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Biomedical subjects

P Cacoub

Publications and source records attributed to P Cacoub.

At least 109 records · Page 6Linked to original sources
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↗
PubMed1999

Anti-endothelial cell auto-antibodies in hepatitis C virus mixed cryoglobulinemia.

BACKGROUND/AIM: Hepatitis C virus (HCV) infection is often associated with mixed cryoglobulins (MC) and may manifest as small-vessel vasculitis. It has been suggested that antibody (Ab) or sensitized T cells to HCV-containing endothelial cells may initiate the vasculitis process. Anti-endothelial cell antibodies (AECA) have been found in various connective tissue disorders, with a high prevalence in systemic vasculitis. The aim of the study was to determine the prevalence of AECA in HCV patients with or without MC-associated vasculitis, and to identify associations with clinical, immunological, virological and liver characteristics. METHODS: Sixty-nine HCV patients (Group 1), 46 of whom had MC (type II=30, type III=16), and 23 without MC, were prospectively studied. HCV-MC-associated vasculitis was noted in 25 patients who had at least one of the following clinical features: peripheral neuropathy, glomerulonephritis, skin purpura, cerebral vasculitis. Group 2 included 20 patients with non-HCV viral diseases: HHV8 (10), miscellaneous (10). Group 3 included 25 patients with biopsy-proven non-HCV chronic liver diseases: hepatitis B virus (10), miscellaneous (15). Controls were 100 blood donors (Group 4). Sera were adsorbed onto a pellet of A549/8 epithelial cells before being evaluated. AECA were then searched using a cellular ELISA, with a permanent cell line (EA.hy 926) as the substrate. All sera were also examined for the presence of cryoglobulin, antinuclear Ab, anticardiolipin Ab, and rheumatoid factor. RESULTS: AECA were more frequently found in HCV patients than in blood donors (41% vs 5%, p=0.0001). The prevalence of AECA was lower in non-HCV than in group 1 patients [group 2=15%, p=0.03; group 3=16%, p=0.01]. There was no significant difference in AECA prevalence between groups 2, 3 and 4. In HCV patients, AECA were associated with age (p<0.001), the presence of MC (p=0.008), cryoglobulin level (p=0.016), HCV-associated vasculitis (p=0.04), genotype 1b (p=0.005) and severity of liver histologic damage. AECA isotypes were not different in the 4 groups. AECA were not associated with antinuclear Ab, anticardiolipin Ab, rheumatoid factor or interferon alpha treatment. CONCLUSION: AECA are a common finding in HCV patients (41%), but not in other viral diseases or in non-HCV chronic liver diseases. In HCV patients, AECA are associated with MC-vasculitis, suggesting that AECA may be a marker for HCV-induced vasculitis.

Adolescent↗
PubMed1999

Treatment of autoimmune and extrahepatic manifestations of hepatitis C virus infection.

Hepatitis C virus (HCV) infects mononuclear cells and may be responsible, as are other viruses, for immunologic disorders. The immunologic abnormalities observed in HCV infections are usually non-specific (i.e. cryoglobulinemia, immune complex deposits, autoantibodies). The association with cryoglobulinemia is clear and cryoglobulinemia-related symptoms are usually improved by interferon alpha treatment, although patients often relapse after the end of treatment. The relationship with other immunologic abnormalities is less clear. The occurrence of antismooth muscle or anti-nuclear antibodies does not seem significantly different in hepatitis C infection than in other hepatic disorders, particularly hepatitis B. However, anti-liver kidney microsomal (LKM1) antibodies are present significantly more often than in patients with other liver diseases. When clinical, histologic and biological findings suggest HCV infection with chronic hepatitis, interferon alpha or combination therapy with ribavirin are treatment options When the clinical context and results of laboratory tests suggest an autoimmune disorder or overlap syndromes (i.e. both autoimmune and viral hepatitis), interferon should not be given as a first intention, since revelation or exacerbation of autoimmune hepatitis has been reported with interferon. A marked prevalence of anti-HCV antibodies has also been reported in patients with sialadenitis, lichen planus and thyroiditis. Interferon may induce or worsen these immunologic diseases, but there are very few studies showing improvement of these manifestations with interferon.

Antiviral Agents↗
PubMed1999

[A comparative study of body temperature using rectal and tympanic measurement].

