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Biomedical subjects

L Guillevin

Publications and source records attributed to L Guillevin.

At least 199 records · Page 11Linked to original sources
PubMed1996

Treatment of mixed cryoglobulinemia with recombinant interferon alpha and adjuvant therapies. A prospective study on 20 patients.

In order to evaluate the efficacy of interferon alpha (IFNa) in mixed cryoglobulinemia (MC), a prospective multicenter clinical trial was conduced in April 1992. It consisted of treating 20 clinically symptomatic MC patients with IFNa for 26 weeks. Hepatitis C virus (HCV) infection was detected in 16 patients. A complete or partial clinical remission was obtained in 12 patients (60%). Eleven of these 12 responders (91.6%) experienced a clinical relapse less than 12 months after the end of therapy. Side effects were noted in 10 patients (50%). It was concluded that subcutaneously administered IFNa does not provide long-term remission.

Adrenal Cortex Hormones↗
PubMed1996

Microscopic polyangiitis: clinical aspects and treatment.

Recently individualized from polyarteritis nodosa (PAN), microscopic polyangiitis (MPA) is defined as a systemic necrotizing vasculitis that clinically and histologically affects small-sized vessels (ie, capillaries, venules or arterioles) without granulomata and is associated with focal segmental necrotizing glomerulonephritis. Males are more frequently affected than females and the average age of onset is about 50 years old. Most patients experience some systemic symptoms before diagnosis of vasculitis. Clinically, renal involvement is the major feature of MPA and is characterized by rapidly progressive glomerulonephritis (RPGN). Most of the patient have renal impairment at admission and renal function deteriorates rapidly without treatment. Lung involvement is also common. Lung hemorrhage is observed in 12 to 29% of the patients with MPA and is an important contributory factor to morbidity and mortality. Some patients with small-vessel lung vasculitis may present clinical, radiologic and functional findings consistent with an interstitial process mimicking idiopathic pulmonary fibrosis. Others clinical features are similar to those observed in PAN. Musculoskeletal involvement (myalgias, arthralgias and arthritis) are present in 65 to 72% of the patients. Cutaneous lesions (purpura, splinter hemorrhages) are found in 44 to 58% of the patients. Gastrointestinal symptoms are characterized by abdominal pain (32 to 58%) and digestive tract bleeding (29%). Peripheral neuropathy is found in only 14 to 36% of the cases, thus occurring less frequently than in PAN. Ocular manifestations and ear, nose and throat lesions are commonly seen, more frequently than in PAN. Non-specific laboratory tests reflect the systemic inflammatory nature. Almost all patients are negative for hepatitis B virus (HBV) surface antigen. Renal insufficiency with creatininemia > 120 microns/l is present in the majority of patients. Antineutrophil cytoplasm antibodies (ANCA) are found in 75% of MPA patients and the majority of these ANCA detected are perinuclear-staining anti-myeloperoxidase ANCA, although anti-proteinase 3 has also be detected. Microaneurysms, commonly present in PAN, are rarely seen on at visceral angiograms. MPA is part of a spectrum of systemic vasculitides. Differentiation between PAN and MPA should be based on clinical manifestations (especially lung and kidney involvement), biologic signs (ANCA, HBV or HCV infection) and angiographic data. The therapeutic strategies for treatment of PAN and MPA do not differ extensively. Prognosis of systemic vasculitides have been transformed by corticosteroids that are the basis of the treatment. Immunosuppressive drugs, especially cyclophosphamide, also contribute to a better prognosis. Considering the high frequency of renal involvement in MPA, most of the patients should considered as having factors or poor prognosis and the high number of relapses that can occur in patients with MPA could justify prolonged steroid administration or immunosuppressive treatment.

Humans↗
PubMed1996

Cyclosporin a therapy in refractory juvenile dermatomyositis. Experience and longterm followup of 6 cases.

