransferase levels at VExh while showing a significant decrease in lactate dehydrogenase at 120 min. We found that AA-KAAA supplementation decreases both the lymphocyte count response in blood and the established biomarkers of muscle damage after intense exercise under a low heat stress environment.

  18. Bovine lymphocytic leukemia: studies of etiology, pathogenesis and mode of transmission. Progress report No. 18, June 1975--June 1978

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    Sorensen, D.K.


    The primary objective of this research is to elucidate the cause(s) and early pathogenesis of the adult form of lymphosarcoma in cattle. Consequently, a major portion of our research is centered around experimental transmission of this disease. Bovine leukemia is believed to be caused by an oncogenic RNA virus designated bovine leukemia virus (BLV). We have consistently demonstrated the presence of BLV particles in leukemic cattle and cattle with a persistent lymphocytosis, but never in normal cattle. These BLV particles have been partially purified and highly concentrated to provide a potent inoculum used to inoculate 12 late stage bovine fetuses (in utero) and two newborn calves. Our current study involves extensive monitoring of these inoculated animals to detect early precancerous changes and obtain a detailed description of the events occurring early in the pathogenesis of bovine lymphosarcoma. From our ongoing monitoring study we will be able to detail when, in what sequence, and to what extent each parameter changes in the course of lymphosarcoma development. In addition to our transmission and monitoring studies we are examining various lymphocyte subpopulations in an attempt to determine which cell type is responsible for BLV production and to determine if this same cell type carries the nuclear pocket abnormality associated with the adult form of bovine lymphosarcoma. (ERB)

  19. Bovine lymphocytic leukemia: studies of etiology, pathogenesis and mode of transmission. Progress report No. 17, July 1976--October 1977

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    Sorensen, D.K.


    The primary objective of the proposed research will be elucidation of the etiology and pathogenesis of bovine leukemia. We have consistently demonstrated C-type particles in mitogen stimulated lymphocyte cultures from leukemic cows and cows with a persistent lymphocytosis. These particles have been concentrated and partially purified by continuous flow, density gradient, ultracentrifugation. Newborn calves and late stage bovine fetuses have been inoculated with these concentrated cell free preparations. Our current study involves extensive monitoring of these inoculated animals to detect early pre-cancerous changes. The following parameters are being measured: the serological titer against a bovine leukemia associated antigen; the percentage of lymphocytes showing nuclear pockets; the percentage of mitogen stimulated lymphocytes with C-type particles adherent to their surface; the percentage of B-lymphocytes in the peripheral circulation; the complete blood count; and the quantity of bovine leukemia virus (BLV) production as determined by the syncytia induction assay. Additional proposals include: using the monitoring parameters to study animals with the juvenile and thymic forms of leukemia; the examination of adult lymphosarcoma cases to determine which tissues harbor BLV; and lymphocyte subpopulation work to further define which cell types are associated with BLV production and tumor formation.

  20. Diagnosis and management of lymphoma in a green iguana (Iguana iguana). (United States)

    Folland, Douglas W; Johnston, Matthew S; Thamm, Douglas H; Reavill, Drury


    CASE DESCRIPTION-A 2-year-old female green iguana was examined for anorexia and swelling and pain on palpation in the cranial cervical area. CLINICAL FINDINGS-Marked soft tissue swelling in the cranial cervical area with corresponding cystic swellings in the pharynx were noted. The iguana was considered to be 50% under the expected body weight, given diet and husbandry conditions. The WBC count was markedly elevated, characterized by heterophilia and lymphocytosis. Surgical exploration of the cranial cervical area and histologic and microbial testing identified lymphoma with secondary infection as the cause of the swelling. TREATMENT AND OUTCOME-The tumor was initially treated with a single 10-Gy fraction of radiation directed at the masses in the neck. A vascular access port was placed in the ventral abdominal vein, and a canine chemotherapy protocol was modified for use in the iguana. During the course of treatment, the protocol was modified twice. At 1,008 days from the initiation of treatment, the iguana appeared to be in remission. CLINICAL RELEVANCE-To our knowledge, this is the first reported use of radiation with doxorubicin, vincristine, cyclophosphamide, and prednisone to successfully manage lymphoma in a reptile. A vascular access port was used effectively for drug administration for an extended period. The doxorubicin, vincristine, cyclophosphamide, and prednisone protocol appeared to be safe and effective in this iguana for the management of lymphoma.

  1. Nickel Nanoparticles Exposure and Reproductive Toxicity in Healthy Adult Rats

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    Lu Kong


    Full Text Available Nickel is associated with reproductive toxicity. However, the reproductive toxicity of nickel nanoparticles (Ni NPs is unclear. Our goal was to determine the association between nickel nanoparticle exposure and reproductive toxicity. According to the one-generation reproductive toxicity standard, rats were exposed to nickel nanoparticles by gavage and we selected indicators including sex hormone levels, sperm motility, histopathology, and reproductive outcome etc. Experimental results showed nickel nanoparticles increased follicle stimulating hormone (FSH and luteinizing hormone (LH, and lowered etradiol (E2 serum levels at a dose of 15 and 45 mg/kg in female rats. Ovarian lymphocytosis, vascular dilatation and congestion, inflammatory cell infiltration, and increase in apoptotic cells were found in ovary tissues in exposure groups. For male rats, the weights decreased gradually, the ratio of epididymis weight over body weight increased, the motility of rat sperm changed, and the levels of FSH and testosterone (T diminished. Pathological results showed the shedding of epithelial cells of raw seminiferous tubule, disordered arrangement of cells in the tube, and the appearance of cell apoptosis and death in the exposure group. At the same time, Ni NPs resulted in a change of the reproductive index and the offspring development of rats. Further research is needed to elucidate exposure to human populations and mechanism of actions.

  2. Dengue fever as a cause of hemophagocytic lymphohistiocytosis. (United States)

    Hein, Noely; Bergara, Gabriel Heiser; Moura, Nathalie Bianchini Vieira; Cardoso, Débora Morais; Hirose, Maki; Ferronato, Angela Espósito; Pastorino, Antônio Carlos; Lo, Denise Swei; Gilio, Alfredo Elias


    Dengue is endemic in more than 100 countries in Southeast Asia, the Americas, the western Pacific, Africa and the eastern Mediterranean regions. The virus is transmitted by Aedes mosquitoes. Dengue disease is the most prevalent arthropod-borne viral disease in humans and is a global and national public health concern in several countries. A seasonal pattern of dengue disease is consistently observed. The highest incidences usually correspond to the period of highest rainfall and humidity, providing suitable conditions for Aedes aegypti breeding and survival. In Brazil for instance it is from January to June. Dengue may cause marked changes in bone marrow that result in hypocellularity and, consequently, thrombocytopenia and leucopenia, along with an increase in hematocrit, which is secondary to capillary leakage. However, those abnormalities are usually self-limited, and do not warrant further investigations, such as a marrow biopsy or a myelogram. The occurrence of persistent reactive hemophagocytosis is uncommon and usually leads to serious adverse outcomes. The authors report the case of an 8-year old girl complaining of high-grade fever, malaise, headache, abdominal pain and a cutaneous rash. Laboratory examination revealed atypical lymphocytosis on peripheral blood count, hyperbilirrunemia, abnormal liver enzymes and clotting tests. Serology was positive for dengue. Because of the persistence of fever and laboratory examinations were consistent with hemophagocytic lymphohistiocytosis (HLH) a bone marrow aspiration was performed, which confirmed the presence of hemophagocytosis. Hence we report a rare presentation of dengue accompanied by self-limited HLH that hopefully evolve to favorable outcome.

  3. Respiratory viral infections in infants with clinically suspected pertussis. (United States)

    Ferronato, Angela E; Gilio, Alfredo E; Vieira, Sandra E


    to evaluate the frequency of respiratory viral infections in hospitalized infants with clinical suspicion of pertussis, and to analyze their characteristics at hospital admission and clinical outcomes. a historical cohort study was performed in a reference service for pertussis, in which the research of respiratory viruses was also a routine for infants hospitalized with respiratory problems. All infants reported as suspected cases of pertussis were included. Tests for Bordetella pertussis (BP) (polymerase chain reaction/culture) and for respiratory viruses (RVs) (immunofluorescence) were performed. Patients who received macrolides before hospitalization were excluded. Clinical data were obtained from medical records. Among the 67 patients studied, BP tests were positive in 44%, and 26% were positive for RV. There was no etiological identification in 35%, and RV combined with BP was identified in 5%. All patients had similar demographic characteristics. Cough followed by inspiratory stridor or cyanosis was a strong predictor of pertussis, as well as prominent leukocytosis and lymphocytosis. Rhinorrhea and dyspnea were more frequent in viral infections. Macrolides were discontinued in 40% of patients who tested positive for RV and negative for BP. the results suggest that viral infection can be present in hospitalized infants with clinical suspicion of pertussis, and etiological tests may enable a reduction in the use of macrolides in some cases. However, the etiological diagnosis of respiratory virus infection, by itself, does not exclude the possibility of infection with BP. Copyright © 2013 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.

  4. [Retrospective study of neuromeningeal cryptococcosis in patients infected with HIV in the infectious diseases unit of university hospital of Casablanca, Morocco]. (United States)

    Dollo, I; Marih, L; El Fane, M; Es-Sebbani, M; Sodqi, M; Oulad Lahsen, A; Chakib, A; El Kadioui, F; Hamdani, A; El Mabrouki, M J; Soussi Abdallaoui, M; Karima, Z; Hassoune, S; Maaroufi, A; Marhoum El Filali, K


    To report the cases of neuromeningeal cryptococcosis and to describe the clinical, paraclinical, therapeutic and outcomes of patients. Retrospective study of 43 patients infected with HIV admitted from January first 2010 to June 30th 2015 in the infectious disease unit of UHC Ibn Rochd, for neuromeningeal cryptococcus. The mean frequency of neuromeningeal cryptococcosis in patients infected with HIV was 1.4%. The mean age was 39 years and a sex ratio of 1.38. The mean CD4 count was 70 cells/mm 3 . The diagnosis of HIV was revealed by neuromeningeal cryptococcus in 77% of cases. Fifteen days interval was reported between the first symptom and hospital admission. Headache (77%) was the most represented clinical sign. The cerebrospinal fluid analysis showed hypoglycorachy (67%), hyperproteinorachy (65%) and lymphocytosis (63%). Chinese ink direct examination for Cryptococcus neoformans in CSF was positive in 86% of cases and all cases were positive after culture on Sabouraud's medium. Patients were treated with monotherapy amphotericin B (42%) or fluconazole (28%) and bitherapy amphotéricine B/fluconazole (28%). Fatal evolution was observed in 60% of cases. Neuromeningeal cryptococcosis remains a severe opportunistic infection in HIV patients with a heavy mortality rate. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  5. [Neuromeningeal cryptococcosis in patients infected with HIV at Agadir regional hospital, (Souss-Massa, Morocco)]. (United States)

    Chadli, S; Aghrouch, M; Taqarort, N; Malmoussi, M; Ouagari, Z; Moustaoui, F; Bourouache, M; Oulkheir, S


    Neuromeningeal cryptococcosis (NMC) is a severe and fatal opportunistic infection. Lethality is frequent in the absence of treatment, especially in the presence of HIV co-infection. To determine the prevalence, epidemiological, clinical, biological and therapeutic aspects as well as the evolution of NMC for patients infected with HIV. This is a retrospective study of 40 cases of neuromeningeal cryptococcosis diagnosed in HIV-infected patients. Data are collected for 7 years (from January 2010 to December 2016) in the registers of the parasitology laboratory and the infectious diseases department at the regional hospital center in Agadir. A reduction in the prevalence of neuromeningeal cryptococcosis in HIV-infected patients was noted from 2010 to 2016 (3.66% to 0.83%). The overall prevalence of NMC was 1.53%. The mean age was 37±10 years old, with 90% of patients aged less than 45 years. The main clinical symptomatology was headache (75%). The main cytochemical abnormalities of cerebrospinal fluid analysis were hyperproteinorachy (60%), hypoglycorachy (63%) and lymphocytosis (50%). The mean CD4 cell count was 47/mm 3 . Patients were initially treated with amphotericin B, relayed with fluconazole. The overall lethality was 35%. Neuromeningeal cryptococcosis is a serious opportunistic infection in patients HIV-infected, and the lethality rate remains unacceptable. Fighting NMC in HIV+ patients requires early diagnosis, increased access to antiretrovirals, rapid introduction of appropriate treatment and the prescription of effective systemic antifungals. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  6. Drug Reaction with Eosinophilia and Systemic Symptom (DRESS) induced by carbamazepine: a case report and literature review (United States)

    EL Omairi, Nissrine; Abourazzak, Sanae; Chaouki, Sanae; Atmani, Samir; Hida, Moustapha


    Drug-induced hypersensitivity or Drug Reaction with Eosinophilia and Systemic Symptom (DRESS) is a severe adverse drug-induced reaction. Diagnosing DRESS is challenging due to the diversity of cutaneous eruption and organs involved. Most of the aromatic anticonvulsants, such as phenytoin, phenobarbital, and carbamazepine, can induce DRESS. Culprit drug withdrawal and corticosteroids constituted the mainstay of DRESS treatment. We describe a 6 year-old boy who presented fever and rash 4 weeks after starting carbamazepine. Investigation revealed leukocytosis, atypical lymphocytosis, and elevated serum transaminases. The diagnosis of DREES syndrome was made, Carbamazepine was stopped and replaced initially by Clobazam and by Valproic acid after discharge, no systemic corticotherapy was prescribed. Symptoms began to resolve within two weeks, and by one month later her laboratory values had returned to normal. The aim of this work is to raise awareness general practitioner and pediatricians to suspect Dress syndrome in patients who present with unusual complaints and skin findings after starting any antiepileptic drug. PMID:25360193

  7. Local graft irradiation in renal transplant rejection

    International Nuclear Information System (INIS)

    Kawamura, Masashi; Kataoka, Masaaki; Itoh, Hisao


    From 1977 to 1988, of 142 renal transplantations, seven recipients (4.9%) received local graft irradiation following rejective reaction refractory to antirejection medical managements. Concurrent with the administration of pulsed high dose methylprednisolone and other antirejection medical managements, the graft was irradiated with a total dose of 6.0 Gy-150 cGy per fraction every other day at the midplane of the graft using two opposing portals of 4MX Linac. The fields were defined by palpation and echography. All patients had improvements in serum creatinine on the 10th day after beginning the irradiation. Four patients with peripheral lymphocytosis during the irradiation combined with pulsed high dose methylprednisolone improved in renal functions. On the other hand, out of 3 patients with lymphcytopenic changes, in two the transplanted graft was removed due to deteriorations, and the other patient is currently suffering from chronic rejection. Local graft irradiation can be useful in maintaining a rejective graft and reversing its functions in some patients whose rejective reaction failed to respond to the antirejection medical managements. (author)

  8. Discordant lymphoma consisting of splenic mantle cell lymphoma and marginal zone lymphoma involving the bone marrow and peripheral blood: a case report

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    Caracciolo Francesco


    Full Text Available Abstract Introduction Discordant lymphomas are rare entities characterized by the simultaneous presence of two distinct types of lymphomas in different anatomic sites. We describe a very rare case of simultaneous occurrence of splenic mantle cell lymphoma and marginal zone lymphoma involving the bone marrow and peripheral blood. Case presentation We report the case of a 60-year-old asymptomatic Caucasian woman in whom discordant lymphomas were discovered when a slight lymphocytosis and a conspicuous splenomegaly were observed. The different morphological, immunophenotypical and immunohistochemical features found in the different pathologic samples obtained from peripheral blood, bone marrow and spleen sections made it possible to differentiate two types of non-Hodgkin B-cell lymphomas: a mantle cell lymphoma infiltrating the spleen and a marginal zone lymphoma involving both the bone marrow and peripheral blood. Since a similar IgH gene rearrangement was found both in the bone marrow and in the spleen, the hypothesis of a common origin, followed by a different clonal selection of the neoplastic lymphocytes may be taken into consideration. Conclusion Our case emphasizes the usefulness of investigating simultaneous specimens from different anatomic sites from the same patient and the relevant diagnostic role of splenectomy.

  9. Revisiting tuberculous pleurisy: pleural fluid characteristics and diagnostic yield of mycobacterial culture in an endemic area. (United States)

    Ruan, Sheng-Yuan; Chuang, Yu-Chung; Wang, Jann-Yuan; Lin, Jou-Wei; Chien, Jung-Yien; Huang, Chun-Ta; Kuo, Yao-Wen; Lee, Li-Na; Yu, Chong-Jen J


    Tuberculous pleurisy is traditionally indicated by extreme lymphocytosis in pleural fluid and low yield of effusion culture. However, there is considerable inconsistency among previous study results. In addition, these data should be updated due to early effusion studies and advances in culture methods. From January 2004 to June 2009, patients with tuberculous pleurisy were retrospectively identified from the mycobacteriology laboratories and the pathology and tuberculosis registration databases of two hospitals in Taiwan where tuberculosis is endemic. Pleural fluid characteristics and yields of mycobacterial cultures using liquid media were evaluated. A total of 382 patients with tuberculous pleurisy were identified. The median lymphocyte percentage of total cells in pleural fluids was 84% (IQR 64-95%) and 17% of cases had a lymphocyte percentage of pleural biopsy specimens. The degree of lymphocyte predominance in tuberculous pleurisy was lower than was previously thought. The lymphocyte percentage in pleural fluid was negatively associated with the probability of a positive effusion culture. With the implementation of a liquid culture method, the sensitivity of effusion culture was much higher than has been previously reported, and the combination of effusion and sputum cultures provided a good diagnostic yield.

  10. Diagnostic value of eosinophils in pleural effusion: a prospective study of 26 cases. (United States)

    Matthai, Smita Mary; Kini, Usha


    Eosinophilic pleural effusions (EPFs), defined as the presence of 10% or more eosinophils in the pleural fluid, are relatively rare. Their diagnostic and prognostic significance, however, remains controversial, as most of the studies are based almost entirely on retrospective case studies. This prospective study examines 26 eosinophilic pleural effusions from among 444 consecutive pleural effusions investigated at this tertiary health care center from October 1999 to April 2002. This study was attempted to unravel the diagnostic and prognostic significance of these eosinophilic effusions and assess their clinical implications, if any. Koss and Light's criteria were applied in the analysis, which comprised macroscopic, biochemical, cytological, and microbiological examinations. Of the 26 EPFs studied, five were associated with tuberculosis and three with metastatic disease. Nineteen patients had significant associated lymphocytosis. Twenty-four patients have been followed up and are in good health to date and have had no recurrence of effusion. Thus, EPF could be associated with inflammatory, benign, and malignant conditions. Hence, a closer search for a definite etiological agent is warranted in the setting of such an effusion, especially in populations endemic for tuberculosis, as in a developing country like India and in populations with a high prevalence of malignancy. Copyright 2003 Wiley-Liss, Inc.

  11. Cis-drivers and trans-drivers of bovine leukemia virus oncogenesis. (United States)

    Safari, Roghaiyeh; Hamaidia, Malik; de Brogniez, Alix; Gillet, Nicolas; Willems, Luc


    The bovine leukemia virus (BLV) is a retrovirus inducing an asymptomatic and persistent infection in ruminants and leading in a minority of cases to the accumulation of B-lymphocytes (lymphocytosis, leukemia or lymphoma). Although the mechanisms of oncogenesis are still largely unknown, there is clear experimental evidence showing that BLV infection drastically modifies the pattern of gene expression of the host cell. This alteration of the transcriptome in infected B-lymphocytes results first, from a direct activity of viral proteins (i.e. transactivation of gene promoters, protein-protein interactions), second, from insertional mutagenesis by proviral integration (cis-activation) and third, from gene silencing by microRNAs. Expression of viral proteins stimulates a vigorous immune response that indirectly modifies gene transcription in other cell types (e.g. cytotoxic T-cells, auxiliary T-cells, macrophages). In principle, insertional mutagenesis and microRNA-associated RNA interference can modify the cell fate without inducing an antiviral immunity. Despite a tight control by the immune response, the permanent attempts of the virus to replicate ultimately induce mutations in the infected cell. Accumulation of these genomic lesions and Darwinian selection of tumor clones are predicted to lead to cancer. Copyright © 2017 Elsevier B.V. All rights reserved.

  12. Intrinsic Plasma Cell Differentiation Defects in B Cell Expansion with NF-κB and T Cell Anergy Patient B Cells

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    Swadhinya Arjunaraja


    Full Text Available B cell Expansion with NF-κB and T cell Anergy (BENTA disease is a novel B cell lymphoproliferative disorder caused by germline, gain-of-function mutations in the lymphocyte scaffolding protein CARD11, which drives constitutive NF-κB signaling. Despite dramatic polyclonal expansion of naive and immature B cells, BENTA patients also present with signs of primary immunodeficiency, including markedly reduced percentages of class-switched/memory B cells and poor humoral responses to certain vaccines. Using purified naive B cells from our BENTA patient cohort, here we show that BENTA B cells exhibit intrinsic defects in B cell differentiation. Despite a profound in vitro survival advantage relative to normal donor B cells, BENTA patient B cells were severely impaired in their ability to differentiate into short-lived IgDloCD38hi plasmablasts or CD138+ long-lived plasma cells in response to various stimuli. These defects corresponded with diminished IgG antibody production and correlated with poor induction of specific genes required for plasma cell commitment. These findings provide important mechanistic clues that help explain both B cell lymphocytosis and humoral immunodeficiency in BENTA disease.

  13. Activated alveolar macrophage and lymphocyte alveolitis in extrathoracic sarcoidosis without radiological mediastinopulmonary involvement

    International Nuclear Information System (INIS)

    Wallaert, B.; Ramon, P.; Fournier, E.C.; Prin, L.; Tonnel, A.B.; Voisin, C.


    Cellular characteristics of BAL were investigated in 18 patients with proved extrathoracic sarcoidosis (that is, sarcoidosis that affected the skin, eyes, parotid glands, stomach, nose, kidneys, or meninges) without clinical or radiological mediastinopulmonary involvement. Computed tomography of the thorax was performed on five patients: four patients were normal, and one had enlarged lymph nodes (these enlargements were not detectable on the patient's chest roentgenogram). The results of pulmonary function tests were normal in all patients. The total BAL cell count did not differ significantly between controls and patients. Abnormal percentages of alveolar lymphocytes (from 18 to 87%) were noted in 15 out of 18 patients. SACE levels were normal in 15 patients. No pulmonary gallium uptake was detected. The chemiluminescence of AM's, whether spontaneous or PMA induced, was increased in five out of seven patients. The percentages of T3+ lymphocytes in sarcoidosis patients did not significantly differ from those in controls. The T4+:T8+ ratio was normal in four patients and slightly increased in one. Follow-up of patients showed that alveolar lymphocytosis is as lasting as extrathoracic involvement. Our data demonstrate increased percentages of lymphocytes and activated AM's in the BAL of patients with extrathoracic sarcoidosis. This may be due to the initial involvement of the respiratory tract in extrathoracic sarcoidosis or to the diffusion of activated macrophages and lymphocytes from an extrathoracic site into the lung

  14. Assessment of tolerant sunfish populations (Lepomis sp.) inhabiting selenium-laden coal ash effluents - 1. Hematological and population level assessment

    Energy Technology Data Exchange (ETDEWEB)

    Lohner, T.W.; Reash, R.J.; Willet, V.E.; Rose, L.A. [American Electrical Power Co., Columbus, OH (United States). Environmental Services Dept.


    Sunfish were collected from coal ash effluent-receiving streams and Ohio River watershed reference sites to assess the effects of exposure to low-level selenium concentrations. Selenium, copper, and arsenic concentrations were statistically higher in tissue samples from exposed fish than in reference fish. Leukopenia, lymphocytosis, and neutropenia were evident in exposed fish and were indicative of metal exposure and effect. White blood cell counts and percent lymphocyte values were significantly correlated with liver selenium concentrations. Plasma protein levels were significantly lower in exposed fish than in fish from the Ohio River, indicating that exposed fish may have been nutritionally stressed. Condition factors for fish from the ash pond-receiving streams were the same as, or lower than, those of fish from the reference sites. There was no evidence that the growth rate of fish in the receiving streams differed from that of fish in the reference streams. Despite liver selenium concentrations which exceeded reported toxicity thresholds and evidence of significant hematological changes, there were no significant differences in fish condition factors, liver-somatic indices, or length-weight regressions related to selenium.

