Autoreactive IgG memory antibodies in patients with systemic lupus erythematosus arise from nonreactive and polyreactive precursors.

Persistent autoantibody production in patients with systemic lupus erythematosus (SLE) suggests the existence of autoreactive humoral memory, but the frequency of self-reactive memory B cells in SLE has not been determined. Here, we report on the reactivity of 200 monoclonal antibodies from single IgG+ memory B cells of four SLE patients. The overall frequency of polyreactive and HEp-2 self-reactive antibodies in this compartment was similar to controls. We found 15% of IgG memory B cell antibodies highly reactive and specific for SLE-associated extractable nuclear antigens (ENA) Ro52 and La in one patient with serum autoantibody titers of the same specificity but not in the other three patients or healthy individuals. The germ-line forms of the ENA antibodies were non-self-reactive or polyreactive with low binding to Ro52, supporting the idea that somatic mutations contributed to autoantibody specificity and reactivity. Heterogeneity in the frequency of memory B cells expressing SLE-associated autoantibodies suggests that this variable may be important in the outcome of therapies that ablate this compartment.

Disease Specific Autoantibodies in Idiopathic Inflammatory Myopathies.

Idiopathic inflammatory myopathies represent still a diagnostic and therapeutic challenge in different disciplines including neurology, rheumatology, and dermatology. In recent years, the spectrum of idiopathic inflammatory myopathies has been significantly extended and the different manifestations were described in more detail leading to new classification criteria. A major breakthrough has also occurred with respect to new biomarkers especially with the characterization of new autoantibody-antigen systems, which can be separated in myositis specific antibodies and myositis associated antibodies. These markers are detectable in approximately 80% of patients and facilitate not only the diagnostic procedures, but provide also important information on stratification of patients with respect to organ involvement, risk of cancer and overall prognosis of disease. Therefore, it is not only of importance to know the significance of these markers and to be familiar with the optimal diagnostic tests, but also with potential limitations in detection. This article focuses mainly on antibodies which are specific for myositis providing an overview on the targeted antigens, the available detection procedures and clinical association. As major tasks for the near future, the need of an international standardization is discussed for detection methods of autoantibodies in idiopathic inflammatory myopathies. Furthermore, additional investigations are required to improve stratification of patients with idiopathic inflammatory myopathies according to their antibody profile with respect to response to different treatment options.

Laparoscopic appendectomy during pregnancy: between personal experiences and scientific evidence.

BACKGROUND: Although laparoscopic appendectomy is a safe and effective procedure for management of acute appendicitis, data about the feasibility and safety during pregnancy are limited. We aimed to study our experience in this field and to review the scientific evidence available. STUDY DESIGN: All patients undergoing laparoscopic appendectomy during pregnancy, from January 2003 to December 2005, were included. Medical files were reviewed retrospectively. In addition, 133 cases from the literature were reviewed. General features of the cases, surgical technique details, and outcomes were analyzed. RESULTS: All laparoscopic procedures were completed without conversion to open operation. No substantial hemodynamic or gasometric changes were detected during the procedures. Tocolytic medication was not administered in any patient. All patients were discharged from hospital within the first 48 postoperative hours, and no complications were recorded during this period or in the followup. All newborns had an adequate weight for gestational age, satisfactory parameters of well-being at birth, and an uneventful development after 1-year followup. CONCLUSIONS: Laparoscopic appendectomy during pregnancy is as effective and safe as the conventional approach and has all the benefits of minimally invasive operation, provided that specific recommendations for these types of patients are strictly followed. It must be mentioned that there is only limited scientific evidence to support this statement.

Endocytosis and intracellular trafficking of fatty acid esters of phenylaminopropanediol, the putative etiologic agents of the toxic oil syndrome (TOS).

