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Biomedical subjects

N Bernard

Publications and source records attributed to N Bernard.

At least 19 recordsLinked to original sources

[Efficacy and safety of pegylated-interferon plus ribavirin in HIV-infected patients co-infected with hepatitis C virus in clinical practice: a 32 cases observational follow-up].

OBJECTIVE: To describe efficacy and safety in clinical practice of pegylated interferon plus ribavirin (INFpeg-Riba) in the treatment of hepatitis C viral infection (HCV) in HIV infected patients. METHODS: Monocentric retrospective study with inclusion of all patients who received at least once INFpeg-Riba before April 1st 2003. All patients were followed up to six months after the end of HCV therapy. RESULTS: Thirty two HIV-positive patients (23 men and 9 women) with chronic hepatitis C treated by INFpeg-Riba were included. The mean age was 43 years. Fourteen patients carried HCV genotype 2 or 3 (43 %) and 18 patients carried genotype 1 or 4 (57%). The Metavir score of fibrosis showed fibrosis F1 (N =3), F2 (N =14), F3 (N =7) and F4 - cirrhosis (N =8). Twenty six patients (81%) were naive for anti hepatitis C drugs. Thirty one per cent of patients were at AIDS stage and 84% were receiving antiretroviral drugs. The mean CD4 cell count was 469 /ml and the plasma RNA HIV was less than 50 copies /ml in 57% of the cases. Adverse events leading to reduction of dose of drugs occurred in 40% and adverse events leading to discontinuation treatment occurred in 12%. A decline of CD4 cell count <200 CD4/ml was observed in 15%. Clearance of HCV-RNA in end of treatment was seen in 46 % and sustained virological response in 34 %. The main predictors of sustained virological response were HCV genotype 2 or 3 (P =0.04) and plasma HIV RNA less than 50 copies/ml (P =0.001). The predictive value of good virological response of a CD4 cell count >350/ml before treatment was very near the statistical significancy (p =0.07). CONCLUSIONS: The efficacy of pegylated interferon plus ribavirin in HIV-HCV co-infected patients is disappointing mainly due to a poor tolerance. In addition to HCV genotype, plasma HIV RNA level and CD4 cell count were essential to predict INFpeg-Riba response and should be taken into account in the process leading to the initiation of such therapy in HIV-HCV co-infected patients.

Adult↗

[Portal vein thrombosis in HIV-infected patients: report of four cases].

Portal vein thrombosis (PVT) seems rare among HIV infected patients. Even though, the report of such cases is of great interest because it may help to determine the factors of occurrence. We describe cases of PVT in 4 HIV-infected men, aged 32 - 64. Two of them were co-infected with hepatitis C virus (HCV). The four patients had a history of disseminated mycobacterial infection (one case of tuberculosis, 3 cases of mycobacterium avium complex infection) with abdominal lymphadenitis. Despite HAART, their immunodeficiency was profound (CD4: 65 to 216/mm(3)). At the time of diagnosis, two patients were treated with protease-inhibitor containing regimen: indinavir (one case), ritonavir-saquinavir (one case). PVT was revealed by haematemesis (one case), abdominal pain (ome case), anasarca (2 cases). In three patients, the diagnosis of PVT was confirmed by imagery (echo-doppler or angio- RMI), and for the last patient, PVT was found during the transjugular intrahepatic portosystemic shunt setup. A low level of C protein was diagnosed in one case. Cirrhosis was not found in HIV-HCV co-infected patients. Two patients died early after diagnosis, one patient died 3 years after the onset of symptoms. Various factors may cause the development of a PVT in HIV infected patient. Serious immunodeficiency, opportunistic infections such as tuberculosis and mycobacterium avium complex related infection with abdominal lymphadenitis can further the development of PVT. Protease-inhibitor might have facilitated the process. Due to the severe prognosis of advanced cases, early evocation of diagnosis is needed.

AIDS-Related Opportunistic Infections↗

Risk factors for lactic acidosis in HIV-infected patients treated with nucleoside reverse-transcriptase inhibitors: a case-control study.