  15. Seasonal influence on the hematological parameters in cultured Nile tilapia from southern Brazil

    Directory of Open Access Journals (Sweden)

    GT. Jerônimo

    Full Text Available This study evaluated seasonality in hematological parameters of Nile tilapia cultured in the state of Santa Catarina, southern Brazil. A total of 240 fish were examined during four seasons between April 2007 and March 2008 in three different fish farms. After being anesthetised in a benzocaine solution, blood samples were withdrawn into syringes containing a drop of 10% EDTA for hematological analysis. The results were compared between fish farms and seasons, which are well delimited in southern Brazil. In a traditional fish farm in Joinville in the summer, there was an increase in the percentage of hematocrit and in the red blood cell count. The highest values of total leukocytes were found in fish from fee-fishing in Blumenau in the autumn while the lowest values occurred in those from swine consorted system in Ituporanga in the summer. Thrombocytosis was observed in the autumn, and lymphocytosis was found in both the autumn and winter in tilapia from all fish farms investigated. Neutrophilia was only observed in winter and autumn in fish from Blumenau and Ituporanga. This work demonstrated the influence of seasonality and the handling characteristics of each fish farm on certain hematological parameters in Nile tilapia.

  16. [Inhalation of gasoline and damage to health in workers at gas stations]. (United States)

    Pranjić, Nurka; Mujagić, H; Pavlović, S


    The aim of this study was to made assessment of chronic health effects in 37 workers exposed to gasoline, and its constituents at gasoline stations between 1985 and 1996. By the study we have involved thirty-seven persons who had been exposed to gasoline for more than five years were examined. The evaluation included a medical/occupational history, hematological and biochemical examination, a physical exam, standardized psychological tests, and ultrasound examination of kidneys and liver. The groups were identical in other common parameters including age, gender (all men), and level of education (P gasoline unexposed controls and 25 workers at gasoline stations exposed to organic lead for only nine months. Peripheral smear revealed basophilic punctuated eritrocytes and reticulocytosis. We found in chronic exposed gasoline workers haematological disorders: mild leukocytosis (7 of 37), lymphocytosis (20 of 37), mild lymhocytopenia (3 of 37), decrease of red blood cells count (11 of 37). Results indicated that they have suffered from liver disorders: lipoid degeneration of liver (14 of 37), chronic functional damages of liver (3 of 37), cirrhosis (1 of 37). Ultrasound examination indicated chronic kidney damages (8 of 37). These results significantly differed from those of controls (P gasoline stations exposed to gasoline for more than 5 years the symptom of depression and decreased reaction time and motor abilities were identified. The summary of diseases of workers exposed to organic lead and gasoline are discussed.

  17. Psoroptes mites infestation in a captive Burmese Red Serow (Capricornis sumatraensis subspecies rubidus) of Indo-Burma bio-diversity hotspot. (United States)

    Shah, Nirali; Borpojari, Dhrubajyoti; Sarma, Kalyan; Ali, M Ayub; Saikia, Basanta; Bayan, Hitesh; Ahmed, Fazal Ali; Das, Gunjan


    An 8 years old male Burmese Red Serow ( Capricornis sumatraensis sub species rubidus ) from Aizawl Zoological Park was presented to the Teaching Veterinary Clinical Complex. An exploratory skin scraping revealed existence of nymphal as well as adult stages of mites of the Psoroptes spp. which were not associated with any overt lesions typical to mite infestation such as pruritus, erythema or scaling of the epidermis. The mites were identified as per their morphology, size and shape. Haemato-biochemical analysis revealed alteration of certain haematological and biochemical parameters. The red blood corpuscles were found to have anucleate cells with mild to absent central pallor. The absolute counts showed neutrophilic leucocytosis with mild monocytosis and lymphocytosis. Eosinophilic count was towards the higher side, indicating that the infestation was mild. The serum calcium, albumin, triglyceride, urea nitrogen (BUN) were found to be lower than normal, whereas serum ALT, AST, LDH, ALP and serum amylase were higher than the established reference indices. Due to lack of haemato-biochemical reference values specific to captive Serow, emphasis was given in this report to establish baseline data for this species.

  18. [Changes in the peripheral blood of workers engaged in ethylbenzene-styrene and synthetic rubber and latex manufacture]. (United States)

    Khristeva, V


    A total of 67 workers were examined from the production of "Ethyl benzene-styrene" and 184 workers from the production of "Synthetic rubber and latex", as well as a control group of 59 employees. The workers from the first production are exposed to the effect of styrene, ethyl benzene and toluene. The concentrations of the substances surpass MAC, with several times, at the majority of the working places. The workers with a length of service over 10 years predominate. The workers from the second production are exposed to the combined effect of styrene and divinyl, their concentrations fluctuating from 2 to 8 times over MAC. The workers with a length of service over 10 years are 71.7%. The deviations, established in the hematological indices studied are compared with the results from a study on the workers from those productions of 6 years ago. Dynamics in the changes was established among the workers from the production of "Synthetic rubber and latex", associated with the duration of occupational exposure to styrene and divinyl. In case of a shorter length of service, the deviations are functional (reduction of peroxidase activity in granulocytes), increase of hemoglobin and hematocrit, associated with the adaptive reaction of organism. Pronounced anemic syndrome was established in a considerable number (24 workers) after an exposure of 10 years as well as lymphocytosis (35 subjects) and leukopenia (9 subjects).

  19. The Efficacy of Reduced-dose Dasatinib as a Subsequent Therapy in Patients with Chronic Myeloid Leukemia in the Chronic Phase: The LD-CML Study of the Kanto CML Study Group (United States)

    Iriyama, Noriyoshi; Ohashi, Kazuteru; Hashino, Satoshi; Kimura, Shinya; Nakaseko, Chiaki; Takano, Hina; Hino, Masayuki; Uchiyama, Michihiro; Morita, Satoshi; Sakamoto, Junichi; Sakamaki, Hisashi; Inokuchi, Koiti


    Objective The aim of this study was to prospectively investigate the efficacy and safety profiles of low-dose dasatinib therapy (50 mg once daily). Methods Patients with chronic myeloid leukemia in the chronic phase (CML-CP) who were being treated with low-dose imatinib (≤200 mg/day), but were resistant to this agent were enrolled in the current study (referred to as the LD-CML study). Results There subjects included 9 patients (4 men and 5 women); all were treated with dasatinib at a dose of 50 mg once daily. Among 8 patients who had not experienced major molecular response (MMR; BCR-ABL1 transcript ≤0.1% according to International Scale [IS]) at study enrollment, 5 attained MMR by 12 months. In particular, 3 of 9 patients demonstrated a deep molecular response (DMR; IS ≤0.0069%) by 18 months. Five patients developed lymphocytosis accompanied by cytotoxic lymphocyte predominance. There was no mortality or disease progression, and all continue to receive dasatinib therapy at 18 months with only 2 patients requiring dose reduction. Toxicities were mild-to-moderate, and pleural effusion was observed in 1 patient (grade 1). Conclusion Low-dose dasatinib can attain MMR and DMR without severe toxicity in patients with CML-CP who are unable to achieve MMR with low-dose imatinib. Switching to low-dose dasatinib should therefore be considered for patients in this setting, especially if they are otherwise considering a cessation of treatment. PMID:29033428

  20. Sensitization to Gliadin Induces Moderate Enteropathy and Insulitis in Nonobese Diabetic-DQ8 Mice (United States)

    Galipeau, Heather J.; Rulli, Nestor E.; Jury, Jennifer; Huang, Xianxi; Araya, Romina; Murray, Joseph A.; David, Chella S.; Chirdo, Fernando G.; McCoy, Kathy D.; Verdu, Elena F.


    Celiac disease (CD) is frequently diagnosed in patients with type 1 diabetes (T1D), and T1D patients can exhibit Abs against tissue transglutaminase, the auto-antigen in CD. Thus, gliadin, the trigger in CD, has been suggested to have a role in T1D pathogenesis. The objective of this study was to investigate whether gliadin contributes to enteropathy and insulitis in NOD-DQ8 mice, an animal model that does not spontaneously develop T1D. Gliadin-sensitized NOD-DQ8 mice developed moderate enteropathy, intraepithelial lymphocytosis, and barrier dysfunction, but not insulitis. Administration of anti-CD25 mAbs before gliadin-sensitization induced partial depletion of CD25+Foxp3+ T cells and led to severe insulitis, but did not exacerbate mucosal dysfunction. CD4+ T cells isolated from pancreatic lymph nodes of mice that developed insulitis showed increased proliferation and proinflammatory cytokines after incubation with gliadin but not with BSA. CD4+ T cells isolated from nonsensitized controls did not response to gliadin or BSA. In conclusion, gliadin sensitization induced moderate enteropathy in NOD-DQ8 mice. However, insulitis development required gliadin-sensitization and partial systemic depletion of CD25+Foxp3+ T cells. This humanized murine model provides a mechanistic link to explain how the mucosal intolerance to a dietary protein can lead to insulitis in the presence of partial regulatory T cell deficiency. PMID:21911598

  1. Clinical and Histologic Mimickers of Celiac Disease. (United States)

    Kamboj, Amrit K; Oxentenko, Amy S


    Celiac disease is an autoimmune disorder of the small bowel, classically associated with diarrhea, abdominal pain, and malabsorption. The diagnosis of celiac disease is made when there are compatible clinical features, supportive serologic markers, representative histology from the small bowel, and response to a gluten-free diet. Histologic findings associated with celiac disease include intraepithelial lymphocytosis, crypt hyperplasia, villous atrophy, and a chronic inflammatory cell infiltrate in the lamina propria. It is important to recognize and diagnose celiac disease, as strict adherence to a gluten-free diet can lead to resolution of clinical and histologic manifestations of the disease. However, many other entities can present with clinical and/or histologic features of celiac disease. In this review article, we highlight key clinical and histologic mimickers of celiac disease. The evaluation of a patient with serologically negative enteropathy necessitates a carefully elicited history and detailed review by a pathologist. Medications can mimic celiac disease and should be considered in all patients with a serologically negative enteropathy. Many mimickers of celiac disease have clues to the underlying diagnosis, and many have a targeted therapy. It is necessary to provide patients with a correct diagnosis rather than subject them to a lifetime of an unnecessary gluten-free diet.

  2. Clinical survey of blood dyscrasias among Hiroshima A-bomb survivors by the periodical health examination, (4)

    Energy Technology Data Exchange (ETDEWEB)

    Taketomi, Y; Abe, T; Kamada, N; Kuramoto, A; Takahashi, H [Hiroshima Univ. (Japan). Research Inst. for Nuclear Medicine and Biology


    Status of leukopenia in a-bomb survivors was studied on 202 cases in which leukopenia (white cell count of below 3900) was recognized during successive 3 years in the periodical health examination of the fiscal years from 1973 to 1975. A white cell count of below 3900 was recogenized in about 4% of the total subjects of the year, and the half overlapped in other years. Incidence of leukopenia was higher in the aged, and there was not a marked difference according to the distance from the explosion center. As to a relationship to anemia, hemoglobin amount of below 11.5 g/dl was recognized in 98 of 202 cases, and aplastic anemia was recognized in 3 cases under medical treatment. Concerning a relationship to other disease, chronic liver dysfunction was recognized in 33 of 202 cases, and anemia, in 14 cases. As to classification of leukocyte, abnormality (neutrocytopenia, lymphocytosis) was not recognized in 70 of 202 cases. About a relationship to anemia and liver dysfunction in cases of lymphocytic abnormality, the incidence of lymphocytic abnormality was higher in cases of liver dysfunction (23 of 33 cases of chronic liver dysfunction, 69.7%), and there was not difference between cases of anemia alone and cases without anemia and liver dysfunction (54 of 84 cases, 64.3%). The incidence of lymphocytic abnormality was higher in cases of liver dysfunction and cases without anemia.

  3. Bovine lymphocytic leukemia: studies of etiology, pathogenesis, and mode of transmission. Progress report No. 19, June 1978-June 1979

    Energy Technology Data Exchange (ETDEWEB)

    Sorensen, D.K.


    Bovine leukemia is believed to be caused by an oncogenic RNA virus designated bovine leukemia virus (BLV). The presence of BLV particles in lymphocyte cultures from leukemic cattle and cattle with a persistent lymphocytosis has been consistentily demonstrated. Concentrated, cell free, BLV preparations were used to inoculate 12 late stage bovine fetuses (in utero) and two newborn calves. Current studies involve extensive monitoring of these inoculated animals to detect precancerous changes and obtain a detailed description of the events preceding the development of lymphosarcoma. Ongoing monitoring studies will provide a complete record of all changes in the various leukemia associated parameters. We will then be able to detail when, in what sequence, and to what extent each parameter changes in the course of lymphosarcoma development. Fourteen animals were successfully inoculated during the study. Eleven remain alive, and comprise the current monitoring program. All eleven of these animals are definitely infected with BLV, and in nine the infection has substantially progressed with respect to the parameters being monitored. In addition to transmission and monitoring studies, various lymphocyte subpopulations were examined to determine which cell type(s) are involved in the pathogenesis of bovine lymphosarcoma. These studies have conclusively established that B-lymphocytes are the target cells for BLV infection and that they carry the morphologic nuclear abnormality associated with this disease.

  4. Cardiac tamponade mimicking tuberculous pericarditis as the initial presentation of chronic lymphocytic leukemia in a 58-year-old woman: a case report

    Directory of Open Access Journals (Sweden)

    Nathan Sandeep


    Full Text Available Abstract Introduction Chronic lymphocytic leukemia is an indolent disease that often presents with complaints of lymphadenopathy or is detected as an incidental laboratory finding. It is rarely considered in the differential diagnosis of patients presenting with tamponade or a large, bloody pericardial effusion. In patients without known cancer, a large, bloody pericardial effusion raises the possibility of tuberculosis, particularly in patients from endemic areas. However, the signs, symptoms and laboratory findings of pericarditis related to chronic lymphocytic leukemia can mimic tuberculosis. Case Presentation We report the case of a 58-year-old African American-Nigerian woman with a history of travel to Nigeria and a positive tuberculin skin test who presented with cardiac tamponade. She had a mild fever, lymphocytosis and a bloody pericardial effusion, but cultures and stains were negative for acid-fast bacteria. Assessment of blood by flow cytometry and pericardial biopsy by immunohistochemistry revealed CD5 (+ and CD20 (+ lymphocytes in both tissues, demonstrating this to be an unusual manifestation of early stage chronic lymphocytic leukemia. Conclusion Although most malignancies that involve the pericardium clinically manifest elsewhere before presenting with tamponade, this case illustrates the potential for early stage chronic lymphocytic leukemia to present as a large pericardial effusion with tamponade. Moreover, the presentation mimicked tuberculosis. This case also demonstrates that it is possible to treat chronic lymphocytic leukemia-related pericardial tamponade by removal of the fluid without chemotherapy.

  5. Severe dapsone hypersensitivity syndrome in a child

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    So Yoon Choi


    Full Text Available Dapsone (4,4'-diaminodiphenylsulfone, DDS, a potent anti-inflammatory agent, is widely used in the treatment of leprosy and several chronic inflammatory skin diseases. Dapsone therapy rarely results in development of dapsone hypersensitivity syndrome, which is characterized by fever, hepatitis, generalized exfoliative dermatitis, and lymphadenopathy. Here, we describe the case of an 11-year-old Korean boy who initially presented with high fever, a morbilliform skin rash, generalized lymphadenopathy, hepatosplenomegaly, and leukopenia after 6 weeks of dapsone intake. Subsequently, he exhibited cholecystitis, gingivitis, colitis, sepsis, aseptic meningitis, disseminated intravascular coagulation, syndrome of inappropriate antidiuretic hormone secretion, pneumonia, pleural effusions, peritonitis, bronchiectatic changes, exfoliative dermatitis, and acute renal failure. After 2 months of supportive therapy, and prednisolone and antibiotic administration, most of the systemic symptoms resolved, with the exception of exfoliative dermatitis and erythema, which ameliorated over the following 4 months. Agranulocytosis, atypical lymphocytosis, aseptic meningitis, and bronchiectatic changes along with prolonged systemic symptoms with exfoliative dermatitis were the most peculiar features of the present case.

  6. Idelalisib-induced colitis and skin eruption mimicking graft-versus-host disease. (United States)

    Hammami, Muhammad Bader; Al-Taee, Ahmad; Meeks, Marshall; Fesler, Mark; Hurley, M Yadira; Cao, Dengfeng; Lai, Jin-Ping


    Idelalisib is a selective inhibitor of the delta isoform of phosphatidylinositol 3-kinase which was approved by the United States Federal Drug Administration in 2014 for the treatment of relapsed chronic lymphocytic leukemia and indolent non-Hodgkin lymphoma. Drug-induced injury of the gastrointestinal tract is a relatively frequent but usually under-recognized disease entity. We report the case of a 56-year-old male with a history of relapsed follicular lymphoma status post allogenic bone marrow transplant who developed severe diarrhea with a skin eruption mimicking graft-versus-host disease (GVHD) 6 months after starting idelalisib. He underwent a colonoscopy demonstrating a grossly normal-appearing colon and terminal ileum. Biopsies taken during the procedure revealed mild active ileitis, colitis, and proctitis with frequent epithelial apoptosis, and focal intra-epithelial lymphocytosis. Skin biopsies revealed sub-acute spongiotic dermatitis suggestive of either contact dermatitis or an eczematous drug reaction. Symptoms were attributed to idelalisib given their resolution with withdrawal of the drug in conjunction with the skin and colonic biopsies. High clinical suspicion and awareness of the histological features of idelalisib-associated colitis is important to distinguish it from potential mimickers such as GVHD and infectious colitis.

  7. GM2-gangliosidosis variant 0 (Sandhoff-like disease) in a family of Japanese domestic cats. (United States)

    Yamato, O; Matsunaga, S; Takata, K; Uetsuka, K; Satoh, H; Shoda, T; Baba, Y; Yasoshima, A; Kato, K; Takahashi, K; Yamasaki, M; Nakayama, H; Doi, K; Maede, Y; Ogawa, H


    A five-month-old, female Japanese domestic shorthair cat with proportionate dwarfism developed neurological disorders, including ataxia, decreased postural responses and generalised body and head tremors, at between two and five months of age. Leucocytosis due to lymphocytosis with abnormal cytoplasmic vacuolations was observed. The concentration of G(M2)-ganglioside in its cerebrospinal fluid was markedly higher than in normal cats, and the activities of beta-hexosaminidases A and B in its leucocytes were markedly reduced. On the basis of these biochemical data, the cat was diagnosed antemortem with G(M2)-gangliosidosis variant 0 (Sandhoff-like disease). The neurological signs became more severe and the cat died at 10 months of age. Histopathologically, neurons throughout the central nervous system were distended, and an ultrastructural study revealed membranous cytoplasmic bodies in these distended neurons. The compound which accumulated in the brain was identified as G(M2)-ganglioside, confirming G(M2)-gangliosidosis. A family study revealed that there were probable heterozygous carriers in which the activities of leucocyte beta-hexosaminidases A and B were less than half the normal value. The Sandhoff-like disease observed in this family of Japanese domestic cats is the first occurrence reported in Japan.

  8. Splenic marginal zone lymphoma: a review of the clinical presentation, pathology, molecular biology, and management

    Directory of Open Access Journals (Sweden)

    Teixeira Mendes LS


    Full Text Available Larissa Sena Teixeira Mendes,1 Ming-Qing Du,2 Estella Matutes,3 Andrew Wotherspoon11Histopathology Department, Royal Marsden Hospital, London, UK; 2Molecular Malignancy Laboratory and Department of Histopathology, University Hospital NHS Foundation Trust/Division of Molecular Histopathology, Department of Pathology, University of Cambridge, Cambridge, UK; 3Hematopathology Unit, Hospital Clinic, Barcelona University, Barcelona, Spain Abstract: Splenic marginal zone lymphoma is a distinct low grade B-cell lymphoma primarily occurring in the spleen and separate from nodal marginal zone lymphoma and extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue. It is characterized by a relative indolent course, splenomegaly, moderate lymphocytosis, and an intrasinusoidal pattern of involvement, especially in the bone marrow. It is postulated that the neoplastic clone originates from persistent antigenic stimulation of marginal zone B-cells. Molecular and cytogenetic studies have failed to show specific alterations. There is no standard criterion to initiate treatment, which may include a watch and wait policy, splenectomy, or chemo/immunotherapy. This review highlights the main features of this entity, reassessing the guidelines for diagnosis, prognostic factors, staging, and management published by the SMZL Working Group (2008. Keywords: splenectomy, villous lymphocytes, guidelines

  9. Lumbar Ureteral Stenosis due to Endometriosis: Our Experience and Review of the Literature

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    Salvatore Butticè


    Full Text Available Endometriosis is a chronic gynaecological disorder characterized by the presence of endometrial tissue outside the uterus. The disease most often affects the ovaries, uterine ligaments, fallopian tubes, and cervical-vaginal region. Urinary tract involvement is rare, accounting for around 1%-2% of all cases, of which 84% are in the bladder. We report a case of isolated lumbar ureteral stenosis due to endometriosis in a 37-year-old patient. The patient came to our observation complaining from lumbar back pain and presented with severe fever. The urological examination found monolateral left positive sign of Giordano. Blood tests evidenced marked lymphocytosis and increased valued of C-reactive protein. Urologic ultrasound showed hydronephrosis of first degree in the left kidney and absence of images related to stones bilaterally. Uro-CT scan evidenced ureteral stenosis at the transition between the iliac and pelvic tracts. We addressed the patient to surgery, and performed laparoscopic excision of the paraureteral bulk, endoscopic mechanical ureteral dilation, and stenting. The histological examination evidenced glandular structures lined by simple epithelium and surrounded by stroma. Immunohistochemical test of the glandular epithelium showed positivity for estrogen and progesterone receptors and moreover stromal cells were positive for CD10. The finding suggested a very rare diagnosis of isolated lumbar ureteral endometriosis.

  10. Biological rational for sequential targeting of Bruton tyrosine kinase and Bcl-2 to overcome CD40-induced ABT-199 resistance in mantle cell lymphoma. (United States)

    Chiron, David; Dousset, Christelle; Brosseau, Carole; Touzeau, Cyrille; Maïga, Sophie; Moreau, Philippe; Pellat-Deceunynck, Catherine; Le Gouill, Steven; Amiot, Martine


    The aggressive biological behavior of mantle cell lymphoma (MCL) and its short response to current treatment highlight a great need for better rational therapy. Herein, we investigate the ability of ABT-199, the Bcl-2-selective BH3 mimetic, to kill MCL cells. Among MCL cell lines tested (n = 8), only three were sensitive (LD50 < 200 nM). In contrast, all primary MCL samples tested (n = 11) were highly sensitive to ABT-199 (LD50 < 10 nM). Mcl-1 and Bcl-xL both confer resistance to ABT-199-specific killing and BCL2/(BCLXL+MCL1) mRNA ratio is a strong predictor of sensitivity. By mimicking the microenvironment through CD40 stimulation, we show that ABT-199 sensitivity is impaired through activation of NF-kB pathway and Bcl-x(L) up-regulation. We further demonstrate that resistance is rapidly lost when MCL cells detach from CD40L-expressing fibroblasts. It has been reported that ibrutinib induces lymphocytosis in vivo holding off malignant cells from their protective microenvironment. We show here for two patients undergoing ibrutinib therapy that mobilized MCL cells are highly sensitive to ABT-199. These results provide evidence that in situ ABT-199 resistance can be overcome when MCL cells escape from the lymph nodes. Altogether, our data support the clinical application of ABT-199 therapy both as a single agent and in sequential combination with BTK inhibitors.


    Lindemann, Dana M; Carpenter, James W; Nietfeld, Jerome C; Gonzalez, Estehela; Hallman, Mackenzie; Hause, Ben M


    A 13-yr-old intact male cheetah (Acinonyx jubatus) presented for evaluation after a 4-mo history of intermittent lethargy and increased expiratory effort. The clinical signs were initially noted after the diagnosis and death of its 13-yr-old male sibling with solitary hepatic T-cell lymphoma. Physical examination findings included thin body condition, harsh lung sounds, peripheral lymphadenopathy, and a cutaneous mass on the right medial tarsus and scrotum. Excisional biopsies diagnosed well-differentiated cutaneous hemangiosarcomas. Thoracic radiographs revealed a cranial mediastinal mass. Complete blood count and serum biochemical analyses showed a leukocytosis with persistent lymphocytosis, progressive azotemia, and markedly elevated alkaline phosphatase. Because of the cheetah's declining quality of life, euthanasia was elected. Postmortem examination, histopathology, and immunohistochemical staining revealed multicentric T-cell lymphoma. Feline leukemia virus (FeLV) enzyme-linked immunosorbent assay, FeLV polymerase chain reaction (whole blood), and viral metagenomic analysis were negative. This is the first case of cutaneous hemangiosarcoma and multicentric T-cell lymphoma reported in a FeLV-negative cheetah.

