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P Cacoub

Publications and source records attributed to P Cacoub.

At least 19 recordsLinked to original sources
PubMed2000

Potentiation of vitamin K antagonists by high-dose intravenous methylprednisolone.

BACKGROUND: Oral anticoagulants and pulse high-dose intravenous methylprednisolone are often administered concomitantly, but no data on potential interactions are available. OBJECTIVE: To assess possible potentiation of oral anticoagulation by high-dose intravenous methylprednisolone. DESIGN: Prospective cohort study. SETTING: University hospital in Paris, France. PATIENTS: 10 consecutive patients concomitantly receiving methylprednisolone and oral anticoagulants (fluindione and acenocoumarol) and 5 consecutive controls receiving methylprednisolone alone. MEASUREMENTS: Serial determinations of the international normalized ratio (INR) and clotting factors during administration of pulse methylprednisolone. The total plasma fluindione concentration was determined in 3 patients. RESULTS: The mean INR was 2.75 (range, 2.02 to 3.81) at baseline and increased to 8.04 (range, 5.32 to 20.0) after methylprednisolone administration. Plasma fluindione concentrations and the INR increased after methylprednisolone administration. Methylprednisolone alone did not increase prothrombin time. CONCLUSIONS: The action of oral anticoagulants is potentiated by intravenous high-dose methylprednisolone. The INR should be monitored daily during concomitant administration of these medications.

Acenocoumarol↗
PubMed2000

Effect of cryopreservation on endothelin-1 productions of human mammary artery.

The aim of this study was to determine the ability of human mammary artery cells to maintain a metabolic activity by measuring the artery concentration of two vasoactive substances, endothelin-1 (ET-1) and cyclic guanosyl monophosphate (cGMP), and a neurohumoral substance-neuropeptide Y (NPY)-prior to and following cryostorage. Ten distal segments of internal mammary arteries were obtained at the time of surgery in patients who had undergone coronary artery bypass grafting. One ring of each vessel served as a fresh control for the other ring that was used in cryopreservation experiments. The arteries were frozen with liquid nitrogen at a controlled rate down to -130 degrees C with an automatic freezing machine and were then stored in a liquid nitrogen vapor at -150 degrees C. After mammary artery extraction, ET-1, cGMP, and NPY concentrations were studied before and after cryopreservation. Cryopreserved, compared to fresh arteries, exhibited an increase in ET-1 (11.11+/-1.61 vs. 3. 09+/-0.06 pg/mg; p=0.004) and a decrease in cGMP (9.88+/-2.04 vs. 8. 55+/-2.07 p moles/mg; p<0.02), whereas there was no significant NPY variation. An increase in ET-1 and decrease in cGMP was found in 10 out of 10 and 6 out of 10 of cryopreserved artery specimen, respectively. There was no significant correlation between ET-1 and cGMP production in fresh or in cryopreserved arteries. The present method of cryostorage is effective in preserving "hormonal" mammary artery activity. However, the particularly high ET-1 concentration without associated cGMP concentration may be deleterious by increasing smooth-muscle cell proliferation and vascular tone of cryopreserved arteries.

Cryopreservation↗
PubMed2000

[Hyperhomocysteinemia and arterial or venous thrombosis. Retrospective study of 75 cases].

OBJECTIVE: Previous studies suggest that hyperhomocysteinemia may be a risk factor for arterial and venous thrombosis. We retrospectively analyzed data from 75 patients with thrombosis. PATIENTS AND METHODS: Thirty-four patients had arterial thrombosis, 22 venous thrombosis and 19 venous and arterial thrombosis. Of the 75 patients (49 men and 26 women, mean age 49 +/- 15 years) about two-thirds had recurrent episodes of thrombosis. RESULTS: Hyperhomocysteinemia was defined as serum homocysteine level above 14.1 mumol/l (mean + 2.7 SD in healthy subjects) and was found in 67 patients (89%, CI95% = 80-95). Mean total homocysteine concentration was 21.6 +/- 13.6 mumol/l for the 75 patients. About half of the patients were smokers, 35% had hypertension and 25% high serum cholesterol. There was no significant relationship between serum homocysteine level and smoking status, hypertension or serum cholesterol level. Ten patients (13%, CI95% = 7-23) had low serum cobalamin (< 150 pmol/l). Serum folates were < or = 10 nmol in 41% of the patients in the arterial thrombosis group (CI95% = 25-59), in 27% in the venous thrombosis group (CI95% = 11-50), and in 31% in the arterial and venous thrombosis group (CI95% = 13-57). Thirteen patients received vitamin B supplementation. Hyperhomocysteinemia decreased in 12/13 patients (CI95% = 64-100) and returned to normal values in 9/13 patients (69%, CI95% = 38-91). CONCLUSION: Our data show that hyperhomocysteinemia is frequently found in arterial and venous thrombosis. Further studies are needed to determine the clinical impact of homocysteine lowering therapy.

