Biomedical subjects
J M Ragnaud
Publications and source records attributed to J M Ragnaud.
Primary coinfection with human immunodeficiency virus and cytomegalovirus presenting as acute rhabdomyolysis.
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Detection of Toxoplasma gondii by PCR and tissue culture in cerebrospinal fluid and blood of human immunodeficiency virus-seropositive patients.
To investigate whether both tissue culture and PCR on a sequence from the repetitive rDNA could contribute to the diagnosis of toxoplasmosis, blood samples and, if they were available, cerebrospinal fluid (CSF) and aqueous humor samples from 72 human immunodeficiency virus-seropositive patients with suspected toxoplasmosis were prospectively tested. For 10 patients with fever of unknown origin but without confirmed toxoplasmosis, no Toxoplasma gondii was detected. For two patients with confirmed toxoplasmic uveitis, only PCR of aqueous humor samples was positive. Of 60 patients (48 with CSF samples) with neurological signs, 25 (from 13 of whom CSF samples were available) had confirmed cerebral toxoplasmosis and 10 had a positive PCR of CSF and/or blood samples, while for 1 patient culture of the CSF sample was also positive. Unlike tissue culture, PCR of rDNA is of value for the detection of cerebral toxoplasmosis in human immunodeficiency virus-seropositive patients, provided that both CSF and blood samples are available (sensitivity, 76.9%; specificity, 100%).
Tuberculosis and HIV infection: a cohort study of incidence and susceptibility to antituberculous drugs, Bordeaux, 1985-1993. Groupe d'Epidémiologie Clinique du SIDA en Aquitaine.
OBJECTIVES: To assess the temporal trends in incidence of tuberculosis (TB) in HIV-infected patients, to evaluate the impact of pulmonary TB on the Centers for Disease Control and Prevention (CDC) 1993 AIDS case definition and to assess the frequency of Mycobacterium tuberculosis strain resistance. DESIGN: A retrospective study within a cohort. SETTING: The Bordeaux University Hospital and three general hospitals in Aquitaine, southwest France. SUBJECTS: Since 1985, HIV-infected in- and outpatients aged > 13 years have been included in the Aquitaine cohort. Reported cases of pulmonary and extrapulmonary TB were investigated and records cross-referenced with the files of the TB reference laboratory. RESULTS: As of 30 June 1993, the Aquitaine cohort (3119 patients) accounted for 6409 person-years (PY) of follow-up. TB was diagnosed in 139 patients (average annual incidence, 2.17 per 100 PY) of whom 79 had bacteriological diagnosis, 13 histological diagnosis and 47 clinical and/or radiological diagnosis. Extrapulmonary TB accounted for 40% of the cases. Intravenous drug use was more frequent in the group who developed TB (50%) than in the rest of the cohort (40%) (P = 0.009). There was an increase in the incidence rate of TB in the cohort between 1985 (0.45 per 100 PY) and 1989 (2.67 per 100 PY) and a stabilization around 1.5-2.0 per 100 PY until 1993. Pulmonary TB was estimated to increase the AIDS cumulative incidence by 0.4% when performing a simulation with the 1993 AIDS case definition. Single drug resistance was documented in 3.4% of the cases and a multiple drug resistance in 5.1%. CONCLUSION: TB incidence has stabilized since 1990 in the Aquitaine cohort with a limited increase of the number of AIDS cases (1993 CDC criteria). Drug resistance was rare.
Simultaneous development of two different B-cell lymphomas in a patient with acquired immune deficiency syndrome evidenced by molecular analysis.
We report a case of a man positive for the human immunodeficiency virus who rapidly died of lymphoma with cerebral, lung, and pericardic involvement. After autopsy, histopathological study of the different tumor sites showed the same morphological feature of immunoblastic lymphoma, with large areas of necrosis. In situ hybridization showed monotypic kappa light chain mRNA within lung lymphoma cells and monotypic lambda light chain mRNA within cerebral lymphoma cells. Polymerase chain reaction analysis showed two different immunoglobulin heavy chain gene rearrangements for lung and cerebral lymphoma. Here the simultaneous association of two malignant lymphomas derived from different B-cell clones indicates that molecular analysis of different tumor sites can distinguish between dissemination of the same lymphoma and simultaneous proliferation of different malignant B-cell clones.
