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Biomedical subjects

P Lebon

Publications and source records attributed to P Lebon.

At least 73 records · Page 4Linked to original sources

[Community-acquired pneumonia in children: importance of Mycoplasma pneumoniae infections and efficacy of antibiotics].

OBJECTIVES: Define a therapeutic management schema adapted to children with community-acquired pneumonia. METHODS: A prospective survey was conducted in 104 children over 18 months of age with community-acquired pneumonia. The pathogen was isolated in 85% of the cases. RESULTS: Viral infection alone was proven in 30 children (respiratory syncytial virus in 10). Pneumococci pneumonia was found in 12 patients; the isolated strains were sensitive to penicillin. Apyrexia was obtained in 11/12 cases with amoxicillin. Mycoplasma infections occurred in 42% of the cases (41 alone and in association with pneumococci in 2 cases). Pneumococci and mycoplasma infections could not be differentiated with standard radiography and laboratory tests. Initial treatment with beta lactamines was always unsuccessful in children with mycoplasma infections. Apyrexia was achieved when antibiotics were changed to macrolides. CONCLUSION: Since lower respiratory tract infections due to pneumococci are much more severe than those due to mycoplasma, beta lactamines should be given as first intention treatment for children over 18 months with pneumonia. Macrolides should be given in case of failure because mycoplasma would then be the most probable infectious agent.

Adolescent↗

Fetal serum interferon-alpha suggests viral infection as the aetiology of unexplained lateral cerebral ventriculomegaly.

We assayed fetal serum interferon-alpha (IFNA), a cytokine produced by leukocytes as a response to viral infection, in a series of 59 consecutive cases of ventriculomegaly diagnosed in utero and in 89 controls. Results were correlated with other findings including karyotype, maternal-fetal screening for serum antibodies to specific infectious pathogens, viral cultures of amniotic fluid, and neuropathological examination or postnatal follow-up. Fetal serum IFNA assay was negative in the five ventriculomegalies associated with a genetic anomaly and positive in the three cases with documented cytomegalovirus infections. In addition, fetal serum IFNA was detected significantly more often in the cases of ventriculomegaly with unexplained pathogenesis (15/51, 29.4 per cent) than in controls (1/89, 1.1 per cent). Detection of IFNA suggestive of viral infection in fetuses with otherwise unexplained ventriculomegaly underscores the need for more extensive viral screening in such cases.

Cerebral Ventricles↗

Constitutive expression of specific interferon isotypes in peripheral blood leukocytes from normal individuals and in promonocytic U937 cells.

Constitutive expression of IFN-alpha5 and IFN-beta was detected in different lymphoid cells including peripheral blood mononuclear cells from normal individuals following amplification of IFN mRNA by reverse transcriptase-polymerase chain reaction and direct sequencing of the amplified product. The activated form of the interferon-induced transcription factor complex ISGF3 was also detected in nuclear extracts from uninduced cells. Culture supernatants from uninduced U937 cells were also found to activate an ISRE cloned upstream of the luciferase reporter gene, indicating the presence of endogenous IFN activity equivalent to approximately 0.3 to 0.5 IU/mL. This endogenous IFN was also shown to play a role in maintaining the basal level of expression of the major histocompatibility class I genes in lymphoid cells. These results suggest that IFN-alpha5 and IFN-beta are produced at low levels in normal tissues and play an important role in the regulation of cell function and in the maintenance of homeostasis.

Base Sequence↗

Myelitis due to varicella-zoster virus in two patients with AIDS: successful treatment with acyclovir.

Only a few cases of varicella-zoster virus (VZV) myelitis have been described, and nearly all have been diagnosed post-mortem. There have been no reports in the literature of successful treatment of VZV myelitis with antiviral medications. We report on two patients with AIDS who had acute severe myelitis accompanied by herpes zoster. The presence of VZV DNA in cerebrospinal fluid (CSF) was documented by the polymerase chain reaction (PCR) technique. Early treatment with acyclovir was followed by a slow but complete recovery after a phase of initial aggravation. After a follow-up of > 1 year, the two patients remained asymptomatic. We conclude that (1) VZV should be considered a curable cause of myelitis in patients with AIDS, (2) PCR assay of CSF will assist in early diagnosis, and (3) early treatment with acyclovir should aid in recovery.