Adult↗
PubMed2000

[Severe gastrointestinal hemorrhage secondary to diffuse angiodysplasia: efficacy of estrogen-progesterone treatment].

BACKGROUND: Vascular abnormalities are being reported with increasing frequency as a cause of major lower gastrointestinal hemorrhage in the elderly. They are occasionally very difficult to treat by conventional means. CASE REPORT: A 66-year-old white man with a history of type 2 diabetes mellitus, coronary artery disease, congestive heart failure, severe peripheral arterial occlusion disease and chronic renal insufficiency presented for five years recurrent major bleeding due to gastrointestinal angiodysplasia, requiring repeated transfusions. He was treated with efficacy using ethinyl-estradiol (30 micrograms) and norethisterone acetate (1 mg) given orally once daily. After six months of treatment, transfusion requirements fell to 0 unit and the patient's hemoglobin was stable at 13 g/dl. Attempts to stop hormone therapy (by the patient himself, without complaint of side effects) led to a fall in hemoglobin. CONCLUSION: Hormonal therapy should be considered when multiple degenerative mucosal vascular bleeding lesions are beyond the reach of therapeutic endoscopy leading to high transfusion needs and when surgical risk is unacceptably high.

Aged↗
PubMed2000

Increased soluble vascular cell adhesion molecule 1 concentrations in patients with primary or systemic lupus erythematosus-related antiphospholipid syndrome: correlations with the severity of thrombosis.

OBJECTIVE: Recent studies have shown that in vitro endothelial cells are activated by antiphospholipid antibodies and may support leukocyte adhesion. We studied levels of soluble intercellular adhesion molecule 1 (sICAM-1, sCD54), soluble vascular cell adhesion molecule 1 (sVCAM-1, sCD106), and soluble E-selectin (soluble endothelial leukocyte adhesion molecule 1 [sELAM-1, sCD62E]) in sera from patients with primary antiphospholipid syndrome (primary APS), and compared them with those from patients with systemic lupus erythematosus-associated APS (SLE-APS) or pure SLE, as well as with those from 2 control groups composed of healthy volunteers and patients with thrombosis unrelated to autoimmune diseases. METHODS: Serum samples from 24 patients with primary APS, 15 patients with SLE-APS, 22 patients with pure SLE, 48 control patients with thrombosis, and 18 healthy volunteers were examined using enzyme-linked immunosorbent assays specific for sICAM-1, sVCAM-1, and sELAM-1. RESULTS: Serum levels of sVCAM-1, but not sICAM-1 or sELAM-1, were significantly increased in all patient study groups compared with thrombosis control patients and healthy volunteers, but did not differ between the groups of patients with primary APS, SLE-APS, or pure SLE. Concentrations of sVCAM-1 were significantly higher in primary APS or SLE-APS patients with severe, recurrent thrombosis and were negatively correlated with platelet counts in primary APS patients. In patients with primary APS, sVCAM-1 levels were higher if there was thrombotic kidney involvement and correlated with creatinemia. CONCLUSION: Serum sVCAM-1 concentrations are increased in patients with primary APS, especially those with repeated thrombotic events or kidney involvement. These findings suggest that endothelial/ monocyte interaction may be important in the pathogenesis of primary APS.

Adult↗
PubMed2000

Presence of antinucleosome autoantibodies in a restricted set of connective tissue diseases: antinucleosome antibodies of the IgG3 subclass are markers of renal pathogenicity in systemic lupus erythematosus.