  12. Increased Aqueous Humor CD4+/CD8+ Lymphocyte Ratio in Sarcoid Uveitis. (United States)

    Dave, Namita; Chevour, Priyanka; Mahendradas, Padmamalini; Venkatesh, Anitha; Kawali, Ankush; Shetty, Rohit; Ghosh, Arkasubhra; Sethu, Swaminathan


    To determine aqueous humor CD4+/CD8+ T-lymphocyte ratio changes in sarcoid and non-sarcoid uveitis with anterior chamber involvement. The case-control study includes 61 patients with either anterior uveitis, intermediate uveitis with anterior spill, or panuveitis. A total of 21 of them were categorized as sarcoid uveitis and 40 as non-sarcoid uveitis according to diagnostic criteria. CD4+/CD8+ ratio in the aqueous humor was determined using flow cytometry. Significantly higher CD4+/CD8+ ratio in the aqueous humor was observed in patients with sarcoid uveitis (6.3 ± 1.4; mean ± SEM) compared to non-sarcoid uveitis (1.6 ± 0.1; mean ± SEM). Whole blood CD4+/CD8+ ratio was not elevated in subjects with sarcoid and non-sarcoid uveitis. Aqueous humor CD4+/CD8+ ratio >3.5 was observed to be associated with sarcoid uveitis (OR 38, 95% CI 7.0-205.2). Increased aqueous humor CD4+/CD8+ ratio in sarcoid uveitis. Immunophenotyping of localized lymphocytosis in aqueous humor could be utilized as an additional confirmatory marker for ocular sarcoidosis.

  13. Clinical survey of blood dyscrasias among Hiroshima A-bomb survivors by the periodical health examination, (4)

    International Nuclear Information System (INIS)

    Taketomi, Yoshinori; Abe, Tsutomu; Kamada, Nanao; Kuramoto, Atsushi; Takahashi, Hiroshi


    Status of leukopenia in a-bomb survivors was studied on 202 cases in which leukopenia (white cell count of below 3900) was recognized during successive 3 years in the periodical health examination of the fiscal years from 1973 to 1975. A white cell count of below 3900 was recogenized in about 4% of the total subjects of the year, and the half overlapped in other years. Incidence of leukopenia was higher in the aged, and there was not a marked difference according to the distance from the explosion center. As to a relationship to anemia, hemoglobin amount of below 11.5 g/dl was recognized in 98 of 202 cases, and aplastic anemia was recognized in 3 cases under medical treatment. Concerning a relationship to other disease, chronic liver dysfunction was recognized in 33 of 202 cases, and anemia, in 14 cases. As to classification of leukocyte, abnormality (neutrocytopenia, lymphocytosis) was not recognized in 70 of 202 cases. About a relationship to anemia and liver dysfunction in cases of lymphocytic abnormality, the incidence of lymphocytic abnormality was higher in cases of liver dysfunction (23 of 33 cases of chronic liver dysfunction, 69.7%), and there was not difference between cases of anemia alone and cases without anemia and liver dysfunction (54 of 84 cases, 64.3%). The incidence of lymphocytic abnormality was higher in cases of liver dysfunction and cases without anemia. (Tsunoda, M.)

  14. Myocarditis exacerbation in a child undergoing inguinal hernioplasty after viral infection

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    Simić Dušica


    Full Text Available Introduction Immunosuppressive effects of general anesthesia and surgery could have unexpected consequences in a child with recent infection. The incidence of myocarditis in childhood is unknown. Case outline During general anesthesia for inguinal hernia repair, a seven-year-old boy suddenly developed heart failure. Clinical presentation included hypotension, pulmonary edema, drop in hemoglobin oxygen saturation, ST segment elevation and premature ventricular contractions. Homodynamic stability and adequate oxygenation were achieved with dopamine and furosemide. Preoperative history, physical examination and complete blood count were unremarkable. Moderate cardiomegaly and pulmonary edema were present on chest radiography. Diminished left ventricular contractility found on echocardiography increased troponin I and CK-MB levels suggested myocardial injury. Increased C-reactive protein with lymphocytosis suggested inflammation as its cause. Parents failed to report rubella 10 days before the operation. A clinical diagnosis of myocarditis as a complication of rubella was based on increased titer of IgM to rubella. With intravenous immunoglobulin, corticosteroids and symptomatic treatment for heart failure, his condition improved and ejection fraction reached 68 % one month after operation. Conclusion In future, we need protocols with instructions for pediatric patients undergoing elective surgery and anesthesia after viral infections.

  15. Large granular lymphocytic leukaemia complicated with histiocytic sarcoma in a dog : clinical communication

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    T. Maruo


    Full Text Available A 10-year-old castrated male Golden retriever, weighing 36.3 kg was referred for evaluation owing to a decline in general condition. Findings from the complete blood count revealed a marked lymphocytosis (113 000/µℓ. Examination of Wright-Giemsa-stained films of peripheral blood revealed the presence of large granular lymphocytes (LGL. Seventy-two per cent (81 360/µℓ of the lymphocytes were found to be 12-17 µm in diameter, containing nuclei with mature clumped chromatin and abundant lightly basophilic cytoplasm with a variable number of fine azurophilic granules. Based on these findings this case was diagnosed as LGL leukaemia. As a result of multiple-agent chemotherapy, the markedly elevated levels of lymphocytes gradually decreased to 7500/µℓ on day 122 and the patient maintained a good quality of life for the following 3 months. However, on around day 237, a soft, raised, bosselated mass on the labial region was noted. The dog was diagnosed as having histiocytic sarcoma based on cytological and histological examination of the mass. Shortly after diagnosis, the dog developed sudden onset of central nervous system signs and died on day 270. A common outcome of canine LGL is the development of acute blast crisis or lymphoma. However, this case was notable for complication with histiocytic sarcoma from another origin.


    Directory of Open Access Journals (Sweden)

    Z.I, Qureshi, L.A. Lodhi, H.A. Samad, N.A. Naz1 and M. Nawaz


    Full Text Available Thirty-two adult riverine buffaloes (Buhalis bubalus in their last trimester of pregnancy were selected and randomly divided into four groups. The buffaloes of group I served as control. Animals in group II, III and IV were treated twice (7 days apart with levamisole hydrochloride (0.5mg/kg b. w. orally, Etosol (Vit E+Se, 10ml, I/m and Bacilli Calmette Guerine (BCG (0.5 ml/animal, s/c, respectively. Blood samples were collected at weekly intervals starting day 0 untill parturition. Total erythrocytic count and packed cell volume values were higher (P<0.05 in levamisole and vit E+Se treated group of buffaloes. Haemoglobin concentration was higher (P<0.05 inVit E+Se treated group. MCV, MCH and MCHC remained unchanged among all the experimental groups. Total leukocyte count was higher (P<0.05 in levamisole treated group of buffaloes. Differential leukocyte counts (relative revealed moderate lymphocytosis in all immunomodulated groups with significantly higher counts in Vit E+Se treated buffaloes. It was inferred that levamisole and vit E-se altered some haematological values, whereas BCG did not affect the haematological parameters.

  17. Nickel nanoparticles exposure and reproductive toxicity in healthy adult rats. (United States)

    Kong, Lu; Tang, Meng; Zhang, Ting; Wang, Dayong; Hu, Ke; Lu, Weiqi; Wei, Chao; Liang, Geyu; Pu, Yuepu


    Nickel is associated with reproductive toxicity. However, the reproductive toxicity of nickel nanoparticles (Ni NPs) is unclear. Our goal was to determine the association between nickel nanoparticle exposure and reproductive toxicity. According to the one-generation reproductive toxicity standard, rats were exposed to nickel nanoparticles by gavage and we selected indicators including sex hormone levels, sperm motility, histopathology, and reproductive outcome etc. Experimental results showed nickel nanoparticles increased follicle stimulating hormone (FSH) and luteinizing hormone (LH), and lowered etradiol (E2) serum levels at a dose of 15 and 45 mg/kg in female rats. Ovarian lymphocytosis, vascular dilatation and congestion, inflammatory cell infiltration, and increase in apoptotic cells were found in ovary tissues in exposure groups. For male rats, the weights decreased gradually, the ratio of epididymis weight over body weight increased, the motility of rat sperm changed, and the levels of FSH and testosterone (T) diminished. Pathological results showed the shedding of epithelial cells of raw seminiferous tubule, disordered arrangement of cells in the tube, and the appearance of cell apoptosis and death in the exposure group. At the same time, Ni NPs resulted in a change of the reproductive index and the offspring development of rats. Further research is needed to elucidate exposure to human populations and mechanism of actions.

  18. The Bruton tyrosine kinase inhibitor PCI-32765 thwarts chronic lymphocytic leukemia cell survival and tissue homing in vitro and in vivo (United States)

    Ponader, Sabine; Chen, Shih-Shih; Buggy, Joseph J.; Balakrishnan, Kumudha; Gandhi, Varsha; Wierda, William G.; Keating, Michael J.; O'Brien, Susan; Chiorazzi, Nicholas


    B-cell receptor (BCR) signaling is a critical pathway in the pathogenesis of several B-cell malignancies, including chronic lymphocytic leukemia (CLL), and can be targeted by inhibitors of BCR-associated kinases, such as Bruton tyrosine kinase (Btk). PCI-32765, a selective, irreversible Btk inhibitor, is a novel, molecularly targeted agent for patients with B-cell malignancies, and is particularly active in patients with CLL. In this study, we analyzed the mechanism of action of PCI-32765 in CLL, using in vitro and in vivo models, and performed correlative studies on specimens from patients receiving therapy with PCI-32765. PCI-32765 significantly inhibited CLL cell survival, DNA synthesis, and migration in response to tissue homing chemokines (CXCL12, CXCL13). PCI-32765 also down-regulated secretion of BCR-dependent chemokines (CCL3, CCL4) by the CLL cells, both in vitro and in vivo. In an adoptive transfer TCL1 mouse model of CLL, PCI-32765 affected disease progression. In this model, PCI-32765 caused a transient early lymphocytosis, and profoundly inhibited CLL progression, as assessed by weight, development, and extent of hepatospenomegaly, and survival. Our data demonstrate that PCI-32765 effectively inhibits CLL cell migration and survival, possibly explaining some of the characteristic clinical activity of this new targeted agent. PMID:22180443

  19. Rearrangements of genes for the antigen receptor on T cells as markers of lineage and clonality in human lymphoid neoplasms. (United States)

    Waldmann, T A; Davis, M M; Bongiovanni, K F; Korsmeyer, S J


    The T alpha and T beta chains of the heterodimeric T-lymphocyte antigen receptor are encoded by separated DNA segments that recombine during T-cell development. We have used rearrangements of the T beta gene as a widely applicable marker of clonality in the T-cell lineage. We show that the T beta genes are used in both the T8 and T4 subpopulations of normal T cells and that Sézary leukemia, adult T-cell leukemia, and the non-B-lineage acute lymphoblastic leukemias are clonal expansions of T cells. Furthermore, circulating T cells from a patient with the T8-cell-predominantly lymphocytosis associated with granulocytopenia are shown to be monoclonal. Finally, the sensitivity and specificity of this tumor-associated marker have been exploited to monitor the therapy of a patient with adult T-cell leukemia. These unique DNA rearrangements provide insights into the cellular origin, clonality, and natural history of T-cell neoplasia.

  20. Rat allotransplantation of epigastric microsurgical flaps: a study of rejection and the immunosuppressive effect of cyclosporin A

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    Carramaschi Fábio R.


    Full Text Available The rejection of allotransplantation of epigastric microsurgical flaps and the effect of immunosuppression have been studied in 58 rats. Three sets of experiments were planned: (1 Wistar Furth isogenic donors and receptors (control set; (2 Brown Norway donors and Wistar Furth receptors (rejection set; and (3 Brown Norway donors and Wistar Furth immunosuppressed receptors (cyclosporin A set. Cyclosporin A (10 mg/kg/d treated rats had a transplantation survival rate of up to 30 days: 83.3% among isogenic animals and 60% among allogeneic. There was 100% rejection by the 9th day after the transplantation in allogeneic non-immunosuppressed rats. Biopsies embedded with historesin were taken from the flap and normal contralateral skin (used as control on the 3rd, 7th, 15th, and 30th days after the surgery. A quantitative study of infiltrating lymphocytes in the flaps, with and without cyclosporin A, was done by evaluating the local inflammatory infiltrate. A significant increase in the number of lymphocytes among the rejection and immunosuppressed groups was seen, as compared to the isogenic set. Local lymphocytosis in allogeneic non-immunosuppressed transplantations reached its highest level on the 3rd day after surgery, before gross findings of rejection, which could only be seen by naked eye on the 5th or 6th day. Therefore, we conclude that cyclosporin A is effective in preserving allogenic transplantation in rats. Biopsies of transplanted areas may contribute to earlier diagnosis of the need for immunosuppressive therapy.

  1. Primary angiitis of the central nervous system: an ante-mortem diagnosis.

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    Singh S


    Full Text Available A rare case of primary angiitis of the central nervous system (PACNS is reported with its clinical and magnetic resonance imaging (MRI features. A 20-year-old girl presented with headache, projectile vomiting, unsteadiness of gait and urgency of micturition. She had left seventh nerve upper motor neuron type paresis, increased tone in all four limbs, exaggerated deep tendon reflexes, cerebellar signs, and papilloedema. Cerebrospinal fluid showed lymphocytosis with elevated protein and normal glucose level. Cerebral computerised tomographic scan and MRI showed bilateral diffuse asymmetric supra- and infra-tentorial lesions (predominantly in the supratentorial and left cerebrum. On MRI, the lesions were hyperintense on T2, and proton density-weighted images and hypointense on T1-weighted images. Based on the clinical findings of raised intracranial tension and MRI features, initial diagnoses of gliomatosis cerebrii, tuberculous meningitis, primary central nervous system lymphoma and chronic viral encephalitis were considered. PACNS was not included in the initial differentials and, an open brain biopsy was advised which established the definitive diagnosis.

  2. Ibrutinib in combination with rituximab in relapsed or refractory mantle cell lymphoma: a single-centre, open-label, phase 2 trial. (United States)

    Wang, Michael L; Lee, Hun; Chuang, Hubert; Wagner-Bartak, Nicolaus; Hagemeister, Frederick; Westin, Jason; Fayad, Luis; Samaniego, Felipe; Turturro, Francesco; Oki, Yasuhiro; Chen, Wendy; Badillo, Maria; Nomie, Krystle; DeLa Rosa, Maria; Zhao, Donglu; Lam, Laura; Addison, Alicia; Zhang, Hui; Young, Ken H; Li, Shaoying; Santos, David; Medeiros, L Jeffrey; Champlin, Richard; Romaguera, Jorge; Zhang, Leo


    Ibrutinib is approved in the EU, USA, and other countries for patients with mantle cell lymphoma who received one previous therapy. In a previous phase 2 study with single-agent ibrutinib, the proportion of patients who achieved an objective response was 68%; 38 (34%) of 111 patients had transient lymphocytosis. We hypothesised that adding rituximab could target mantle cell lymphoma cells associated with redistribution lymphocytosis, leading to more potent antitumour activity. Patients with a confirmed mantle cell lymphoma diagnosis (based on CD20-positive and cyclin D1-positive cells in tissue biopsy specimens), no upper limit on the number of previous treatments received, and an Eastern Cooperative Oncology Group performance status score of 2 or less were enrolled in this single-centre, open-label, phase 2 study. Patients received continuous oral ibrutinib (560 mg) daily until progressive disease or unacceptable toxic effects. Rituximab 375 mg/m(2) was given intravenously once per week for 4 weeks during cycle 1, then on day 1 of cycles 3-8, and thereafter once every other cycle up to 2 years. The primary endpoint was the proportion of patients who achieved an objective response in the intention-to-treat population and safety assessed in the as-treated population. The study is registered with, number NCT01880567, and is still ongoing, but no longer accruing patients. Between July 15, 2013, and June 30, 2014, 50 patients were enrolled. Median age was 67 years (range 45-86), and the median number of previous regimens was three (range 1-9). At a median follow-up of 16·5 months (IQR 12·09-19·28), 44 (88%, 95% CI 75·7-95·5) patients achieved an objective response, with 22 (44%, 30·0-58·7) patients achieving a complete response, and 22 (44%, 30·0-58·7) a partial response. The only grade 3 adverse event in >=10% of patients was atrial fibrillation, which was noted in six (12%) patients. Grade 4 diarrhoea and neutropenia occurred in one

  3. Asymptomatic Primary Infection with Epstein-Barr Virus: Observations on Young Adult Cases. (United States)

    Abbott, Rachel J; Pachnio, Annette; Pedroza-Pacheco, Isabela; Leese, Alison M; Begum, Jusnara; Long, Heather M; Croom-Carter, Debbie; Stacey, Andrea; Moss, Paul A H; Hislop, Andrew D; Borrow, Persephone; Rickinson, Alan B; Bell, Andrew I


    Epstein-Barr virus (EBV) is typically acquired asymptomatically in childhood. In contrast, infection later in life often leads to infectious mononucleosis (IM), a febrile illness characterized by anti-EBV IgM antibody positivity, high loads of circulating latently infected B cells, and a marked lymphocytosis caused by hyperexpansion of EBV-specific CD8 + T cells plus a milder expansion of CD56 dim NKG2A + KIR - natural killer (NK) cells. How the two situations compare is unclear due to the paucity of studies on clinically silent infection. Here we describe five prospectively studied patients with asymptomatic infections identified in a seroepidemiologic survey of university entrants. In each case, the key blood sample had high cell-associated viral loads without a marked CD8 lymphocytosis or NK cell disturbance like those seen in patients during the acute phase of IM. Two of the cases with the highest viral loads showed a coincident expansion of activated EBV-specific CD8 + T cells, but overall CD8 + T cell numbers were either unaffected or only mildly increased. Two cases with slightly lower loads, in whom serology suggests the infection may have been caught earlier in the course of infection, also showed no T or NK cell expansion at the time. Interestingly, in another case with a higher viral load, in which T and NK cell responses were undetectable in the primary blood sample in which infection was detected, EBV-specific T cell responses did not appear until several months later, by which time the viral loads in the blood had already fallen. Thus, some patients with asymptomatic primary infections have very high circulating viral loads similar to those in patients during the acute phase of IM and a cell-mediated immune response that is qualitatively similar to that in IM patients but of a lower magnitude. However, other patients may have quite different immune responses that ultimately could reveal novel mechanisms of host control. IMPORTANCE Epstein-Barr virus

  4. Does This Patient Have Infectious Mononucleosis?: The Rational Clinical Examination Systematic Review. (United States)

    Ebell, Mark H; Call, Marlene; Shinholser, JoAnna; Gardner, Jack


    , 0.71-0.99; positive LR range, 1.9-6.6). Symptoms are of limited value for the diagnosis of mononucleosis; sore throat and fatigue are sensitive (range, 0.81-0.83) but nonspecific. The presence of atypical lymphocytosis significantly increases the likelihood of mononucleosis (summary LR, 11.4 [95% CI, 2.7-35] for atypical lymphocytes ≥10%, 26 [95% CI, 9.6-68] for those with 20%, and 50 [95% CI, 38-64] for those with 40%). The combination of a patient having greater than 50% lymphocytes and greater than 10% atypical lymphocytes also is useful (specificity, 0.99; positive LR, 54 [95% CI, 8.4-189]). In adolescent and adult patients presenting with sore throat, the presence of posterior cervical, inguinal or axillary adenopathy, palatine petechiae, splenomegaly, or atypical lymphocytosis is associated with an increased likelihood of mononucleosis.

  5. Swiss cheese ventricular septal defect with myocarditis - A rare coexistence in a neonate

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    A R Saboo


    Full Text Available Myocarditis is defined as acute inflammation of the myocardium, usually following a non-specific flu-like illness, and encompasses a wide range of clinical presentations ranging from mild or subclinical disease to heart failure. We report a 12-day-old healthy full-term neonate who presented with abrupt onset of congestive cardiac failure (CCF following a viral prodrome. Examination revealed persistent sinus tachycardia, lymphocytosis, gross cardiomegaly, nonspecific electrocardiogram changes with echocardiography showing Swiss cheese ventricular septal defect (VSD. VSD alone very rarely presents as early-onset cardiac failure in the absence of other precipitating factors like anemia, sepsis, hypoglycemia etc. Myocarditis, however, can mimic VSD and can present as fulminant cardiac failure in an otherwise healthy newborn. Myocarditis is usually diagnosed based on circumstantial evidence such as a recent viral infection and the sudden onset of cardiac dysfunction while ruling out other diagnostic possibilities. Elevated troponin T level is one of the most crucial noninvasive diagnostic modalities. Several trials have concluded that levels >0.055 ng/ml are statistically significant for diagnosing myocarditis in children. In our case an abrupt onset of cardiac failure following a viral prodrome and markedly elevated cardiac troponin T without sepsis and in the presence of normal coronary anatomy clinched the diagnosis of myocarditis. An early and aggressive treatment for CCF along with regular long-term follow-up plays a key role in the management of myocarditis. Role of high-dose Intravenous immunoglobulin in myocarditis has been studied by many trials with different outcomes. This is the first case report showing coexistence of VSD with myocarditis in a neonate presenting as early-onset acute cardiac failure. The report highlights the importance of screening for myocarditis in all previously normal babies presenting primarily with cardiogenic

  6. [Lower lymphocyte response in severe cases of acute bronchiolitis due to respiratory syncytial virus]. (United States)

    Ramos-Fernández, José Miguel; Moreno-Pérez, David; Antúnez-Fernández, Cristina; Milano-Manso, Guillermo; Cordón-Martínez, Ana María; Urda-Cardona, Antonio


    Acute bronchiolitis (AB) of the infant has a serious outcome in 6-16% of the hospital admitted cases. Its pathogenesis and evolution is related to the response of the T lymphocytes. The objective of the present study is to determine if the lower systemic lymphocytic response is related to a worse outcome of AB in hospitalised infants. Retrospective observational-analytical study of cases-controls nested in a cohort of patients admitted due to RSV-AB between the period from October 2010 to March 2015. Those with a full blood count in the first 48hours of respiratory distress were included. Infants with underlying disease, bacterial superinfection, and premature infants <32 weeks of gestation were excluded. The main dichotomous variable was PICU admission. Other variables were: gender, age, post-menstrual age, gestational and post-natal tobacco exposure, admission month, type of lactation, and days of onset of respiratory distress. Lymphocyte counts were categorised by quartiles. Bivariate analysis was performed with the main variable and then by logistic regression to analyse confounding factors. The study included 252 infants, of whom 6.6% (17) required PICU admission. The difference in mean±SD of lymphocytes for patients admitted to and not admitted to PICU was 4,044±1755 and 5,035±1786, respectively (Student-t test, P<.05). An association was found between PICU admission and lymphocyte count <3700/ml (Chi-squared, P=.019; OR: 3.2) and it was found to be maintained in the logistic regression, regardless of age and all other studied factors (Wald 4.191 P=.041, OR: 3.8). A relationship was found between lymphocytosis <3700/ml in the first days of respiratory distress and a worse outcome in previously healthy infants <12 months and gestational age greater than 32 weeks with RSV-AB. Copyright © 2017. Publicado por Elsevier España, S.L.U.

  7. Defective immunoregulatory T-cell function in chronic lymphocytic leukemia

    International Nuclear Information System (INIS)

    Han, T.; Ozer, H.; Henderson, E.S.; Dadey, B.; Nussbaum-Blumenson, A.; Barcos, M.