[Epidemiological, clinical, biological and developmental aspects of leptospirosis: apropos of 30 cases in Aquitaine].
We have studied retrospectively 30 cases of leptospirosis observed in Aquitaine (South West France) from 1980 till 1992. This review was made in three internal and a nephrology department in Bordeaux hospital. Most cases occurred by indirect contact with infected animals or by occupational exposures. Onset was brutal with fever often associated with painful syndrome and sometimes conjunctival suffusion. Jaundice (70%), acute renal failure (67%), meningitis (50%) and hemorrhagic signs (50%) were among the major visceral manifestations. Diagnosis was always confirmed by micro-agglutination test. Leptospira ictero-hemorrhage was the predominant serogroup found. The outcome was favorable in 22 patients; reversible complications were seen in six cases (five acute renal failure with hemodialysis myocarditis and pulmonary edema in two hemodialysed patients, polyradiculoneuritis). Two patients died (acute respiratory failure and meningo-encephalitis with diffuse hemorrhagic syndrome). The characteristic of our series is the high frequency of hepatorenal syndrome due to the importance of our nephrologist recruitment. Furthermore our study confirm the vital prognostic characters of the pulmonary, renal, hemorrhagic and neurologic complications. No absolute relationship was found between the clinical and laboratory findings and the serotype of leptospira. Penicillin remains the treatment of choice and should be started as soon as possible the avoid the life threatening visceral complications.
[Clinical, biological and developmental aspects of cytomegalovirus infection in immunocompetent patients: apropos of 34 hospitalized patients].
We reviewed the thirty cases of cytomegalovirus infections with occurred in previously healthy patients, hospitalised for fever from 1981 to 1992. Pregnant women, transplant recipients, HIV infected persons and all immunocompromised subjects were excluded. We observed 34 cases (18 women, 16 men) whose mean age was 34 years (17 to 79). Fever appeared progressively (73%), persisted more than 15 days (87%) and was well tolerated. The main functional symptoms were headaches, myalgia (53%), profuse sweat (50%), abdominal pain, diarrhea, recent loss of weight, dry cough (51%). Splenomegaly was present in 24% of the cases. Chest X ray was always normal. Differential blood count was always inverse and an authentic mononucleosis syndrome was present in 91%: it appeared mainly 13 days after onset of symptoms. Hepatic abnormalities were nearly constant, especially cytolytic (97%) (transaminases three or four times upper the normal limit) but also cholestatic (62%). Thrombopenia has been noticed once (48,000/mm3). Serological diagnosis was confirmed with Elisa test (anti CMV Ig M: 30 cases) or complement fixation test (seroconversion: one, significant increase of the titers: two). CMV viremia, studied in seven patients, was positive in three. Spontaneous or treated (NSAI in 30%) outcome was nearly always favourable (97%). Two patients presented severe complications: meningo encephalitis and spleen rupture. CMV infection in previously healthy patients has to be suspected, without waiting for the mononucleosis syndrome, in view of a prolonged, well tolerated febrile illness, without pharyngitis, associated with hyperlymphocytosis and mild cytolysis. A careful follow-up is needed to detect the rare but severe complications.
Circulating autoantibodies directed against conjugated fatty acids in sera of HIV-1-infected patients.
Several reports have demonstrated that major changes occur in the fatty acid content of HIV-infected cells. In order to evaluate if these changes are recognized by the immune system, we have attempted to assay the possible presence of autoantibodies (autoAb) directed against conjugated fatty acids (CFA). Using an adapted ELISA, anti-CFA autoAb were assayed in sera of 150 HIV-1-infected patients and 116 controls (healthy donors and patients suffering from other diseases). Significantly increased anti-CFA autoAb of IgG class were found in HIV-1-infected patients (alpha < 0.001). Using our ELISA method and CFA differing in their length and their degree of unsaturation (lauric, myristic, palmitic, palmitoleic, stearic, oleic, linolenic, linoleic, lignoceric, arachidonic, eicosapentaenoic and docosahexaenoic acids), it was demonstrated that the acyl chain of CFA is the immunodominant part recognized by these autoAb. Anti-CFA autoAb were present in 15/52 asymptomatic carriers, 14/36 symptomatic carriers, 16/39 ARC patients, but only 3/23 AIDS patients. Anti-CFA activity seemed to be linked with the CD4+ T cell count, and was not related to the total IgG amounts. Anti-CFA autoAb could result from self-antigen presentation to immunological cells, and may reflect lipid membrane modifications occurring in HIV-infected cells.