OBJECTIVE: To study the frequency and disease specificity of antinucleosome antibody reactivity in diverse connective tissue diseases (CTD), and to determine factors, such as antibody subclass, that may influence the pathogenicity of these antibodies in relation to disease activity. METHODS: IgG and IgM antinucleosome activities on nucleosome core particles from 496 patients with 13 different CTD and 100 patients with hepatitis C were measured by enzyme-linked immunosorbent assay (ELISA). Of the patients with CTD, 120 had systemic lupus erythematosus (SLE), 37 had scleroderma (systemic sclerosis; SSc), 20 had mixed connective tissue disease (MCTD), and 319 had other CTD, including Sjögren's syndrome, inflammatory myopathy, rheumatoid arthritis, primary antiphospholipid syndrome, Wegener's granulomatosis, Takayasu arteritis, giant cell arteritis, relapsing polychondritis, Behçet's syndrome, and sarcoidosis. Antinucleosome-positive sera were further analyzed, by isotype-specific ELISA, for antinucleosome and anti-double-stranded DNA (anti-dsDNA) IgG subclasses. RESULTS: SLE, SSc, and MCTD were the only 3 CTD in which antinucleosome IgG were detected (71.7%, 45.9%, and 45.0% of patients, respectively). Antinucleosomes of the IgG3 subclass were present at high levels in patients with active SLE and were virtually absent in those with SSc, MCTD, or inactive SLE, and their levels showed a positive correlation with SLE disease activity. Of note, an increase in levels of antinucleosome of the IgG3 isotype was observed during SLE flares, and this increase was found to be closely associated with active nephritis. Levels of antinucleosome of the IgG1 subclass showed a trend toward an inverse correlation with SLE disease activity. No significant fluctuation in the anti-dsDNA isotype profile was observed in relation to SLE severity or clinical signs. CONCLUSION: Our data suggest that IgG antinucleosome is a new marker that may help in the differential diagnosis of CTD; antinucleosome of the IgG3 isotype might constitute a selective biologic marker of active SLE, in particular, of lupus nephritis.

Antibodies, Antinuclear↗
PubMed2000

[Viral quantitation of hepatitis C virus: present and future].

INTRODUCTION: Hepatitis C virus (HCV) plasmatic load, also called HCV viremia, is expressed in copies per milliliter or viral particle equivalents per milliliter. CURRENT KNOWLEDGE AND KEY POINTS: The methods used to measure HCV viremia are based on two principles: the quantitation of viral proteins (measure of antigenemia using monoclonal antibodies), and the quantitation of viral nucleic acid using PCR after reverse transcription (RT-PCR), or signal amplification (branched DNA). There is no relationship between viremia and liver histologic activity. FUTURE PROSPECTS AND PROJECTS: The use of HCV quantitative viremia in a treatment algorithm, including other factors such as age, genotype, degree of viral genetic heterogeneity, and liver fibrosis score will help adapt therapeutic associations for each individual.

Hepacivirus↗
PubMed2000

Extrahepatic manifestations associated with hepatitis C virus infection. A prospective multicenter study of 321 patients. The GERMIVIC. Groupe d'Etude et de Recherche en Medecine Interne et Maladies Infectieuses sur le Virus de l'Hepatite C.