    Chronic lymphocytic leukemia (CLL) of B-cell origin results in the malignant proliferation of small immunoglobulin-bearing lymphocytes. There is currently a controversy in the literature regarding both the ability of this leukemic population to differentiate into mature plasma cells, as well as the ability of apparently normal T cells from these patients to regulate allogeneic B-cell differentiation. In the present study we have examined the lymphocytes of CLL patients in various clinical stages of their disease and with different surface phenotypes of their leukemic B-cell population. Our results show that leukemic CLL B cells from all 20 patients (including one patient with a monoclonal IgM paraprotein and another with a monoclonal IgG paraprotein) are incapable of further differentiation even in the absence of suppressor T cells and the presence of helper T lymphocytes. This lack of capacity to differentiate is unaffected by clinical stage, by therapy, or by the phenotype of the malignant population. Since the leukemic B population did not suppress normal allogeneic B-cell differentiation, the maturation deficit is evidently intrinsic to the leukemic clone rather than a result of activity of non-T suppressor cells. T helper function was also variably depressed in the blood of some patients with CLL, and this depression did not correlate with clinical stage, with therapy, or with the degree of lymphocytosis. Dysfunction of radiosensitive T suppressor cells was found to be the most consistent regulatory deficit of CLL T cells. Each of 11 patients whose leukemic cell population was of the μdelta, μα, or μ phenotype had both helper and suppressor cell defects

  8. Multidimensional scaling analysis identifies pathological and prognostically relevant profiles of circulating T-cells in chronic lymphocytic leukemia. (United States)

    Rissiek, Anne; Schulze, Christian; Bacher, Ulrike; Schieferdecker, Aneta; Thiele, Benjamin; Jacholkowski, Anita; Flammiger, Anna; Horn, Christiane; Haag, Friedrich; Tiegs, Gisa; Zirlik, Katja; Trepel, Martin; Tolosa, Eva; Binder, Mascha


    Antitumor immunity in chronic lymphocytic leukemia (CLL) is hampered by highly dysfunctional T-cells. Although certain T-cell subsets have been reported to be of prognostic significance in this disease, their interplay is complex and it remains incompletely understood which of these subsets significantly drive CLL progression. Here, we determined immunological profiles of 24 circulating T-cell subsets from 79 untreated individuals by multiparametric flow cytometry. This screening cohort included healthy donors, patients with monoclonal B-cell lymphocytosis (MBL), Rai 0 CLL and advanced CLL. We applied multidimensional scaling analysis as rigorous and unbiased statistical tool to globally assess the composition of the circulating T-cell environment and to generate T-cell scores reflecting its integrity. These scores allowed clear distinction between advanced CLL and healthy controls, whereas both MBL and Rai 0 CLL showed intermediate scores mirroring the biological continuum of CLL and its precursor stages. T-cell stimulation and suppression assays as well as longitudinal T-cell profiling showed an increasingly suppressive regulatory function initiating at the MBL stage. Effector function was impaired only after transition to CLL and partially recovered after chemoimmunotherapy. In an independent validation cohort of 52 untreated CLL cases, aberrant T-cell profiles were significantly associated with shorter time to treatment independently of other prognostic parameters. Random forest modeling predicted regulatory T-cell, gamma/delta and NKT-cells, as well as exhaustion of the CD8+ subset as potential drivers of progression. Our data illustrate a pathological T-cell environment in MBL that evolves toward a more and more suppressive and prognostically relevant profile across the disease stages. © 2014 UICC.

  9. Bovine leukemia virus reduces anti-viral cytokine activities and NK cytotoxicity by inducing TGF-β secretion from regulatory T cells. (United States)

    Ohira, Kosuke; Nakahara, Ayako; Konnai, Satoru; Okagawa, Tomohiro; Nishimori, Asami; Maekawa, Naoya; Ikebuchi, Ryoyo; Kohara, Junko; Murata, Shiro; Ohashi, Kazuhiko


    CD4(+)CD25(high)Foxp3(+) T cells suppress excess immune responses that lead to autoimmune and/or inflammatory diseases, and maintain host immune homeostasis. However, CD4(+)CD25(high)Foxp3(+) T cells reportedly contribute to disease progression by over suppressing immune responses in some chronic infections. In this study, kinetic and functional analyses of CD4(+)CD25(high)Foxp3(+) T cells were performed in cattle with bovine leukemia virus (BLV) infections, which have reported immunosuppressive characteristics. In initial experiments, production of the Th1 cytokines IFN-γ and TNF-α was reduced in BLV-infected cattle compared with uninfected cattle, and numbers of IFN-γ or TNF-α producing CD4(+) T cells decreased with disease progression. In contrast, IFN-γ production by NK cells was inversely correlated with BLV proviral loads in infected cattle. Additionally, during persistent lymphocytosis disease stages, NK cytotoxicity was depressed as indicated by low expression of the cytolytic protein perforin. Concomitantly, total CD4(+)CD25(high)Foxp3(+) T cell numbers and percentages of TGF-β(+) cells were increased, suggesting that TGF-β plays a role in the functional declines of CD4(+) T cells and NK cells. In further experiments, recombinant bovine TGF-β suppressed IFN-γ and TNF-α production by CD4(+) T cells and NK cytotoxicity in cultured cells. These data suggest that TGF-β from CD4(+)CD25(high)Foxp3(+) T cells is immunosuppressive and contributes to disease progression and the development of opportunistic infections during BLV infection.

  10. BL-7010 demonstrates specific binding to gliadin and reduces gluten-associated pathology in a chronic mouse model of gliadin sensitivity.

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    Justin L McCarville

    Full Text Available Celiac disease (CD is an autoimmune disorder in individuals that carry DQ2 or DQ8 MHC class II haplotypes, triggered by the ingestion of gluten. There is no current treatment other than a gluten-free diet (GFD. We have previously shown that the BL-7010 copolymer poly(hydroxyethyl methacrylate-co-styrene sulfonate (P(HEMA-co-SS binds with higher efficiency to gliadin than to other proteins present in the small intestine, ameliorating gliadin-induced pathology in the HLA-HCD4/DQ8 model of gluten sensitivity. The aim of this study was to investigate the efficiency of two batches of BL-7010 to interact with gliadin, essential vitamins and digestive enzymes not previously tested, and to assess the ability of the copolymer to reduce gluten-associated pathology using the NOD-DQ8 mouse model, which exhibits more significant small intestinal damage when challenged with gluten than HCD4/DQ8 mice. In addition, the safety and systemic exposure of BL-7010 was evaluated in vivo (in rats and in vitro (genetic toxicity studies. In vitro binding data showed that BL-7010 interacted with high affinity with gliadin and that BL-7010 had no interaction with the tested vitamins and digestive enzymes. BL-7010 was effective at preventing gluten-induced decreases in villus-to-crypt ratios, intraepithelial lymphocytosis and alterations in paracellular permeability and putative anion transporter-1 mRNA expression in the small intestine. In rats, BL-7010 was well-tolerated and safe following 14 days of daily repeated administration of 3000 mg/kg. BL-7010 did not exhibit any mutagenic effect in the genetic toxicity studies. Using complementary animal models and chronic gluten exposure the results demonstrate that administration of BL-7010 is effective and safe and that it is able to decrease pathology associated with gliadin sensitization warranting the progression to Phase I trials in humans.


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    Jameel Al-Ghazaly


    Full Text Available Background and objectives: Delay in the diagnosis of visceral leishmaniasis (VL particularly in non-endemic areas is associated with higher mortality. In our experience, we found that marked bone marrow eosinopenia was a very frequent accompaniment of VL and might be a useful clue for the diagnosis, which indicates the opportunity for further morphological assessment. The aim of this study was to describe the hematological characteristics including peripheral blood and bone marrow findings of Yemeni adults and children with VL. Methods: We conducted a descriptive analytic study to evaluate systematically peripheral blood and bone marrow findings of Yemeni adults and children with VL. Peripheral blood and bone marrow aspiration of patients with bone marrow aspirate confirmed VL were examined. Forty-seven patients with the main age (±SD of 17.34±11.37 years (Range: 1-60 were included in the study. Fifty-one non-VL subjects with splenomegaly and pancytopenia or bicytopenia served as control group. Results: All patients with VL had anemia, 41 (87% leukopenia, 42 (89% neutropenia, 44 (94% thrombocytopenia, 42 (89% eosinopenia, 34 (72% pancytopenia and 13 (28% had bicytopenia. In bone marrow examination 40 (85% showed hypercellularity, 44 (94% eosinopenia, 24 (51% dyserythropoiesis, 22 (47% lymphocytosis, 8 (17% plasmacytosis, 27 (57% decreased iron stores and 20 (43% showed decreased sideroblasts. Comparison of VL patients with the control group showed significantly more frequent peripheral blood eosinopenia and lymphopenia and marrow eosinopenia. There was no significant difference between adults and children in any of the hematological features. Conclusion: Anemia, leukopenia, neutropenia, thrombocytopenia, eosinopenia, pancytopenia and marked bone marrow eosinopenia were the most common findings. The finding of marked bone marrow eosinopenia is a significant clue for the diagnosis of visceral leishmaniasis in patients who present with

  12. Ibrutinib for treatment of chronic lymphocytic leukemia. (United States)

    Vela, Cory M; McBride, Ali; Jaglowski, Samantha M; Andritsos, Leslie A


    The pharmacology, pharmacokinetics, pharmacodynamics, clinical efficacy, and safety of ibrutinib are described. Ibrutinib is a first-in-class oral inhibitor of Bruton tyrosine kinase (BTK) approved for treatment of relapsed chronic lymphocytic leukemia (CLL). Ibrutinib blocks downstream signaling of the B-cell receptor, disrupting stromal microenvironment interactions and B-cell cytokine signaling. BTK inhibition has been shown to be effective in relapsed or refractory CLL. A recent Phase III study evaluated ibrutinib (420 mg daily) versus ofatumumab (consistent with labeling) in relapsed or refractory CLL with a primary endpoint of progression free survival (PFS, n = 391). After a median follow-up period of 9.4 months, a PFS was not attained in ibrutinib-treated individuals with and without deletion 17p. In contrast, ofatumumab-treated individuals experienced a PFS of 8.1 months and those with deletion 17p experienced a PFS of 5.8 months. Major hemorrhage was reported in 2 (1%) patients treated with ibrutinib, and a total of 8 (4%) patients discontinued treatment due to toxicity or adverse reactions. Partial response or partial response with lymphocytosis was achieved in 63% of ibrutinib-treated individuals as determined by independent assessments. Overall, ibrutinib reduced the rate of mortality by 57%. Ibrutinib is a first-in-class, orally active, irreversible BTK inhibitor with a novel mechanism of action. This unique mechanism of action and high overall response rates observed in clinical trials make ibrutinib an attractive second-line option in patients who have disease progression while receiving monoclonal antibody therapy or chemoimmunotherapy. Copyright © 2016 by the American Society of Health-System Pharmacists, Inc. All rights reserved.

  13. Ibrutinib: A Review in Chronic Lymphocytic Leukaemia. (United States)

    Deeks, Emma D


    Ibrutinib (Imbruvica ® ) is an oral irreversible inhibitor of Bruton's tyrosine kinase, a B-cell receptor (BCR) signalling kinase expressed by various haematopoietic cells, B-cell lymphomas and leukaemias. The drug is indicated for the treatment of certain haematological malignancies, including chronic lymphocytic leukaemia (CLL)/small lymphocytic lymphoma (SLL), which are the focus of this review. In phase III CLL/SLL trials, ibrutinib monotherapy was more effective than chlorambucil in the first-line treatment of elderly patients (RESONATE-2) and more effective than ofatumumab in previously-treated adults (RESONATE). Likewise, a combination of ibrutinib, bendamustine and rituximab was more effective in previously-treated adults than bendamustine plus rituximab in a phase III placebo-controlled study (HELIOS). These ibrutinib regimens were associated with significantly better progression-free survival, overall response rates, and overall survival than the comparators (in protocol-specified or planned analyses), with ibrutinib therapy providing benefit regardless of adverse prognostic factors, such as del(17p)/TP53 mutation and del(11q). Ibrutinib has an acceptable tolerability profile, although certain adverse events (e.g. bleeding and atrial fibrillation) require consideration. Redistribution lymphocytosis can occur, but is not indicative of disease progression. Although longer-term data would be beneficial, ibrutinib is a welcome treatment option for patients with CLL, including those who have higher-risk disease or are less physically fit. Indeed, current EU and US guidelines recommend/prefer the drug for the first- and/or subsequent-line treatment of certain patients, including those with del(17p)/TP53 mutation.

  14. Targeting BTK with ibrutinib in relapsed chronic lymphocytic leukemia. (United States)

    Byrd, John C; Furman, Richard R; Coutre, Steven E; Flinn, Ian W; Burger, Jan A; Blum, Kristie A; Grant, Barbara; Sharman, Jeff P; Coleman, Morton; Wierda, William G; Jones, Jeffrey A; Zhao, Weiqiang; Heerema, Nyla A; Johnson, Amy J; Sukbuntherng, Juthamas; Chang, Betty Y; Clow, Fong; Hedrick, Eric; Buggy, Joseph J; James, Danelle F; O'Brien, Susan


    The treatment of relapsed chronic lymphocytic leukemia (CLL) has resulted in few durable remissions. Bruton's tyrosine kinase (BTK), an essential component of B-cell-receptor signaling, mediates interactions with the tumor microenvironment and promotes the survival and proliferation of CLL cells. We conducted a phase 1b-2 multicenter study to assess the safety, efficacy, pharmacokinetics, and pharmacodynamics of ibrutinib (PCI-32765), a first-in-class, oral covalent inhibitor of BTK designed for treatment of B-cell cancers, in patients with relapsed or refractory CLL or small lymphocytic lymphoma. A total of 85 patients, the majority of whom were considered to have high-risk disease, received ibrutinib orally once daily; 51 received 420 mg, and 34 received 840 mg. Toxic effects were predominantly grade 1 or 2 and included transient diarrhea, fatigue, and upper respiratory tract infection; thus, patients could receive extended treatment with minimal hematologic toxic effects. The overall response rate was the same in the group that received 420 mg and the group that received 840 mg (71%), and an additional 20% and 15% of patients in the respective groups had a partial response with lymphocytosis. The response was independent of clinical and genomic risk factors present before treatment, including advanced-stage disease, the number of previous therapies, and the 17p13.1 deletion. At 26 months, the estimated progression-free survival rate was 75% and the rate of overall survival was 83%. Ibrutinib was associated with a high frequency of durable remissions in patients with relapsed or refractory CLL and small lymphocytic lymphoma, including patients with high-risk genetic lesions. (Funded by Pharmacyclics and others; number, NCT01105247.).

  15. Lymphocytic Arteritis in Epstein-Barr Virus Vulvar Ulceration (Lipschütz Disease): A Report of 7 Cases. (United States)

    Barrett, Mary M; Sangüeza, Martin; Werner, Betina; Kutzner, Heinz; Carlson, John A


    Epstein-Barr virus (EBV) infection can rarely present as painful genital ulcers, mostly in young female adolescents. Typically diagnosed by clinical findings, EBV vulvar ulceration (EBVVU) is rarely biopsied. Herein, the authors report the histopathology in 8 biopsies from 7 EBVVU patients, all serologically confirmed for acute (4/7) or reactivated-chronic (3/7) EBV infection. The 7 women all presented with 1 or more painful, punched-out vulvar ulcers. Only patients with acute EBV infection showed other clinical findings: fever and/or atypical lymphocytosis affected 75% (3/4); lymphadenopathy in 50%; and malaise/fatigue, dysuria and/or hepatomegaly in 25%. All reactivated-chronic EBVVU had a solitary ulcer, and 2 had history of a similar episode of vulvar ulceration (aphthosis). Histopathologically, lymphocytic arteritis was identified in 88% (7/8); a submucosal scar was found in the eighth specimen. Other histopathologies included venulitis (62%), endarteritis obliterans (38%), thrombosis (25%), neutrophilic sebaceous adenitis (25%), and mucosal lymphoid hyperplasia (12%). Dense angiocentric CD3 CD4 T-cell lymphocyte-predominant infiltrates were found, regionally or diffusely. In 2 specimens, neutrophils compromised half of the infiltrate. Minor components of CD8, CD20, and CD30 lymphocytes, CD123 plasmacytoid monocytes, CD68 macrophages, and plasma cells were present. Small-vessel endothelium and smooth muscle adjacent to the ulcers faintly expressed cytoplasmic EBV latent membrane protein-1 (LMP1). In situ hybridization for early EBV mRNA (EBER) identified rare solitary or scattered clustered positive lymphocytes in 38%. Polymerase chain reaction for EBV DNA was positive in one EBER positive biopsy. EBV infection has been documented in muscular vessel vasculitis. Based on the aforementioned, EBVVU appears to be the consequence of localized lymphocytic arteritis.

  16. Splenectomy associated changes in IgM memory B cells in an adult spleen registry cohort.

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    Paul U Cameron

    Full Text Available Asplenic patients have a lifelong risk of overwhelming post-splenectomy infection and have been reported to have low numbers of peripheral blood IgM memory B cells. The clinical value of quantitation of memory B cells as an indicator of splenic abnormality or risk of infection has been unclear. To assess changes in B cell sub-populations after splenectomy we studied patients recruited to a spleen registry (n = 591. A subset of 209 adult asplenic or hyposplenic subjects, and normal controls (n = 140 were tested for IgM memory B cells. We also determined a changes in IgM memory B cells with time after splenectomy using the cross-sectional data from patients on the registry and b the kinetics of changes in haematological markers associated with splenectomy(n = 45. Total B cells in splenectomy patients did not differ from controls, but memory B cells, IgM memory B cells and switched B cells were significantly (p<0.001 reduced. The reduction was similar for different indications for splenectomy. Changes of asplenia in routine blood films including presence of Howell-Jolly bodies (HJB, occurred early (median 25 days and splenectomy associated thrombocytosis and lymphocytosis peaked by 50 days. There was a more gradual decrease in IgM memory B cells reaching a stable level within 6 months after splenectomy. IgM memory B cells as proportion of B cells was the best discriminator between splenectomized patients and normal controls and at the optimal cut-off of 4.53, showed a true positive rate of 95% and false positive rate of 20%. In a survey of 152 registry patients stratified by IgM memory B cells around this cut-off there was no association with minor infections and no registry patients experienced OPSI during the study. Despite significant changes after splenectomy, conventional measures of IgM memory cells have limited clinical utility in this population.

  17. Analysis of chromosomal aberrations, micronuclei and hematological disorders among workers of wireless communication instruments and cell phone (Mobile) users

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    Eldawy, H.A.; Khattab, F.I.; Hassan, N.H.A.; Amin, Y.M.; Mahmoud, M.M.A.


    This study was carried out to investigate the hazardous effect of electromagnetic radiation (EMR) such as chromosomal aberration, disturbed micronucleus formation and hematological disorders that may detected among workers of wireless communication instruments and mobile phone users. Seven individuals ( 3 males and 4 females) of a central workers in the microwave unit of the wireless station and 7 users of Mobil phone (4 males and 3 females ) were volunteered to give blood samples. Chromosomes and micronucleus were prepared for cytogenetic analysis as well as blood film for differential count. The results obtained in the microwave group indicated that, the total summation of all types of aberrations (chromosomes and chromatid aberrations) had a frequency of 6. 14% for the exposed group, whereas, the frequency in the control group amounted to 1.57%. In Mobil phone users, the total summation of all types of aberrations(chromosome and chromatid aberrations) had a frequency of 4.43% for the exposed group and 1.71% for the control group. The incidence of the total number of micronuclei in the exposed microwave group was increased 4.3 folds as compared with those of the control group The incidence of the total number of micronuclei in the exposed mobile phone group was increased 2 fold as compared with those in the control group. On the other hand, normal ranges of total white blood cells counts were determined for mobile phone users but abnormalities in the differential counts of the different types of the white blood cells such as neutropenia, eosinophilia and lymphocytosis were observed in the individuals number 1,2,3,7 in microwave group

  18. Exercise and the Athlete With Infectious Mononucleosis. (United States)

    Shephard, Roy J


    To determine appropriate management of the active individual with infectious mononucleosis (IM), including issues of diagnosis, the determination of splenomegaly, and other measures of disease status, the relationship of the disease to chronic fatigue syndrome (CFS), and the risks of exercise at various points in the disease process. An Ovid/MEDLINE search (January 1996-June 2015) was widely supplemented by "similar articles" found in Ovid/MEDLINE and PubMed, reference lists, and personal files. Clinical diagnoses of IM are unreliable. Traditional laboratory indicators (lymphocytosis, abnormal lymphocytes, and a heterophile-positive slide test) can be supplemented by more sensitive and more specific but also more costly Epstein-Barr antigen determinations. Clinical estimates of splenomegaly are fallible. Laboratory determinations, commonly by 2D ultrasonography, must take account of methodology, the formulae used in calculations and the individual's body size. The SD of normal values matches the typical increase of size in IM, but repeat measurements can help to monitor regression of the disease. The main risks to the athlete are spontaneous splenic rupture (seen in 0.1%-0.5% of patients and signaled by acute abdominal pain) and progression to chronic fatigue, best avoided by 3 to 4 weeks of restricted activity followed by graded reconditioning. A full recovery of athletic performance is usual with 2 to 3 months of conservative management. Infectious mononucleosis is a common issue for young athletes. But given accurate diagnosis and the avoidance of splenic rupture and progression to CFS through a few weeks of restricted activity, long-term risks to the health of athletes are few.

  19. Multiple granulomatous lung lesions in a patient with Epstein-Barr-virus-induced mononucleosis and new-onset systemic lupus erythematosus: a case report

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    Sakurai Aki


    Full Text Available Abstract Introduction Granulomatous lesions are commonly encountered abnormalities in pulmonary pathology, and often pose a diagnostic challenge. We report an unusual case of granulomatous lung disease with uncommon characteristics, which developed following Epstein-Barr-virus-induced mononucleosis and new-onset systemic lupus erythematosus. We aim to highlight a diagnostic approach for the condition and to raise awareness of the possibility of it being related to the immunological reaction caused by Epstein-Barr virus infection. Case presentation A 36-year-old Japanese man, who had been diagnosed with Epstein-Barr-virus-induced infectious mononucleosis, new-onset systemic lupus erythematosus, and secondary Sjögren’s syndrome three weeks previously, presented to our facility with fever and diffuse pulmonary infiltrates. A computed tomography scan of the chest revealed multiple small nodules in both lungs. Fiberoptic bronchoscopy with bronchoalveolar lavage revealed lymphocytosis with predominance of T lymphocytes. A histological examination of a lung biopsy taken during video-assisted thoracic surgery showed randomly distributed tiny granulomatous lesions with infiltration of eosinophils. The differential diagnoses included hypersensitivity pneumonitis, sarcoidosis, and pulmonary involvement of Crohn’s disease, systemic lupus erythematosus, and Sjögren’s syndrome, but the clinical and pathological findings were not consistent with any of these. Our patient’s condition did not improve; therefore, prednisolone therapy was started because of the possibility of specific immunological reactions associated with Epstein-Barr virus infection. After steroid treatment, our patient showed radiological and clinical improvement. Conclusions To the best of our knowledge, this is the first case of a patient developing randomly distributed multiple granulomatous lung lesions with eosinophilic infiltrates after Epstein-Barr virus infection and systemic

  20. LLC: critérios diagnósticos, imunofenotipagem e diagnóstico diferencial CLL: diagnostic criteria, immunophenotyping and differential diagnosis

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    Irene Lorand-Metze


    Full Text Available O diagnóstico da LLC é baseado em dados do hemograma e da imunofenotipagem dos linfócitos periféricos: linfocitose acima de 5 (ou 10 x 10(9/L com fenótipo CD19, CD5, CD23 e expressão fraca de imunoglobulinas de superfície monoclonais. A expressão de CD38 ocorre em cerca da metade dos casos e tem relação com o estado não mutado de Ig V. A biópsia de medula só deverá ser realizada antes do tratamento ou quando os dois exames acima não permitirem um diagnóstico definitivo. O diagnóstico diferencial é com os outros linfomas B indolentes, que freqüentemente apresentam células neoplásicas circulantes. Este diagnóstico diferencial é baseado na imunofenotipagem, biópsia de medula ou linfonodo.The diagnosis of CLL is based on the finding of peripheral lymphocytosis of over 5 (or 10 x 10(9/L presenting the CD19, CD5, CD23 phenotype and a weak monoclonal expression of membrane immunoglobulins. The CD38 expression is observed in half of the cases and is correlated with the unmutated status of the Ig V gene. Bone marrow biopsy should only be performed before starting treatment or if necessary for the differential diagnosis with other low-grade lymphomas. This differential diagnosis is based on the morphology of circulating lymphocytes, their immunophenotypes and pattern of bone marrow infiltration.