AIDS-Related Opportunistic Infections↗

Serum alpha-interferon in lower respiratory tract infections of children.

BACKGROUND: Serum alpha-interferon (IFN-alpha) concentrations are high in some children with viral meningitis and other viral infections. We have tried to assess the utility of determining serum IFN-alpha concentrations as a marker of acute viral respiratory infections. METHODS: Measurement of IFN-alpha via a biologic assay on Madin-Darby bovine kidney cells was performed in 138 patients with lower respiratory tract infection in whom a pathogen was identified. RESULTS: Serum IFN-alpha was detectable at the early stage of respiratory infections in the era of 59 of 75 (78.7%) of patients with a viral infection and in 4 of 63 (6.3%) of those with bacterial infection (P < 0.001). In the 4 patients with positive IFN-alpha and bacterial infection, a concomitant viral infection was found. The production of IFN-alpha is independent of age, and detectable levels are found in young infants, including the first 3 months of life, and in children with an acute viral disease. CONCLUSION: This test could be useful in distinguishing between bacterial and viral origins in lower respiratory tract infection (the specificity was 94% and the sensitivity was 79%) and could help guide the use of antibiotics, but more rapid techniques, available in a matter of hours, are required.

Acute Disease↗

Multicenter evaluating of a commercially available PCR assay for diagnosing enterovirus infection in a panel of cerebrospinal fluid specimens.

Thirteen laboratories participated in blind tests of a panel of 20 coded cerebrospinal fluid specimens (7 uninfected samples, 3 samples infected with 1 50% tissue culture infective dose [TCID50]/0.1 ml [nonenterovirus strains], and 10 samples infected with 10, 1, or 0.1 TCID50/0.1 ml [three different enterovirus serotypes]) on the Amplicor enterovirus PCR assay (Roche Diagnostic Systems). The panel was also evaluated by in-house PCR (two nested-PCR and three one-step PCR assay) or tissue culture (eight laboratories). The viral load was shown to influence greatly the sensitivity of the assay. The average sensitivity of the Amplicor test ranged from 67 to 98% for viral titers of 1 to 10 TCID50/0.1 ml, respectively; titers of 0.1 TCID50/0.1 ml resulted in a sensitivity of only 16%. The overall specificity of the Amplicor test was 98%. The Amplicor assay compared favorably to the five in-house PCR tests (no significant difference in either sensitivity or specificity) and was much more sensitive than tissue culture (P < 0.001), even for high viral loads. It was easy to perform, rapid (about 6 h), well-standardized, and appeared to be suitable for the diagnosis of enterovirus meningitis on a routine basis in laboratories trained in molecular biology techniques.

Base Sequence↗

Analysis of herpes simplex virus type 1 glycoprotein D nucleotide sequence in human herpes simplex encephalitis.

Viral factors responsible for HSV neurovirulence in humans are still unknown. The aim of this work was to investigate the hypothesis that viral variants might contribute to the specific neurovirulence of some HSV strains. HSV-1 DNA was recovered from cerebrospinal fluid (CSF) in ten patients with HSV encephalitis (HSE) and the regions of HSV-1 gD gene corresponding to known antigenic sites were analyzed by direct sequencing of PCR products. Twenty-two mutations were found among a total of 6580 bp analyzed over a portion of 1000 bp of gD gene, of which 20 were silent whereas two conferred amino acid substitution. One missense mutation (E117D) was found in two CSF samples as well as in two control laboratory strains. The other one (A269T) was found in a single CSF sample, and lies within a region corresponding to a functionally essential antigenic site. These are the first mutations of the gene encoding gD of HSV identified in vivo in human encephalitis samples. Overall, the results argue against the role of gD in neurovirulence in humans.

Adolescent↗

The acute promyelocytic leukaemia-associated PML gene is induced by interferon.