A case-control study was undertaken to determine risk factors for lactic acidosis in human immunodeficiency virus-infected patients treated with nucleoside reverse-transcriptase inhibitors (NRTIs). From May 1996 to June 2000, 9 patients with lactic acidosis (defined as a plasma lactic acid level of >5 mM and plasma pH of <7.38) were identified. Control patients were randomly selected from among a large cohort of patients who initiated a dual NRTI regimen in 1996 or after. Two factors were associated with an increased risk of lactic acidosis: first, a creatinine clearance of <70 mL/min before lactic acidosis (OR, 15.8 [range, 3.0-86.5], P<10(-4)), and, second, a low nadir CD4+ T lymphocyte count before the inception of NRTI therapy (OR, 8.4 [range, 1.2-infinity], P=.03). The total cumulative exposure to NRTIs was not associated with an increased risk of lactic acidosis, nor was the cumulative exposure to any of the 4 NRTIs studied. According to these results, monitoring of creatinine clearance, especially in patients with a low nadir CD4+ T lymphocyte count, could lead to modifications in antiretroviral therapy in order to diminish the risk of occurrence of lactic acidosis.

Acidosis, Lactic↗

[Severe lactic acidosis in HIV-infected patients treated with nucleosidic reverse transcriptase analogs: a report of 9 cases].

PURPOSE: Symptomatic lactic acidosis requiring intensive care is a rare and severe adverse event related to the mitochondrial toxicity of the nucleoside analog reverse transcriptase inhibitors (NRTIs). METHOD: We retrospectively investigated the clinical and biological features of HIV-infected patients who developed severe lactic acidosis syndrome at the University teaching hospital of Bordeaux and the regional community hospital, during 1996-2000. RESULTS: Nine patients were identified (incidence: 0,9/1000 NRTI treated patient-years), 4 men and 5 women with a median age of 36 years. They had a moderate immunodeficiency (median CD4+ T lymphocyte counts: 197/mm(3)) and only one of them presented a virological failure. The causes of hospital admission were abdominal pain (n = 6), dyspnea (n = 6), asthenia (n = 5), jaundice (n = 4), and vomiting (n = 2). Hepatomegaly was present in 6 patients. Lactic acidosis was found in all cases: median pH: 7.28, bicarbonate: 12 mmol/l, anion gap: 27 mEq/l, plasma lactic acid: 13 mmol/l. Cytolysis (n = 8), cholestasis (n = 6), hepatic failure (n = 4), rhabdomyolysis (n = 4) and pancreatitis (n = 2), were also present. Despite medical intensive care, seven patients died. The only two post-mortem examinations revealed severe hepatic steatosis. Median duration of NRTI therapy was 4 years. At presentation, five patients were receiving lamivudine, five didanosine, four stavudine and three zidovudine. Six patients were coinfected by HCV and/or HBV, four had chronic renal failure and five an immediately preceding infectious disease. CONCLUSION: The prognosis of lactic acidosis is severe. Nucleosid-analog therapy needs clinical and biological monitoring, specially in patients with comorbidities.

Abdominal Pain↗

A cohort study of nevirapine tolerance in clinical practice: French Aquitaine Cohort, 1997-1999.

We performed a retrospective study to evaluate, under routine circumstances, the tolerance and immunovirological changes associated with antiretroviral regimens that contain nevirapine in 137 patients (88% were antiretroviral experienced). During a mean follow-up of 11 months, 33% of patients reported side effects attributed to nevirapine, and 21% discontinued treatment because of poor tolerance. Administration of antihistamines or corticosteroids at the initiation of treatment was not protective against adverse events (relative risk, 0.82; 95% confidence interval, 0.49-1.38). The proportion of patients with hepatitis C virus (HCV) and/or hepatitis B virus (HBV) coinfection who had alanine aminotransferase levels of >100 IU/L increased from 19.4% at baseline to 42.9% at month 12 of follow-up (P=.02). We noticed a significant increase of the proportion of patients with total cholesterol levels of >5.5 mM (P=.02). We have shown that there is a high level of discontinuation of nevirapine therapy in clinical practice and that side effects were not prevented by administration of antihistamines or corticosteroids. Coinfection with HCV or HBV increased the risk of hepatotoxicity, which lead to the cautious use of nevirapine for such patients.

Adult↗

Correlations of soluble interleukin-2 and tumor necrosis factor type II receptors with immunologic and virologic responses under HAART.