  1. Richter transformation driven by Epstein-Barr virus reactivation during therapy-related immunosuppression in chronic lymphocytic leukaemia. (United States)

    García-Barchino, Maria J; Sarasquete, Maria E; Panizo, Carlos; Morscio, Julie; Martinez, Antonio; Alcoceba, Miguel; Fresquet, Vicente; Gonzalez-Farre, Blanca; Paiva, Bruno; Young, Ken H; Robles, Eloy F; Roa, Sergio; Celay, Jon; Larrayoz, Marta; Rossi, Davide; Gaidano, Gianluca; Montes-Moreno, Santiago; Piris, Miguel A; Balanzategui, Ana; Jimenez, Cristina; Rodriguez, Idoia; Calasanz, Maria J; Larrayoz, Maria J; Segura, Victor; Garcia-Muñoz, Ricardo; Rabasa, Maria P; Yi, Shuhua; Li, Jianyong; Zhang, Mingzhi; Xu-Monette, Zijun Y; Puig-Moron, Noemi; Orfao, Alberto; Böttcher, Sebastian; Hernandez-Rivas, Jesus M; Miguel, Jesus San; Prosper, Felipe; Tousseyn, Thomas; Sagaert, Xavier; Gonzalez, Marcos; Martinez-Climent, Jose A


    The increased risk of Richter transformation (RT) in patients with chronic lymphocytic leukaemia (CLL) due to Epstein-Barr virus (EBV) reactivation during immunosuppressive therapy with fludarabine other targeted agents remains controversial. Among 31 RT cases classified as diffuse large B-cell lymphoma (DLBCL), seven (23%) showed EBV expression. In contrast to EBV - tumours, EBV + DLBCLs derived predominantly from IGVH-hypermutated CLL, and they also showed CLL-unrelated IGVH sequences more frequently. Intriguingly, despite having different cellular origins, clonally related and unrelated EBV + DLBCLs shared a previous history of immunosuppressive chemo-immunotherapy, a non-germinal centre DLBCL phenotype, EBV latency programme type II or III, and very short survival. These data suggested that EBV reactivation during therapy-related immunosuppression can transform either CLL cells or non-tumoural B lymphocytes into EBV + DLBCL. To investigate this hypothesis, xenogeneic transplantation of blood cells from 31 patients with CLL and monoclonal B-cell lymphocytosis (MBL) was performed in Rag2 -/- IL2γc -/- mice. Remarkably, the recipients' impaired immunosurveillance favoured the spontaneous outgrowth of EBV + B-cell clones from 95% of CLL and 64% of MBL patients samples, but not from healthy donors. Eventually, these cells generated monoclonal tumours (mostly CLL-unrelated but also CLL-related), recapitulating the principal features of EBV + DLBCL in patients. Accordingly, clonally related and unrelated EBV + DLBCL xenografts showed indistinguishable cellular, virological and molecular features, and synergistically responded to combined inhibition of EBV replication with ganciclovir and B-cell receptor signalling with ibrutinib in vivo. Our study underscores the risk of RT driven by EBV in CLL patients receiving immunosuppressive therapies, and provides the scientific rationale for testing ganciclovir and ibrutinib in EBV + DLBCL. Copyright © 2018 Pathological

  2. Relato de caso de leucemia de células pilosas Case report of hairy cell leukemia

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    Lacy Cardoso de Brito Junior


    Full Text Available A leucemia de células pilosas (LCP é um tipo raro de linfoma não Hodgkin de células B. O quadro clínico inclui esplenomegalia, pancitopenia e linfocitose. Estudos de carcinogênese da doença revelam sua associação a agentes químicos agrícolas. O objetivo deste estudo foi o relato de um caso de paciente com LCP, masculino, tratorista, com pancitopenia, lesões de pele, sem esplenomegalia e com marcadores positivos para linfócitos B (CD19, CD20, CD22, CD79b, CD23, Lambda, imunoglobulina M [IgM], CD25 e CD103. Embora a LCP seja uma doença rara, a demora em seu diagnóstico pode levar a sérias complicações e à morte do paciente antes do diagnóstico.Hairy cell leukemia (HCL is a rare type of B-cell non-Hodgkin's lymphoma. The clinical symptoms include splenomegaly, pancytopenia, and lymphocytosis. Studies on its carcinogenesis reveal association with exposure to agricultural chemical agents. The objective of this study was to report the case of a male patient, tractor operator, diagnosed with HCL, pancytopenia, cutaneous lesions, without splenomegaly and positive markers for B-cell lymphocytes (CD19, CD20, CD22, CD79b, CD23, Lambda, immunoglobulin M [IgM], CD25 and CD103. Although HCL is a rare disease, late diagnosis may ultimately lead to severe complications and patient's death.

  3. Infectious mononucleosis due to epstein-barr virus infection in children: A profile from eastern India

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    Madhumita Nandi


    Full Text Available Objective: The objective of this study is to delineate the clinical and laboratory profile of infectious mononucleosis due to Epstein-Barr virus (EBV infection in children admitted to tertiary care teaching hospitals. Materials and Methods: Retrospective observational multicentric analysis of clinical and laboratory features of children between 1 month to 12 years with a diagnosis of infectious mononucleosis due to EBV infection confirmed by positive serology over a 12-month period after seeking approval from the Institutional Ethics Committee. Results: Out of 66 children screened, 53 were included in final analysis. The majority were aged between 5 and 8 years with male: female ratio of 1.2:1. Most presentations were during the monsoon months. The common clinical features were fever (100%, splenomegaly (86.7%, and cervical lymphadenopathy (73.5% in contrast to the classical triad of fever, sore throat, and generalized lymphadenopathy described in the literature. There were no age differences in clinical findings except for generalized and cervical lymphadenopathy and hepatomegaly which were commoner in 9–12 years age band. Although the incidence of common findings matched with previously published studies, there were some notable differences. While frequencies of upper eyelid edema, epitrochlear lymphadenopathy, and splenomegaly were more, those of rash and sore throat were less. Lymphocytosis and presence of atypical lymphocytes were relatively less common in our series. All children recovered. Conclusions: This multicentric study on profiling childhood infectious mononucleosis, possibly first of its kind from Eastern India, has documented clinical and laboratory features associated with this condition. These data can serve as a reference for future studies.

  4. Stevens-Johnson syndrome and toxic epidermal necrolysis due to anticonvulsants share certain clinical and laboratory features with drug-induced hypersensitivity syndrome, despite differences in cutaneous presentations. (United States)

    Teraki, Y; Shibuya, M; Izaki, S


    Drug-induced hypersensitivity syndrome (DIHS)/drug rash with eosinophilia and systemic symptoms (DRESS) syndrome is characterized by late disease onset, fever, rash, hepatic dysfunction, haematological abnormalities, lymphadenopathy and often, human herpesvirus (HHV) reactivation. The diagnosis of DIHS is based on the combined presence of these findings. Anticonvulsants are a major cause of DIHS and may also cause Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). We examined whether SJS/TEN due to anticonvulsants display similar clinical and laboratory features seen in DIHS. Patients diagnosed with SJS or TEN due to anticonvulsants (n = 8) were examined and their clinical features and laboratory findings were compared with patients with anticonvulsant-related DIHS (n = 6). Seven of the eight patients with SJS/TEN developed symptoms > 3 weeks after starting anticonvulsants. Hepatic dysfunction was present in six patients with SJS/TEN and five patients with DIHS. Leucocytosis and/or eosinophilia was noted in seven patients with SJS/TEN and four patients with DIHS. Only one patient in the SJS/TEN group had atypical lymphocytosis; this was present in four patients with DIHS. Reactivation of HHV-6 was detected in one of the four patients tested in the SJS/TEN group, although it was seen in five of the six patients with DIHS. TSJS/TEN due to anticonvulsants may exhibit some clinical and laboratory features of DIHS. The nature of the cutaneous involvement should be emphasized in the diagnosis of DIHS. © 2009 The Author(s). Journal compilation © 2009 British Association of Dermatologists.

  5. Atypical lymphocytes in malaria mimicking dengue infection in Thailand

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    Polrat Wilairatana


    Full Text Available Polrat Wilairatana1, Noppadon Tangpukdee1, Sant Muangnoicharoen1, Srivicha Krudsood2, Shigeyuki Kano31Department of Clinical Tropical Medicine, 2Department of Tropical Hygiene, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand; 3Department of Tropical Medicine and Malaria, Research Institute, National Center for Global Health and Medicine, Tokyo, JapanAbstract: Patients with uncomplicated falciparum or vivax malaria usually present with acute febrile illness and thrombocytopenia similar to dengue infection. We retrospectively studied atypical lymphocytes (AL and atypical lymphocytosis (ALO, defined as AL > 5% of total white blood cells in 1310 uncomplicated malaria patients. In 718 falciparum malaria patients, AL and ALO on day 0 were found in 53.2% and 5.7% of the patients, respectively, with median AL on admission of 1% (range 0%–10%, whereas in 592 vivax malaria patients, AL and ALO on day 0 were found in 55.4% and 9.5% of the patients, respectively, with median AL on admission of 1% (range 0%–14%. After antimalarial treatment, AL and ALO declined in both falciparum and vivax malaria. However, AL and ALO remained in falciparum malaria on days 7, 14, and 21, whereas AL and ALO remained in vivax malaria on days 7, 14, 21, and 28. In both falciparum and vivax malaria patients, there was a positive correlation between AL and total lymphocytes, but a negative correlation between AL and highest fever on admission, white blood cells, and neutrophils, eosinophils, and platelets (P < 0.05. In conclusion, AL or ALO may be found in uncomplicated falciparum and vivax malaria mimicking dengue infection. In tropical countries where both dengue and malaria are endemic, presence of AL or ALO in any acute febrile patients with thrombocytopenia (similar to the findings in dengue malaria could not be excluded. Particularly if the patients have risk of malaria infection, confirmative microscopic examination for malaria should be carried out

  6. Bovine milk fat enriched in conjugated linoleic and vaccenic acids attenuates allergic airway disease in mice. (United States)

    Kanwar, R K; Macgibbon, A K; Black, P N; Kanwar, J R; Rowan, A; Vale, M; Krissansen, G W


    It has been argued that a reduction in the Western diet of anti-inflammatory unsaturated lipids, such as n-3 polyunsaturated fatty acids, has contributed to the increase in the frequency and severity of allergic diseases. We investigated whether feeding milk fat enriched in conjugated linoleic acid and vaccenic acids (VAs) ('enriched' milk fat), produced by supplementing the diet of pasture-fed cows with fish and sunflower oil, will prevent development of allergic airway responses. C57BL/6 mice were fed a control diet containing soybean oil and diets supplemented with milk lipids. They were sensitized by intraperitoneal injection of ovalbumin (OVA) on days 14 and 28, and challenged intranasally with OVA on day 42. Bronchoalveolar lavage fluid, lung tissues and serum samples were collected 6 days after the intranasal challenge. Feeding of enriched milk fat led to marked suppression of airway inflammation as evidenced by reductions in eosinophilia and lymphocytosis in the airways, compared with feeding of normal milk fat and control diet. Enriched milk fat significantly reduced circulating allergen-specific IgE and IgG1 levels, together with reductions in bronchoalveolar lavage fluid of IL-5 and CCL11. Treatment significantly inhibited changes in the airway including airway epithelial cell hypertrophy, goblet cell metaplasia and mucus hypersecretion. The two major components of enriched milk fat, cis-9, trans-11 conjugated linoleic acid and VA, inhibited airway inflammation when fed together to mice, whereas alone they were not effective. Milk fat enriched in conjugated linoleic and VAs suppresses inflammation and changes to the airways in an animal model of allergic airway disease.

  7. New Therapeutic Possibilities of the Post-Irradiation Haemorrhagic Syndrome

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    Pospisil, J.; Dienstbier, Z. [Institute of Biophysics and Nuclear Medicine, Faculty of General Medicine, Charles University, Prague, Czechoslovak Socialist Republic (Czech Republic); Skala, E. [Central Military Hospital, Prague-Stresovice, Czechoslovak Socialist Republic (Czech Republic)


    Haemorrhagic diathesis is one of the dominant symptoms of acute post-irradiation lesion. Haemorrhagic syndrome is caused by the disturbance of haemocoagulation during simultaneous lesion of the vascular system. In our study we have tried to affect the post-irradiation haemocoagulation disturbance. Epsilon- amino-caproic acid (EACA) administered between the 8{sup th} and the 18{sup th} day (0.4 g/kg per day) to whole- body irradiated dogs (600 R) partially regulated the post-irradiation disturbance of haemocoagulation. The favourable effect of EACA was verified by in vitro experiments in which the blood of irradiated dogs was used. A repeated administration of EACA in the dose of 0.4 g/kg per day to whole-body irradiated rats (600 R) did not substantially affect the post-irradiation changes in the number of white blood elements; however, its administration to healthy animals caused lymphocytosis. In whole-body irradiated dogs (600 R) we have found lower levels of EACA in the blood up to the 8 day following irradiation as compared with healthy dogs after oral application of EACA. The whole-body irradiation of mice did not increase the acute toxicity of EACA. The daily administration of 0.4 g EACA/kg to whole-body irradiated mice (600 and 700 R) did not change the mortality induced by irradiation. The authors consider EACA to be a suitable compound for a complex therapy of radiation sickness. The administration of para-amino-methyl-benzoic acid (PAMBA), in spite of a certain improvement of postirradiation haemocoagulation disturbance, is less efficient. Our recent experiments with ellagic acid which significantly affects the post-traumatic haemorrhage in whole-body irradiated rats seem to be very promising. (author)

  8. Comparative clinical and haematological investigations in lactating cows with subclinical and clinical ketosis

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    Vania Marutsova


    Full Text Available Ketosis of lactating cows is among the most common metabolic diseases in modern dairy farms. The economic importance of the disease is caused by the reduced milk yield and body weight loss, poor feed conversion, lower conception rates, culling and increased mortality of affected animals. In the present study, a total of 47 high-yielding dairy cows up to 45 days in milk (DIM are included. All animals were submitted to physical examination wich included checking the rectal body temperature, heart rate, respiratory and rumen contraction rates, and inspection of visible mucous coats. The body condition was scored, and blood β-hydroxybutyrate (BHBA concentrations were assayed. The cows were divided into 3 groups: first group (control (n=24 with blood β-hydroxybutyrate level 2.6 mmol/l (clinical ketosis. Whole blood samples were obtained and analyzed for Red Blood Cell (RBC, 1012/l, Hemoglobin (HGB, g/l, Hematocrit (HCT, %, Mean Corpuscular Volume (MCV, fl, Mean Corpuscular Hemoglobin (MCH, pg, Mean Corpuscular Hemoglobin Concentration (MCHC, g/l, White Blood Cell (WBC, 109/l, Lymphocytes (LYM, 109/l, Monocytes (MON, 109/l, Granulocytes (GRA, 109/l, Red Blood Distribution Width (RDW, %, Red Blood Cell Distribution Width Absolute (RDWa, fl, Platelets (PLT, 109/l and Mean Platelet Volume (MPV, fl. In this study, deviations in the clinical parameters in the control group and in those with subclinical ketosis were not identified. The cows from the third group (clinical ketosis exhibited hypotonia, anorexia and body weight loss vs. control group. Hematological analysis showed leukocytosis and lymphocytosis in cows with subclinical ketosis vs. control group. In cows with clinical ketosis WBC counts decreased (leukopenia, while hemoglobin content and hematocrit values are higher vs. control group. Blood BHBA values are higher in both groups of ketotic cows vs. the control group. The other analyzed parameters (RBC, MCH, MCHC, MCV, RDW, RDWa, MON, GRA, PLT

  9. Collagenous gastritis: a morphologic and immunohistochemical study of 40 patients. (United States)

    Arnason, Thomas; Brown, Ian S; Goldsmith, Jeffrey D; Anderson, William; O'Brien, Blake H; Wilson, Claire; Winter, Harland; Lauwers, Gregory Y


    Collagenous gastritis is a rare condition defined histologically by a superficial subepithelial collagen layer. This study further characterizes the morphologic spectrum of collagenous gastritis by evaluating a multi-institutional series of 40 patients (26 female and 14 male). The median age at onset was 16 years (range 3-89 years), including 24 patients (60%) under age 18. Twelve patients (30%) had associated celiac disease, collagenous sprue, or collagenous colitis. Hematoxylin and eosin slides were reviewed in biopsies from all patients and tenascin, gastrin, eotaxin, and IgG4/IgG immunohistochemical stains were applied to a subset. The distribution of subepithelial collagen favored the body/fundus in pediatric patients and the antrum in adults. There were increased surface intraepithelial lymphocytes (>25 lymphocytes/100 epithelial cells) in five patients. Three of these patients had associated celiac and/or collagenous sprue/colitis, while the remaining two had increased duodenal lymphocytosis without specific etiology. An eosinophil-rich pattern (>30 eosinophils/high power field) was seen in 21/40 (52%) patients. Seven patients' biopsies demonstrated atrophy of the gastric corpus mucosa. Tenascin immunohistochemistry highlighted the subepithelial collagen in all 21 specimens evaluated and was a more sensitive method of collagen detection in biopsies from two patients with subtle subepithelial collagen. No increased eotaxin expression was identified in 16 specimens evaluated. One of the twenty-three biopsies tested had increased IgG4-positive cells (100/high power field) with an IgG4/IgG ratio of 55%. In summary, collagenous gastritis presents three distinct histologic patterns including a lymphocytic gastritis-like pattern, an eosinophil-rich pattern, and an atrophic pattern. Eotaxin and IgG4 were not elevated enough to implicate these pathways in the pathogenesis. Tenascin immunohistochemistry can be used as a sensitive method of collagen detection.

  10. Cystoisospora belli Infection of the Gallbladder in Immunocompetent Patients: A Clinicopathologic Review of 18 Cases. (United States)

    Lai, Keith K; Goyne, Hannah E; Hernandez-Gonzalo, David; Miller, Kennon A; Tuohy, Marion; Procop, Gary W; Lamps, Laura W; Patil, Deepa T


    Cystoisospora belli, previously known as Isospora belli, is an obligate intracellular coccidian parasite that is most often associated with gastrointestinal disease in immunocompromised patients. In this study, we detail the clinicopathologic features of 18 cases of Cystoisospora infection affecting the gallbladder in immunocompetent individuals and compare them with a control group. Each case was reviewed for cholecystitis (none, acute, chronic), epithelial disarray, presence of intraepithelial lymphocytes (none, rare [≤5 per 20 epithelial cells], present [>5 per 20 epithelial cells]), architectural distortion, intramucosal eosinophilia, and mural thickening/serositis. The mean age of patients with Cystoisospora infection was 33 years and the male to female ratio 1:4.3. Cholecystectomy was performed for biliary dyskinesia (n=7), abdominal pain (n=7), suspected cholelithiasis (n=5), and cholecystitis (n=3). In 2 cases, Cystoisospora was found in donor gallbladders resected at the time of liver transplantation. Each case was characterized by eosinophilic, oval or banana-shaped intraepithelial parasites within perinuclear parasitophorous vacuoles. Most cases showed epithelial disarray and minimal intraepithelial lymphocytosis. Of the 11 cases with an average follow-up of 15 months, none had evidence of disease related to Cystoisospora infection within the biliary tract or elsewhere in the gastrointestinal tract. We present the largest series of gallbladder cystoisosporiasis in immunocompetent patients to date. Cystoisospora infection is underrecognized in the gallbladders of immunocompetent patients, in part due to the subtle findings in routine cholecystectomy specimens. On the basis of the clinical follow-up, gallbladder cystoisosporiasis in immunocompetent individuals appears to be a self-limited infection.

  11. Long term evolution of the immune response in the rat irradiated at mean and high doses

    International Nuclear Information System (INIS)

    Malarbet, J.L.; Veyrat, M.; Le Go, R.; Prudhomme, J.; Genest, L.; Castelnau, L.


    In irradiated animals, the lymphocytes, immunity vectors, are quickly and quantitatively depressed. Their ability to respond to an antigenic stimulus was tested in rats during post-irradiation lymphopenia and after restoration of normal lymphocytosis. The antigenic stimulus, sheep erythrocytes, was applied first 2 and 3 weeks, then 1, 2 and 3 months after exposures to 60 Co gamma rays (doses 300 and 600 rads). This study covered the 3rd through the 10th day after immunisation. Blood lymphocytes were separated by the Ficoll-Contrix gradient method and spleen lymphocytes were obtained by crushing. A lymphocyte sub-population separation was obtained from centrifugation on 4 discontinuous Ficoll-Contrix gradients. Size distribution spectra show that the lighter sub-population is made up of large-sized cells and that the heavier the cells, the smaller they are. The determination of surface immunoglobulins with fluorescent antigens shows that cells bearing immunoglobulins are predominant in the low-density sub-population. The measurement of electrophoretic mobility shows a low-mobility, low-density population and a higher density, faster mobility population which could reflect a higher proportion of B-cells in the low density population and of T-cells in the higher density population. The immune response was tested on the sub-populations. The rosette-forming ability was depressed during 1 month after irradiation then became progressively normal. The cellular plaque-forming ability was markedly suppressed 15 days after irradiation, but was soon active again. These results show the qualitative aspect of the post-irradiation immune defect [fr

  12. The utility of flow cytometry in differentiating NK/T cell lymphoma from indolent and reactive NK cell proliferations. (United States)

    de Mel, Sanjay; Li, Jenny Bei; Abid, Muhammad Bilal; Tang, Tiffany; Tay, Hui Ming; Ting, Wen Chang; Poon, Li Mei; Chung, Tae Hoon; Mow, Benjamin; Tso, Allison; Ong, Kiat Hoe; Chng, Wee Joo; Liu, Te Chih


    The WHO defines three categories of NK cell malignancies; extra nodal NK/T cell lymphoma (NKTCL), aggressive NK cell leukemia, and the provisional entity chronic lymphoproliferative disorder of NK cells (CLPD-NK). Although the flow cytometric (FC) phenotype of CLPD-NK has been described, studies on FC phenotype of NKTCL are limited. To the best of our knowledge ours is the first study to compare the phenotype of NKTCL, CLPD-NK, reactive NK lymphocytosis (RNKL), and normal NK cells using eight color (8C) FC. Specimens analyzed using the Euroflow8C NK Lymphoproliferative Disorder (NKLPD) panel between 2011 and 2014 were identified from our database. All samples were analyzed on the FACSCantoII cytometer. NK cells were identified as CD45+, smCD3-, CD19-, CD56+ and normal T-cells served as internal controls. The majority of NKTCL were CD56 bright, CD16 dim, CD57-, and CD94+. CLPD-NK and RNKL were predominantly CD56+ or dim with positive expression of CD16 and CD57 and weak CD94 expression. Antigen based statistical analyses showed robust division of samples along the NKTCL/normal CD56 bright NK cell and CLPD-NK/RNKL/normal CD56 positive NK cell groups. It was concluded that FC can reliably distinguish NKTCL from CLPD-NK, normal NK cells of CD56+ phenotype, and RNKL. It was proposed that the typical phenotype for NKTCL is: CD56 bright, CD16 dim with positive CD2, CD7, CD94, HLADR, CD25, CD26, and absent CD57. This resembles the phenotype of the CD56 bright immunoregulatory subset of NK cells which we therefore hypothesize is the cell of origin of NKTCL. © 2017 International Clinical Cytometry Society. © 2017 International Clinical Cytometry Society.

  13. Haematological indices in Trypanosoma brucei brucei (Federe isolate infected Nigerian donkeys (Equus asinus treated with homidium and isometamidium chloride of ciprofloxacin in broiler chickens after single intravenous and intraingluvial administration

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    Queen Nneka Oparah


    Full Text Available The efficacy of intramuscular administration of Homidium chloride (Novidium® and Isometamidium chloride (Sécuridium® in Nigerian donkeys (Equus asinus experimentally infected with T. b. brucei (Federe isolate was investigated. Changes in haematological and serum biochemical indices were evaluated using clinical haematology and biochemistry methods. Red blood cell (RBC count for the negative control group was significantly higher than for the positive control, Novidium® and Sécuridium®-treatment groups. Haemoglobin (Hb concentration significantly reduced in the infected untreated group compared with other groups. Packed cell volume (PCV was significantly different between negative and positive controls, and also between the infected untreated and treatment groups. There was significant reduction in platelet counts post-infection and post-treatment. Mean corpuscular volume (MCV increased significantly in the treatment groups while mean corpuscular haemoglobin concentration (MCHC significantly reduced only in the Sécuridium®-treatment group. Lymphocyte count for infected untreated was non-significantly higher than for the uninfected controls, but treatment with both trypanocides recorded further increases, which were higher compared with that of the uninfected group. Post infection and treatment, aspartate aminotransferase (AST levels increased significantly. There were non-significant differences in electrolyte ion concentrations across the groups except for chloride ion which recorded a significant reduction in the Novidium®-treatment group. This experiment revealed that Nigerian donkeys infected with T. brucei brucei (Federe isolate developed symptoms of trypanosomosis; anaemia, lymphocytosis and thrombocytopenia. Treatment with the trypanocides ameliorated effects of the infection, and results suggest that immunosuppression may not be a substantial clinical manifestation of T. brucei brucei (Federe isolate trypanosomosis in Nigerian

  14. Assessment of hemato-biochemical parameters on exposure to low level of deltamethrin in mouse model

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    Anita Tewari


    Full Text Available Aim: In this study, sub-acute toxicity of deltamethrin on hematological and biochemical blood parameters of male albino Swiss mice was evaluated. Materials and Methods: Generally, the maximum permissible residue level (MRL of deltamethrin for food products lies between 0.01 to 0.5 mg/kg body weight. So the mice were exposed orally with two doses of pesticide i.e. 0.1 and 0.5 mg/kg body weight. The doses were given on a daily basis for a period of 15 days and 30 days respectively. Ground nut oil was used as control treatment. Samples of blood were collected at the end of the treatment. Hepatotoxicity was evaluated by quantitative analysis of the serum enzymes alanine transaminase (ALT, aspartate transaminase (AST, alkaline phosphatase (ALKP, total bilirubin (TBIL and serum urea. Alterations of hematological parameters were analysed by total leukocyte, differential leukocyte count and hemoglobin levels. Results: Significant increase in the levels of hepatic enzymes (ALT, AST, ALKP were observed for both doses, but no considerable differences were found by histological analysis. The hematological parameters showed significant alterations for 0.5 mg/kg body weight dose which is indicated by leukocytosis, lymphocytosis and neutropenia in long duration study. Conclusions: The results indicated that even very low dose of deltamethrin can promote hematological and hepatic alterations. Thus it is imperative to do further studies on the detrimental effect of the low levels of pyrethroid commonly present in our food, which further necessitate the reduction of maximum permissible levels of residual synthetic pyrethroid levels in foods and feed.