From January 1996 to January 1997, 321 patients with an average age of 46 +/- 16 years and chronically infected with hepatitis C virus (HCV) were prospectively enrolled in a study designed to determine the prevalence of extrahepatic manifestations associated with HCV infection in a large cohort of HCV patients, to identify associations between clinical and biologic manifestations, and to compare the results obtained in human immunodeficiency virus (HIV)-positive versus HIV-negative subsets. In a cross-sectional study, clinical extrahepatic manifestations, viral coinfections with HIV and/or hepatitis B virus, connective tissue diseases, and a wide panel of autoantibodies were assessed. Thirty-eight percent (122/321) of patients presented at least 1 clinical extrahepatic manifestation including arthralgia (60/321, 19%), skin manifestations (55/321, 17%), xerostomia (40/321, 12%), xerophthalmia (32/321, 10%), and sensory neuropathy (28/321, 9%). Main biologic abnormalities were mixed cryoglobulins (110/196, 56%), thrombocytopenia (50/291, 17%), and the presence of the following autoantibodies: antinuclear (123/302, 41%), rheumatoid factor (107/280, 38%), anticardiolipin (79/298, 27%), antithyroglobulin (36/287, 13%) and antismooth muscle cell (27/288, 9%). At least 1 autoantibody was present in 210/302 (70%) of sera. By multivariate logistic regression analysis, 4 parameters were significantly associated with cryoglobulin positivity: systemic vasculitis (p = 0.01, odds ratio OR[ = 17.3), HIV positivity (p = 0.0006, OR = 10.2), rheumatoid factor positivity (p = 0.01, OR = 2.8), and sicca syndrome (p = 0.03, OR = 0.27). A definite connective tissue disease was noted in 44 patients (14%), mainly symptomatic mixed cryoglobulinemia and systemic vasculitis, HIV coinfection (23%) was associated with 3 parameters: anticardiolipin (p = 0.003, OR = 4.18), thrombocytopenia (p = 0.01, OR = 3.56), and arthralgia or myalgia (p = 0.017, OR = 0.23). HIV-positive patients presented more severe histologic lesions (p = 0.0004). Extrahepatic clinical manifestations in HCV patients involve primarily the skin and joints. The most frequent immunologic abnormalities include mixed cryoglobulins, rheumatoid factor, antinuclear, anticardiolipin, and antithyroglobulin antibodies. Cryoglobulin positivity is associated with systemic vasculitis and rheumatoid factor and HIV positivity. HIV coinfection is associated with arthralgia or myalgia, anticardiolipin antibodies, and thrombocytopenia.

Adolescent↗
PubMed2000

Mixed cryoglobulinemia in hepatitis C patients. GERMIVIC.

Cryoglobulins are immunoglobulins that persist in the serum, precipitate with cold temperature and resolubilize when rewarmed. Types II and III are mixed cryoglobulins (MC), composed of different immunoglobulins, with a monoclonal component in type II and only polyclonal immunoglobulins in type III. Mixed cryoglobulins are associated with connective-tissue disease, malignant hematological disorder (type B lymphoproliferation) or obvious infectious process. Mixed cryoglobulinemia syndrome is characterized by the clinical triad of purpura, arthralgia and asthenia associated with type II or type III MC. The disorder is the consequence of an immune-complex-type vasculitis as supported by clinical features, analysis of the cryoglobulins, the usually depressed level of complement during the active phase of the disease, and the deposition of immunoglobulins and complement in the lesions. Such cryoglobulinemia vasculitis may involve numerous organs, particularly the peripheral nervous system and the kidneys. MC is frequently associated with clinical and biological evidence of liver disease. There has been some controversy about which comes first, MC or chronic liver disease, but it seems fairly clear that MC is often a manifestation of underlying chronic active or persistent hepatitis. In MC patients, the hepatotropic antigen(s) capable of triggering production of antibodies which can later form immune complexes has been sought for many years. In the last ten years, numerous studies have demonstrated that infection with hepatitis C virus is involved in the pathogenesis of most mixed cryoglobulinemia. This review analyzes the main published data on hepatitis C virus-mixed cryoglobulinemia, the role of liver alterations, the predictive factors associated with MC production in HCV patients and its symptomatic nature or not, and the different types of vasculitis associated with HCV chronic infection.

Arthralgia↗
PubMed2000

Lymphoproliferative diseases and hepatitis C virus infection.

The putative role of hepatitis C virus (HCV) infection in the pathophysiology of lymphoproliferative diseases (LPD) is supported by north-American and south-European studies reporting high HCV seroprevalence in patients with B-cell-non-Hodgkin lymphoma (NHL). However, controversial data were reported from other areas. The review of available reports to data on HCV-associated LPD points to some features: predominance of low-grade malignant lymphoma, frequent involvement of extranodal sites, absence of particular HCV genotype distribution (except in Italy for genotype 2), important geographical seroprevalence discrepancies. In our experience in 43 cases of HCV-associated LPD in France, we noted a predominance of B-cell NHL (31/43 cases), and the frequency of LPD among HCV-infected patients approximates 2.5%. Pathophysiology hypotheses are discussed, particularly in view of the lympho tropism of HCV. HCV is frequently associated with type II mixed cryoglobulinemia, a benign monoclonal lymphoproliferation which sometimes evolves to overt B-cell lymphoma. The recent finding of HCV binding on CD81, a surface-expressed protein present on lymphocyte membrane, enhances the putative role of HCV in lymphomagenesis. Further investigations are needed to characterize interaction between B lymphocytes and HCV, and to determine putative cofactors involved in the multistep process leading to clonal lymphoproliferation in HCV patients.

