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Biomedical subjects

L Guillevin

Publications and source records attributed to L Guillevin.

At least 127 records · Page 7Linked to original sources
PubMed1999

Growth factors and proinflammatory cytokines in the renal involvement of POEMS syndrome.

The POEMS syndrome is a multisystemic syndrome associated with plasma cell dyscrasia, characterized by the combination of polyneuropathy, organomegaly, endocrinopathy, M protein, and skin changes. Renal involvement in POEMS syndrome is rare (26 reported cases). It has been described as membranoproliferative glomerulonephritis-like lesions (MPGN-like), mesangiolytic glomerulonephritis, or thrombotic microangiopathy. Proinflammatory cytokines (TNF-alpha, IL-1, IL-6) have been implicated in the physiopathogenesis of POEMS syndrome, particularly when there is renal involvement. Growth factors (FGF-beta, TGF-beta, PDGF) have been implicated in renal lesions of the same histological type but of different origins. An increase in serum vascular endothelial growth factor (VEGF) has been reported in POEMS syndrome (20 of 22 cases). Circulating levels of these factors were determined in 4 patients with POEMS and renal involvement (3 MPGN-like, 1 MPGN-like, and mesangiolysis) and compared with those obtained in 4 patients with POEMS without clinical renal involvement and in 4 patients with primitive membranoproliferative glomerulonephritis (MPGN). TNF-alpha, IL-1beta, and IL-6 were determined with an immunoradiometric assay, and VEGF, PDGF, FGF-beta, and TGF-beta with an enzyme-linked immunosorbent assay. Among the patients with POEMS syndrome, there was no difference in proinflammatory cytokines and growth factors between those with or without renal involvement. VEGF is the only growth factor that differentiates MPGN in POEMS syndrome from primitive MPGN.

Adult↗
PubMed1999

Double-blind, randomised, multicentre endocrine trial comparing two letrozole doses, in postmenopausal breast cancer patients.

Letrozole is an orally competitive aromatase inhibitor. This double-blind, randomised, multicentre trial was carried out to evaluate the endocrine effects of two doses of letrozole, 0.5 mg versus 2.5 mg orally daily, in postmenopausal advanced breast cancer patients progressing after tamoxifen. The pharmacokinetics of letrozole was also assessed. 46 patients entered the trial, 22 on letrozole 0.5 mg and 24 on 2.5 mg. A significant suppression of oestrone and oestradiol levels was achieved by both letrozole doses. Neither letrozole dose induced any changes in cortisol and aldosterone production at rest or after Synacthen stimulation. Androstenedione, testosterone, 17 alpha-OH progesterone, triiodothyronine (T3) thyroxine, (T4) and thyroid-stimulating hormone (TSH) plasma levels did not show any significant changes. Sex hormone binding globulin (SHBG), follicle-stimulating hormone (FSH) and luteinising hormone (LH) levels increased significantly over time. Plasma letrozole concentrations increased until reaching steady-state values after 1 month at the dose of 0.5 mg and after 2 months at 2.5 mg. In conclusion, both letrozole doses suppressed oestrogen levels without affecting adrenal activity.

Adult↗
PubMed1999

Temporal 67gallium uptake is increased in temporal arteritis.

OBJECTIVE: We evaluated temporal 67gallium (Ga) uptake in temporal arteritis (TA) and the contribution of Ga scans to the diagnosis of TA. METHODS: Ga scans were performed prospectively in 19 patients with biopsy-proven TA and five TA patients with negative temporal artery biopsy. Controls were 18 elderly patients undergoing Ga scans for various inflammatory diseases. The temporal region of interest on head profiles was defined for comparison of uptake with a control parietal region of the same area. The Ga uptake ratio (GaUR) [(temporal region - parietal region)/parietal region] was evaluated for each temple by a computer and intra- and intergroup comparisons were made. RESULTS: GaUR was significantly higher in biopsy-proven TA patients (0.35+/-0.19) and biopsy-negative TA patients (0.31+/-0.03) than in controls (0.18+/-0.12) (P < 0.001), independently of recent temporal artery biopsy or short-duration steroid therapy. High GaUR (>0.4) had a 94% specificity and a 90% positive predictive value for TA diagnosis. After 6 months of steroid therapy, when patients were in remission, GaUR returned to baseline. CONCLUSION: Ga is specifically incorporated into the temporal area in TA patients which may be due to the granulomatous vasculitic process. Ga uptake ceases during remission. A high GaUR may contribute to TA diagnosis in temporal artery biopsy-negative patients and its role in the diagnosis of other localizations of the disease requires further evaluation.