  15. Coeliac disease and gastrointestinal symptom screening in adult first-degree relatives. (United States)

    Vaquero, Luis; Rodríguez-Martín, Laura; Alvarez-Cuenllas, Begoña; Hernando, Mercedes; Iglesias-Blazquez, Cristina; Menéndez-Arias, Cristina; Vivas, Santiago


    The first-degree relatives (FDRs) of patients with coeliac disease are the main risk group for disease development. The study aims to evaluate the screening strategy in FDRs with negative coeliac serology based on human leukocyte antigen (HLA) genotyping, followed by duodenal biopsy, and to analyze the prevalence of gastrointestinal symptoms and the influence of gluten intake. Adult FDRs with negative coeliac serology were invited to participate (n = 205), and a total of 139 completed the study protocol. HLA genotyping, transglutaminase antibody assessment, and duodenal biopsy were performed. Symptomatology was assessed using questionnaires during the various phases of dietary modification (baseline diet, gluten-free diet, and gluten overload). The study included 139 participants (mean age, 42 years; 53.2% women). HLA-DQ2/8 was positive in 78.4% of the participants (homozygous, 15.1%; heterozygous, 63.3%). Histopathological alterations were noted in 37.1% of participants who underwent duodenal biopsy (Marsh I, 32.7%; Marsh IIIa, 4.4%). At baseline, symptoms were observed in 45.7% of the participants, and the proportion decreased to 24.5% after the gluten-free diet (P < 0.001). Symptoms were not associated with the presence of histological alterations or genetic risk. However, younger age (odds ratio [OR] = 0.91), female sex (OR = 2.9), and the presence of autoimmune disorders (OR = 2.8) were independently associated with a significant symptom response to the gluten-free diet. Duodenal lymphocytosis and atrophy are frequently noted in FDRs, despite negative serological markers. In addition, gastrointestinal symptoms are commonly present and associated with gluten intake regardless of the histological pathology. © 2017 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

  16. [Demonstration of subclinical pulmonary alveolitis in spondylarthropathies]. (United States)

    Jeandel, P; Bonnet, D; Chouc, P Y; Molinier, S; Raphenon, G; Martet, G; Merouze, F; de Muizon, H


    Restrictive ventilatory dysfunction, lowered diffusing capacity, and apical fibrosis have been reported in ankylosing spondylitis. To investigate the pathogenesis of these abnormalities, we studied distal airspace cytology by performing bronchoalveolar lavage in 34 spondyloarthropathy patients (ankylosing spondylitis, n = 16; reactive arthritis, n = 4; axial psoriatic arthritis, n = 2; and undifferentiated spondyloarthropathy with HLA B27-positivity in every case but one, n = 12). Mean age was 32.4 +/- 13.7 years. None of the study patients had apical fibrosis, lower respiratory tract infection, or exposure to airborne pollutants other than tobacco smoke. The control group was composed of nine subjects who had no lung or inflammatory diseases and were not using medications. Significantly higher proportions of lymphocytes were found in bronchoalveolar lavage specimens from patients, as compared with controls. This difference was not influenced by smoking or medication use (non steroidal antiinflammatory drugs, sulfasalazopyridine). Alveolar lymphocytosis was not correlated with laboratory tests for disease activity (erythrocyte sedimentation rate, serum IgA levels) or with the presence of restrictive ventilatory dysfunction. Increases in the proportion of lymphocytes were of similar magnitude in patients with ankylosing spondylitis and in those with other spondyloarthropathies. Absolute total cell counts and relative neutrophil counts were similar in patients and controls. However, among the patients with spondyloarthropathies, those with a disease duration of more than five years had a significantly higher proportion of neutrophils than those with a disease duration of less than five years. These findings demonstrate that spondyloarthropathy patients have subclinical lymphocyte alveolitis. Although of unclear significance, this alveolitis may be related to the development of apical fibrosis in some patients with ankylosing spondylitis.

  17. Correlation between HRCT findings, pulmonary function tests and bronchoalveolar lavage cytology in interstitial lung disease associated with rheumatoid arthritis

    International Nuclear Information System (INIS)

    Biederer, J.; Muhle, C.; Heller, M.; Reuter, M.; Schnabel, A.; Gross, W.L.


    A prospective study correlating high-resolution computed tomography (HRCT), lung function tests (PFT) and bronchoalveolar lavage (BAL) cytology in patients with interstitial lung disease (ILD) associated with rheumatoid arthritis (RA). Fifty-three RA patients with suspected ILD (19 men, 34 women) underwent 71 HRCT (14 of 53 with sequential HRCT, mean follow-up 24.3 months). The HRCT evaluation by two observers on consensus included a semi-quantitative characterisation of lesion pattern and profusion on representative anatomical levels. Fifty-two HRCT were followed by PFT and BAL. Agreement or discordance of HRCT-, PFT- and BAL findings were analysed with Pearson's correlation, κ score and McNemar's test. Tobacco-fume exposure was estimated in pack years. Smoking/non-smoking groups were compared with Student's t test. In 49 of 53 patients, HRCT was suggestive of ILD associated with RA (66 of 71 HRCT). Reticular lesions were found in 40 of 53 patients, in 15 of 40 presenting as mixed pattern with ground-glass opacities (GGO). Pure reticular patterns predominated in patients with long duration of ILD (p>0.01). Pure GGO were not observed. Lesion profusion was highly variable and correlated moderately negative with diffusion capacity (mean 88.2% (SD±20.9%); r=-0.54; p 0.2), but not towards lymphocytosis (κ=0.10; p=0.23; McNemar test p>0.2). Differences in smoking history were not significant (p>0.1). The HRCT appears most appropriate for the detection and follow-up of ILD associated with RA. The PFT and BAL correlate only partially with lesion profusion or grading on HRCT, but they contribute valuable information about dynamic lung function and differential diagnoses (pneumonia, medication side effects). (orig.)

  18. Splenectomy Associated Changes in IgM Memory B Cells in an Adult Spleen Registry Cohort (United States)

    Cameron, Paul U.; Jones, Penelope; Gorniak, Malgorzata; Dunster, Kate; Paul, Eldho; Lewin, Sharon; Woolley, Ian; Spelman, Denis


    Asplenic patients have a lifelong risk of overwhelming post-splenectomy infection and have been reported to have low numbers of peripheral blood IgM memory B cells. The clinical value of quantitation of memory B cells as an indicator of splenic abnormality or risk of infection has been unclear. To assess changes in B cell sub-populations after splenectomy we studied patients recruited to a spleen registry (n = 591). A subset of 209 adult asplenic or hyposplenic subjects, and normal controls (n = 140) were tested for IgM memory B cells. We also determined a) changes in IgM memory B cells with time after splenectomy using the cross-sectional data from patients on the registry and b) the kinetics of changes in haematological markers associated with splenectomy(n = 45). Total B cells in splenectomy patients did not differ from controls, but memory B cells, IgM memory B cells and switched B cells were significantly (psplenectomy. Changes of asplenia in routine blood films including presence of Howell-Jolly bodies (HJB), occurred early (median 25 days) and splenectomy associated thrombocytosis and lymphocytosis peaked by 50 days. There was a more gradual decrease in IgM memory B cells reaching a stable level within 6 months after splenectomy. IgM memory B cells as proportion of B cells was the best discriminator between splenectomized patients and normal controls and at the optimal cut-off of 4.53, showed a true positive rate of 95% and false positive rate of 20%. In a survey of 152 registry patients stratified by IgM memory B cells around this cut-off there was no association with minor infections and no registry patients experienced OPSI during the study. Despite significant changes after splenectomy, conventional measures of IgM memory cells have limited clinical utility in this population. PMID:21829713

  19. Physiological effects of some synthetic food colouring additives on rats. (United States)

    Aboel-Zahab, H; el-Khyat, Z; Sidhom, G; Awadallah, R; Abdel-al, W; Mahdy, K


    Three different synthetic chocolate colourant agents (A, B and C) were administered to healthy adult male albino rats for 30 and 60 day periods to evaluate their effects on body weight, blood picture, liver and kidney functions, blood glucose, serum and liver lipids, liver nucleic acids (DNA and RNA), thyroid hormones (T3 and T4) and growth hormone. In addition, histopathological examinations of liver, kidney and stomach sections were studied. These parameters were also investigated 30 days after colourant stoppage (post effect). Ingestion of colourant C (brown HT and indigocarmine) significantly decreased rat body weight, serum cholesterol and HDL-cholesterol fraction, while, T4 hormone, liver RNA content, liver enzymes (S. GOT, S. GPT and alkaline phosphatase), total protein and globulin fractions were significantly elevated. Significant increases were observed in serum total lipids, cholesterol, triglycerides, total protein, globulin and serum transaminases in rats whose diets were supplemented with chocolate colours A and B (sunset yellow, tartrazine, carmoisine and brilliant blue in varying concentrations). Haematological investigations demonstrated selective neutropenia and lymphocytosis with no significant alterations of total white blood cell counts in all rat groups, while haemoglobin concentrations and red blood cell counts were significantly decreased in the rats who were administered food additives A and B. Eosinophilia was noted in rats fed on colourant A only. No changes were recorded for blood glucose, growth hormone and kidney function tests. Histopathological studies showed brown pigment deposition in the portal tracts and Van Küpffer cells of the liver as well as in the interstitial tissue and renal tubular cells of the kidney mainly induced by colourant A. Congested blood vessels and areas of haemorrhage in both liver and renal sections were revealed in those rats who were given colourants B and C. There were no-untoward-effects recorded in the

  20. Lymphocytic Colitis: Pathologic predictors of response to therapy. (United States)

    Setia, Namrata; Alpert, Lindsay; van der Sloot, Kimberley Wj; Colussi, Dora; Stewart, Kathleen O; Misdraji, Joseph; Khalili, Hamed; Lauwers, Gregory Y


    While the presence of intraepithelial lymphocytosis with surface epithelial damage is a unifying feature of lymphocytic colitis, there are non-classical features that create morphologic heterogeneity between cases. Limited data are available on the significance of these secondary histologic features. Cases of lymphocytic colitis diagnosed between 2002 and 2013 were identified using the Research Patient Data Registry of a tertiary referral center. Diagnostic biopsy slides were reviewed and evaluated for histologic features of lymphocytic colitis. Clinical data including type of therapy and response to treatment were collected. Chi-square (or Fischer's exact test) and logistic regression analysis were used where appropriate. Thirty-two cases of lymphocytic colitis with complete clinical data and slides available for review were identified. The mean age was 56.4 years, and the female-to-male ratio was 3:2. Eleven (11) patients improved with minimal intervention (Group 1), 14 patients responded to steroid therapy (Group 2), and 7 patients responded to mesalamine, bismuth subsalicylate and/or cholestyramine therapy (Group 3). Histologic differences in the characteristics of the subepithelial collagen table (p=0.018), the severity of lamina propria inflammation (p=0.042) and the presence of eosinophil clusters (p=0.016) were seen between groups 2 and 3. Patients in group 1 were more likely to have mild crypt architectural distortion in their biopsies than patients in groups 2 and 3. Lymphocytic colitis is a heterogeneous disease and the evaluation of histologic factors may help identify various subtypes and predict therapy response. Copyright © 2018. Published by Elsevier Inc.

  1. The composition of T cell subtypes in duodenal biopsies are altered in coeliac disease patients.

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    Janni V Steenholt

    Full Text Available One of the hallmarks of Celiac disease (CD is intraepithelial lymphocytosis in the small intestine. Until now, investigations to characterize the T cell subpopulations within the epithelial layer have not discriminated between the heterodimeric co-receptor molecule, CD8αβ, and the possibly immunoregulatory CD8αα homodimer molecule. Besides TCRαβ+ CD4+ cells, no other phenotypes have been shown to be gluten-reactive. Using flow cytometry on lymphocytes from duodenal biopsies, we determined that the number of B cells (CD3- CD19+ and the number of CD3+ CD4- CD8- double-negative (DN T cells were elevated 6-7 fold in children with CD. We next isolated and quantified intraepithelial lymphocytes (IELs from biopsies obtained from patients (both children and adults with CD, potential CD and non-CD controls. Flow cytometric analysis of the duodenal T cell subpopulations was performed including the markers TCRαβ, TCRγδ, CD4, CD8α and CD8β. Proportions of γδ T cells and CD8αβ+ cells among IELs were increased in CD patients, whereas proportions of CD4+ CD8αα+ and CD4+ single-positive T cells were decreased. Additionally, two gluten-reactive T cell lines (TCLs derived from CD biopsies were analyzed for changes in proportions of T cell subsets before and after gluten stimulation. In a proliferation assay, dividing cells were tracked with carboxyfluorescein succinimidyl ester (CFSE, and both αβ and γδ T cells proliferated in response to gluten. Changes in duodenal T cell subpopulations in potential CD patients followed the same pattern as for CD patients, but with less pronounced effect.

  2. Chemical and biological studies of β-carotene after exposure to Cannabis sativa smoke

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    Dulciana S. do Monte

    Full Text Available Considering the increase in consumption of Cannabis sativa and the use of the compound β-carotene (BC as supplement, we investigated potential changes in the chemical and biological proprieties of BC after exposure to C. sativa smoke (CSS. Our results showed that the BC exposed to CSS underwent 98.8% degradation and suffered loss of its antiradical activity. The major degradation products identified were 3-hydroxy-2,4,4-trimethylpentyl2-methylpropanoate and (2-ethyl-3-hydroxyhexyl2-methylpropanoate compounds. These are found in higher levels in the exhalations of colorectal cancer patients and are similar to the toxic products associated with lipid peroxidation of polyunsaturated fatty acids. In toxicological assays using micro-crustacean Artemia salina the BC was non-toxic, while the BC degraded by CSS had a toxicity of LC50 = 397.35 μg/mL. In Wistar rats, females treated with BC degraded by CSS (BCCSS showed whitish liver spots, alterations in liver weight and in bilirubin and alkaline phosphatase levels, and decrease in the number of leukocytes associated with atypical lymphocytosis. In male rats, there was an increase in the number of leukocytes when compared to the control group. In the histopathological analysis, the cortical region of the kidneys showed the presence of discrete amorphous eosinophilic material (cylinders in the lumen of the proximate and distal convoluted tubules. In general, the BC in contact with CSS undergoes chemical changes and exhibits toxicity to rats and Artemia salina. Keywords: Cannabis sativa smoke, β-Carotene, Toxicity, Degradation

  3. Changing haematological parameters in dengue viral infections

    International Nuclear Information System (INIS)

    Jamil, T.; Mehmood, K.; Mujtaba, G.; Choudhry, N.


    Background: Dengue Fever is the most common arboviral disease in the world, and presents cyclically in tropical and subtropical regions of the world. The four serotypes of dengue virus, 1, 2, 3, and 4, form an antigenic subgroup of the flaviviruses (Group B arboviruses). Transmission to humans of any of these serotypes initiates a spectrum of host responses, from in apparent to severe and sometimes lethal infections. Complete Blood count (CBC) is an important part of the diagnostic workup of patients. Comparison of various finding in CBC including peripheral smear can help the physician in better management of the patient. Material and Methods: This cross sectional study was carried out on a series of suspected patients of Dengue viral infection reporting in Ittefaq Hospital (Trust). All were investigated for serological markers of acute infection. Results Out of 341 acute cases 166 (48.7%) were confirmed by IgM against Dengue virus. IgG anti-dengue was used on 200 suspected re-infected patients. Seventy-one (39.5%) were positive and 118 (59%) were negative. Among 245 confirmed dengue fever patients 43 (17.6%) were considered having dengue hemorrhagic fever on the basis of lab and clinical findings. Raised haematocrit, Leukopenia with relative Lymphocytosis and presence atypical lymphocytes along with plasmacytoid cells was consistent finding at presentation in both the patterns of disease, i.e., Dengue Haemorrhagic fever (DHF) and Dengue fever (DF). Conclusion: Changes in relative percentage of cells appear with improvement in the symptoms and recovery from the disease. These findings indicate that in the course of the disease, there are major shifts within cellular component of blood. (author)

  4. Blood Profile of Rabbits Infected with Eimeria magna

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    A Hana


    Full Text Available Abstract. The research aimed at determining the blood profile of local rabbits infected with different dose of Eimeria magna oocysts. This research used 45 male rabbits with the age of 4 month old, range from 1.5 to 1.8 kg, clinically healthy and free from coccidiosis. The rabbits were randomly divided into 3 groups, group I as control (K-0 was given 1.0 ml distilled water/rabbit orally, group II (K-10 was infected with single dose of 10x106 oocysts of E. magna/rabbit orally, and group III (K-20 was infected with single dose of 20x106 oocysts of E. magna/rabbit orally. After infection, rabbits were examined for clinical signs, body weight and temperature daily for five days. Blood samples were drawn from the vena marginalis to examine the number of erythrocytes, hemoglobine, packed cell volume (PCV, leukocytes and its deferent, total protein plasma (TPP and fibrinogen, activities of alkaline phosphatase (ALP, alanine amino transferase (ALT, and aspartat aminotransferase (AST. The data were statistically analyzed by two-way anova using factorial design. The results of this research showed that the infection of E. magna in rabbits caused fever and weight loss, accompanied by normochromic microcytic anemia (at doses of 10x106 oocysts, macrocytic normochromic (at doses of 20x106 oocysts, leukocytosis, lymphocytosis, hiperfibrinogenemia, and increased of ALP activity. There were correlations between clinical symptoms and blood profile of rabbits infected with E. magna for five days. The higher the dose and the longer the infection of E. magna in rabbits caused weight loss, increased body temperature, MCV (microcytic to macrocytic, leukocyte, fibrinogen and ALP activity. These findings were useful to have a better understanding of pathophysiology of E. magna infection in  rabbits. Key Words: Eimeria magna, oocyst, rabbit, blood profile A Hana et al/Animal Production 13(3:185-190 (2011

  5. Increased expression of the regulatory T cell-associated marker CTLA-4 in bovine leukemia virus infection. (United States)

    Suzuki, Saori; Konnai, Satoru; Okagawa, Tomohiro; Ikebuchi, Ryoyo; Nishimori, Asami; Kohara, Junko; Mingala, Claro N; Murata, Shiro; Ohashi, Kazuhiko


    Regulatory T cells (Tregs) play a critical role in the maintenance of the host's immune system. Tregs, particularly CD4(+)CD25(+)Foxp3(+) T cells, have been reported to be involved in the immune evasion mechanism of tumors and several pathogens that cause chronic infections. Recent studies showed that a Treg-associated marker, cytotoxic T-lymphocyte antigen 4 (CTLA-4), is closely associated with the progression of several diseases. We recently reported that the proportion of Foxp3(+)CD4(+) cells was positively correlated with the number of lymphocytes, virus titer, and virus load but inversely correlated with IFN-γ expression in cattle infected with bovine leukemia virus (BLV), which causes chronic infection and lymphoma in its host. Here the kinetics of CTLA-4(+) cells were analyzed in BLV-infected cattle. CTLA-4 mRNA was predominantly expressed in CD4(+) T cells in BLV-infected cattle, and the expression was positively correlated with Foxp3 mRNA expression. To test for differences in the protein expression level of CTLA-4, we measured the proportion of CTLA-4-expressing cells by flow cytometry. In cattle with persistent lymphocytosis (PL), mean fluorescence intensities (MFIs) of CTLA-4 on CD4(+) and CD25(+) T cells were significantly increased compared with that in control and aleukemic (AL) cattle. The percentage of CTLA-4(+) cells in the CD4(+) T cell subpopulation was positively correlated with TGF-β mRNA expression, suggesting that CD4(+)CTLA-4(+) T cells have a potentially immunosuppressive function in BLV infection. In the limited number of cattle that were tested, the anti-CTLA-4 antibody enhanced the expression of CD69, IL-2, and IFN-γ mRNA in anti-programmed death ligand 1 (PD-L1) antibody-treated peripheral blood mononuclear cells from BLV-infected cattle. Together with previous findings, the present results indicate that Tregs may be involved in the inhibition of T cell function during BLV infection. Copyright © 2014 Elsevier B.V. All rights

  6. Strongyle Infection and Gut Microbiota: Profiling of Resistant and Susceptible Horses Over a Grazing Season

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    Allison Clark


    Full Text Available Gastrointestinal strongyles are a major threat to horses' health and welfare. Given that strongyles inhabit the same niche as the gut microbiota, they may interact with each other. These beneficial or detrimental interactions are unknown in horses and could partly explain contrasted susceptibility to infection between individuals. To address these questions, an experimental pasture trial with 20 worm-free female Welsh ponies (10 susceptible (S and 10 resistant (R to parasite infection was implemented for 5 months. Fecal egg counts (FEC, hematological and biochemical data, body weight and gut microbiological composition were studied in each individual after 0, 24, 43, 92 and 132 grazing days. R and S ponies displayed divergent immunological profiles and slight differences in microbiological composition under worm-free conditions. After exposure to natural infection, the predicted R ponies exhibited lower FEC after 92 and 132 grazing days, and maintained higher levels of circulating monocytes and eosinophils, while lymphocytosis persisted in S ponies. Although the overall gut microbiota diversity and structure remained similar during the parasite infection between the two groups, S ponies exhibited a reduction of bacteria such as Ruminococcus, Clostridium XIVa and members of the Lachnospiraceae family, which may have promoted a disruption of mucosal homeostasis at day 92. In line with this hypothesis, an increase in pathobionts such as Pseudomonas and Campylobacter together with changes in several predicted immunological pathways, including pathogen sensing, lipid metabolism, and activation of signal transduction that are critical for the regulation of immune system and energy homeostasis were observed in S relative to R ponies. Moreover, S ponies displayed an increase in protozoan concentrations at day 92, suggesting that strongyles and protozoa may contribute to each other's success in the equine intestines. It could also be that S individuals

  7. [Small vessel-childhood primary angiitis of the central nervous system: a case report and literature review]. (United States)

    Deng, J; Fang, F; Wang, X H; Ge, M; He, L J; Zhang, N


    Objective: To summarize the clinical and pathological features of small vessel-childhood primary angiitis of the central nervous system (SV-cPACNS), discuss the immune therapy and increase the attention to brain biopsy in SV-cPACNS. Methods: The clinical data, pathology of brain biopsy, treatment and outcome of an SV-cPACNS patient hospitalized in Beijing Children's Hospital in February 2016 were analyzed retrospectively. The cases reported at Pubmed, CNKI and Wanfang databases from 2007 to 2017 were searched, the clinical and pathological features, immunotherapy and prognosis of the disease were summarized according to the literature review. Results: A 70 months old girl had 6 times relapses during 5 months' disease course. Symptoms included convulsions, limb paralysis, blurred vision and speech difficulty. Multiple cortical lesions were found successively in brain MRI but CT angiography was negative. The pathology of brain biopsy revealed thickening of small vessel walls together with lymphocytic infiltration. After the treatment with rituximab, remission was achieved and remained stable without recurrence in 1 year follow up. A total of 44 pathologically confirmed cases reported in nearly 10 years were retrieved. Male to female ratio was 1∶3.5. The average onset age was 9.8 years. Clinical manifestations included seizures (37/45, 82%), headache (35/45, 78%), cognitive decline (28/45, 62%), speech regression(20/45, 44%), paralysis (15/45, 33%), and so on; 70% (19/27) patients experienced relapses. Erythrocyte sedimentation rate and C-reactive protein slightly elevated, antinuclear antibody and other autoimmune antibodies were mostly negative. Mild lymphocytosis in cerebrospinal fluid was found in 67%(29/43) patients. 53%(23/43) patients had elevated CSF protein level, several had elevated IgG and positive oligoclonal band. Bilateral multifocal lesions were revealed in 80% (36/45) brain MRIs, meanwhile all angiographies were unremarkable. The pathology showed

  8. The Transcription Profile of Tax-3 Is More Similar to Tax-1 than Tax-2: Insights into HTLV-3 Potential Leukemogenic Properties (United States)

    Chevalier, Sébastien A.; Durand, Stéphanie; Dasgupta, Arindam; Radonovich, Michael; Cimarelli, Andrea; Brady, John N.


