[Ganciclovir and neonatal acquired cytomegalovirus infection].
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Biomedical subjects
Publications and source records attributed to F Freymuth.
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Diarrhea in marrow transplant recipients is a frequent complication attributable to non-infectious events such as acute GVHD or infectious events such as viral gastroenteritis. Rotavirus and enteric adenovirus are the most frequent viral pathogens. To determine the frequency of these infections, we prospectively examined the stool specimens of 94 patients who underwent autologous BMT (34 cases) or allogeneic BMT (60 cases). Stool specimens were examined from patients twice weekly. Nineteen of the 94 patients were infected with viral pathogens. This study showed: (1) an incidence of viral gastroenteritis identical in autologous and allogeneic BMT (20%), (2) a persistent risk despite treatment in laminar air flow rooms, (3) a significant association with severe acute GVHD, and (4) a significant risk of multiple viral infections in autologous BMT recipients. Rotavirus and adenovirus are a cause of enteritis involvement in patients undergoing BMT and they may be underdiagnosed and confused with GVHD. Screening of stool specimens after BMT should be directed to prevention and treatment of these viral infections to decrease the morbidity and mortality associated with BMT.
Dilated cardiomyopathy is so called when an etiological investigation is negative and no cause can be found for ventricular dilatation-hypokinesia. Current research points to genetic, immunological and infectious factors, often associated, and the passage of subclinical viral myocarditis to chronic disease. There is a lot of evidence in favour of this hypothesis. In the experimental model, the relationship between viral myocarditis and dilated cardiomyopathy has been demonstrated with, as cofactors, a genetic predisposition and an immunitary deficiency leading to an auto-immune subacute myocarditis. In the clinical setting, the enterovirus with a high cardiac tropism seems to play an epidemiological role in the genesis of dilated cardiomyopathy. The concentrations of neutralising anti-coxsackie B virus antibodies is higher in subjects with dilated cardiomyopathy than in a control population. The frequency of lymphocytic infiltration, a marker of dysimmunitary myocarditis, is variable from study to study but the presence of sequences of enterovirus genome in the myocardium could explain slow replication of the virus progressively destroying the myocytes. Techniques of molecular hybridization with or without prior genic amplification by the "Polymerase Chain Reaction" have demonstrated such sequences of specific enterovirus genome but discordant results require further studies.
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Cytomegalovirus (CMV) is an important cause of morbidity in organ transplant recipients with two major clinical effects: allograft rejection and pneumonitis. The issue of effective therapy has increased the need for accurate and rapid laboratory methods for diagnosis of viral infections. ELISA, as the most serological sensitive tests, are useful for the identification of active CMV infection, and the serological response can be sometimes detected before viral excretion. There are several commercial reagents for the detection of IgG or IgM CMV antibody, and a great variability in terms of sensibility and specificity. Because of the slow process of isolating CMV in cell cultures, immediate-early antigen detection in infected cells within one or two days of culture, increases twice the sensitivity of viral isolation for leukocyte or bronchoalveolar (BAL) specimens. Differences in sensitivity of the direct detection of CMV antigen in BAL specimens has been reported. Direct detection of CMV antigen in leukocytes is particularly important because CMV viremia is considered to be predictive of significant CMV disease. CMV antigen detection within leucocytes, by immunofluorescence with the aid of monoclonal antibodies to CMV phosphoprotein PP-65, appears to be as specific, more sensitive, and allows a more rapid diagnosis than virus isolation techniques. Some specific CMV probes are now available, but the hybridization techniques involving dot-blot assays of urine or BAL are not enough sensitive to detect small amounts of virus. Closely sensitivity to isolation in culture has nevertheless been reported in the polymorphonuclear fraction of the blood cells.(ABSTRACT TRUNCATED AT 250 WORDS)
Ureaplasma urealyticum and Mycoplasma hominis were recovered from nasopharyngeal aspirates from 25% of 63 infants admitted to a neonatal unit; this proportion is significantly higher than that seen in a control population of maternity ward babies (0%). Birth by cesarean section was associated with a reduced risk of recovery of mycoplasmas. No specific diseases were significantly associated with recovery of mycoplasmas; furthermore, no obstetrical factors were associated with recovery of mycoplasmas from the neonates and no association was found between mycoplasma infection and respiratory distress. However, fetal distress, probably of multifactorial origin, was found in 44% of neonates with positive cultures for Ureaplasma urealyticum; this proportion was significantly elevated as compared with the subgroup of infants negative for U. urealyticum, suggesting that fetal distress may increase the infectivity of this opportunistic organism.