Adrenal Cortex Hormones↗
PubMed1999

Churg-Strauss syndrome. Clinical study and long-term follow-up of 96 patients.

Churg-Strauss syndrome (CSS) is a systemic vasculitis characterized by the presence of asthma, hypereosinophilia, and necrotizing vasculitis with extravascular eosinophil granulomas. In this retrospective study of 96 patients between 1963 and 1995, we analyzed clinical manifestations, identified prognostic factors, and assessed the long-term outcome. CSS was diagnosed when asthma, hypereosinophilia > 1,500/mm3 or > 10%, and clinical manifestations consistent with systemic vasculitis, with or without histologic evidence, were present. Asthma was the most frequently observed manifestation at presentation, with mononeuritis multiplex the second. Other common manifestations were weight loss, fever, myalgia, skin involvement, paranasal sinusitis, arthralgia, pulmonary infiltrate, and gastrointestinal involvement. Mean eosinophilia at presentation was 7.193 +/- 6.706/mm3; ANCA, present in 20 of 42 (47.6%) patients, predominantly gave the perinuclear labeling pattern. All the patients were treated with corticosteroids alone or in combination with cyclophosphamide or plasma exchanges. Clinical remission was obtained in 91.5%; 22 (25.6%) patients relapsed. Twenty-three patients died during follow-up: 11 of these deaths were directly due to vasculitis. The presence of severe gastrointestinal tract or myocardial involvement was significantly associated with a poor clinical outcome. The long-term prognosis of CSS is good and does not differ from that of polyarteritis nodosa, although most patients need low doses of oral corticosteroids for persistent asthma, even many years after clinical recovery from vasculitis.

Adolescent↗
PubMed1999

111Indium antimyosin antibody imaging of primary myocardial involvement in systemic diseases.

OBJECTIVE: The diagnosis of primary myocardial involvement in systemic diseases is clinically relevant but difficult in the absence of specific criteria. Whatever the underlying disease, myocytes degeneration is observed during the active phase of myocardial damage. The aim of this study was to assess the diagnostic value of scintigraphic imaging with 111Indium antimyosin antibody (AM), a specific marker of the damaged myocyte, for ongoing myocardial damage related to systemic diseases. METHODS: 40 patients with histologically confirmed systemic diseases were studied. They were classified into two groups according to the presence (group 1, n = 30), or the absence (group 2, n = 10) of clinical, electrocardiographic (ECG) or echocardiographic signs suggestive of myocardial involvement. Planar and tomographic acquisitions were obtained 48 hours after injection of AM (90 MBq). Rest 201thallium (T1) scintigraphy was also performed to assess myocardial perfusion and scarring. Clinical, ECG, and echocardiographic +/- scintigraphic evaluations were repeated during follow up (17 +/- 19 months) in 36 of 40 patients. RESULTS: In group 1, 13 of 30 patients (43%) showed diffuse significant AM uptake throughout the left ventricle (LV), and no or mild T1 abnormality. Two of these were asymptomatic, four had normal ECG, and two had no clinical or echographic LV dysfunction. All patients in group 2 had negative AMA scintigraphy and normal T1 scintigraphy. During follow up of 12 AM positive patients, cardiac status improved after immunosuppressive treatment was intensified in nine cases, worsened in two cases, and remained stable in one. During follow up of 24 AM negative patients, cardiac status remained stable in 23 cases despite treatment not being increased in 20, including two patients with sequellary myocardial involvement. The last patient developed mild LV dysfunction after 36 months. CONCLUSION: AM scintigraphy allows detection of active myocardial damage related to systemic diseases, with increased specificity compared with conventional methods, and increased sensitivity in some cases. Further studies are needed to assess the potential value of AM scintigraphy as a therapeutic guide.

