Interstitial lung fibrosis and rheumatic disorders in patients with hepatitis C virus infection

A possible aetiopathogenetic role of hepatitis C virus (HCV) has been reported in various immune-mediated disorders, such as mixed cryoglobulinaemia, which may be complicated by interstitial lung involvement; moreover, different viruses, including HCV, have been correlated with idiopathic pulmonary fibrosis. Here, a cohort of eight HCV-positive patients (M/F = 4/4, mean age 61 +/- 8 S.D. yr) with interstitial lung fibrosis and a variable number of rheumatic disorders are described. Interstitial lung involvement appeared medially 4.5 +/- 3.2 S.D. yr after the clinical onset of chronic hepatitis. During the clinical follow-up, some rheumatic symptoms were also recorded: articular involvement (four patients): mild sicca syndrome (one patient); severe polymyositis and cranial neuropathy (one patient); serum cryoglobulins and/or autoantibodies (eight patients). In all patients, a moderate (four patients) or severe (four patients) lung fibrosis was evaluated by means of high-resolution computed tomography. The presence of parenchymal radiotracer uptake on 67Ga scan (7/7 patients) and increased percentages of neutrophils (4/4 patients) and lymphocytes (2/4) at bronchoalveolar lavage suggested an active lung involvement. Different degrees of reduction of single breath diffusing capacity for carbon monoxide (DLco) (mean value 57.6 +/- 15%, range 37- 80) were observed in all cases, while spirometric abnormalities, consistent with a global restrictive pattern, were less frequently found. In all cases, anti-HCV antibodies and HCV viraemia were demonstrated: viral genome was also detected in peripheral lymphocytes from 4/4 subjects and in one case in lung biopsy specimens. A desquamative interstitial pneumonia pattern was demonstrated in two cases by lung biopsy. The present work supports the hypothesis that HCV chronic infection could represent a trigger factor for interstitial lung fibrosis and various rheumatic disorders.      

Prevalence and predictors of Toxoplasma seropositivity in women with and at risk for human immunodeficiency virus infection

We assessed the prevalence and predictors of latent Toxoplasma infection in a large group of human immunodeficiency virus (HIV)-infected and HIV-uninfected at-risk US women. The prevalence of latent Toxoplasma infection was 15% (380 of 2525 persons) and did not differ by HIV infection status. HIV-infected women aged > or =50 years and those born outside of the United States were more likely to have latent Toxoplasma infection, with prevalences of 32% and 41%, respectively.     

Immunohistochemical characterization of a 183 KD myeloid-specific-DNA- binding protein in B5 fixed, paraffin-embedded tissues, and bone marrow aspirates by monoclonal antibody BM-1

A monoclonal antibody, designated BM-1, which is reactive in B5 formalin-fixed, paraffin-embedded tissues, has been generated against a cytoplasmic and nuclear antigen expressed in human myeloid precursor cells and derived leukemias. Using the avidin-biotin-complex immunoperoxidase procedure, BM-1 was found to stain selectively myeloid precursor cells in normal bone marrow and mature granulocytes in the blood. In a screen of 26 normal adult and fetal human organs fixed in B5 formalin, BM-1 was negative in all nonhematopoietic tissues with the exception of tissue granulocytes and scattered cells in the peripheral cortex of the thymus. Likewise a screen of 30 solid tumor cell lines including a spectrum of carcinomas, sarcomas, and neural-derived tumors was negative. BM-1 was also negative with 21 T and B cell lymphomas and 11 Hodgkin's disease tumors. A preliminary study of tumors of the hematopoietic system revealed that BM-1 was reactive with M2 and M3 acute myelogenous leukemias (AML), chronic myelogenous leukemias (CML) and myelomonocytic leukemias, and granulocytic sarcomas. M1, M4, M5, and M6 AML clot preparations were negative in this study, indicating that BM-1 may have a role in the histopathologic diagnosis of myelogenous leukemia. Myeloid leukemic cell lines HL-60, ML-2, KG1, and TPH-1-O showed BM-1 nuclear and/or cytoplasmic reactivity in a subpopulation of cells, but erythroid and lymphoid leukemias and all lymphoma cell lines were negative. Immunoperoxidase studies of a panel of fetal tissues showed BM-1 positive cells in the peripheral cortex of the thymus and portal myelopoietic regions of the liver at 18 weeks gestation. Finally, DNA-cellulose and solid phase radioimmunoassay (RIA) techniques developed in our laboratory demonstrate that the BM-1 antigenic domain is reactive only after binding to eukaryotic but not prokaryotic single- or double-stranded DNA. Immunoblot techniques using a DNA-cellulose purified protein sample revealed that BM-1 recognizes a 183 kD protein. These studies indicate that BM-1 is recognizing a myeloid-specific antigen that, because of its DNA binding characteristics, may have an important role in the differentiation of myeloid cells at the molecular level.     

