Brain-derived neurotrophic factor and nerve growth factor correlate with T-cell activation in primary Sjogren's syndrome.

OBJECTIVES: Identification of factors associated with disease activity and B and T cell activation is a challenge in primary Sjogren's syndrome (pSS). Neurotrophins (NTs), recently reported as B cell antiapoptotic, and T-cell activation factors seem to be implicated in autoimmune diseases such as systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). METHODS: Samples from 18 pSS patients and 12 control subjects were studied to determine serum levels of nerve-growth factor (NGF) and brain-derived neurotrophic factor (BDNF), and their relationships with T- and B-cell activation and disease activity. Peripheral blood mononuclear cells (PBMCs) from patients with pSS and controls were examined by flow cytometry for HLA-DR expression by activated T cells. B cell activation was evaluated by B cell activating factor (BAFF) serum levels measured by enzyme-linked immunosorbent assay (ELISA) and immunoglobulin (Ig) and free light chain (FLC) levels. RESULTS: Mean serum levels of BDNF in pSS patients were significantly higher than in healthy controls and correlated directly with disease activity. NGF levels were associated with the subgroup of patients with hypergammaglobulinaemia. The pSS group was characterized by peripheral CD4+ and CD8+ T cell activation that correlated positively with BDNF and NGF levels, respectively. CONCLUSION: NT levels are potential biomarkers for lymphocyte activation in pSS patients.

Use of both CD63 up regulation and IgE down regulation for the flow cytometric analysis of allergen induced basophil activation. Definition of an activation index.

OBJECTIVE AND DESIGN: The aim of this study was to compare the use of a late (CD63) and an early (IgE) marker of basophil activation in the flow cytometric diagnosis of beta-lactam induced allergic hypersensitivity reactions. SUBJECTS: Twelve patients who had had a clear cut betalactam induced immediate reaction and 16 controls were selected, as well as 11 patients who had had an immediate reaction to bee or wasp stings. METHODS: Leukocyte suspensions were incubated with allergen dilutions as well as 2 positive controls (anti-IgE and NFormyl- Methionyl-Leucyl-Phenylalanine (fMLP)). Basophils were labelled with an anti-IgE FITC (fluorescein isothiocyanate) and an anti-CD63 PE (phycoerythrin). Results were expressed as percentage CD63 expression and index calculated according to a specific algorithm including the two activation markers. RESULTS: Significant CD63 expression (>5 %) was observed in 3/12 cases for the beta-lactam sensitized population, in 0/16 cases for the controls and in 11/11 cases for the venom sensitized population. A significant index (determined by a ROC analysis) was observed in 11/12 beta-lactam sensitized patients and in 0/16 controls. CONCLUSION: These results show that IgE (an early activation marker) is more sensitive than CD63 (a later activation marker) in the diagnosis of beta-lactam allergy.

[One episode of meningoencephalitis, three diagnoses]. / Méningo-encéphalite herpétique, aciclovir et maladie VIH, une histoire en 3 actes.

Meningo-encephalitis is a set of threatening diseases. The treatment needs to be started quickly for pathogens such as herpes simplex virus type 1 or Listeria monocytogenes. Apart from these classical etiologies, many other diseases may induce meningo-encephalitis. We report the case of a patient, infected with HIV, who presented a history of meningo-encephalitis due to herpes simplex type 1. Three weeks later, he presented an encephalopathy due to aciclovir and then we discovered a chronic meningitis in relation with his HIV infection.

[Cutaneous drug reactions induced by glycopeptides]. / Toxidermies induites par les glycopeptides.

Glycopeptides are a class of antibiotics used with a rising frequency because of the increasing number of infections due to Methicillin-resistant staphylococci. The dermatological adverse effect of vancomycin are well-known: "red man syndrome", maculopapular exanthema, etc., with some distinctive features such as Ig A linear dermatosis. Drug eruptions are less common but not insignificant when using teicoplanin, a more recent molecule. A given glycopeptide cannot be considered as an alternative for every patient "allergic" to another, because of cases of cross-reaction and the morbi-mortality of some cutaneous drug reactions. This emphasizes the importance to recognize early clinical signs. In this article, we review the various dermatological adverse drug reactions induced by glycopeptides, and suggest a possible management to clinicians who could be confronted with this problem.

[Disseminated aspergillosis after intra-articular corticosteroid infiltrations]. / Aspergillose disséminée à point de départ articulaire après infiltrations.