Adult↗
PubMed1999

A large subset of neutrophils expressing membrane proteinase 3 is a risk factor for vasculitis and rheumatoid arthritis.

It has been shown previously that proteinase 3 (PR3), a neutrophil intracellular protease that is the main antigen of antineutrophil cytoplasm (ANCA) autoantibodies, is present on the plasma membrane of a subset of freshly isolated neutrophils. This study shows that the size of this subset of membrane PR3-positive (mPR3+) neutrophils is a stable feature of a given individual, most likely genetically controlled. It ranges from 0 to 100% of neutrophils and allows us to define a new polymorphism in the healthy population, with three discrete phenotypes corresponding respectively to less than 20% mPR3 + neutrophils (mPR3low) or to a mean percentage of 47% (mPR3intermediate) and 71.5% (mPR3high) mPR3+ neutrophils. The frequency of the mPR3high phenotype was significantly increased in patients with ANCA-associated vasculitis (85% versus 55% in healthy subjects). The percentage of mPR3+ neutrophils was not affected by disease activity, relapses, or therapy, and did not reflect in vivo cell activation. In addition, mPR3+ phenotypes were normally distributed in cystic fibrosis patients, indicating that infection and/or inflammation per se do not lead to a high percentage of mPR3+ neutrophils. The frequency of the mPR3high phenotype was not related to anti-PR3 autoimmunization, since it was increased in vasculitic patients regardless of the ANCA specificity (anti-PR3, anti-myeloperoxidase, or unknown). Interestingly, the frequency of the mPR3high phenotype was also increased in patients with rheumatoid arthritis. It was normal in type I-diabetes, a T cell-dependent autoimmune disease. It is proposed here that a high proportion of membrane PR3-positive neutrophils could favor the occurrence or the progression of chronic inflammatory diseases.

Adult↗
PubMed1999

Lymph node tuberculosis in the suburbs of Paris: 59 cases in adults not infected by the human immunodeficiency virus.

We report 59 cases of lymph node tuberculosis in adults not infected by the human immunodeficiency virus (HIV), observed over a period of 5 years in the North Eastern suburbs of Paris. There were 31 women and 28 men; 84.7% were aged under 44 years; 69.5% were not French, and 78% had exclusive lymph node tuberculosis. A superficial distribution was found in 52 cases and a deep pattern in 17 cases. Cervical and supraclavicular lymphadenopathies were the most common (64.4%). General symptoms were present in 63% of cases. The diagnosis was established by fine needle aspiration in 10 cases and by biopsy in 36 cases. Three cases of primary resistance to anti-tuberculosis therapy were described. Lymph node tuberculosis is still present in the Paris region, independently of HIV infection, probably due to poor social conditions.

Adolescent↗
PubMed1999

[Physiopathology of viral vasculitis].

Viral infections can cause vasculitides via mechanisms that remain incompletely understood but may involve circulating immune complexes or endothelial cell infection. Many viruses are capable of infecting the endothelial cells and modifying their phenotype, thus facilitating thrombosis and inflammatory cell recruitment. Although the main animal models of vasculitis are virus-induced, viruses are responsible for only a minority of cases of vasculitis in humans. However, a role of undetected viruses in vasculitides currently classified as primary cannot be completely ruled out.

Animals↗
PubMed1999

[Treatment of viral vasculitis].