Antigens, CD↗
PubMed2000

Treatment of autoimmune and extra-hepatic manifestations of HCV infection.

Hepatitis C virus (HCV) infects mononuclear cells and may, like other viruses, cause immunological disorders. Immunological abnormalities observed in HCV infections are usually nonspecific (e.g. cryoglobulinemia, immune complex deposits, autoantibodies). There is a clear association between cryoglobulinemia and hepatitis C and cryoglobulinemia related symptoms are usually improved by treatment with interferon alpha, although patients usually relapse after treatment end. The relationships between hepatitis C and other immunological abnormalities are unclear. The association between chronic hepatitis C and anti-smooth muscle or anti-nuclear antibodies does not appear to be significantly different from that in other hepatic disorders, particularly hepatitis B. Conversely, patients with hepatitis C have significantly more often anti-liver kidney microsomal (LKM1) antibodies than patients with other causes of liver diseases. When clinical, histological and biological findings are indicative of HCV infection with chronic hepatitis, interferon alpha or combination therapy with ribavirin are treatments options. Conversely, when clinical context and results of laboratory tests are in favor of an autoimmune disorder or of overlap-syndromes (i.e. both autoimmune and viral hepatitis), interferon should not be given in first intention, since revelation or exacerbation of autoimmune hepatitis have been reported under interferon. An important prevalence of anti-HCV antibodies has also been reported in patients with sialadenitis, lichen planus and thyroiditis. It has been clearly demonstrated that interferon may induce or worsen such immunological diseases, but there are very few studies showing improvement of these manifestations under interferon. In conclusion, interferon may be appropriate in patients with HCV infection and extrahepatic manifestations linked to immune complex deposition, whereas, in other cases, careful assessment of patients with autoimmune processes is necessary before choosing any treatment strategy.

Antiviral Agents↗
PubMed1999

[Transmitted transfusion virus: a new hepatotropic virus...in search for a disease].

AN UBIQUITOUS VIRUS: The family of hepatitis viruses now has a new member discovered in 1997 by a Japanese team. The TTV (transmitted transfusion virus) is a small ubiquitous DNA virus probably largely distributed throughout the world. Prevalence in blood donors is about 2 to 10%. TRANSMISSION AND PERSISTENCE: TTV is generally transmitted via the parenteral route but can probably be transmitted via orofecal and matemo-fetal routes. The natural history of TTV has been studied in retrospective studies, particularly in hemophiliacs. After a post-transfusional peak, the virus appears to persist for long periods in the organism without causing liver damage nor any change in transaminase levels. PATHOGENICITY: Although no proof is yet available, the TTV does probably not have any intrinsic pathogenic power. It would rather be a ìsurrogate virusî transmitted at the same time as another virus yet to be discovered and which causes the rare cases of non A-non-G post-transfusional hepatitis.

Blood↗
PubMed1999

Octreotide treatment of chronic intestinal pseudoobstruction secondary to connective tissue diseases.

Chronic intestinal pseudoobstruction (CIPO) is a rare syndrome that may occur in association with connective tissue diseases (CTD). Effective management is a major challenge. We report 3 cases in which subcutaneous octreotide was efficacious in the treatment of digestive symptoms in CIPO. In 2 of the 3 cases, previous treatment with domperidone, cisapride, or erythromycin had been unsuccessful. All 3 patients underwent a regimen of oral antibiotics along with octreotide to stimulate small bowel motility. The effects of octreotide were evident within 48 hours after the first injection in all patients. In 2, the efficacy seemed to decrease after 1 week and 6 months respectively, but increasing the dosage led to another remission. CIPO in CTD is a severe condition that can evolve regardless of the underlying disease activity. Octreotide appears to be efficacious in improving both clinical symptoms and manometric patterns. When its therapeutic effect diminishes, increasing the dosage can be useful.