We assessed the correlations between some plasma markers of immune activation (soluble receptors of interleukin 2 (sIL2-R) and TNFap75 (sTNFII-R) and usual markers of HIV infection in patients treated with protease-inhibitors (PI). Forty-six PI-naive HIV-1-infected adults were included in a 1-year prospective cohort from the initiation of a P1-containing regimen (M0). Measurements of CD4+cell count, plasma HIV-RNA, sIL2-R and sTNFII-R were performed at M0, M6, and M12. The evolution of sIL2-R from baseline to M12 was significantly different between immunological responders (IR) (CD4+count above 200/mm3 for subject having less than 200 CD4 +/mm3 at inclusion, or increase of at least 50 CD4+/mm3 for others) (58 UI/ml) and non-IR (+28 UI/ml) (P =0.01). The evolution of sTNFII-R between M0 and M12 was significantly different between virological responders (VR) (plasma HIV-1 RNA less than 500 copies/ml at M12) (-2.5 ng/ml) and non-VR (+0.2 ng/ml) (P = 0.02). Our study shows significative correlations between the evolutions of soluble interleukin-2 and TNFR-II receptors and those of CD4+T-lymphocytes or HIV-RNA responses in patients under HAART.

Adult↗

Sarcoidosis-associated hepatitis C virus infection.

Although several reports of sarcoidosis have been reported in hepatitis C virus (HCV)-infected patients treated with interferon-alpha, this association has never been described in nontreated HCV patients. We report two cases of sarcoidosis associated with chronic hepatitis C infection. The patients developed multivisceral sarcoidosis (cutaneous, lungs, nodes) at two and at least six years after the presumed date of infection. One patient obtained remission of sarcoidosis with corticosteroid treatment but the other remained corticodependent. The levels of hepatic enzymes were not significantly modified throughout the course of corticosteroid therapy. In conclusion, these case reports suggest that HCV itself could induce a granulomatous reaction in chronic HCV-infected patients through the stimulation of the cellular immune system. It could be of interest to test for HCV infection all patients diagnosed with sarcoidosis and to watch over every treated or nontreated hepatitis C infected patient for the development of granulomatous lesions.

Adult↗

Prognostic value of plasma markers of immune activation in patients with advanced HIV disease treated by combination antiretroviral therapy.

We assessed the prognostic role of plasma levels of beta2-microglobulin, TNF-alpha, sTNFR-II, and IFN-gamma on the progression to AIDS in patients mostly treated with combination antiretroviral therapies. HIV-1-infected patients with advanced HIV disease (baseline CD4+ cell count between 50 and 250 x 10(6)/L) were included in a prospective cohort followed up for 36 months. In the 113 patients included, 22 first AIDS-defining events were reported. Cumulative probability of AIDS was 12% at M12, 18% at M24, and 20% at M36. Using a Cox model, the baseline level of sTNFR-II (hazard ratio of 3.75 for sTNFR-II > or =10 ng/ml vs < 10 ng/ml, P = 0.01) was associated with progression to AIDS. sTNFR-II remained a prognostic factor before and after the introduction of combinations of antiretrovirals. Whether or not this marker is of value in patients exclusively treated with highly active antiretroviral therapy needs to be assessed in specific studies.

Adult↗

[Sarcoidosis and comorbidity: retrospective study of 32 cases].

PURPOSE: A retrospective study was set up to investigate active pathologic processes associated with sarcoidosis diagnosed in 32 patients. METHODS: Eighteen patients had two identified granulomatous localizations (56%) and 14 patients had three localizations or more (27%). Comorbidity was noticed in nine patients (28% of cases). Sarcoidosis was associated with an infectious disease five times (hepatitis C virus [HCV] infection three times, including one case after recombinant interferon alpha therapy, and HIV and HCV co-infection two times). The association of sarcoidosis with a chronic immunologic inflammatory disease was noticed four times (lupus erythematosus two times, myasthenia and primary biliary cirrhosis). Finally, in two cases sarcoidosis was associated with a neoplasia (non-Hodgkin's lymphoma in a co-infected HIV-HCV patient, ovarian cystadenocarcinoma in another patient). Sarcoidosis preceded or revealed the comorbidity four times.

Adult↗

The absence of hyperbilirubinaemia is highly predictive of treatment failure in advanced HIV-infected patients treated with indinavir.