The toxic oil syndrome (TOS) caused by ingestion of rapeseed oil adulterated with aniline is characterized by symptoms of an allergic and/or autoimmune illness associated with vessel wall lesions similar to those of atherosclerosis. Fatty acid esters of 3-(N-phenylamino)-1,2-propanediol (PAP) have been incriminated as the etiologic agents of TOS. However, the pathogenesis of TOS is yet unknown. Here, we addressed whether PAP fatty acid esters are incorporated into lipoproteins, which after transport to vascular endothelial cells are taken up to initiate TOS vasculopathy. After loading (14)C-dioleyl-ester of PAP into LDL labeled with 1,1'-dioctadecyl-3,3,3',3'-tetramethylindolcarbocyanine (DiI) we assessed receptor mediated endocytosis and intracellular localization of these lipopoproteins in vascular endothelial cells. Our data suggest that these lipoprotein-derivatives are internalized into endothelial cells by LDL receptor mediated endocytosis. Confocal microscopy revealed that DiI-LDL loaded with dioleyl-ester of PAP and incubated for 60 min with endothelial cells colocalizes with the lysosomotropic compound LysoTracker Green, indicating that internalized PAP-loaded LDL are targetted to the endolysosomal compartment for further processing. Subcellular fractionation of endothelial-like ECV-304 cells after incubation with LDL loaded with the (14)C-dioleyl-ester of PAP for 6h showed that the radioactive label accumulated in fractions containing endosomes, the Golgi apparatus and the endoplasmic reticulum.

Experience with a Spanish-language laparoscopy website.

INTRODUCTION: Although there are no clearly defined electronic tools for continuing medical education (CME), new information technologies offer a basic platform for presenting training content on the internet. Due to the shortage of websites about minimally invasive surgery in the Spanish language, we set up a topical website in Spanish. MATERIALS AND METHODS: This study considers the experience with the website between April 2001 and January 2005. To study the activity of the website, the registry information was analyzed descriptively using the log files of the server. To study the characteristics of the users, we searched the database of registered users. RESULTS: We found a total of 107,941 visits to our website and a total of 624,895 page downloads. Most visits to the site were made from Spanish-speaking countries. The most frequent professional profile of the registered users was that of general surgeon. CONCLUSION: The development, implementation, and evaluation of Spanish-language CME initiatives over the internet is promising but presents challenges.

Nicotine and biochanin A, but not cigarette smoke, induce anti-inflammatory effects on keratinocytes and endothelial cells in patients with Behçet's disease.

During periods of smoking, patients with Behçet's disease have less oral aphthae than in abstinence. To elucidate this observation, human keratinocytes and dermal microvascular endothelial cells (HMEC-1) were incubated with serum of 20 patients with Behçet's disease and 20 healthy controls for 4 hours. Maximum non-toxic concentrations were determined and the cells were further treated with 6 microM nicotine, 3.3% cigarette smoke extract (CES), 100 microM biochanin A, and 6.25/12.5 microM pyrrolidine dithiocarbamate alone and in combinations for 24 hours. Serum IL-8 levels of patients were significantly lower than those of controls. However, after 4 hours incubation with patients' sera, IL-8 release by both cell types was markedly increased when compared with the corresponding serum levels. The levels of IL-6 and vascular endothelial growth factor (VEGF) release were after 4 hours similar with the corresponding levels in serum. IL-1 was not detected. Nicotine significantly decreased IL-8 and -6 release by HMEC-1 maintained in both patients' and controls' sera, but only IL-6 release by keratinocytes maintained in patients' sera. VEGF release by both cells was markedly increased after nicotine treatment in either serum. CES significantly decreased IL-8 release and increased production of VEGF in keratinocytes maintained in patients' serum. The phytoestrogen biochanin A alone and in combination with nicotine further decreased the secretion of IL-8, -6, and VEGF in all experimental settings. Our data support a specific anti-inflammatory effect of nicotine on keratinocytes and endothelial cells maintained in the serum of patients with Behçet's disease. Moreover, biochanin A is likely to exhibit similar and even more profound results than nicotine.

El componente social de la mortalidad perinatal: su estudio en el Hospital General Municipal Docente de Remedios / The social component of perinatal mortality: its study at the Hospital General Municipal Docente de Remedios

Se realizan consideraciones sobre la influencia que tienen los factores sociales en la morbimortalidad perinatal. Se estudia su participación en 109 muertes perinatales que tuvieron lugar en el Hospital General Municipal Docente de Remedios, Viila Clara, en el período de 1979 al 1982, ambos inclusive. Se observa que los factores sociales estuvieron presentes en el 60% del total de las muertes perinatales ocurridas. Se concluye con el señalamiento de la importancia de la realización de una investigación aplicada donde se consideren los factores sociales asociados con la mortalidad perinatal