The PML protein concentrates within discrete nuclear structures known as nuclear bodies, also called NDs or PODs, which contain several proteins including the interferon (IFN)-inducible SP100 product. The function of these structures remains elusive. We and others have shown recently that they represent specific targets for adenovirus and herpes simplex virus. This prompted us to investigate whether PML, like SP100, might be induced by IFN and to explore the role of PML in viral infection. Here we report that PML mRNA levels increase rapidly in response to interferon treatment. This accumulation of PML transcripts is a primary IFN response since it does not require de novo protein synthesis. The IFN-induced activation of the PML gene is accompanied by enhanced protein expression as revealed by immunolabelling. Both the intensity of the staining and the number of labelled structures increased upon interferon exposure. To probe the role of PML in IFN action, we compared the antiviral state established by alpha-interferon in embryonic fibroblasts (EFs) derived from null mutant mice for PML and from wild-type control mice. The resistance to viral infection conferred by IFN-alpha was identical in both PML+/+ and PMLm/m fibroblasts indicating that PML is not an essential mediator of the antiviral effect of interferon. We also noted that DNA-binding factors are normally activated by IFN in PMLm/m cells.

Base Sequence↗

Activity of the interferon-induced 2',5'-oligoadenylate synthetase in patients with chronic hepatitis C.

The interferon-induced 2',5'-oligoadenylate synthetase (2-5OAS) is responsible, at least in part, for the antiviral state established in cells in response to viral infections. The purpose of this work was to study the relationship between hepatitis C virus (HCV) infection and 2-5OAS in patients with chronic hepatitis C. Peripheral blood mononuclear cells (PBMC) of 27 patients with chronic hepatitis C were investigated, as well as PBMC of 10 control subjects. Then, the patients were treated with 3 mu interferon-alpha 2a three times per week. At month 3 of therapy, PBMC were sampled. Of the total PBMC samples obtained, half were used for determination of in vivo 2-5OAS activity. The remaining cells were cultured for 24 h in either the absence or presence of 500 U/ml of interferon-alpha 2a for the determination of in vitro 2-5OAS activity. The mean basal in vivo 2-5OAS activities were 3.6 +/- 2.8 nmol/10(6) cells in patients versus 1.6 +/- 1.1 nmol/10(6) cells in controls (p < 0.01). Basal in vivo 2-5OAS activity did not correlate with mean HCV viremia, quantified by a "branched DNA"-based assay. Before treatment, interferon-alpha was detected in the serum of 2 patients in 27. After a 24 h culture of PBMC in the presence of interferon, in vitro 2-5OAS activity was significantly induced in the PBMC of both the patients and the controls. However, in vitro induction of 2-5OAS activity was significantly lower in the PBMC of the patients than in the PBMC of the controls (p < 0.01). At month 3 therapy, in vivo 2-5OAS activity was significantly induced (20.5 +/- 17.9; p < 0.0001). In vitro IFN inductions of 2-5OAS activity in PBMC before treatment and at month 3 of therapy were not significantly different. In conclusion, in vivo 2-5OAS activity is significantly induced in patients with chronic hepatitis C, but endogenously produced interferon-alpha does not seem to be involved. Chronic induction of 2-5OAS activity results in a decreased sensitivity of PBMC to exogenous interferon induction. Whether this phenomenon plays a role in the resistance of chronic hepatitis C to interferon therapy remains uncertain.

2',5'-Oligoadenylate Synthetase↗

Relapse of herpes simplex encephalitis.

We report five children who had recurrent central nervous system signs after conventional acyclovir therapy for herpes simplex encephalitis. Secondary exacerbation was characterized clinically by severe ballismic movement disorder in all five children, associated with fever, impairment of consciousness, and seizures. Biologic analysis in all children and magnetic resonance imaging and neuropathology studies of the brain in three cases were compatible with inflammatory reaction. In contrast, all viral cultures remained negative, herpes simplex virus antigen in one child and DNA tested by polymerase chain reaction in four children were undetectable in the first samples of cerebrospinal fluid during the relapse, suggesting a postinfectious, immune-mediated mechanism of relapse in these patients.

Acyclovir↗

[Extra-capillary proliferation complicating the development of an extramembranous idiopathic glomerulonephritis].

Occurrence of crescentic formation superimposed to idiopathic membranous glomerulopathy worsens severely its prognosis with evolution to end stage renal disease. We report the case of a 65 years old man with nephrotic idiopathic membranous glomerulopathy who subsequently developed an acute renal failure secondary to crescentic formation. Pulse of high dose methylprednisolone administration improved renal function. Seven similar observations are analysed and pathogenic mechanisms discussed.

Acute Kidney Injury↗

[Presentation of an acute and painful giant, necrotic ileal leiomyoma].