Adult↗
PubMed1999

Extrahepatic manifestations of chronic hepatitis C. MULTIVIRC Group. Multidepartment Virus C.

OBJECTIVE: To assess the prevalence of clinical and biologic extrahepatic manifestations of hepatitis C virus (HCV) infection and to identify associations between clinical and biologic manifestations. METHODS: To analyze the natural history of extrahepatic manifestations of HCV infection, we reviewed only the data recorded prospectively during the first visit of 1,614 patients with chronic HCV infection, coming from a single monocenter cohort. Exclusion criteria were positivity for hepatitis B surface antigen or human immunodeficiency virus. The prevalence of dermatologic, rheumatologic, neurologic, and nephrologic manifestations; diabetes; arterial hypertension; autoantibodies; and cryoglobulins were assessed. Then, using multivariate analysis, we identified demographic, biochemical, immunologic, virologic, and liver histologic factors associated with the presence of extrahepatic manifestations. RESULTS: At least 1 clinical extrahepatic manifestation was observed in each of 1,202 patients (74%). Five manifestations had a prevalence >10%: arthralgia (23%), paresthesia (17%), myalgia (15%), pruritus (15%), and sicca syndrome (11%). Four biologic abnormalities had a prevalence >5%: cryoglobulins (40%), antinuclear antibodies (10%), low thyroxine level (10%), and anti-smooth muscle antibodies (7%). Only vasculitis, arterial hypertension, purpura, lichen planus, arthralgia, and low thyroxine level were associated with cryoglobulin positivity. By univariate and multivariate analyses, the most frequent risk factors for the presence of clinical and biologic extrahepatic manifestations were age, female sex, and extensive liver fibrosis. CONCLUSION: Extrahepatic clinical manifestations are frequently observed in HCV patients and involve primarily the joints, muscles, and skin. The most frequent immunologic abnormalities include mixed cryoglobulins, antinuclear antibodies, and anti-smooth muscle antibodies. The most frequent risk factors for the presence of clinical and biologic extrahepatic manifestations are advanced age, female sex, and extensive liver fibrosis.

Adult↗
PubMed1999

Role of endothelial and smooth muscle cells in the physiopathology and treatment management of pulmonary hypertension.

Pulmonary hypertension can occur either as primary or secondary disease following cardiac or pulmonary illnesses. In either cases, histological lung biopsies reveal vascular remodelling i.e. smooth muscle cells proliferation with medial hypertrophy, arteriolar muscularization and endothelial cell proliferation. Subsequent intimal thickening, fibrosis and in situ thrombosis, altogether lead to vaso-occlusive alterations referred to as plexiform lesions. Theories concerning the detailed physiopathology of pulmonary hypertension have focused on endothelial and smooth muscle cells' chemical factors production and response to different mediators. The endothelium produces vasoconstrictor and growth-promoting factor such as endothelin-1 (ET-1) as well as vasodilator and growth-inhibitor factors like prostacyclin and nitric oxide (NO). ET-1 has been noted in high concentrations in some clinical cases and experimental models of pulmonary hypertension, coupled with ET-1 receptors' modulation and altered endothelin converting enzyme activities, suggesting their active role in both arteriolar vasoconstriction and occlusion. Vascular thrombosis which has been noted by pathologists in pulmonary hypertension, could be related to an imbalance between thrombotic inducing factors (such as anti-phospholipid antibodies, ET-1 and thromboxane) and decreased fibrinolytic activity and antiaggregant endothelial factors (like prostacyclin, NO, thrombomodulin). The discovery of an endothelial cells' monoclonal proliferation in plexiform lesions of patients with primary pulmonary hypertension may reinforce the cellular proliferation hypothesis to understand the histopathology of this disease. In view of these new findings, the treatments available for pulmonary hypertension have been expanded from the previously employed oxygen therapy, calcium-channel blockers and anticoagulants, to intravenous prostacyclin analogues (epoprostenol) and inhaled nitric oxide.

Antibodies, Antiphospholipid↗