The aim of this study was to evaluate the diagnostic usefulness of percutaneous liver biopsy and screening for hepatitis C virus antibodies with 1st and 2nd generation ELISA in asymptomatic blood donors with persistent (> 1 year) and moderate elevation (> 1.5 times the upper limit of normal) of serum alanine aminotransferase. The diagnosis was established from clinical, biological and ultrasound data before biopsies were obtained, then compared to the histological diagnosis. Thirty one of 56 blood donors who satisfied the preceding criteria accepted liver biopsy and were subsequently included in the study. An accurate diagnosis was proposed before biopsy in 20 cases. This was in agreement with the histological results in 19 cases but in 2 of these, unexpected lobular hepatitis was associated with the expected steatosis. Positive hepatitis C virus tests corresponded to chronic hepatitis in all cases (n = 5). No accurate diagnosis could be proposed in the 11 remaining cases owing to the lack of evidence of any etiology (n = 4) or because several potential etiologies were possible for the same subject (n = 7). Histological diagnoses were: isolated steatosis (n = 12), steatosis associated with lobular hepatitis (n = 7) or with chronic persistent hepatitis (n = 1), chronic active (n = 2) or chronic persistent hepatitis (n = 3), alcoholic hepatitis (n = 2), hemochromatosis (n = 1), and normal liver (n = 3). Liver biopsy is essential to the accurate etiological diagnosis of persistent and moderate elevation of aminotransferases despite hepatitis virus C tests which are associated with the correct diagnosis of chronic hepatitis in 16% of cases.(ABSTRACT TRUNCATED AT 250 WORDS)
The occurrence of cytomegalovirus (CMV) viremia after transplantation is predictive of visceral lesions. Three-hundred and sixty blood samples were collected from 21 transplant recipients and examined. Direct CMV antigen detection was positive in 41 samples (11.4 percent), rapid viral isolation in 24 samples (6.7 percent) and conventional cell culture in 9 cases (2.5 percent). Direct detection of CMV antigen in blood leucocytes is as specific as, and more sensitive and rapid than isolation in culture. In 50 percent of secondary infections the antigenaemia assay and serology were equally sensitive, and antigenemia appeared earlier in 2 primary infections.
Enteroviruses are considered to be the most common agents implicated in myocarditis and cardiomyopathy. Recent studies have suggested persistent enterovirus infection in chronic disease showing the presence of enteroviral RNA in the myocardium. We used gene amplification by PCR which can demonstrate directly the presence of enteroviral sequences in endomyocardial biopsies. The primers were chosen in the 5' non-coding region of the genome representing highly conserved sequences among enteroviruses and therefore allowed the amplification of the majority of enteroviruses. The hybridization of the amplified products was effected with specific general riboprobe derived from 5' non-coding sequences internal of the amplified fragments. The results include 105 patients distributed in 6 groups: 45 idiopathic dilated cardiomyopathies with 66.7%, 17 alcoholic cardiomyopathies with 52.9%, 10 myocarditis with 30%, 5 multifactorial cardiomyopathies with 40%, 5 patients with immunosuppressive therapy with 100%, and 23 control group without viral etiology with 39.1% positive samples. The study suggested a positive link between viral infection and cardiomyopathies, but did not allow a direct relation between enterovirus infection and idiopathic dilated cardiomyopathy to be established.
BACKGROUND: Respiratory syncytial viral (RSV) infection can be rapidly differentiated from influenza viral infection by immunofluorescence techniques. These tests were used to identify some epidemiological and clinical characteristics of both infections. METHODS AND PATIENTS: 77 RSV and 22 influenza viral infections were detected during an outbreak (November 1989 to March 1990) in 210 children less than 6 years admitted for lower respiration tract infections. The fluorescent antibody assay was performed on nasal aspirates. RESULTS: The RSV outbreak ran from November to March, while the influenza outbreak was shorter, during December and January. The patients infected with RSV were younger (mean age: 6.7 months) than those infected with influenza virus (mean age: 20.9 months) (p < 0.001). Those with influenza virus infection presented with higher temperatures, more often had initial seizures (p < 0.05) and displayed fewer clinical or X-ray respiratory symptoms (p < 0.001). Mean durations of hospitalization were 9.9 days for RSV infection and 7.7 days for influenza virus infection. The therapeutic use of bronchial dilators, oxygen and steroids was correlated with the degree and duration of respiratory manifestations. A 3 month follow-up was insufficient to show any difference between recurrences or complications in the two groups. CONCLUSION: The clinical and radiological differences in these two groups of patients viral-infected are similar to those described in the literature. Variability from one outbreak to another precludes any extrapolation to other populations and justifies the systematic use of the fluorescent antibody assay, especially when a specific antiviral therapy is considered.