In order to determine prognostic factors associated with treatment failure (TF) in advanced HIV-infected patients treated with a regimen including indinavir, a prospective cohort study of 80 patients was set up between 1 March and 31 December 1996. TF time was calculated using the Kaplan-Meier method, from treatment induction to the first of the following events: treatment modification for adverse event or lack of significant virological and/or immunological response, AIDS-defining diagnosis or death. Date of point was 31 December 1998. Multivariate analysis was performed using a Cox model. At baseline, 60% of the patients were AIDS-free, median viral load and CD4+ count were respectively 4.8 log/ml and 79/microl. After a median follow-up of 26 months, 70% of the patients experienced a TF in a median time of 8 months. Seventy-two per cent presented an hyperbilirubinaemia (>2 mg/dl). In multivariate analysis, initial AIDS stage (hazard ratios [HR]=1.94, P=0.04) and digestive intolerance (HR=2.32, P=0.003) were predictive of TF. Conversely, hyperbilirubinaemia was associated with a better outcome (HR=0.35, P<0.0001). These 2 latter parameters very likely reflected patients' treatment compliance.

Adult↗

Hepatitis C virus infection and lymphoproliferative diseases in France: a national study. The GERMIVIC Group.

The putative role of hepatitis C virus (HCV) infection in the pathophysiology of lymphoproliferative diseases (LPD) is supported by North American and southern European studies reporting high HCV seroprevalence in patients with B-cell-non-Hodgkin lymphoma (NHL). In order to evaluate the situation in France, we conducted a retrospective national study about the association of chronic HCV infection and LPD. 72 Internal Medicine and Infectious Diseases departments were contacted. Response rate was 51.4%. We recorded 43 LPD (19 males, 24 females): 31 B-cell-NHL, 4 Waldenström's macroglobulinemia, 3 chronic lymphocytic leukemia, 2 multiple myeloma, 2 lymphomas of the mucosa-associated lymphoid tissue, and 1 Hodgkin's disease. Mean age at HCV diagnosis was 62 years (range 33-84). In 16 cases, LPD occurred in patients known to be HCV-infected. For 11 patients, LPD diagnosis preceded the diagnosis of HCV infection, whereas diagnosis was done simultaneously in 11 patients. For those with accurate infection date, mean interval between both events was 15.2 years. Fourteen patients had HCV extrahepatic manifestations: 9 mixed cryoglobulinemia, including 7 with NHL, 5 sicca syndrome (5 NHL), and both in one patient. Cohort of HCV-infected patients could be accurately determined for 16 departments, totaling 1,485 patients and 37 cases. Thus, from our data the frequency of LPD among HCV-infected patients approximates 2. 49%. Despite possible bias inherent to this retrospective study, our data support the hypothesis of HCV-associated LPD and particularly B-cell-NHL. In France, this association is much lower than in Italy. Further studies are needed to assess the precise role of HCV in the multistep process leading to monoclonal proliferation.

Adult↗

[Multiple medullary and extramedullary plasmacytomas in an HIV infected female patient].

INTRODUCTION: Before the HIV infection era, plasmocyte tumor rarely occurred in patients younger than 40 years of age. Less frequent than lymphomas, the incidence of these blood diseases has however substantially increased in HIV-infected patients. In these patients, in addition to onset at earlier age, their clinical presentation is quite different and extramedullary plasmocytomas in unexpected locations are more common. EXEGESIS: We report the case of a 29-year-old HIV-infected female patient in whom were diagnosed occipital, parotidal, sphenoidal, epidural, and uterine plasmocytomas for which chemotherapy and subsequent radiotherapy were successful. The increase in the incidence of plasmocyte tumors in HIV-infected patients might be facilitated by Epstein Barr Virus (EBV) co-infection, HIV-related chronic antigenic stimulation, and secretion of interleukin 6 by infected lymphocytes. CONCLUSION: Plasmocyte tumors belong to neoplasia whose incidence is increased in HIV infection. Their currently poor diagnosis should be improved by highly active antiretroviral therapies allowing enhanced chemotherapy with possibility of autograft.

AIDS-Related Opportunistic Infections↗

Cyclooxygenases 1 and 2 and thromboxane synthase in kidneys of Lyon hypertensive rats.