[Cerebral toxoplasmosis in AIDS. 73 cases. Clinical Epidemiology Group on AIDS in Aquitania].
A presumptive diagnosis of toxoplasmic encephalitis was made in 73 of the 428 AIDS patients followed in the Bordeaux Regional Hospital between 1985 and 1990. The sex ratio (M:F) was 2.8:1. The mean age was 36.2 years. Forty-three percent were homosexuals, 30 percent intravenous drug abusers. The encephalitis revealed the HIV infection in 10 percent of the cases; it was the first opportunistic infection in 27 percent. The clinical manifestations were: focal neurologic deficit (62 percent), fever (58 percent), headaches (47 percent), altered consciousness (45 percent), seizures (18 percent). The CT scan findings were focal lesions with (60 percent) or without (40 percent) ring enhancement. Oedema was present in 58 percent of the lesions, and multiple lesions in 59 percent. At the time of diagnosis, the mean CD4 lymphocyte count was 72 per mm3. The initial therapeutic regimens were: pyrimethamine (P) plus sulfadiazine (n = 57), P plus clindamycin (n = 11) and P plus clarithromycin (n = 5). Following acute therapy the patients had a complete (64 percent) or partial (18 percent) response, and 18 percent died. Adverse reactions were noticed in 53 percent. Sixty patients received a maintenance therapy; after a mean follow-up of 8 months, 12 relapsed and died of toxoplasmic encephalitis; 17 died of another cause. The median survival after toxoplasmosis was diagnosed was 7.5 months.
Mycoplasmas in HIV-1 seropositive patients.
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Pharmacokinetics of intravenous and intraperitoneal ceftazidime in chronic ambulatory peritoneal dialysis.
The pharmacokinetics of ceftazidime have been investigated in eight patients with chronic renal failure undergoing continuous ambulatory peritoneal dialysis. Each subject was given ceftazidime 1 g intravenously and 1 g intraperitoneally at an interval of 1 week. Ceftazidime was assayed by high-pressure liquid chromatography. After intravenous administration, the pharmacokinetic parameters of ceftazidime were: elimination plasma half-life (t1/2 beta) = 24.6 +/- 4.6 hours; apparent volume of distribution (V(area)): 0.37 +/- 0.09 1/kg, total plasma clearance (CL): 11.9 +/- 3.3 mL/minute, peritoneal clearance (CLp): 1.7 +/- 0.3 mL/minute. Over 72 hours, only 15.6 +/- 4.7% of the dose was eliminated by the peritoneal route. After intraperitoneal administration, ceftazidime appeared in the plasma rapidly, and the peak plasma concentration of 24.5 +/- 5.2 mg/L was achieved at the fourth hour; the elimination half-life (t1/2ke) was 20.8 +/- 1.7 hours. The absorption of ceftazidime from the peritoneal space was 74.1 +/- 7.4%. These data suggest that ceftazidime has bidirectional exchange characteristics through the peritoneal membrane. A single 1-g intraperitoneal dose led to serum and dialysate concentrations of ceftazidime above the minimum concentrations for susceptible pathogen germs for 24 hours.
[Neurologic manifestations in Lyme disease. Apropos of 22 cases].
The main clinical and biological features of 22 cases of neurological forms of Lyme disease are reviewed. Radiculitis (n = 15), cranial nevritis (n = 7), meningitis (n = 5) and encephalitis (n = 4) are often associated. Tick bites were previously noticed in only 40% of cases; erythema chronicum migrans in 73%, "one to six months before the onset of neurological symptoms". Titers of Borrelia Burgdorferi antibodies were always above 1/256. Among 18 patients, DR W2 HLA haplotype was present in 15.
[Prognostic role of pregnancy on the course of HIV infection: a retrospective cohort study (1985-92)].
