Jean Marc Durand

Human interleukin-17 : A T cell-derived proinflammatory cytokine produced by the rheumatoid synovium

OBJECTIVE To investigate the presence and role of interleukin-17 (IL-17) in rheumatoid arthritis (RA), and its regulation by antiinflammatory cytokines. METHODS The production of IL-17 was measured in supernatants of RA, osteoarthritis (OA), and normal synovial tissue pieces cultured ex vivo. Quantification of IL-17 was performed using a specific biologic assay. IL-17 gene expression was investigated by reverse transcriptase-polymerase chain reaction (RT-PCR)-techniques. Immunohistochemistry was used to evaluate the frequency of IL-17-positive cells in synovium. The secretion of IL-17 by synovium was measured in the presence of IL-4, IL-13, and IL-10. In addition, the contributions of exogenous and endogenous IL-17 to IL-6 production by RA synovium were studied. RESULTS Functional IL-17 was spontaneously produced by 16 of 18 RA (mean +/- SEM 41.7+/-11.4 units/ml), 2 of 12 OA (5.3+/-4.5 units/ml), and 0 of 3 normal synovial explant cultures. IL-17 messenger RNA expression was demonstrated by RT-PCR in 4 of 5 RA and 0 of 3 OA synovial samples. By immunostaining of RA synovium, IL-17-producing cells were found in the T cell-rich area. Addition of both IL-4 and IL-13 completely inhibited the production of IL-17, whereas IL-10 had no effect. Addition of exogenous IL-17 to RA synovium resulted in an increase in IL-6 production, whereas that of a blocking anti-IL-17 antibody reduced production of IL-6. CONCLUSION The T cell cytokine IL-17 was found to be highly produced by RA, but not by OA, synovium. Its production and function were down-regulated by IL-4 and IL-13. These results indicate that IL-17 contributes to the active, proinflammatory pattern that is characteristic of RA. Through the contribution of IL-17, some Th1-like T cells appear to mediate synovial inflammation.

Clinical StudiesDapsone for thrombocytopenic purpura related to human immunodeficiency virus infection

Abstract purpose: The purpose of this study was to determine the effect of dapsone on platelet count in patients with human immunodeficiency virus (HIV)-related autoimmune thrombocytopenia. patients And Methods:Eleven patients with HIV-related thrombocytopenia received dapsone (50 to 125 mg/day) for 2 to 43 months. Patients with the acquired immunodeficiency syndrome were not enrolled. results: Of the 11 patients, six developed platelet counts above 50 × 10 9 /L and did not require any other specific therapy. No significant side effects were observed. conclusion: We conclude that dapsone may be effective in some patients with HIV-related thrombocytopenia.

Anti-Neutrophil Cytoplasmic Antibodies (ANCA) and Infection

As ANCA are occasionally noted in patients with infectious disorders independently of any vasculitis process, we examined serum from patients with acute infection (n = 22) and septic shock (n = 57). Only two patients with acute infection were ANCA positive as determined by indirect immunofluorescence and western blot analysis. The clinical recovery of both patients was associated with negative immunofluorescence and western blot tests.

Successful treatment with rituximab in an elderly patient with acquired factor VIII inhibitor

We report here on an elderly patient, aged 88 years, who developed acquired hemophilia, with a high titer of factor VIII inhibitors and severe hemorrhage, in the absence of a detectable cause. Marked and prolonged efficacy was observed after rituximab.

Still's-like disease, breast prosthesis, and collagen implants

Abstract. Silicone-induced connective tissue disease raises a controversial issue. We report a case of Stills disease associated with silicone and collagen implants that showed improvement on steroids, but remained steroid-dependent despite removal of the silicone implants. This observation complements four previous cases in the literature and questions the role of breast implants in the pathogenesis of Stills disease. The number of cases studied is insufficient for conclusions, but silicone-implant-associated syndrome may be confused with Stills disease. We consequently propose the use of ferritinemia and its serum glycosylated fraction level as discriminating factors. Collagen has been associated with some inflammatory diseases, but never previously with Stills disease. However, considering this observation and previous data in the literature, its role may be postulated as an exacerbating factor or a pathogenic agent.

JAW CLAUDICATION AS AN ATYPICAL MANIFESTATION OF AORTIC THORACIC DISSECTION IN ELDERLY PEOPLE

ventricular function returned to normal 7 days later. This report demonstrates that T-wave inversion on telemetry monitoring might be useful for detecting the onset of tako-tsubo cardiomyopathy in patients in a coma. Since tako-tsubo cardiomyopathy was first reported in 1990, this disorder has been recognized worldwide. Most patients have been elderly women, symptoms are similar to those of acute myocardial infarction, and patients have often experienced emotional or physical stress before onset. Tako-tsubo cardiomyopathy should be considered in the differential diagnoses of acute myocardial infarction. In our case, acute stress due to brain infarction could have been a precipitating factor leading to tako-tsubo cardiomyopathy. Because apical ballooning of tako-tsubo cardiomyopathy is transient and resolves dramatically in a short time, its prognosis is generally favorable, although recent reports have demonstrated early life-threatening complications, including left ventricular rupture, arrhythmia, heart failure, cardiogenic shock, and apical thrombus formation. Early diagnosis and subsequent treatment are required to prevent these complications even in patients with tako-tsubo cardiomyopathy. Tako-tsubo cardiomyopathy often occurs as a complication of noncardiac disorders. The development of takotsubo cardiomyopathy may be diagnosed at a later stage or overlooked, especially in patients who are in a coma. Clinicians should recognize that there is a possibility of the development of tako-tsubo cardiomyopathy when T-wave inversion appears in patients with noncardiac disorders during hospitalization. Transthoracic echocardiography or repeated electrocardiogram should be performed routinely in these patients.

CASE REPORT: β-Carotene-Induced Hepatic Fibrosis

A 66-year-old woman, an alcohol drinker, presented with anicteric cholestasis of two years duration. She has been treated during the last 30 years for a pigmentary retinopathy with anthocyanosides associated with -carotene (total dose 165 g). The clinical examination was normal. Biology confirmed cholestatic changes: serum alkaline phosphatase 1364 IU/liter (normal 200), gammaglutamyltranspeptidase 144 IU/liter, (normal 35), aspartate aminotransferases 52 IU/ liter, and alanine aminotransferases 60 IU/liter, (normal 35). Ultrasonography and endoscopic retrograde cholangiopancreatography were normal. The liver biopsy showed a pronounced portal fibrosis. Bile ducts were normal; there was no evidence of portal inflammation. The usual causes of chronic hepatic diseases, especially primary biliary cirrhosis and chronic hepatitis C, were excluded. All infectious, immunologic, and metabolic investigations were normal. The blood level of vitamin A was 0.43 g/liter (normal range: 0.5–0.8g/ liter). We observed a favorable course within six months, after -carotene therapy was stopped and ursodeoxycholic acid supplementation was given (alkaline phosphatase 290 IU/liter, gammaglutamyltranspeptidase 44 IU/liter). Subsequently, the patient has remained stable for three years despite continued alcohol intoxication.