INTRODUCTION: Tympanic temperature measuring is more and more used currently. We wanted to test this method's accuracy in an internal medicine service. METHODS: First, we compared rectal and tympanic temperatures in 37 consecutive patients. Tympanic temperature was assessed by two examiners. Secondly, we compared, in 32 other patients, the readings given by tympanic thermometer used in the first part, with those given by nine other tympanic thermometers used in other hospital departments. RESULTS: We did not find any difference between right and left auricular temperature, nor between the temperatures assessed by the two examiners. However, there was a difference between the average tympanic and rectal temperatures (36.88 degrees C +/- 0.63 vs 37.36 degrees C +/- 0.57; P < 0.001). The correlation coefficient between tympanic and rectal temperature was only 0.77. If a threshold of temperature of > or = 38 degrees C were given for fever, only 29% of febrile patients would have been detected with a tympanic thermometer (Kappa coefficient = 0.406 [0.326-0.485]). Fever was especially underestimated for high temperatures. The comparison of different tympanic thermometers gives different averages for these ten thermometers between 36.5 degrees C and 37.2 degrees C. CONCLUSION: Though tympanic temperature measure is an easy method, it is not sensitive enough to detect fever.

Analysis of Variance↗
PubMed1999

[1977 mortality rate in HIV-infected patients presenting with hepatitis C cirrhosis. Results of the GERMIVC multicenter survey conducted in French departments of internal medicine or infectious disease].

PURPOSE: Hepatitis C (HCV) has a high prevalence (10-30%) among human immunodeficiency virus (HIV)-infected patients. However, little information is available regarding the impact of hepatitis C on survival. The objective of our study was to determine the incidence of hepatitis C-related deaths in HIV-HCV co-infected patients. METHODS: The study was a retrospective (1-year), multicenter cohort survey conducted in 63 departments of either internal medicine or infectious diseases in France. It included 26,497 HIV-infected patients, of whom 4,465 (16.8%) presented coinfection due to the hepatitis C virus. The following parameters were studied for the year 1997: total number of deaths, number of deaths related to either AIDS, cirrhosis, hepatocellular carcinoma, or other causes. RESULTS: Among the 26,497 patients, 543 deaths (incidence: 2%) were observed in 1997; 543 deaths were due to AIDS (incidence: 1.7%), 36 to cirrhosis and/or hepatocellular carcinoma (incidence: 0.13%), and 48 (incidence: 0.18%) to another cause. In the subgroup including 4,465 HIV-HCV-coinfected patients, 29 deaths (incidence: 0.64%) were due to either HCV-related cirrhosis or hepatocellular carcinoma. These results were compared with those of a previous similar survey conducted in 1995, before the era of highly active antiretroviral therapy. The only significant difference is the dramatic regression of deaths due to AIDS. CONCLUSION: The impact of hepatitis C virus on the mortality among HIV-infected patients whose follow-up took place in departments of either internal medicine or infectious diseases in France was very low in 1997. The expected increase in the life span in these patients could modify these results in the future, due to recent improvements in the HIV infection treatment.

Adult↗
PubMed1999

[Resistance to activated protein C and portal vein thrombosis: two new cases and review of the literature].

INTRODUCTION: Resistance to activated protein C is the most common inherited factor at the origin of deep venous thrombosis. As portal vein thrombosis is rare, causes such as cirrhosis, intra-abdominal infection, primary hepatocellular carcinoma, myeloproliferative disorders or coagulation abnormalities must be investigated. EXEGESIS: We report two cases of portal vein thrombosis associated with resistance to activated protein C. This association is not frequent, as only 12 cases have been reported in the literature. These studies show that resistance to activated protein C was rarely the only factor, as other prothrombotic abnormalities were present in more than 70% of cases. CONCLUSION: Resistance to activated protein C is rarely associated with portal vein thrombosis. When present, other causes should not be overlooked. The potential existence of resistance to activated protein C should be systematically investigated in case of either portal vein thrombosis in patients with personal or familial thrombosis history, association with multiple thrombosis, or when the disease etiology remains unknown.

Activated Protein C Resistance↗
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

Response to interferon alpha treatment and disappearance of cryoglobulinaemia in patients infected by hepatitis C virus.