In a hospital-based cohort study of HIV-infected patients, we compare the progression of the disease (occurrence of CDC group IV, death, decline of CD4 below 200/mm3) between 55 women with delivery and 89 matched control HIV positive women with no history of pregnancy. After a mean follow-up of three years, no significant difference was observed between the two groups even after adjustment on prognostic variables.
[Joint manifestations and parvovorus B19 infections: 8 cases].
Human Parvovirus B19 (PB19) may cause joint manifestations. We report eight cases of polyarthritis associated with PB19 IgM: six cases of acute polyarthritis spontaneously resolving within a few days, and two other cases suggesting that PB19 should be responsible for accutisation of chronic disease (lupus with Kikuchi's disease and HLA B27 related arthritis).
Herpes zoster and human immunodeficiency virus infection: a cohort study of 101 coinfected patients. Groupe d'Epidémiologie clinique du SIDA en aquitaine.
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[Septicemia in patients with human immunodeficiency virus infection (excluding Mycobacteria). Apropos of 58 cases].
We reviewed the characteristics of 58 episodes of septicemia which occurred in 53 HIV infected adults over a 30-month period. This cases represented 10.1% of HIV infected hospitalized patients. At the time of septicemia, 79.3% patients were at AIDS stage; mean CD4 count was 72/mm3. Nosocomial septicemia occurred significatively more often in patients with previous AIDS defining illness and in neutropenic patients (p < or = 0.05 and p < or = 0.001 respectively). Staphylococcus coagulase negative (n = 17), Staphylococcus aureus (n = 11) and Salmonella (n = 8) were the most common organisms. The source of infection was found more frequently in nosocomial septicemia than in community-acquired septicemia (78% versus 46%; p < 0.02), mainly intravenous catheter (60%). Staphylococcus aureus, AIDS stage and nosocomial septicemia have high fatality rates. Mortality was not higher than previously reported in the general population.
Analysis of HIV-1 expression in vivo with in situ hybridization and the polymerase chain reaction.
The objective of the present study was to compare the data of in situ hybridization (ISH), RNA polymerase chain reaction (PCR/RNA) and p24 core antigen (p24 Ag) enzyme immunoassay (EIA) for the detection of HIV-1 expression in peripheral blood mononuclear cells (PBMCs) and in plasma of infected patients at various CDC stages. PBMCs of 24 patients mostly of CDC stage II were obtained from heparinized blood samples, cytocentrifuged and hybridized with a (35S) labelled single-stranded RNA probe specific for gag-pol of LAVBru HIV-1 allowing the detection of genomic and/or messenger RNA. The corresponding plasma samples were used for the determination of p24 Ag by EIA and detection of HIV-1 genomic RNA by RT-PCR using specific primers in the LTR, gag and env regions. Whereas p24 was detected in only six out of 24 patients, both ISH and PCR/RNA enabled the detection of viral RNAs in more than 60% of the patients; cumulation of positive results of ISH and RT-PCR showed that 100% of patients at stage IV and 83% of patients at stages II/III have molecular signs of HIV expression therefore indicating that transcription of the provirus is a highly frequent event, even in the early stages of the disease, and, pleading for undertaking a very early antiviral chemotherapy.
Short-term effect of red wine (consumed during meals) on insulin requirement and glucose tolerance in diabetic patients.
OBJECTIVE: To determine the effect of wine on insulin requirement or glucose tolerance. RESEARCH DESIGN AND METHODS: Five men with insulin-treated diabetes and 10 men with non-insulin-treated diabetes ate the same lunch with the same volume of either water or red wine (2 glasses). Insulin requirement was determined with an artificial pancreas (Biostator). Glucose tolerance was evaluated from the postprandial glycemic level. RESULTS: There was no significant difference in insulin requirement determined with an artificial pancreas in the insulin-treated patients after the two meals (31.5 +/- 4.21 U with water and 31.8 +/- 4.3 U with wine). Glucose tolerance in the non-insulin-treated patients was lower after the meal with wine. CONCLUSIONS: Moderate prandial wine consumption has no adverse effect on the glycemic control of diabetic patients. Thus, it appears unnecessary to proscribe the consumption of red wine in moderation with meals to diabetic patients. Wine contains tannins and phytates that can explain its action.