We report on a case of giant necrotic ileal leiomyoma presenting uncommonly as a painful pelvic mass mimicking a sigmoid inflammatory process. The classical symptoms and clinical aspects of intestinal leiomyoma are briefly summarized. The CT and US aspects are described with peculiar attention to color Doppler which played an important role in the diagnosis of our patient.

Acute Disease↗

[Development of interferon antibodies during the treatment of skin diseases with low-dose recombinant interferon alpha-2a].

In this study, we determined the frequency of interferon antibodies in patients with skin diseases treated with low doses of recombinant interferon alpha 2a (1.5 - 18 x 10(6) IU). We assayed serum specimens from 181 patients with malignant melanoma or cutaneous T cell lymphomas (78 patients treated with recombinant interferon alpha 2a and 103 patients in control group) for interferon antibodies before treatment and every 6 months for at least 18 months. Neutralizing interferon alpha 2a antibodies were detected in 27 of 77 treated patients (35%), but none in control group (p < 10(-6)): 38.2% in melanoma and 12.5% in T cell lymphomas. However antibody formation was not correlated with nonresponse or with frequency of interferon antibodies in patients receiving the combined therapy: interleukin-2 and interferon alpha 2a.

Adult↗

[Prenatal diagnosis of fetal varicella in the second trimester of pregnancy].

The first case of prenatal diagnosis of congenital varicella by amniotic fluid viral culture and PCR is reported. Chickenpox is a benign disease in children, but it can lead to severe complications in the adult, especially in the pregnant woman. Five percent of women in childbearing age are not immunised, and the incidence of gestational chickenpox is between 1 and 7 per 10,000. The consequences of this primary infection during pregnancy can be severe for the mother, because of the risk of serious varicella pneumonia, and for the fetus. The fetal infection depends on the gestational age at which the maternal infection occurs. The 2% evaluated risk of fetopathy is maximal between the 7th and 20th week of amenorrhoea. The reported congenital abnormalities are essentially cutaneous, neurological, ophthalmological and musculo-squeletal lesions. A prenatal diagnosis can be suggested: the revelation of defects by ultrasound scan confirms the fetal affection, and can justify pregnancy termination; on the other hand, amniocentesis and cordocentesis are not totally safe, and cannot always assert the fetal contamination or its level of affection. From the therapeutical point of view, prevention with polyvalent gamma-globulin is prescribed to non-immunised pregnant women who have been in contact with the virus. On the opposite, in case of contracted chickenpox, the treatment of the mother with an association of polyvalent gamma-globulin and acyclovir is still controversial since, although probably effective, it may not be safe for the fetus. The solution may reside in the vaccination, soon available, of non-immunised women in childbearing age.

Acyclovir↗

Detection of enteroviruses in cerebrospinal fluids: enzymatic amplification and hybridization with a biotinylated riboprobe.

Cerebrospinal fluids from 54 children with meningitis syndrome were examined for the presence of enteroviruses by cell culture, by enzymatic amplification of viral cDNA and by hybridization. Viral sequences were found in 37/39 CSF specimens positive by cell culture (95%) and in 6/15 (40%) CSF specimens negative by cell culture. Thus, PCR, as a specific and sensitive technique, may be suitable for rapid diagnosis of enteroviral meningitis in clinical specimens from which enteroviruses are difficult to isolate.

Base Sequence↗

Varicella zoster virus infection during pregnancy: the limits of prenatal diagnosis.

In a mother with clinical evidence of chicken-pox at 12.5 weeks, fetal herpes varicella zoster infection was revealed by transient fetal ascites with liver calcifications at 27 weeks routine ultrasound. At 27 and 35 weeks fetal blood sampling and amniocentesis failed to demonstrate fetal viral infection. However, the diagnosis was confirmed postnatally based on thoracic herpes zoster at 8 months in an otherwise healthy infant. Polymerase chain reaction (PCR) on stored amniotic cells performed retrospectively was positive for varicella zoster virus (HVZV). This observation suggests that (1) in contrast to PCR, conventional fetal biology lacks sensitivity for prenatal diagnosis of HVZV infection, (2) the association of fetal sonographic abnormalities and positive amniotic PCR can be associated with a favorable pediatric outcome. Therefore, prenatal diagnosis of HVZV infection should be considered with the greatest caution.

Adult↗