BACKGROUND: Mixed cryoglobulinaemia is closely associated with hepatitis C virus (HCV) infection. AIM: To assess in a prospective open study the efficiency of interferon alpha treatment of cryoglobulinaemia, as reflected by the disappearance of cryoglobulins and clinical manifestations of the disease, and to analyse the factors predictive of a response to interferon. METHOD: Eighty seven consecutive patients with chronic hepatitis C treated for the first time with interferon at a dose of 3 x 10(6) international units three times a week for six months were studied. Forty three patients had cryoglobulins, which were responsible for clinical manifestations in 12. RESULTS: At the end of interferon treatment, cryoglobulins had disappeared in 39% of the patients. A clinical improvement (except for neuropathies) was observed in all patients. Six months after interferon treatment was stopped, the same rate of response (normal alanine aminotransferase values and undectable HCV RNA) was observed in patients with or without cryoglobulins. Only 14% of patients still had undetectable cryoglobulins, and all of them also had undetectable serum HCV RNA. The disappearance of cryoglobulins was found less frequently in patients with clinical symptoms than in asymptomatic ones, but the difference was not significant. Sustained responders were more often men, infected by genotype 2 or 3, with a lower pretreatment viral load. CONCLUSION: The presence of cryoglobulins does not seem to affect the response to interferon in HCV infected patients. The improvement in cryoglobulinaemia is strongly associated with a virological response, reinforcing the hypothesis of a direct role for HCV in the pathogenesis of this disease.

Adult↗
PubMed1999

Massive ovarian haemorrhage complicating oral anticoagulation in the antiphospholipid syndrome: a report of three cases.

We report three cases of severe haemorrhagic rupture of luteal ovarian cyst requiring surgical haemostasis in young women treated with long-term oral anticoagulation for antiphospholipid syndrome (APS) who used no contraception. At the time of bleeding, the international normalized ratios were 3.78, 4.24, and 7.11. Anticoagulation was resumed post-operatively, in association with antigonadotropic progestins to induce ovulatory suppression. A systematic use of these progestins should probably be discussed in young women receiving long-term warfarin for APS. Ovarian haemorrhage must be considered when such patients develop acute abdominal pain.

Administration, Oral↗
PubMed1999

[Cryoglobulinemia and hepatitis c: worsening of peripheral neuropathy after interferon alpha treatment].

We report 4 cases of peripheral neuropathy induced by type II IgM kappa mixed cryoglobulinemia associated with hepatitis C virus infection. Worsening of peripheral neuropathy was observed 2 to 13 weeks after the initiation of interferon. The evolution of the hepatic and neurological diseases did not coincide, as all patients decreased or normalized transaminases with interferon. After stopping interferon, peripheral neuropathy worsened (1 case), stabilized (1 case), improved (2 cases). Low doses of interferon alpha may cause worsening of peripheral neuropathy in patients with hepatitis C virus infection associated with mixed cryoglobulinemia.

Aged↗
PubMed1998

Pacemaker infective endocarditis.

We identified 33 patients with definite pacemaker endocarditis--that is, with direct evidence of infective endocarditis, based on surgery or autopsy histologic findings of or bacteriologic findings (Gram stain or culture) of valvular vegetation or electrode-tip wire vegetation. Most of the patients (75%) were > or = 60 years of age (mean 66 +/- 3; range 21 to 86). Pouch hematoma or inflammation was common (58%), but other predisposing factors for endocarditis were rare. At the time that pacemaker endocarditis was found, the mean number of leads was 2.4 +/- 1.1 (range 1 to 7). The interval from the last procedure to diagnosis of endocarditis was 20 +/- 4 months (range 1 to 72). Endocarditis appeared after pacemaker implantation, early (< 3 months) in 10 patients and late (> or = 3 months) in 23 patients. Fever was the most common symptom, being isolated in 36%, associated with a poor general condition in 24%, and associated with septic shock in 9%. Transthoracic echocardiography showed vegetations in only 2 of 9 patients. Transesophageal echocardiography demonstrated the presence of lead vegetations (n = 20) or tricuspid vegetations (n = 3) in 23 of 24 patients (96%; p <0.0001 compared with transthoracic echocardiography). Pulmonary scintigraphy showed a typical pulmonary embolization in 7 of 17 patients (41%). Pathogens were mainly isolated from blood (82%) and lead (91%) cultures. The major pathogens causing pacemaker endocarditis were Staphylococcus epidermidis (n = 17) and S. aureus (n = 7). S. epidermidis was found more often in early than in late endocarditis (90% vs 50%; p = 0.05). All patients were treated with prolonged antibiotic regimens before and after electrode removal. Electrode removal was achieved by surgery (n = 29) or traction (n = 4). Associated procedures were performed in 9 patients. After the intensive care period, only 17 patients needed a new permanent pacemaker. Overall mortality was 24% after a mean follow-up period of 22 +/- 4 months (range 1 to 88). Eight patients who were significantly older (74 +/- 3 vs 63 +/- 3 years; p = 0.05) died < or = 2 months after electrode removal, whereas 25 were alive and asymptomatic.

Adult↗