Bone and joint infections due to Aspergillus are rare and occur more commonly in immunosuppressed patients. We report the case of an 84-year-old woman who developed septic arthritis caused by Aspergillus fumigatus after corticosteroid infiltration. This patient had presented with arthritis of the left knee for several months but no microorganism had been found despite numerous arthrocenteses. This arthritis was resistant to treatment by numerous corticosteroid infiltrations. During an arthroscopy, analysis of the synovial fluid yielded A. fumigatus. Thereafter, other explorations showed disseminated aspergillosis with osteo-articular destruction, blood and urinary dissemination. A systemic treatment by voriconazole associated to intra-articular injections and surgical debridement was initiated but the patient died. Septic arthritis caused by A. fumigatus is very rare but must be considered as a differential diagnosis of septic arthritis after corticosteroid infiltration. Their complications can be very important and destructive.

[Investigation of allergic reactions to platinum salts]. / Exploration d'une allergie aux sels de platine.

INTRODUCTION: We report two cases occurring in 2004 of patients being treated for pleural mesothelioma with a combination of cisplatin or carboplatin and pemetrexed. Investigation by skin tests and flow cytometry confirmed the clinical diagnosis in both cases. CASE REPORTS: Case 1: a man of 62 developed, after 12 courses of cisplatin-pemetrexed, an anaphylactic reaction 5 minutes after the infusion of cisplatin. Treatment was withdrawn permanently. Case 2: a man of 66 developed, after 7 courses of cisplatin-pemetrexed, an anaphylactic reaction within the first minute of the infusion of cisplatin. Subsequently, in March 2004, he received pemetrexed alone without any problems. In August 2004 he was prescribed carboplatin-pemetrexed. Within 5 minutes he developed urticaria, pruritus and abdominal pain. He was treated later with pemetrexed alone with no problems. CONCLUSION: Hypersensitivity to platinum salts usually occurs after several courses of treatment. Skin tests and flow cytometry are a simple, concordant, and reliable way of confirming the diagnosis.

[Idiopathic orbital myositis]. / Myosite orbitaire idiopathique.

INTRODUCTION: Orbital myositis is a subtype of nonspecific orbital inflammation confined to one or more of the extraocular muscles. EXEGESIS: Three female patients presented presumed orbital myositis, in each of whom the diagnosis was suspected clinically and confirmed by the computed tomography (CT) scan appearances. All presented with orbital pain, diplopia and periorbital edema. All patients responded to systemic corticosteroid with prompt resolution of symptoms and signs, but one patient had recurrent episodes of myositis, leading to the prescription of azathioprine. The clinical and radiological constellation of findings allowing a definitive diagnosis of the nonspecific orbital inflammatory syndrome in most cases is discussed. CONCLUSION: The nonspecific orbital inflammatory syndromes are a heterogenous group of conditions and the CT scan is a valuable tool in differentiating these conditions. Most cases of idiopathic orbital myositis require corticosteroids, but therapeutic alternatives to corticosteroids in refractory diseases are warranted.

Androgen receptors in human preadipocytes and adipocytes: regional specificities and regulation by sex steroids.

Various clinical and epidemiological evidence strongly suggests a major role for sex steroid hormones in the determination of anatomical specificities of fat distribution in human. To date, no studies have examined the possible presence of androgen receptors (AR) in human adipocytes and preadipocytes. We have studied AR in preadipocytes from various anatomical locations (intra-abdominal and subcutaneous) in middle-aged men and women during the proliferation and differentiation processes (adipogenesis). Androgen binding sites quantified by [3H]R-1881-specific binding in whole cell extracts were twofold higher in intra-abdominal than in subcutaneous preadipocytes but identical for the same fat depots in men and women. Western blot analysis revealed 1) the presence of AR in the nuclear and cytosolic fractions of human preadipocytes, 2) a decrease of AR expression during adipogenesis, and 3) an upregulation of AR by androgens in vitro. RT-PCR experiments showed the presence of AR mRNA in human preadipocytes and adipocytes and also the regional specificity of AR distribution. However, AR mRNA expression was found to increase during adipogenesis. The same results were observed in rat preadipocytes. In conclusion, this study clearly demonstrates the presence of AR in human preadipocytes and adipocytes and suggests that androgens may contribute, through regulation of their own receptors, to the control of adipose tissue development.