Imaging Modalities in the Diagnosis of Acute Aortic Dissection

The management of patients with acute aortic dissection requires a rapid diagnosis and precise information about the localization and extent of the dissection. Four imaging techniques are currently available to diagnose aortic dissection: aortography; contrast-enhanced computerized tomography (CECT); magnetic resonance imaging (MRI); and transesophageal echocardiography (TEE). All of these techniques have their specific advantages and inherent limitations. Recent studies have demonstrated that MRI may best provide a comprehensive and detailed evaluation of the thoracic aorta, therefore proposing this technique as a "new gold standard" in the diagnosis of acute aortic dissection. TEE, however, may be the best alternative technique, as it combines high sensitivity and specificity with high practicality. The practicality is particularly important in hemodynamically unstable patients in whom a rapid bedside imaging modality is required. CECT might be necessary in selected cases in whom TEE fails to provide a definite diagnosis. Aortography may be necessary in patients in whom clinical signs are suggestive of organ ischemia and in whom coronary anatomy needs to be delineated before operation.     

Penicillin-G degradation products inhibit in vitro granulopoiesis

38% of penicillin-G in solution decays at 20 degrees C within 24 h, 50% at 37 degrees C and 66% within 3 h at 56 degrees C. These degraded penicillin-G solutions strongly inhibit growth and maturation of granulocytic stem cells in vitro. Inhibitory concentrations are in the range obtainable with high dose penicillin therapy in vivo. No cytotoxicity of degraded penicillin solutions on bone marrow cells was seen over 24 h. It is suggested that penicillin-G degradation products are responsible for severe granulocytopenia observed after high dose penicillin-G therapy.     

From fish to FISH: the comparative pathology of neuroblastomas in humans, mice and fish

Neuroblastoma is a malignant cancer of the sympathetic nervous system and is one of the most frequent solid cancers in young children. Only a few of the many advances in our understanding of basic genetic and cellular mechanisms leading to neuroblastoma development have translated to clinical practice, and the prognosis for children with neuroblastoma, particularly at advanced stages, has remained poor. Major directions for neuroblastoma management and control include the application of prognostic parameters, particularly amplified MYCN, which can be readily visualized by chromosomal fluorescence in situ hybridization (FISH), for individual therapy design, as well as the initiation of a presymptomatic screening program for early tumor detection to reduce the fraction of advanced-stage tumors. In addition, new and innovative therapeutic approaches are being sought. The understanding of molecular and cellular pathways resulting in spontaneous regression in up to 10% of neuroblastoma patients, possibly by apoptosis, could provide the basis for new biologically based therapeutic interventions. Unlike most other pediatric cancers, neuroblastoma can be studied in two experimental animal systems. One is the fish system Xiphophorus, where neuroblastomas can be induced in specific strains by exposure to mutagens/carcinogens; the second is mice that carry MYCN as a transgene. These animal systems demonstrate that neuroblastomas are evolutionarily conserved tumors. Their study could well result in a better understanding of neuroblastoma development. At the same time they represent systems in which experimental therapies can be preclinically tested. Received: 31 October 1998 / Accepted: 12 November 1998     

Myeloid-related protein 8/14 complex is released by monocytes and granulocytes at the site of coronary occlusion: a novel, early, and sensitive marker of acute coronary syndromes.

AIMS: We investigated whether myeloid-related protein 8/14 complex (MRP8/14) expressed by infiltrating monocytes and granulocytes may represent a mediator and early biomarker of acute coronary syndromes (ACS). METHODS AND RESULTS: Immunohistochemistry of coronary thrombi was done in 41 ACS patients. Subsequently, levels of MRP8/14 were assessed systemically in 75 patients with ACS and culprit lesions, with stable coronary artery disease (CAD), or with normal coronary arteries. In a subset of patients, MRP8/14 was measured systemically and at the site of coronary occlusion. Macrophages and granulocytes, but not platelets stained positive for MRP8/14 in 76% of 41 thrombi patients. In ACS, local MRP8/14 levels [22.0 (16.2-41.5) mg/L] were increased when compared with systemic levels [13.4 (8.1-14.7) mg/L, P = 0.03]. Systemic levels of MRP8/14 were markedly elevated [15.1 (12.1-21.8) mg/L, P = 0.001] in ACS when compared with stable CAD [4.6 (3.5-7.1) mg/L] or normals [4.8 (4.0-6.3) mg/L]. Using a cut-off level of 8 mg/L, MRP8/14 but not myoglobin or troponin, identified ACS presenting within 3 h from symptom onset. CONCLUSION: In ACS, MRP8/14 is markedly expressed at the site of coronary occlusion by invading phagocytes. The occurrence of elevated MRP8/14 in the systemic circulation prior to markers of myocardial necrosis makes it a prime candidate for the detection of unstable plaques and management of ACS.     

A pathway of coagulation on bovine capillary endothelial cells

In this report cultured bovine capillary endothelial cells are demonstrated to specifically bind factors IX and X and also their activated forms. Bound factor IXa and cell-associated factor VIII can activate factor X. The product of this reaction, factor Xa, can then interact with a factor V-like molecule expressed by capillary endothelial cells promoting thrombin formation. The thrombin formed can cleave fibrinogen leading to release of fibrinopeptide A and clot formation. Endotoxin-treatment of capillary endothelial cells leads to induction of tissue factor activity which, in the presence of factor VIIa, promotes activation of factors IX and X. The amount of factor Xa formed endotoxin-treated endothelial cells incubated with factors VIIa, IX, VIII and X, is 8 times greater than cells incubated with factors VIIa and X alone. This indicates that on the perturbed endothelial cell surface factors VIII and IX do play an important role in factor X activation by the tissue factor pathway. The perturbed capillary endothelial cell can thus provide a model of the thrombotic state promoting initiation and propagation of a procoagulant pathway leading to thrombin formation. This pathway of coagulation is endothelial cell-dependent, since it requires expression of tissue factor and factor V by capillary endothelial cells, as well as interaction of coagulation factors with the surface of capillary endothelial cells.     