Necrotizing vasculitis is a heterogeneous group of systemic diseases characterized by inflammation of blood vessel walls. There is current agreement that viral infections can play a central role in the pathophysiology of systemic vasculitides responsible for a broad spectrum of clinical patterns. The hepatitis B and C viruses (HBV and HCV), the parvovirus B19, the human immunodeficiency virus, the HTLV 1, and the cytomegalovirus are the viruses most often implicated. Only the HBV and HCV are associated with fairly well-defined clinical pictures. The conventional management of systemic vasculitis rests on administration of a corticosteroid with an immunosuppressive (usually cyclophosphamide). The decision to treat rests on the nature and severity of the vasculitis. In viral vasculitis, the goal of therapy is to treat both the systemic condition and its cause at the same time. In this situation, conventional immunosuppressive therapy promotes perpetuation of the viral infection, exposing the patient to chronic lesions and to relapses. Antiviral therapy has demonstrated clear evidence of efficacy in vasculitis related to the HBV and, to a lesser degree, the HCV. For the other viruses data, in the literature are scant.

Adrenal Cortex Hormones↗
PubMed1999

The spectrum of reactive hemophagocytic syndrome in systemic lupus erythematosus.

We address the relationship between reactive hemophagocytic syndrome (RHS), systemic lupus erythematosus (SLE) activity, and treatment in 4 female patients with SLE. Febrile pancytopenia was related to cytologically proven RHS in all patients. Followup was 45+/-7 months from RHS onset. No causal infection could be identified. Outcome could be classified as: (1) RHS onset during a SLE flare and complete efficacy of high dose steroids; (2) death despite therapy for concomitant severe RHS and active SLE; (3) severe RHS in inactive SLE under immunosuppressants, with remission after steroid tapering and cyclophosphamide withdrawal. Three patients were treated with intravenous IgG. We conclude that (1) when SLE is active, RHS should be considered a specific manifestation and treated with steroids; (2) RHS occurring in otherwise inactive SLE might be related to iatrogenic immunosuppression; (3) intravenous IgG treatment might be indicated in both situations.

Acyclovir↗
PubMed1999

IgA glomerulonephritis associated with microscopic polyangiitis or Churg-Strauss syndrome.

When renal insufficiency occurs in classical antineutrophil cytoplasm antibody- (ANCA) associated vasculitides, histological examination usually finds pauci-immune focal segmental glomerulonephritis. We report on 2 cases of histologically proven necrotizing vasculitis associated with IgA nephropathy. Concomitant vasculitis and IgA nephropathy has only rarely been reported but this joint occurrence may not be coincidental as its pathophysiology is not known. Among vasculitides, IgA nephropathy has more frequently been associated with Henoch-Schoenlein purpura: one microscopic polyangiitis unusual because the patient simultaneously presented ANCA and microaneurysms, and the other Churg-Strauss syndrome associated with mild renal insufficiency. This uncommon association might represent a possible overlap syndrome between these ANCA-associated vasculitides and IgA nephropathy or simply a new type of glomerulonephritis that must be taken into account in these vasculitides.

Antibodies, Antineutrophil Cytoplasmic↗
PubMed1999

[Common variable immunodeficiency: one or multiple illnesses? 3 clinical cases].

Common variable immunodeficiency (CVID) is a major antibody-deficiency syndrome, associated with increased risk of bacterial infection, as well as autoimmune and granulomatous disease. The clinical and immunological features are heterogeneous. This heterogeneity is expressed by the case reports of three selected patients. These observations will be discussed, with reference to a recent classification of CVID distinguishing four different clinical entities: i) CVID presenting with clinical and immunological features of X-linked agammaglobulinemia; ii) CVID presenting with clinical and immunological features of X-linked hyper-IgM syndrome; iii) CVID associated with systemic granulomatous disease; and iiii) CVID associated with autoimmune manifestations.

Adult↗
PubMed1999

Concomitant polymyositis and myasthenia gravis reveal malignant thymoma. A case report and review of the literature.

The frequency of thymona associated with autoimmune diseases has been reported to be increased, with 50% of thymoma patients also having myasthenia gravis (MG). Other autoimmune disorders, such as autoimmune erythroblastopenia and polymyositis (PM), have been less frequently associated with thymoma. The association of MG and PM with thymoma is rare. We here report the case of a 66-year-old woman whose concomitant MG and PM revealed malignant thymoma and review the other published cases of this association.

Aged↗