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Viral pneumonia is not very frequent in healthy adults; it is mostly observed in elderly subjects infected with an influenza virus, a respiratory syncytial virus (RSV) or an adenovirus (AdV). In immunocompromised subjects, cytomegalovirus (CMV) is the most common of causal agents. From the point of view of clinicians, virological diagnostic methods must be rapid and specific, and for this reason direct examination techniques for respiratory specimens and immunological detection of virus are currently being developed in virology laboratories. These techniques make it possible, for example, to identify in less than two hours influenza viruses, RSV or AdV in bronchial secretions and CMV in bronchoalveolar lavage fluid after celle centrifugation. Virus isolation in cell cultures is the reference method, but the result is often delayed and the search for seroconversion may take several weeks.
A fluorescence antibody test with monoclonal antibodies was used to determine the subgroup (A or B) of respiratory syncytial virus from infants hospitalized in Caen, France, over eight consecutive epidemics from 1982 to 1990. From 1982 to 1985, 27 (30%) out of 90 frozen nasal slides were classified as subgroup A strains and 63 (70%) were classified as subgroup B. B strains predominated over A in 1983-1984 and 1984-1985. From 1985 to 1990, 284 respiratory syncytial virus field strains were reisolated from frozen materials; 115 (40.5%) were typed as subgroup A and 169 (59.5%) were typed as subgroup B. In 1985-1986, 1986-1987, and 1988-1989, both subgroups were present in almost equal numbers; subgroup A (88.3%) predominated in 1987-1988, and subgroup B (84.5%) predominated in 1989-1990. In conclusion, both subgroups occur together each year, and one subgroup rarely predominates, e.g., subgroup A in 1987-1988 and subgroup B in 1983-1984 and 1989-1990. Therefore, there is a gradual change of the predominant subgroup into another over a period of about 5 years; the relative frequency of subgroup A strains increased from 1983 to 1988, whereas the percentage of subgroup B decreased during the same period.
A rapid enzyme immunoassay (EIA) membrane test, the Directigen respiratory syncytial virus (Becton Dickinson), was compared with cell culture, an indirect immunofluorescence (IF) test, the Monofluokit respiratory syncytial virus (Diagnostics Pasteur), and a conventional enzyme immunoassay antigen test, the Abbott respiratory syncytial virus enzyme immunoassay in nasal aspirates specimens from children with suspected respiratory syncytial virus (RSV) bronchiolitis. The sensibility and specificity of the Directigen, respiratory syncytial virus were 91% and 98% respectively, as compared with those of culture, and of 93% and 86% as compared with the Monofluokit respiratory syncytial virus. In the comparison of the two enzyme immunoassays, Directigen respiratory syncytial virus detected more positive specimens: 68/127 than the other: 46/127. Directigen respiratory syncytial virus is a very rapid test, (15-min), sensitive and specific, which can be used as an alternative technique for detection of respiratory syncytial virus in nasal samples when viral isolation or immunofluorescence direct are not available.
Enteroviruses were specifically detected in crude clinical specimens or in cell cultures in which the viruses were amplified by dot hybridization by using poliovirus type 1-derived, subgenomic radiolabeled cRNA probes (riboprobes). The sensitivity of this test varied from 2.5 to 33%, when clinical specimens without cell culture were examined, and was about 85% in cell culture lysates. The specificity of the test was 90 to 100%. The riboprobe corresponding to the 5'-noncoding sequence specifically detected the majority of enteroviruses (56 of 57 tested); the riboprobe derived from the VPI capsid region hybridized with the three poliovirus serotypes and with some coxsackieviruses type A and with echovirus type 7. Echovirus 22 did not hybridize with any riboprobe. In stool specimens, nasal aspirates, and cerebrospinal fluids from patients with meningitis, only one type of virus was identified in different clinical samples from the same patient by the seroneutralization test. Hybridization allowed the detection of enteroviral RNAs easily in stool specimens and nasal aspirates but with a low efficiency in cerebrospinal fluids without amplification of the viruses in cell cultures.
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A new commercial latex-agglutination test using a monoclonal antibody for detection of rotavirus (Slidex Rota-Kit 2) was compared with three other tests (Slidex Rota-Kit, Rotalex, Rotazyme II) using immunoelectron microscopy and a monoclonal enzyme immunoassay as reference tests. Slidex Rota-Kit 2 was more sensitive and specific than the other tests, and would thus appear to be a practical and accurate rotavirus assay for use in routine laboratory work.
Biotin and 32P-labelled HBV probes were compared in 150 sera analysed with a spot hybridization test. In 144 cases (96%) results were concordant. The non-isotopic procedure was therefore not only simple and rapid to perform, but also sensitive and specific. Since it overcame the problems associated with 32P, it allowed more diagnostic applications of HBV-DNA determination in serum.