    Human T-cell Lymphotropic Viruses type 1 (HTLV-1) is the etiological agent of Adult T-cell Leukemia/Lymphoma. Although associated with lymphocytosis, HTLV-2 infection is not associated with any malignant hematological disease. Similarly, no infection-related symptom has been detected in HTLV-3-infected individuals studied so far. Differences in individual Tax transcriptional activity might account for these distinct physiopathological outcomes. Tax-1 and Tax-3 possess a PDZ binding motif in their sequence. Interestingly, this motif, which is critical for Tax-1 transforming activity, is absent from Tax-2. We used the DNA microarray technology to analyze and compare the global gene expression profiles of different T- and non T-cell types expressing Tax-1, Tax-2 or Tax-3 viral transactivators. In a T-cell line, this analysis allowed us to identify 48 genes whose expression is commonly affected by all Tax proteins and are hence characteristic of the HTLV infection, independently of the virus type. Importantly, we also identified a subset of genes (n = 70) which are specifically up-regulated by Tax-1 and Tax-3, while Tax-1 and Tax-2 shared only 1 gene and Tax-2 and Tax-3 shared 8 genes. These results demonstrate that Tax-3 and Tax-1 are closely related in terms of cellular gene deregulation. Analysis of the molecular interactions existing between those Tax-1/Tax-3 deregulated genes then allowed us to highlight biological networks of genes characteristic of HTLV-1 and HTLV-3 infection. The majority of those up-regulated genes are functionally linked in biological processes characteristic of HTLV-1-infected T-cells expressing Tax such as regulation of transcription and apoptosis, activation of the NF-κB cascade, T-cell mediated immunity and induction of cell proliferation and differentiation. In conclusion, our results demonstrate for the first time that, in T- and non T-cells types, Tax-3 is a functional analogue of Tax-1 in terms of transcriptional activation and

  9. Analysis of sarcoidosis in the Oporto region (Portugal

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    A.V. Cardoso


    Full Text Available Background: Sarcoidosis is a systemic granulomatous disease of unknown etiology. Epidemiological studies of different populations are essential because clinical presentation, organ involvement, disease severity, and prognosis vary significantly according to region and population. The aim of this study was to assess epidemiological and clinical characteristics, staging factors, and clinical course in patients with sarcoidosis from a tertiary hospital in Oporto, Portugal. Methods: A retrospective analysis of patients with sarcoidosis and at least 2 years of follow-up evaluated at the Centro Hospitalar de São João between 2000 and 2014. Results: We identified 409 patients with sarcoidosis (females, 58.9%; mean age at diagnosis, 38.9 ± 13.4 years; smokers, 14.4%]. All the patients were diagnosed according to the ERS/ATS/WASOG consensus statement and 64.1% had evidence of noncaseating epithelioid cell granulomas in biopsy specimens. Bronchoalveolar lavage was performed as part of the diagnostic work-up in 289 patients and 90.2% had lymphocytosis (CD4/CD8 ratio ≥ 3.5 in 60.9% of cases. Exertion dyspnea, cough, and constitutional symptoms were the most common presenting symptoms; 10.1% of patients were asymptomatic, 22.8% had Löfgren syndrome, and 50.5% had extrathoracic involvement. Radiographic stages of disease according to the Scadding criteria were as follows: stage 0 (5.2%, stage I (33.7%, stage II (47.0%, stage III (8.4%, and stage IV (5.7%. Impaired respiratory function was observed in 45.6% patients and was mostly mild. Systemic treatment was administered in 58.6% of cases. Overall, 45.3% of patients experienced disease resolution. Conclusion: The epidemiological and clinical characteristics of this cohort of patients with sarcoidosis from the Oporto region in northern Portugal revealed epidemiological and clinical characteristics that were generally similar to those described in other Western Europe populations and

  10. HaNDL syndrome: Correlation between focal deficits topography and EEG or SPECT abnormalities in a series of 5 new cases. (United States)

    Barón, J; Mulero, P; Pedraza, M I; Gamazo, C; de la Cruz, C; Ruiz, M; Ayuso, M; Cebrián, M C; García-Talavera, P; Marco, J; Guerrero, A L


    Transient headache and neurological deficits with cerebrospinal fluid lymphocytosis (HaNDL) is characterised by migraine-like headache episodes accompanied by neurological deficits consisting of motor, sensory, or aphasic symptoms. Electroencephalogram (EEG) and single photon emission computed tomography (SPECT) may show focal abnormalities that correspond to the neurological deficits. We aim to evaluate the correlation between focal deficit topography and EEG or SPECT abnormalities in 5 new cases. We retrospectively reviewed patients attended in a tertiary hospital (January 2010-May 2014) and identified 5 patients (3 men, 2 women) with a mean age of 30.6 ± 7.7 (21-39) years. They presented 3.4 ± 2.6 episodes of headache (range, 2-8) of moderate to severe intensity and transient neurological deficits over a maximum of 5 weeks. Pleocytosis was detected in CSF in all cases (70 to 312 cells/mm3, 96.5-100% lymphocytes) with negative results from aetiological studies. At least one EEG was performed in 4 patients and SPECT in 3 patients. Patient 1: 8 episodes; 4 left hemisphere, 3 right hemisphere, and 1 brainstem; 2 EEGs showing left temporal and bilateral temporal slowing; normal SPECT. Patient 2: 2 episodes, left hemisphere and right hemisphere; SPECT showed decreased left temporal blood flow. Patient 3: 3 left hemisphere deficits; EEG with bilateral frontal and temporal slowing. Patient 4: 2 episodes with right parieto-occipital topography and right frontal slowing in EEG. Patient 5: 2 episodes, right hemisphere and left hemisphere, EEG with right temporal slowing; normal SPECT. The neurological deficits accompanying headache in HaNDL demonstrate marked clinical heterogeneity. SPECT abnormalities and most of all EEG abnormalities were not uncommon in our series and they did not always correlate to the topography of focal déficits. Copyright © 2014 Sociedad Española de Neurología. Published by Elsevier España, S.L.U. All rights reserved.

  11. The production of the oral mucosa of antiendomysial and anti-tissue-transglutaminase antibodies in patients with celiac disease: a review. (United States)

    Compilato, Domenico; Campisi, Giuseppina; Pastore, Luca; Carroccio, Antonio


    Celiac disease (CD) is a lifelong, T cell-mediated enteropathy, triggered by the ingestion of gluten and related prolamins in genetically susceptible subjects, resulting in minor intestinal mucosal injury, including villous atrophy with crypt hyperplasia and intraepithelial lymphocytosis, and subsequent nutrient malabsorption. Although serological tests for antiendomysial (EMA) and anti-tissue transglutaminase (anti-tTG) autoantibodies are used to screen and follow up on patients with CD, diagnostic confirmation is still based on the histological examination of the small intestinal mucosa. Although the small intestinal mucosa is the main site of the gut involved in CD, other mucosal surfaces (such as gastric, rectal, ileal, and esophageal) belonging to the gastrointestinal tract and the gut-associated lymphoid tissue (GALT) can also be involved. A site that could be studied less invasively is the mouth, as it is the first part of the gastrointestinal system and a part of the GALT. Indeed, not only have various oral ailments been reported as possible atypical aspects of CD, but it has been also demonstrated that inflammatory changes occur after oral supramucosal application and a submucosal injection of gliadin into the oral mucosa of CD patients. However, to date, only two studies have assessed the capacity of the oral mucosa of untreated CD patients to EMA and anti-tTG antibodies. In this paper, we will review studies that evaluate the capacity of the oral mucosa to produce specific CD autoantibodies. Discrepancies in sensitivity from the two studies have revealed that biopsy is still not an adequate procedure for the routine diagnostic purposes of CD patients, and a more in-depth evaluation on a larger sample size with standardized collection and analysis methods is merited. However, the demonstration of immunological reactivity to the gluten ingestion of the oral mucosa of CD, in terms of IgA EMA and anti-tTG production, needs to be further evaluated in order to

  12. Leucemia de grandes linfócitos granulares Large granular lymphocyte leukemia

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    Bruno Terra


    Full Text Available O presente estudo tem como objetivo o estabelecimento de fundamentação teórica atualizada baseada em revisão bibliográfica sobre a leucemia de grandes linfócitos granulares (LGLG, doença onco-hematológica, que, devido à sua relativa raridade, é pouco conhecida e subdiagnosticada. A LGLG é caracterizada pela proliferação clonal de linfócitos T ou NK na medula óssea e/ou no sangue periférico. Dentre as manifestações clínico-laboratoriais, podem ocorrer citopenias (anemia e/ou neutropenia e/ou plaquetopenia, linfocitose (não costuma ser acentuada, linfadenomegalia, hepatoesplenomegalia, alterações imunológicas e sintomas constitucionais (emagrecimento, febre e sudorese. O curso clínico da LGLG é bastante variável, sendo que no subtipo T costuma ser indolente ou oligossintomática, enquanto no subtipo NK a evolução costuma ser desfavorável. O diagnóstico é firmado através de imunofenotipagem por citometria de fluxo e estudo de clonalidade por métodos de biologia molecular. Seu tratamento é bastante diversificado e é definido de acordo com a apresentação clínica da doença.This is a literature review about large granular lymphocyte leukemia (LGLL, a rare and misdiagnosed oncohematological disease, characterized by a clonal expansion of T-cells (T-LGLL or NK-cells (NK-LGLL in the bone marrow and/or peripheral blood. The clinical features of LGLL include cytopenias (anemia, neutropenia and thrombocytopenia, lymphocytosis (usually discrete, lymphadenopathy, hepatomegaly, splenomegaly, immune abnormalities and constitutional symptoms (fever, night sweats and weight loss. The diagnosis is based on the confirmation of the clonality of T-cells or NK-cells (polymerase chain reaction and Southern blot are the two methods most commonly used and typical findings of the immunophenotypic analysis of peripheral blood lymphocytes (flow cytometry analyses for specific surface antigens. In contrast to the chronic and indolent

  13. First clinical case report of Cytauxzoon sp. infection in a domestic cat in France. (United States)

    Legroux, Jean-Pierre; Halos, Lénaïg; René-Martellet, Magalie; Servonnet, Marielle; Pingret, Jean-Luc; Bourdoiseau, Gilles; Baneth, Gad; Chabanne, Luc


    Feline cytauxzoonosis is an emerging infection caused by tick-transmitted apicomplexan parasites of the genus Cytauxzoon. The association of clinical disease with Cytauxzoon infection appears to be limited to C. felis infections in the Americas. Sporadic infections of wild and domestic felids with Cytauxzoon sp. were recently described in European countries but clinical reports of the infection are rare and incomplete. This case report brings new interesting information on cytauxzoonosis expression in Europe. A 9-years-old castrated European shorthair cat living in rural area of north-eastern France (Saint Sauveur, Bourgogne-Franche-Comté region), without any travel history was presented for consultation due to hyperthermia, anorexia, depression and prolonged fever that didn't respond to antibiotic therapy. The cat had outdoor access with a history of vagrancy and was adequately vaccinated (core vaccines and FeLV vaccine). During biological investigations, intraerythrocytic inclusions were observed on blood smear and were further investigated by PCR analysis and sequencing. Molecular analyses confirmed Cytauxzoon sp. infection. The cat was treated with a subcutaneous injection of imidocarb dipropionate (3.5 mg/kg). One week after treatment, the cat improved clinically, although parasitic inclusions within erythrocytes persisted, and only a mild lymphocytosis was found. Two weeks after treatment, the cat appeared in excellent health, appetite was normal and parasitemia was negative. However, one month after treatment the cat relapsed with hyperthermia, anorexia, and depression. Blood smears and PCR were once again positive. Subsequently, the cat received an additional dose of imidocarb dipropionate (3.5 mg/kg SC) and recovered rapidly without other clinical signs. Two weeks after the second imidocarb injection, the cat was hit by a car and died. This case provides the first clinical description of infection by Cytauxzoon sp. in a domestic cat in France. These

  14. Fatal pneumonia by Legionella in a farmer with hypersensitivity pneumonitis Neumonía por Legionella con desenlace fatal en un granjero con neumonitis por hipersensibilidad

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    Vega García López


    Full Text Available Background: The retrospective investigation of a fatal sporadic Legionnaires' disease identified an unknown case of occupational hypersensitivity pneumonitis in a swine breeder. Methods: Chest high-resolution computed tomography, bronchoalveolar lavage, lung biopsy, arterial gasometry, pulmonary function tests and autopsy were performed. It was studied the presence of Legionella by serology and risk water samples were analyzed to identify the Legionella's source. Results: HP and Legionella pneumophila pneumonia diagnostics were confirmed. Lung fibrosis, a restrictive functional pattern, decreased diffusion, hypoxemia and bronchoalveolar lavage lymphocytosis were evidenced. Legionella´s source was detected in a shower and a positive serology in the patient. Autopsy verified pulmonary fibrosis and the septic shock leaded to Legionella causing the death. Conclusions: Chronic cough and pulmonary infiltrates in a farmer should suspect the presence of hypersensitivity pneumonitis. Later diagnosis carries a worse prognosis, the offending antigens exposure can't be avoided and fibrotic stage enhanced opportunity infection disease.Introducción: La investigación retrospectiva sobre un fallecimiento aislado por Legionelosis, hizo aflorar un caso de neumonitis por hipersensibilidad en un granjero cuidador de cerdos. Métodos: Se realizaron las siguientes pruebas: tomografía axial computerizada de alta resolución, lavado broncoalveolar, biopsia pulmonar, gasometría arterial, pruebas de función respiratoria y autopsia. Se estudió la presencia de Legionella por serología y se analizaron las muestras de fuentes de riesgo para identificar el foco de Legionella. Resultados: El estudio confirmó los diagnósticos de neumonitis por hipersensibilidad y neumonía por Legionella pneumophila. Las pruebas realizadas objetivaron la fibrosis pulmonar, un patrón respiratorio funcional restrictivo, un descenso de la difusión pulmonar, hipoxemia y la presencia de

  15. The Production of the Oral Mucosa of Antiendomysial and Anti—Tissue-Transglutaminase Antibodies in Patients with Celiac Disease: A Review

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    Domenico Compilato


    Full Text Available Celiac disease (CD is a lifelong, T cell—mediated enteropathy, triggered by the ingestion of gluten and related prolamins in genetically susceptible subjects, resulting in minor intestinal mucosal injury, including villous atrophy with crypt hyperplasia and intraepithelial lymphocytosis, and subsequent nutrient malabsorption. Although serological tests for antiendomysial (EMA and anti—tissue transglutaminase (anti-tTG autoantibodies are used to screen and follow up on patients with CD, diagnostic confirmation is still based on the histological examination of the small intestinal mucosa. Although the small intestinal mucosa is the main site of the gut involved in CD, other mucosal surfaces (such as gastric, rectal, ileal, and esophageal belonging to the gastrointestinal tract and the gut-associated lymphoid tissue (GALT can also be involved. A site that could be studied less invasively is the mouth, as it is the first part of the gastrointestinal system and a part of the GALT. Indeed, not only have various oral ailments been reported as possible atypical aspects of CD, but it has been also demonstrated that inflammatory changes occur after oral supramucosal application and a submucosal injection of gliadin into the oral mucosa of CD patients. However, to date, only two studies have assessed the capacity of the oral mucosa of untreated CD patients to EMA and anti-tTG antibodies. In this paper, we will review studies that evaluate the capacity of the oral mucosa to produce specific CD autoantibodies. Discrepancies in sensitivity from the two studies have revealed that biopsy is still not an adequate procedure for the routine diagnostic purposes of CD patients, and a more in-depth evaluation on a larger sample size with standardized collection and analysis methods is merited. However, the demonstration of immunological reactivity to the gluten ingestion of the oral mucosa of CD, in terms of IgA EMA and anti-tTG production, needs to be further

  16. Tomographic findings of acute pulmonary toxoplasmosis in immunocompetent patients. (United States)

    de Souza Giassi, Karina; Costa, Andre Nathan; Apanavicius, Andre; Teixeira, Fernando Bin; Fernandes, Caio Julio Cesar; Helito, Alfredo Salim; Kairalla, Ronaldo Adib


    Toxoplasmosis is one of the most common human zoonosis, and is generally benign in most of the individuals. Pulmonary involvement is common in immunocompromised subjects, but very rare in immunocompetents and there are scarce reports of tomographic findings in the literature. The aim of the study is to describe three immunocompetent patients diagnosed with acute pulmonary toxoplasmosis and their respective thoracic tomographic findings. Acute toxoplasmosis was diagnosed according to the results of serological tests suggestive of recent primary infection and the absence of an alternative etiology. From 2009 to 2013, three patients were diagnosed with acute respiratory failure secondary to acute toxoplasmosis. The patients were two female and one male, and were 38, 56 and 36 years old. Similarly they presented a two-week febrile illness and progressive dyspnea before admission. Laboratory tests demonstrated lymphocytosis, slight changes in liver enzymes and high inflammatory markers. Tomographic findings were bilateral smooth septal and peribronchovascular thickening (100%), ground-glass opacities (100%), atelectasis (33%), random nodules (33%), lymph node enlargement (33%) and pleural effusion (66%). All the patients improved their symptoms after treatment, and complete resolution of tomographic findings were found in the followup. These cases provide a unique description of the presentation and evolution of pulmonary tomographic manifestations of toxoplasmosis in immunocompetent patients. Toxoplasma pneumonia manifests with fever, dyspnea and a non-productive cough that may result in respiratory failure. In animal models, changes were described as interstitial pneumonitis with focal infiltrates of neutrophils that can finally evolve into a pattern of diffuse alveolar damage with focal necrosis. The tomographic findings are characterized as ground glass opacities, smooth septal and marked peribronchovascular thickening; and may mimic pulmonary congestion

  17. Molecular Study of Parvovirus B19 Infection in Children with (United States)

    Tharwat Abou El-Khier, Noha; Darwish, Ahmad; El Sayed Zaki, Maysaa


    Background: Parvovirus B19 is a common viral infection in children. Nearby evidences are present about its association with acute leukemia, especially acute lymphoblast leukemia. Nevertheless, scanty reports have discussed any role in acute myeloid leukemia (AML). Purpose: To evaluate the frequency of virological markers of B19 infection including its DNA along with specific immunoglobulins G (IgG) and M (IgM) among children with newly diagnosed AML. Besides, describing the clinical importance of Parvovirus B19 infection in those patients. Patients and methods: A case-control retrospective study was conducted on 48 children recently diagnosed with AML before and during chemotherapy induction and 60 healthy control. Specific serum IgM and IgG levels were determined by enzyme linked immunosorbant assay (ELISA) and DNA detection by polymerase chain reaction (PCR). Results: Parvovirus DNA was detected in 20 patients with AML. IgM was found in sera of four patients and one case had positive DNA and IgG (5%). Patients with recent parvovirus B19 infection had a significantly reduced hemoglobin levels, RBCs counts, platelet counts, neutrophil counts and absolute lymphocytosis (p=0.01, p=0.0001, p=0.01, p=0.02, p=0.0003, respectively). There were no clinical findings with statistically significant association to recent infection. Half of the patients with AML had positive PCR and/or IgM for parvovirus B19. Among children with AML under chemotherapy, there were reduced hemoglobin levels (P=0.03), reduced platelet counts (P=0.0001) and absolute neutropenia (mean±SD, 1.200 ±1.00) in those with parvovirus B19 infection. More than half of patients with parvovirus B19 (72.2%) had positive PCR and/or IgM and 36.4% of them had positive IgG. Conclusion: This study highlights that parvovirus B19 is common in children with AML either at diagnosis or under chemotherapy. There are no clinical manifestations that can be used as markers for its presence, but hematological laboratory


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    Kuchma I.U


    the serum; CBC was performed, the determination of CD3, CD4, CD8, CD16, CD19, IgM, IgG, IgA, IgE, CEC serum cytokines and sIgA in the oropharyngeal fluid. Results and discutions. Group of patients who are not identified in the throat S. pyogenes and S. aureus revealed EBV DNA and identified EVB-EA-IgG and EVB-VCA-IgM was 20 people (chronic tonsillitis associated with EBV infection. A group of patients in whom there was no EBV DNA in saliva and throat was isolated S. pyogenes, S. aureus was 60 people (chronic tonsillitis associated with bacterial infection. Control group consisted of relatively healthy people - 20 people. Patients with EBV infection was observed leukocytosis, lymphocytosis; increasing the number of B lymphocytes (CD19, IgM, IgА and IgE, increasing the CEC, ІNF- , L-1, IL-4, IL-6, IL-10, IL-17 and sIg A. Patients mentioned bacterial tonsillitis increased Ig G, IgA, and IgE, and a significant increase in CEC; increase ІNF- , IL-1, IL-4, IL-6, IL-17. ІNF-, IL-10 levels were not significantly different from the control. Number sIg A was reduced. Conclusions:1. Relationship between exacerbation of tonsillitis and EBV infection was confirmed by the presence of fluid in the oropharyngeal EBV DNA and antibodies to EBV early antigens. 2. For acute EBV infection is characterized by leukocytosis, lymphocytosis; possibly in the presence of abnormal blood mononuclear cells in a small amount. 3. For acute EBV infection is characterized by increase in the number of B-lymphocytes and levels of IgM, IgА and IgE in serum, as well as increasing the CEC. 4. In the local cytokine status for acute EBV infection, in contrast to bacterial tonsillitis characterized by increased levels ІNF- and IL-10. 5. The treatment of acute exacerbations of chronic tonsillitis often empirically prescribers ampicillin and amoxicillin. In the case of EBV infection activation function of these antibiotics is contraindicated and may cause allergic reactions, up to anaphylactic

  19. Interferon therapy of acute respiratory viral infections in children

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    A.E. Abaturov


    within the age limit and corresponded to the temperature response. Analyzing the dynamics of clinical symptoms of acute respiratory viral infection in both groups, it should be noted that there was a persistent tendency to lower body temperature in patients, both in the main and control groups. However, in the group of patients receiving Laferobionum®, the decrease in the temperature curve occurred faster, its normalization was noted already on the 4th day of therapy in 100 % of patients, whereas in the control group on the 4th day of the disease the body temperature remained subfebrile in 12 (28.6 %, on the 5th day — in 2 (4.8 % children. Complete blood count in children of the main and control groups at the beginning of the disease showed leukopenia of varying severity, relative lymphocytosis, and accelerated erythrocyte sedimentation rate (ESR. On the 5th day of therapy in patients of the main group, the number of leukocytes was normalized, the relative lymphocytosis persisted against the background of a decrease in ESR. While in the control group, the number of leukocytes in peripheral blood remained lower with an elevated level of ESR. During the whole period of observation, the presence and nature of possible complications of acute respiratory viral infection was assessed. The total duration of the observation period was 14 days. During the observation period, no complications were detected in any of the patients in the main or control groups. During the time of the clinical trial, no adverse reactions were recorded that could be associated with the administration of Laferobionum®. There were no cases of exacerbation of existing chronic diseases in the children of the main group, while 1 (2.4 % person from the control group had exacerbation of chronic tonsillitis. Evaluation of the effectiveness of therapy with the drug was carried out on the 5th day of treatment. Since one of the effectiveness criteria was the absence of clinical signs of the disease at the

  20. Pleural mesothelioma in differential diagnostics of a tubercular exudative pleuritis

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    O.M. Raznatovskaya


    Rivalta’s test, a lymphocytosis of 93–100 %, a proliferation of mesothelium with dystrophia signs in cytoplasma, groups of cells with enlarged nucleoluses in cell cores; aspirate of epithelial lining fluid (even in the absence of pathology of a tracheobronchial tree is presented by alveolus cells and bronchial epithelium, glandular groups of cells with hyperplasia signs; typical signs of pleura mesothelioma of pleural cavity at ultrasound examination were: identification of formations of rounded shape, various echogenicity, the sizes and quantity (depending on a form: nodular or diffusive, with accurate contours of masses which intimately adjoins to visceral pleura and the structure often contains from single to numerous small hyperechogenic inclusions against the background of liquid; in all cases video-assisted thoracoscopy data of visceral pleura was confirmed by pathohistological examination. Conclusions. All applied diagnostic methods were high-informative that allowed quickly diagnose and prescribe the correct treatment. On their basis the algorithm of differential diagnostics of specific exudative pleuritis and caused pleura mesotheliomas were roentgenography of thoracic organs (if possible computer tomography, an ultrasonic examination of thoracic organs, cytologic research of pleural liquid, video thoracoscopy with biopsy of parietal pleura, research of pleura smear and pathohistological examination of biopsy material.