OBJECTIVE: Cyclosporin A (CyA) has been reported to be an effective treatment of adult polymyositis (PM) and dermatomyositis (DM) refractory to corticosteroid therapy. We aimed to determine the effectiveness of CyA in the treatment of juvenile dermatomyositis (JDM) refractory to corticosteroids and cytotoxic agents. METHODS: Retrospective study of 6 patients with refractory JDM based on medical charts. RESULTS: Better clinical control of the disease was obtained in all cases and corticosteroid doses could be markedly decreased or stopped. 4 patients relapsed, 3 after discontinuation of CyA, but recovered after its reinitiation. Trough CyA levels were maintained between 51 and 247 ng/ml, and side effects were rare and minor during a mean followup of 51.5 months. CONCLUSION: CyA seems to be an effective treatment of JDM and should be considered in case of severe or refractory disease.

Biomarkers↗
PubMed1996

Cyclophosphamide/mitoxantrone/melphalan (CMA) regimen prior to autologous bone marrow transplantation (ABMT) in metastatic breast cancer.

Dose-intensive treatment followed by ABMT is currently used in different approaches to treat breast cancer patients. An active non cross-resistant regimen combining cyclophosphamide (C), mitoxantrone (M) and melphalan (A) (CMA), was developed as the conditioning regimen before ABMT. The purpose of this phase II study was to evaluate this protocol and the duration of its effect in metastatic patients, who responded to chemotherapy. Criteria for inclusion included histologically documented breast cancer, age < 55 years and the first detection of measurable metastatic lesions. Following first-line chemotherapy in responding patients, histologically negative bone marrow was collected and cryopreserved. Then, intensification with cyclophosphamide (120 mg/kg), mitoxantrone (60 mg/m2), and melphalan (140 mg/m2) was followed by ABMT. Sixty-one metastatic breast cancer patients with a mean age of 40 years were included. Sites of measurable metastases included: liver 24, lung 14, central nervous system four, pleura three, skin six, and chest wall six, nodes eight and bone marrow one. Nineteen patients had lesions in two or more sites, and 22 had bone involvement. The response of 60 patients could be evaluated: before ABMT 31 were in clinical complete response (CR), 22 in partial response > 50% (PR), and seven had new progression. After ABMT, 36 patients were in CR, 16 in PR, one progressed and one was stable. Seven (11.5%) toxic deaths occurred. Mean time for hematological recovery was 32.5 days, without hematopoietic growth factors. Median survival was 33 +/- 9.4 months from the start of therapy, and 25.7 +/- 4.6 months from the date of ABMT. Median event-free survival was 20 months from the start of therapy, and 13 +/- 2 months from ABMT. With a median follow-up of 51 months, probability of actuarial survival, measured from the beginning of initial chemotherapy, was 36%, and event-free survival was 18%. In metastatic breast cancer responding to chemotherapy, high-dose consolidation with CMA and ABMT resulted in a median survival of 33 months. These results lay the ground work for evaluation in a randomized trial in metastatic breast cancer.

Adult↗
PubMed1996

[Acute cholecystitis in periarteritis nodosa. 8 cases].

OBJECTIVES: Analyze clinical manifestations and laboratory findings in patients with periarteritis nodosa who developed acute cholecystitis in order to determine their value for prognosis and management. PATIENTS AND METHODS: We report 8 cases of acute cholecystitis which revealed or occurred as a complication of periarteritis nodosa. These were 4 men and 4 women, mean age 50 years. Periarteritis nodosa was diagnosed on the basis of histological evidence and/or clinical expression. Complimentary explorations included: sonography of the biliary tree, cholecystogram or cholangiogram in addition to diagnostic work-up for periarteritis nodosa. RESULTS: The clinical or sonographic presentation was similar to common cases of cholecystitis. However, no stone were observed in 2/8 cases. Histologically, the gall bladder showed characteristic vascular lesions suggestive of periarteritis nodosa in 7 out of 8 cases (no operation in 1 case). Cholecystitis was the inaugural sign in 2 cases. Surgery was performed for lithiasic forms. Medical management with methylprednisolone i.v. was used successfully in the alithiasic forms. In the 2 cases with inaugural solitary acute cholecystitis. lithiasis was found in the surgical specimen in 1 case; the pathology examination gave the etiological diagnosis. There was no lithiasis in one case with inaugural cholecystitis. CONCLUSIONS: The development of acute cholecystitis in patients with periarteritis nodosa is uncommon but should be treated surgically in case of lithiasis or when the cholecystitis is the inaugural sign. Unlike digestive tract involvement, periarteritis nodosa does not aggravate the clinical course. Alithiasic forms may be treated medically with corticosteroids. In our opinion, therapeutic abstention, sometimes proposed in patients with necrotizing angiitis of the gall bladder, is not always indicated as some patients can benefit from medical treatment of the underlying periarteritis nodosa.