Compared with their two normotensive (LN and LL) controls, genetically hypertensive rats of the Lyon strain (LH) exhibit increased renal vascular resistance and a blunted pressure natriuresis function as well as an increased urinary excretion of vasoconstrictor prostanoids. The aim of this study was to assess in the kidneys of these animals the synthesis of vasoconstrictor or sodium-retaining prostanoids. The relative abundance of the mRNAs of cyclooxygenases (COX) 1 and 2 and of thromboxane A2 synthase (TXS), was measured by reverse-transcription polymerase chain reaction (RT-PCR) in renal cortex and medulla dissected in groups of male LH, LN, and LL rats either in baseline conditions or after 1 week of salt loading (1.5% NaCl in the drinking water). In basal conditions, at 3 and 11 weeks of age COX1 was expressed in the kidneys of all rats more markedly in medulla than in cortex. COX2 was poorly expressed in the whole kidney. TXS expression was usually too low to be quantified. No difference could be observed among LH, LN, and LL rats. After salt loading, the expression of COX1 was enhanced in the medulla and that of COX2 reduced in the cortex. LH rats differed from controls by a significantly more marked increase in medullary COX1 expression. The present work excludes any primary generalized increase in the renal expression of the genes that control the synthesis of vasoconstrictor prostanoids in LH rats, but suggests that medullary COX1 is upregulated by salt in these animals.

Animals↗

A possible association between Chlamydiae psittacci infection and temporal arteritis.

Some arguments are in favor of the role of Chlamydia in the pathogenesis of atherosclerosis and some vasculitis. Illustrating this possible relation, we report the case of a patient developing consecutively a Chlamydia psittacci infection and a temporal arteritis. A 73-year-old woman, with no significant medical history, was hospitalized for constitutional symptoms. Three weeks before, she had described fever and sore throat of two days' duration. Since that time, she had remained exhausted and developed a mild intermittent claudication of the jaws. Clinical examination was poor. A biological inflammatory syndrome was noticed. Chest X-ray revealed bilateral interstitial opacities. The titer of anti-C. psittaci antibodies was significant (positive 1g G at 1/2048). Soon after initiation of doxycycline, a temporal arteritis biopsy was performed, due to the persistence of clinical symptoms and high inflammatory syndrome, conclusive for the diagnosis of temporal arteritis. Corticotherapy was added to antibiotic therapy, resulting in the decrease of inflammatory syndrome and an improvement in the general status of the patient. X-ray opacities decreased in three weeks. Serological control after three months showed a decrease of the titer of anti-C. psittacci antibodies to 1/256, confirming the initial diagnosis of Chlamydia pneumopathy. Our observation could provide one more argument for the role of bacteria-like Chlamydia in the pathogenesis of vascular diseases. Prospective seroepidemiological and molecular biology studies could allow us to clarify the association between Chlamydia infections and inflammatory vasculitis-like temporal arteritis.

Adrenal Cortex Hormones↗

Prognostic factors of survival of HIV-infected patients with cytomegalovirus disease: Aquitaine Cohort, 1986-1997. Groupe d'Epidémiologie Clinique du SIDA en Aquitaine (GECSA).

OBJECTIVE: To analyse survival of HIV-infected patients who developed cytomegalovirus (CMV) disease and to identify prognostic factors of their survival. METHODS: Cases of CMV disease diagnosed in the Aquitaine Cohort of HIV-infected patients (n = 4297) during the 1986-1996 period, were reviewed using standardised definitions. Follow-up was extended to December 1997. Cox model was used to determine factors associated with survival after the initial manifestations of CMV disease, considering protease inhibitor (PI) prescription and anti-CMV treatment as time dependent covariates. RESULTS: 253 patients presented a CMV disease of which 221 (87.3%) died (median survival: 7 months). A better prognosis for survival was associated with: PI prescription [relative hazard (RH): 0.26; 95% confidence interval (CI): 0.11-0.59], anti-CMV treatment (RH: 0.37; CI: 0.25-0.54), CD4+ lymphocyte cell count > 50/mm3 (RH: 0.66; CI: 0.47-0.94) and absence of neoplasia (RH: 0.70; CI: 0.52-0.94) whereas the disseminated CMV disease worsened prognosis (RH: 1.83; CI: 1.20-2.80). CONCLUSION: Antiretroviral treatment including PI, improved short-term prognosis of CMV disease regardless of its clinical manifestations.

AIDS-Related Opportunistic Infections↗