A duplicated copy of DMRT1 in the sex-determining region of the Y chromosome of the medaka,Oryzias latipes

The genes that determine the development of the male or female sex are known in Caenorhabditis elegans, Drosophila, and most mammals. In many other organisms the existence of sex-determining factors has been shown by genetic evidence but the genes are unknown. We have found that in the fish medaka the Y chromosome-specific region spans only about 280 kb. It contains a duplicated copy of the autosomal DMRT1 gene, named DMRT1Y. This is the only functional gene in this chromosome segment and maps precisely to the male sex-determining locus. The gene is expressed during male embryonic and larval development and in the Sertoli cells of the adult testes. These features make DMRT1Y a candidate for the medaka male sex-determining gene.     

The use of interferon alpha in Behçet disease: review of the literature

Objectives

To evaluate the efficacy and safety of interferon (IFN) alpha for the treatment of Behçet’s disease (BD) and discuss its possible mechanisms of action.

Methods

Reports published until July 2002 in all languages were identified by the PubMed Database and the BD conference proceedings and abstract booklets. The indexing terms used were “Behçet” and “interferon.”

Results

Thirty-two original reports and 4 selected abstracts were included in the analysis. Systemic IFN-α was administered to 338 patients. One hundred eighty-two patients with acute ocular disease were treated with IFN-α. Two hundred sixty-four patients received IFN-α2a, and 74 received IFN-α2b. Eighty-six percent of the patients with mucocutaneous symptoms, 96% with arthritis, and 94% with uveitis exhibited a partial or complete response. Higher IFN doses were more effective than low-dose regimens and led to up to 56% long-term remissions after discontinuation of IFN-α were reported. IFN-α2a apparently was superior to IFN-α2b, with more complete remissions, but this probably was the result of a bias caused by the larger number of patients treated with IFN-α2a. Side effects were dose-dependent and similar to those noted in patients with hepatitis C.

Conclusions

Although the comparability of the studies is hampered because of different study designs, IFN-α is effective for the treatment of BD. It was beneficial even in resistant posterior uveitis, in which long-term remissions with preservation of visual acuity was achieved. In contrast, mostly partial remissions were reported for mucocutaneous symptoms.     

Phagocytosis-independent antimicrobial activity of mast cells by means of extracellular trap formation

These days it has been increasingly recognized that mast cells (MCs) are critical components of host defense against pathogens. In this study, we have provided the first evidence that MCs can kill bacteria by entrapping them in extracellular structures similar to the extracellular traps described for neutrophils (NETs). We took advantage of the ability of MCs to kill the human pathogen Streptococcus pyogenes by a phagocytosis-independent mechanism in order to characterize the extracellular antimicrobial activity of MCs. Close contact of bacteria and MCs was required for full antimicrobial activity. Immunofluorescence and electron microscopy revealed that S pyogenes was entrapped by extracellular structures produced by MCs (MCETs), which are composed of DNA, histones, tryptase, and the antimicrobial peptide LL-37. Disruption of MCETs significantly reduced the antimicrobial effect of MCs, suggesting that intact extracellular webs are critical for effective inhibition of bacterial growth. Similar to NETs, production of MCETs was mediated by a reactive oxygen species (ROS)-dependent cell death mechanism accompanied by disruption of the nuclear envelope, which can be induced after stimulation of MCs with phorbol-12-myristate-13-acetate (PMA), H(2)O(2), or bacterial pathogens. Our study provides the first experimental evidence of antimicrobial extracellular traps formation by an immune cell population other than neutrophils.     

Predictors of disease-related concerns and other aspects of health-related quality of life in outpatients with inflammatory bowel disease

OBJECTIVE: Disease-related concerns are a major dimension of health-related quality of life in inflammatory bowel disease (IBD). The aim of this study was to assess the concerns of IBD patients in an outpatient sample, and to determine the impact of psychological and disease factors on concerns and on other variables of health-related quality of life. METHODS: Seventy-two outpatients with IBD were assessed with regard to disease-related concerns [with the Rating Form of IBD Patients' Concerns (RFIPC)], psychological symptoms and somatic complaints non-specific to IBD as dependent variables. Coping with illness, health locus of control, and disease variables were assessed as predictor variables. Multiple regression analyses determined the independent contribution of each predictor on the dependent variables. RESULTS: Women reported more intense concerns than men. No difference in concerns was found between patients with Crohn's disease and ulcerative colitis. The highest predictive value for the RFIPC total score was found for depressive coping. It explained a greater proportion of variance on the RFIPC total score (23%) than demographic (10%) and disease variables (7%), and comparably impinged on RFIPC subscores. Furthermore, depressive coping was significantly associated with psychological distress, the self-rated health status and somatic complaints non-specific to IBD. CONCLUSIONS: Our findings suggest that in IBD psychological variables, particularly depressive coping, are more predictive than medical variables for disease-related concerns and other variables of health-related quality of life. Further studies are needed to examine the effects that the way of coping with disease have on long-term outcome in IBD.