Acute Disease↗
PubMed1996

[Course of ischemic risk in treated atheromatous hypertensive patients. The PRIHAM study (Prognosis of Ischemic Risk in Atheromatous Patients under Mediatensyl)].

Hypertension is one of the major cardiovascular risk factors. However it seldom occurs alone in a patient and the antihypertensive treatment should be taken into account when assessing global cardiovascular status. The PRIHAM study was an open study which enrolled 3,216 hypertensive atheromatous patients who already has had a clinical ischaemic accident. Patients were followed-up for 3 years. The lowering effect on cardiovascular risk, starting from the fifteenth month was confirmed to the end of 36-month study. The effect on blood pressure was observed from the third month. Stabilized blood pressure observed within the first year persisted throughout the three years without tachyphylaxis. It was effective on SBP (-14.4%) and on DBP (-15%) while maintaining a stable heart rate both in the supine position or immediately upon standing or after 3 minutes in the standing position. Tolerance was globally judged as good or very good by the investigating practitioners and the patients expressed an improvement in their feeling of well-being. In conclusion, from the level of effectiveness obtained and the low incidence of adverse effects, urapidil appears well adapted and easy to manage in a population with a particularly high cardiovascular risk.

Adult↗
PubMed1996

[Immunosuppressive and immunomodulator treatment of severe systemic lupus].

Immunosuppressor and immunomodulator therapies are widely used for the treatment of patients with severe systemic lupus erythematosus. In case of certain organ involvement (kidney, brain, heart), corticosteroids should be associated with immunosuppressors, especially cyclophosphamide. Cyclophosphamide, a powerful immunosuppressor, is generally given in an intravenous bolus rather than orally. Aziathioprine is proposed after cyclophosphamide or in less forms at onset. The therapeutic strategy in severe forms may require plasma exchange, carefully synchronized with the cyclophosphamide bolus. Depleted antibodies following plasma exchange induces a stimulation of B clones which produce antibodies sensitive to cyclophosphamide. Other immunomodulator treatments have also been used, for example cyclosporine or intravenous immunoglobulins. Cyclosporine has not been shown to be effective in severe lupus. Inversely, in certain conditions, cyclosporine can be used to limit other treatments although it does not have a significant effect on autoantibody levels. Intravenous immunoglobulins have been used at high dosages but only in selected cases due to undesirable side effects. Certain cases of renal failure induced by immunoglobulins have been described. Immunosuppressor or immunomodulator therapy is often required in systemic lupus erythematosus. Treatment modalities must however be carefully established in order to limit the predictable side effects while achieving maximal efficacy.

Adjuvants, Immunologic↗
PubMed1995

Measurement of 4-hydroxycyclophosphamide in serum by reversed-phase high-performance liquid chromatography.

A reversed-phase high-performance liquid chromatographic method was developed for the measurement of 4-hydroxycyclophosphamide (4-OH-CP) in human serum, since no such assay has been described to date. In the present procedure, the serum sample was treated with semicarbazide at pH 7.4 to derivatize the 4-OH-CP to its aldophosphamide semicarbazone form. Derivatization was performed at 60 degrees C for 60 min and the product was extracted with ethyl acetate-chloroform (75:25, v/v). The derivatives formed were chromatographed on a C8 reversed-phase column with a mobile phase of 0.025 M phosphate buffer-acetonitrile (18:82, v/v) and a detection wavelength of 230 nm. The limit of detection of the assay was 0.025 mg/l for 1 ml of serum with a signal-to-noise ratio of 2. The between-assay coefficients of variation at concentrations of 0.2 and 0.4 mg/l were 7.7 and 7.0% respectively. The simplicity and specificity of this method make it directly applicable to clinical studies on 4-OH-CP pharmacokinetics.