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    Kirsanova T.O.


    moderately severe and severe forms. Analysis of clinical data showed that almost all children with acute illness began with symptoms of intoxication, temperature up to 38,0-400C, headache, some children had vomiting. Rash appeared mostly often by the end of the second day. Items were rash as spots 1-3 mm in diameter, round, pink with sharp edges. Subsequently, they were transformed into papules, vesicles, crusts, which were located on noninfiltrated background skin, usually separately without a tendency to merge. New elements of rash appear after 1-2 days and accompanied by fever. Almost half part of children forming vesicles recorded in the mucous membranes of the mouth, genitals and conjunctiva during 4-5 days. In hemogramma of patients revealed leukopenia, lymphocytosis. A quarter of children with CP occurred complications that are most often developed for third-eighth day of the appearance of lesions regardless of severity of clinical manifestations of the disease. The structure dominated by non-specific complications of skin lesions with the development of inflammatory diseases streptococcal and staphylococcal etiology. The structure of specific complications observed CNS with the development of meningitis, encephalitis and meningoencephalitis. Conclusions. Over the past five years in the Kharkiv region incidence of children with CP remains high with the major indices among children under 15 years. The most vulnerable are children with organized groups (especially closed children's institutions residing in the city. There has stable tendency to increasing number of complications, particularly specific. High incidence, frequency and severity of complications dictate the need for mandatory vaccination against CP in children. First of all, in our view, it is necessary to consider compulsory vaccination of children from child care centers closed, and may in the future enter into the National calendar of vaccination of healthy children Ukraine. The use of mandatory

  2. Usefulness of jejunal biopsy in the study of intestinal malabsorption in the elderly Utilidad de la biopsia yeyunal en el estudio de la malabsorción intestinal en el anciano

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    B. Lobo


    Full Text Available Background: small bowel structure and function are not different between elderly people and young people. Thus, in principle it is advisable to perform diagnostic investigation of elderly patients as well as younger patients when they present with symptoms suggestive of intestinal malabsorption. A key test for the etiologic diagnosis of intestinal malabsorption, jejunal biopsy, has not been specifically examined to assess its usefulness and risk of complications in this advanced age patients. Aim: to establish the usefulness of jejunal biopsy with the Watson's capsule in the elderly patients with suspected intestinal malabsorption. Patients: patients older than 65 years referred to our Unit for performance of a jejunal biopsy from 1996 to 2001 for suspicion of intestinal malabsorption. Results: forty-seven patients were included. Appropriate biopsy sample was obtained in 45 cases, although in 3 patients a second try was required. Histologic findings: partial villous atrophy in 10 cases (22.2%, complete villous atrophy in 5 cases (11.1%, intraepithelial lymphocytosis in 5 cases (11.1%, and single cases of intestinal lymphangiectasia, amyloidosis, unspecific jejunitis, and Whipple's disease. Histology was normal in 19 cases (42%. Definitive diagnosis was celiac disease in 14 patients, bacterial overgrowth in 3, jejunitis in 3, Whipple's disease in 1, lymphangiectasia in 1, atrophic gastritis in 3, amyloidosis in 1, and ischemic colitis in 1. Jejunal biopsy achieved an etiologic diagnosis in 20 patients. There were no cases of perforations or bleeding. Conclusion: jejunal biopsy is a useful and safe test for the etiologic diagnosis of intestinal malabsorption in elderly patients.Fundamento: la estructura y función del intestino delgado en el anciano sano y en el joven no difieren. Por este motivo ante la sospecha clínica de malabsorción intestinal en el anciano siempre deben realizarse las pruebas necesarias para identificar su causa. Una prueba

  3. Síndrome de Gianotti-Crosti: aspectos clínicos, laboratoriais e perfis sorológicos observados em 10 casos procedentes de Belém-PA (Brasil Gianotti-Crosti syndrome: clinical, laboratorial features, and serologic profiles of 10 cases from Belém, State of Para, Brazil

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    Daniela A. Lima


    as well as to investigate the role of viral pathogens in the etiology of GCS cases from Belem (PA, Brazil. PATIENTS AND METHODS: From August 1996 to December 2002, ten children with a clinical diagnosis of GCS were investigated through routine laboratory exams and serologically screened for several virus specific antibodies. A diagnosis of GCS was considered for cases that presented clinical aspects considered suggestive, together with one or more of the following criteria: elevated titers of hepatic enzymes, lymphocytosis, positive viral serology or history of a prior vaccination. RESULTS: Six out of 10 children (60% showed evidence of HHV6 primary infection, as demonstrated through specific IgM-antibody positivity. CONCLUSION: Anti-HHV6-IgM antibody positivity in 6/10 patients suggests that the pathogen can play a role in the etiology of GCS. Consequently, the authors recommend that this virus is added to the routine serological tests when exanthematous processes are concerned, especially those with a morphology suggestive of GCS.

  4. Eritrodermia: estudo clínico-laboratorial e histopatológico de 170 casos Erythroderma: a clinico-laboratorial and histopathological study of 170 cases

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    Nurimar C. Fernandes


    areas. RESULTS - from 92 male and 78 female aging 30 to 80 years, a preexisting dermatosis was identified in 99 cases (58,23%, reaction to internal drugs in 37 cases (21,77%, T cell cutaneous lymphomas in 18 cases (10,58%; in 16 cases (9,47%, a causative factor could not be disclosed. Chills, pruritus, lymphadenopathy, lower limbs edema were the most freqüent signs/symptoms. Elevated erythrocyte sedimentation rate, eosinophilia, leukocytosis, peripheral blood lymphocytosis and anemia were the most common laboratory findings. Among the idiopathic cases, two histological patterns were noticed: psoriasiform and inespecific dermatitis. CONCLUSION - the main cause of erythroderma was psoriasis; three simultaneous skin biopsies can enhance the accuracy of the histopathologic diagnosis.

  5. Toxicidade pulmonar induzida pela rapamicina Lung toxicity induced by rapamycin

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    C Damas


    complication associated to this medication. Interstitial pneumonitis and more rarely alveolar haemorrhage have been described. The authors describe 4 cases (3 men and 1 woman between 46-71 years, transplanted three years ago (1 patient and 7 years ago (3 patients. All of them were medicated with micofenolato mofetil, prednisone and sirolimus. All patients had fever at admission, 3 patients had dyspnoea and 2 productive cough. Diffuse pulmonary infiltrates with basal predominance in HRCT scan were present in the four patients. BAL showed lymphocytic alveolitis in 3 cases, however with a different CD4/CD8 ratio. In additio to lymphocytosis, neutrophilia was observed in 2 patients. One patient showed serious alveolar haemorrhage in BAL. Pulmonary infections were ruled out by specific BAL staining and cultures. After drug suspension, all patients showed a clear improvement. These case studies show some diversity in clinical presentation and in the features of some exams, namely in BAL. This may suggest different underlying pathophysiology entities induced by sirolimus.

  6. Assessment of coeliac disease prevalence in patients with Down syndrome in Poland - a multi-centre study. (United States)

    Szaflarska-Popławska, Anna; Soroczyńska-Wrzyszcz, Anetta; Barg, Ewa; Józefczuk, Jan; Korczowski, Bartosz; Grzybowska-Chlebowczyk, Urszula; Więcek, Sabina; Cukrowska, Bożena


    The results of studies assessing whether patients with Down syndrome have increased risk of coeliac disease are contradictory. The prevalence of coeliac disease in patients with Down syndrome is estimated at a wide range between 1% to as much as 18.6%. To assess coeliac disease prevalence in patients with Down syndrome in Poland. The study enrolled 301 patients with Down syndrome from six centres in Poland (Wroclaw, Sandomierz, Rzeszow, Grudziadz, Katowice, and Bydgoszcz). We measured the concentration of anti-tissue transglutaminase IgA antibodies and anti-deamidated gliadin peptide IgG antibodies in all patients. Patients with abnormal positive (> 10 U/ml) or inconclusive (7-10 U/ml) result of the serological test were offered endoscopic biopsy of the small intestine in the main centre. In 31 (10.3%) patients increased concentrations of the investigated antibodies were found, including 19 (6.3%) patients with increased tTg-IgA concentration, 27 (8.97%) patients with increased concentration of DGP-IgG, and 15 (4.98%) patients with increased concentration of both types of antibodies. Endoscopic biopsy of the small intestine was planned for all 31 patients with abnormal results of at least one antibody test and for 2 patients with inconclusive results. One of them suffered from previously diagnosed and histologically confirmed coeliac disease. Biopsy was not conducted in 9 patients due to contraindications, lack of their consent, or introduction of a gluten-free diet by the parents before the examination. In a group of 23 patients who underwent endoscopic biopsy of the small intestine, in 15 patients the histopathological picture of the small intestinal mucosa was typical for coeliac disease, 2 patients were diagnosed with lesions of grade 1 according to the classification by Marsh-Oberhuber, 1 patient was diagnosed with focal shortening of villi and hypertrophy of the crypts with no intraepithelial lymphocytosis (remains under gastrological observation), 2 patients

  7. Temporal evolution of hemogram in children with malaria Evolución temporal del hemograma en niños con malaria

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    Jaime Carmona Fonseca


    . During the acute episode of malaria, the leukocyte count was normal and it changed to very mild leukocytosis within the next 30 days. Leukocyte analysis revealed decreased neutrophils and basophils, increased eosinophils, mild lymphocytosis and marked monocytopenia, both of them stable. Lymphocytosis and monocytopenia were in contrast with the findings of other studies. Conclusions: These children with malaria (90% P. vivax, intestinal parasites and chronic malnutrition, had anemia (mild, homogeneous, normocytic before therapy, but they recovered from it in 30 days after effective antimalarial treatment; 80% also suffered from thrombocytopenia; at day 1, they showed neutropenia, basopenia, and eosinophilia, along with normal lymphocytes and severe monocytopenia. It is necessary to treat simultaneously these diseases in order to improve the health status of these children.


     Introducción: los estudios colombianos sobre las relaciones entre paludismo, parásitos intestinales, desnutrición y comportamiento del hemograma son muy escasos.Objetivos: conocer los cambios del hemograma en niños de 4 a 10 años de edad, con malaria, seguidos durante 30 d

  8. Ibrutinib for patients with relapsed or refractory chronic lymphocytic leukaemia with 17p deletion (RESONATE-17): a phase 2, open-label, multicentre study. (United States)

    O'Brien, Susan; Jones, Jeffrey A; Coutre, Steven E; Mato, Anthony R; Hillmen, Peter; Tam, Constantine; Österborg, Anders; Siddiqi, Tanya; Thirman, Michael J; Furman, Richard R; Ilhan, Osman; Keating, Michael J; Call, Timothy G; Brown, Jennifer R; Stevens-Brogan, Michelle; Li, Yunfeng; Clow, Fong; James, Danelle F; Chu, Alvina D; Hallek, Michael; Stilgenbauer, Stephan


    The TP53 gene, encoding tumour suppressor protein p53, is located on the short arm of chromosome 17 (17p). Patients with 17p deletion (del17p) chronic lymphocytic leukaemia have poor responses and survival after chemoimmunotherapy. We assessed the activity and safety of ibrutinib, an oral covalent inhibitor of Bruton's tyrosine kinase, in relapsed or refractory patients with del17p chronic lymphocytic leukaemia or small lymphocytic lymphoma. We did a multicentre, international, open-label, single-arm study at 40 sites in the USA, Canada, Europe, Australia, and New Zealand. Patients (age ≥18 years) with previously treated del17p chronic lymphocytic leukaemia or small lymphocytic lymphoma received oral ibrutinib 420 mg once daily until progressive disease or unacceptable toxicity. The primary endpoint was overall response in the all-treated population per International Workshop on Chronic Lymphocytic Leukaemia 2008 response criteria modified for treatment-related lymphocytosis. Preplanned exploratory analyses were progression-free survival, overall survival, sustained haematological improvement, and immunological improvement. Patient enrolment is complete, but follow-up is ongoing. Treatment discontinuation owing to adverse events, unacceptable toxicity, or death were collected as a single combined category. This study is registered with, number NCT01744691. Between Jan 29, 2013, and June 19, 2013, 145 patients were enrolled. The all-treated population consisted of 144 patients with del17p chronic lymphocytic leukaemia or small lymphocytic lymphoma who received at least one dose of study drug, with a median age of 64 years (IQR 57-72) and a median of two previous treatments (IQR 1-3). At the prespecified primary analysis after a median follow-up of 11·5 months (IQR 11·1-13·8), 92 (64%, 95% CI 56-71) of 144 patients had an overall response according to independent review committee assessment; 119 patients (83%, 95% CI 76-88) had an overall

  9. Enfermedad de Chagas congenita en la Ciudad de Salta, Argentina Congenital Chagas' disease in Salta, Argentina

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    Mario Zaidenberg


    presence of T. cruzi in blood, explored in fresh smears by serial micro-hematocrite and/or by xenodiagnosis, was the only criterion to define infection in NB. All NB were followed up by direct agglutination (DA with or without 2 mercaptoethanol (DA-w2ME, DA-wo2ME and IIF in order to establish the specific antibody kinetics. Clinical studies on NB with T. cruzi infection include routine laboratory tests. Benznidazole (3 to 7 mg/kg/day and, in 1 case, nifurtimox (15 mg/kg/day were employed as therapeutic agents. T. cruzi infection was confirmed in 149 PW (15.9%, table I. These chagasic mothers delivered 6 chagasic NB (CCHD-NB, (4%. Diagnosis of congenital Chagas' disease accounted for a total of 12 NB out of the 968 studied. 4 out of them were positive by both micro-hematocrite and blood smears and 7 by micro-hematocrite alone. Xenodiagnosis was performed in 2 NB resulting positive in both cases, table II. The most usual clinical findings included hepatomegaly (present in all cases, splenomegaly 8/12, jaundice 10/12 and prematurity 5/12, table 3. Laboratory findings showed anemia to be of hypochromic microcytic type in all cases. Other laboratory findings included lymphocytosis, normal erythrosedimentation, slight to moderate increase of transaminases in all cases, and elevated indirect bilirrubin in cases with jaundice, table 4. Analysis of cerebro spinal fluid in 6 CCh-NB revealed the presence of T. cruzi in 2 cases, plus abnormal cytochemical content in one of them, table 4. The serological reactions of infected and treated NB became negative between 4th and 8th month in all but 1 case that remained positive until 14th, fig. 1. A close correlation was found between DA and IIF. DA-w2ME liter showed a significant drop during the initial phase of the controls. Benznidazole was successful in 11 out of the 12 CCh-NB. The remaining NB was effectively treated with nifurtimox. Therapeutic tolerance was satisfactory for both agents. These observations showed that congenital Chagas

  10. Respiratory viral infections in infants with clinically suspected pertussis

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    Angela E. Ferronato


    Full Text Available Objective: to evaluate the frequency of respiratory viral infections in hospitalized infants with clinical suspicion of pertussis, and to analyze their characteristics at hospital admission and clinical outcomes. Methods: a historical cohort study was performed in a reference service for pertussis, in which the research of respiratory viruses was also a routine for infants hospitalized with respiratory problems. All infants reported as suspected cases of pertussis were included. Tests for Bordetella pertussis (BP (polymerase chain reaction/culture and for respiratory viruses (RVs (immunofluorescence were performed. Patients who received macrolides before hospitalization were excluded. Clinical data were obtained from medical records. Results: Among the 67 patients studied, BP tests were positive in 44%, and 26% were positive for RV. There was no etiological identification in 35%, and RV combined with BP was identified in 5%. All patients had similar demographic characteristics. Cough followed by inspiratory stridor or cyanosis was a strong predictor of pertussis, as well as prominent leukocytosis and lymphocytosis. Rhinorrhea and dyspnea were more frequent in viral infections. Macrolides were discontinued in 40% of patients who tested positive for RV and negative for BP. Conclusion: the results suggest that viral infection can be present in hospitalized infants with clinical suspicion of pertussis, and etiological tests may enable a reduction in the use of macrolides in some cases. However, the etiological diagnosis of respiratory virus infection, by itself, does not exclude the possibility of infection with BP. Resumo: Objetivo: avaliar a frequência das infecções por vírus respiratórios em lactentes hospitalizados com suspeita clínica de coqueluche e analisar suas características admissionais e evolutivas. Métodos: foi realizado um estudo de coorte histórica, em um serviço sentinela para coqueluche, no qual a pesquisa de v

  11. Hematopoietic Acute Radiation Syndrome (Bone marrow syndrome, Aplastic Anemia): Molecular Mechanisms of Radiation Toxicity. (United States)

    Popov, Dmitri

    Radiation Toxins (SRD-4) to radiation naive animals in doses 0.1 mg/kg; 0,5 mg/kg; 1 mg/kg; 2 mg/kg; 3 mg/kg up to 30 mg/kg. Results: After I/V or I/M administration of Hematotoxic Radiation Toxins to radiation -naive animals the induction of specific clinical signs was observed- including thrombocytopenia, lymphocytosis followed by lymphocytopenia, granulocytopenia , aplastic anemia, and the clinical manifestations- ecchymosis, hemorrhage and coagulopathy. These observed clinical signs mimic the acute/hematopoietic acute radiation syndrome. Conclusions: Administration of Hematopoietic Radiation Toxins (SRD-4) to radiation naive animals in doses 0.1 mg/kg;0,5 mg/kg; 1 mg/kg; 2 mg/kg; 3 mg/kg up to 30 mg/kg produced specific toxic reactions with the development of signs and symptoms consistent with the hematological form of Acute Radiation Syndromes. Administration of high doses of Hematopoietic Radiation Toxins developed a clinical picture identical to severe Acute Radiation Exposure Syndrome and induces Toxic Multiple Organ Failure (TMOF) and Toxic Multiple Organ Involvement (TMOI) {i.e. pneumonitis, renal failure, renal hypo-perfusion, acute tubular necrosis, hepatic failure, etc.} essentially as which occurs as an acute consequence of radiation toxemia. Aplastic anemia is an important clinical and pathological process which develops after animals receive high doses of both radiation and administered radiation toxins.

  12. Caracterização imunofenotípica das subpopulações de linfócitos do lavado broncoalveolar de pacientes com silicose Phenotypic characterization of lymphocyte subsets in bronchoalveolar lavage of patients with silicosis

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    dusts. The aim of this study was to characterize the lymphocyte subsets in bronchoalveolar lavage of patients with silicosis. Bronchoalveolar lavage was carried out in 26 workers with different forms of silicosis: simple form (n = 12, complicated (n = 13 and 1 patient with acute form of the disease. As a control group, 7 healthy individuals were included. Compared to the control group, silicotic patients showed intense pleocytosis constituted mainly by alveolar macrophages with slight lymphocytosis. Lymphocyte subsets present in the bronchoalveolar fluid (BAL of normal individuals were mature lymphocytes with phenotype CD2+TCRab (87.3% and only 2.9% were CD2+TCRgd. CD4/CD8 ratio was 1.8 with few (16% immature double negative T cells subsets (CD4-CD8-. In contrast, silicotic patients showed reduction of the more mature lymphocyte subset CD2+CD4+, CD2+CD8+ and a great increase (47% of immature (CD4-CD8- T cell subsets. No increase in the NK (CD56+ cell population was observed. Biochemical analysis of protein contents and determination of the Ig/albumin ratio characterized local immunoglobulin production within the pulmonary microenvironment. Furthermore, lack of increase of plasma cells, as well as the maintenance of the percentage of B lymphocyte population (CD19+ in the BAL of silicotic patients, favors the hypothesis that the cells responsible for Ig production are possibly located in the interstitial space. Altogether the results suggest development of lymphopoiesis and tertiary lymphoid tissue within the pulmonary microenvironment during the clinical course of silicosis.

  13. Surtos de tripanossomíase por Trypanosoma evansi em eqüinos no Rio Grande do Sul: aspectos epidemiológicos, clínicos, hematológicos e patológicos Outbreaks of trypanosomiasis in horses by Trypanosoma evansi in the state of Rio Grande do Sul, Brazil: epidemiological, clinical, hematological, and pathological aspects

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    Aline Rodrigues


    ão sentado". Os encéfalos de 5 eqüinos com quadro encefálico foram submetidos à técnica de imunoistoquímica estrepto-avidina-biotina; em todos eles observou-se a marcação de números moderados ou elevados de espécimes de T. evansi pelo anticorpo específico nos espaços intravasculares e na neurópila. Os aspectos epidemiológicos, clínicos, hematológicos e patológicos da tripanossomíase por T. evansi em eqüinos são discutidos.Cases of trypanosomiasis by Trypanosoma evansi were diagnosed in horses in the state of Rio Grande do Sul, Brazil, between 2003 and 2004. In one stud farm (Farm A with 125 horses, 52 died. Additionally, around 80 mares were sent to Farm A to be bred. Of those, 66 became ill and 56 died after being returned to their farms of origin. Twenty one horses clinically affected by the disease were observed. Clinical signs included loss of weight (despite voracious appetite, lethargy, incoordination and instability of hindlimbs, atrophy of the large muscles of the hindlimbs, muscle weakness and paleness of mucosae. Specimens of T. evansi were detected in the blood drawn from four affected horses. Normocytic normochromic anemia with PCVs ranging from 15 to 31%, leucocytosis due to lymphocytosis associated to large atypical lymphocytes was observed in several affected horses. High levels of antibodies against T. evansi were detected in the serum of six horses from Farm A. Eight horses presented encephalic neurological signs such as circling, ataxia, blindness, excitation, falls, listlessness, proprioception deficits and head tilt. One horse assumed a "dog-seating position". Necropsy findings included muscle atrophy, enlargement and lymphoid hyperplasia of the spleen and lymphnodes, edema and softening of the white and grey matter of the brain. Histologically, an overwhelming necrotizing panencephalitis was observed in the seven horses with encephalic signs. This panencephalitis was characterized by marked edema, demyelination and necrosis and


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    Olkhovska O.M.


    fever, symptoms of intoxication, tonsillitis (lacunar tonsillitis, and the increase in size of submandibular and cervical lymph nodes, difficulty in nasal breathing. At the same time, 22 (21,6% children had slow onset, which was characterized by catarrhal symptoms and gradual rise in temperature. Serous discharges from the nose, nasal congestion, dry cough that gradually became moist, appearance of "snoring" during sleep were the main catarral symptoms. An acute respiratory disease was diagnosed for children at the first visit to the pediatrician, and symptomatic therapy was used during three to five days as a primary treatment. However, the fever persisted, catarrhal manifestations and signs of intoxication intensified, and parents started to pay attention on the neck lumps of. Prolonged fever and swollen lymph nodes were a major cause of hospitalization. Clinical examination of children, who proceeded to the hospital, had revealed the symptoms of tonsillitis. But membranes on the tonsils were found only in 10 patients; the other patients had hyperaemia or "looseness" of the oropharynx mucosa. The ultrasound of the abdomen was conducted for all patients during the hospital stay, which showed an increase in the size of the liver, signs of parenchymal reaction of liver. At the same time, increasing the size of the spleen was observed in 67 patients (65,7%, and in 36 patients (35,3% signs of hepatosplenitis were found. An increase in aminotransferase levels was found in biochemical analysis of liver samples in 21 children (20,6%, but these figures decreased to physiological norms at the time of discharge from the hospital. Despite the known contraindications on the use of Ampicillin in the treatment for IM, this drug was prescribed for 11 patients (10,8% in the outpatient basis, which led to appearance of immunocomplex rash with the hemorrhagic component in 2 (1,9% of them. In peripheral blood leucocytosis (15,48±2,78*109 /L and lymphocytosis (72,66±3,58%, monocytosis