Asymmetric polyarthritis as an initial presentation of Rosai‐Dorfman disease

Rosai‐Dorfman disease (RDD) is a rare benign reactive lymphoproliferative disorder characterised by a histopathological pattern with sinus histiocytosis and hemophagocytosis. It usually presents with fever, elevated erythrocyte sedimentation rate, cervical lymphadenopathy, other lymph node and extra‐nodal site involvement. We present the case of a 25‐year‐old female patient with polyarthritis mimicking rheumatoid arthritis (RA). When the para‐aortic lymph node was biopsied, it showed extensive histiocytic proliferation; some clusters of plasma cells, lymphocytes and rare multinucleated cells were seen, suggesting a diagnosis of RDD. There is nothing in the literature regarding the polyarthritic presentation of the disease. To the best of our knowledge, our patient is the first case of RDD presenting with a clinical picture mimicking atypical seronegative RA.     

Arg-Gly-Asp-dependent occupancy of GPIIb/IIIa by applaggin: evidence for internalization and cycling of a platelet integrin

Using indirect immunofluorescence microscopy we examined the distribution and cycling of GPIIb/IIIa after binding to applaggin, a high-affinity Arg-Gly-Asp (RGD)--containing ligand. Resting, unfixed platelets were incubated with applaggin for 30 minutes at 37 degrees C, and bound applaggin was detected by an affinity-purified rabbit anti- applaggin antibody. Examination of intact cells showed a rim pattern for applaggin, consistent with its binding to the platelet surface. Staining of Triton X-100--permeabilized cells showed an intracellular pool of applaggin. Competition of applaggin binding by either AP-2, an anti-GPIIb/IIIa monoclonal antibody (MoAb) that blocks fibrinogen binding, or the synthetic peptide RGDW eliminated both surface and intracellular staining, indicating that applaggin is binding to GPIIb/IIIa in an RGD-dependent manner. Inhibition of platelet activation by PGE1 and theophylline had no effect on the observed staining patterns, indicating that cellular activation is not required for surface binding and subsequent internalization. To evaluate whether occupancy of functional binding sites on GPIIb/IIIa is required for internalization, we used mAb15, an anti-GPIIIa antibody that neither blocks fibrinogen binding nor induces the expression of ligand-induced binding sites on GPIIb/IIIa. In these studies mAb15 was internalized in a manner analogous to both AP-2 and applaggin, showing that occupancy of the RGD binding site is not required to initiate receptor internalization. To estimate the size of the newly internalized pool of applaggin, 125I-applaggin--binding studies were performed. Displacement of bound 125I-applaggin by excess unlabeled applaggin or EDTA showed that at least 17% of bound applaggin was nondisplaceable when binding was performed under conditions permitting membrane flow and internalization. These data indicate that GPIIb/IIIa is internalized in unstimulated platelets independent of cellular activation or occupancy of the functional binding site(s) of GPIIb/IIIa by RGD-containing ligands. Thus, internalization of GPIIb/IIIa may represent a mechanism by which the surface expression of this adhesion receptor is regulated.     

Quality of Life Questionnaires for the Assessment of Pelvic Organ Prolapse: Use in Clinical Practice

Over the past decade, the use of quality of life (QOL) questionnaires in the evaluation of pelvic organ prolapse (POP) has become a standard part of most clinical studies. Investigators have attempted to correlate QOL scores with objective findings and treatment efficacy and as outcome measures in comparing different treatment modalities. Many of the QOL questionnaires are available in short forms, making them easier to adapt to clinical settings. This article includes an overview of several validated QOL questionnaires and their application in studies whose results provide useful guidelines for health care professionals who diagnose and manage women with POP.     

Prediction of invasive candidal infection in critically ill patients with severe acute pancreatitis

Introduction

Patients with severe acute pancreatitis are at risk of candidal infections carrying the potential risk of an increase in mortality. Since early diagnosis is problematic, several clinical risk scores have been developed to identify patients at risk. Such patients may benefit from prophylactic antifungal therapy while those patients who have a low risk of infection may not benefit and may be harmed. The aim of this study was to assess the validity and discrimination of existing risk scores for invasive candidal infections in patients with severe acute pancreatitis.

Methods

Patients admitted with severe acute pancreatitis to the intensive care unit were analysed. Outcomes and risk factors of admissions with and without candidal infection were compared. Accuracy and discrimination of three existing risk scores for the development of invasive candidal infection (Candida score, Candida Colonisation Index Score and the Invasive Candidiasis Score) were assessed.

Results

A total of 101 patients were identified from 2003 to 2011 and 18 (17.8%) of these developed candidal infection. Thirty patients died, giving an overall hospital mortality of 29.7%. Hospital mortality was significantly higher in patients with candidal infection (55.6% compared to 24.1%, P = 0.02). Candida colonisation was associated with subsequent candidal infection on multivariate analysis. The Candida Colonisation Index Score was the most accurate test, with specificity of 0.79 (95% confidence interval [CI] 0.68 to 0.88), sensitivity of 0.67 (95% CI 0.41 to 0.87), negative predictive value of 0.91 (95% CI 0.82 to 0.97) and a positive likelihood ratio of 3.2 (95% CI 1.9 to 5.5). The Candida Colonisation Index Score showed the best discrimination with area under the receiver operating characteristic curve of 0.79 (95% CI 0.69 to 0.87).

Conclusions

In this study the Candida Colonisation Index Score was the most accurate and discriminative test at identifying which patients with severe acute pancreatitis are at risk of developing candidal infection. However its low sensitivity may limit its clinical usefulness.