Chromatography, High Pressure Liquid↗
PubMed1995

Corticosteroids plus pulse cyclophosphamide and plasma exchanges versus corticosteroids plus pulse cyclophosphamide alone in the treatment of polyarteritis nodosa and Churg-Strauss syndrome patients with factors predicting poor prognosis. A prospective, randomized trial in sixty-two patients.

OBJECTIVE: To define the most effective treatment for severe polyarteritis nodosa (PAN) and Churg-Strauss syndrome (CSS) and to investigate the indication for plasma exchange treatment. METHODS: We conducted a prospective, randomized, multicenter trial in which 62 patients were randomly assigned to receive either prednisone plus cyclophosphamide (intravenous bolus) (group A; n = 28) or prednisone plus cyclophosphamide (intravenous bolus) plus plasma exchanges (group B; n = 34) as first-line treatment for severe PAN or CSS. Factors predicting poor prognosis were renal symptoms, gastrointestinal tract involvement, cardiomyopathy, central nervous system involvement, weight loss > 10% of body weight, and age > 50 years old. Patients with hepatitis B virus-related PAN were not included in this study. The end point of the study was control of the disease (recovery or remission) or death. RESULTS: Clinical symptoms and laboratory findings did not differ significantly in the 2 groups. Initial control of the disease was similar in both groups. Relapse after initial control of the disease was observed in 7 patients (4 in group A and 3 in group B). The mean +/- SD followup period was 31.1 +/- 20 months for group A and 35.9 +/- 16.8 months for group B. At 5 years of followup, 38 patients (61.3%) were cured (16 in group A and 22 in group B), and 5 (8.1%) were in remission without treatment but had not yet completed the cure-defining period of 18 months (3 in group A and 2 in group B). Eight (12.9%) (2 in group A and 2 in group B) were considered to be in clinical remission and required a maintenance regimen of low-dose corticosteroids. Eleven patients died during the study period (7 in group A [25%], 4 in group B [11.8%]). Uncontrolled vasculitis was responsible for 4 deaths (2 in each group), and treatment side effects caused the death of 1 patient in group A. There was no significant difference between the 5-year cumulative survival rates of the 2 groups (75% and 88%, respectively). CONCLUSION: Based on our data, combined treatment with prednisone, cyclophosphamide, and plasma exchanges is not superior to treatment with prednisone and cyclophosphamide alone, and plasma exchanges should not be systematically proposed for initial treatment of severe PAN or CSS.

Adolescent↗
PubMed1995

Polyarteritis nodosa related to hepatitis B virus. A prospective study with long-term observation of 41 patients.

Hepatitis B virus (HBV)-related polyarteritis nodosa (PAN) is a rare disease whose frequency has been decreasing over the past 10 years. We evaluated 41 patients with HBV-related PAN to determine the circumstances leading to infection, the clinical features of vasculitis, the prognostic factors, and the response to therapy. Most patients were first treated briefly with corticosteroids, and all were included in 2 nonrandomized prospective therapeutic trials of an antiviral agent (35 patients with vidarabine, 6 patients with interferon-alpha 2b) and plasma exchanges. The mean duration of follow-up was 69.6 +/- 44.8 months. At the end of the study, 21 (51.2%) patients had seroconverted to anti-HBeAb and 10 (24.4%) also had seroconverted to anti-HBsAb. In all, 23 (56%) patients no longer expressed serologic evidence of HBV replication. All 33 (80.5%) patients still alive at the end of follow-up recovered from PAN. Nineteen also recovered from HBV infection and were considered to be cured; 13 patients had persistent HBV infection and were considered to be in clinical recovery; and 1 patient was in remission, maintained with steroid therapy. Eight patients died during the study period; 3 deaths were directly attributable to PAN. HBV-related PAN is an acute disease, occurring shortly after infection and sharing the characteristics of classic PAN. It is not an antineutrophil cytoplasm antibodies (ANCA)-mediated vasculitis. The outcome was good for patients treated with short-term steroid therapy, antiviral agents, and plasma exchanges. We propose this protocol as the first treatment for HBV-related PAN, because it surpasses the conventional treatment with corticosteroids and cyclophosphamide, which facilitates viral replication and the development of chronic HBV infection.

Adolescent↗
PubMed1995

Factors associated with Pneumocystis carinii pneumonia in Wegener's granulomatosis.

OBJECTIVE: To determine the factors associated with the occurrence of Pneumocystis carinii pneumonia (PCP) in Wegener's granulomatosis (WG). METHODS: We retrospectively compared a group of 12 patients with WG and PCP (PCP group), with 32 WG patients without PCP followed over the same period in the same centres (control group). RESULTS: The mean delay of onset of PCP after the start of the immunosuppressive therapy was 127 (SD 128) days. Before treatment, the clinical and biological features of the two groups were similar, except for the mean lymphocyte count which was lower in the PCP group than in the control group (1060/mm3 v 1426/mm3; p = 0.04). During treatment, both groups were lymphopenic. There was a significant difference between the lowest absolute lymphocyte count in each group (244/mm3 in the PCP group v 738/mm3 in the control group; p = 0.001). During the first three months of treatment, the lymphocyte count was less than 600/mm3 at least once in 10 of the 12 patients in the PCP group and in 11 of the 32 patients in the control group (p < 0.01). The mean cumulative dose of cyclophosphamide was greater in the PCP group than in the control group at the end of both the second (1.55 mg/kg/day v 0.99 mg/kg/day; p = 0.05) and the third (1.67 mg/kg/day v 0.97 mg/kg/day; p = 0.03) months. However, in multivariate analysis, the only two factors independently and significantly associated with the occurrence of PCP were the pretreatment lymphocyte count (p = 0.018) and the lymphocyte count three months after the start of the immunosuppressive treatment (p = 0.014). CONCLUSIONS: The severity of lymphocytopenia before and during immunosuppressive treatment is the factor best associated with PCP in WG.

Female↗
PubMed1995

Hepatitis B virus-related polyarteritis nodosa and membranous nephropathy.

We report the case of man with a history of post-transfusion chronic persistent hepatitis due to hepatitis B virus (HBV), who secondarily developed polyarteritis nodosa (PN) and membranous nephropathy (MN) simultaneously. At that time, liver biopsy yielded the diagnosis of active chronic hepatitis, and serological tests showed a high replication rate of HBV. PN was due to HBV infection, but the etiology of MN was uncertain, as it has never been described in PN, even in its microscopic form. There was no evidence of paraneoplastic syndrome or other causes of MN. Although the renal biopsy did not give any indication of HBV-related glomerulonephritis, the patient was considered to have an association of classic PN and MN, both related to HBV. Treatment combined plasmapheresis and interferon-alpha.

Aged↗
PubMed1995

Anti-neutrophil cytoplasm antibodies in patients with ACR criteria for polyarteritis nodosa: help for systemic vasculitis classification?

The american college of rheumatology (ACR) proposed in 1990 revised clinical criteria for systemic vasculitis classification to define homogeneous group of patients for clinical trials. However, microscopic polyarteritis (MPA) was not clearly identified from polyarteritis nodosa (PAN). Since anti-neutrophil cytoplasm antibodies (ANCA) are markers of disease activity of small vessel vasculitides including MPA, we tested the clinical significance of ANCA in 24 patients with PAN according to the ACR 1990 criteria. Two of 24 patients had ANCA, as defined by indirect immunofluorescence on normal human neutrophils, antigen-specific ELISA and Western blot analysis. However, they exhibited histologically proven small vessel but not medium vessel vasculitis. Furthermore, they had neither artery microaneurysms nor large organ injury consequent upon large vessel occlusion. Although they satisfied ACR criteria for PAN, they probably were misclassified and should be considered as MPA. We conclude that: (i) ANCA are not found in patients with classical PAN in the absence of MPA features; (ii) caution should be exercised when defining PAN according to the ACR 1990 criteria; (iii) ANCA may help systemic vasculitis classification.

Adult↗