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1.  Low immunogenicity of seasonal trivalent influenza vaccine among patients receiving docetaxel for a solid tumour: results of a prospective pilot study 
British Journal of Cancer  2011;104(11):1670-1674.
Patients receiving cytotoxic therapy for solid tumours are at risk of severe influenza. However, few data are available regarding the immunogenical efficacy of influenza vaccine in these patients.
In this prospective study, 25 patients with breast (n=13) or prostate (n=12) cancer received a trivalent inactivated influenza vaccine along with docetaxel (Taxotere) administration. The influenza virus type A and B antibody titres were measured using haemagglutinin inhibition (Garten et al, 2009) before and 21 days after the vaccination. Seroconversion rate was defined as the percentage of patients with an increase in the serum titres ⩾4 after vaccination.
Median age was 65 years (range: 33–87 years); 52% were females. Seroconversion rates were low: 28% (95% CI: 23.1–33.3) for H1N1, 8% (95% CI: 7.7–8.3) for H3N2 and 16% (95% CI: 7.7–25) for the B strain. The geometric mean titres ratios were 2.16 (H1N1), 1.3 (H3N2) and 1.58 (B). No serious adverse event (AE) related to the vaccine was reported. All the reported AE were from mild-to-moderate intensity.
In the patients receiving docetaxel for solid tumours, influenza vaccine triggers an immune response in only one third. Strategies using more immunogenic influenza vaccines must be evaluated in such patients.
PMCID: PMC3111157  PMID: 21540859
influenza; vaccine; chemotherapy
2.  A second locus for Aicardi‐Goutières syndrome at chromosome 13q14–21 
Journal of Medical Genetics  2005;43(5):444-450.
Aicardi‐Goutières syndrome (AGS) is an autosomal recessive, early onset encephalopathy characterised by calcification of the basal ganglia, chronic cerebrospinal fluid lymphocytosis, and negative serological investigations for common prenatal infections. AGS may result from a perturbation of interferon α metabolism. The disorder is genetically heterogeneous with approximately 50% of families mapping to the first known locus at 3p21 (AGS1).
A genome‐wide scan was performed in 10 families with a clinical diagnosis of AGS in whom linkage to AGS1 had been excluded. Higher density genotyping in regions of interest was also undertaken using the 10 mapping pedigrees and seven additional AGS families.
Our results demonstrate significant linkage to a second AGS locus (AGS2) at chromosome 13q14–21 with a maximum multipoint heterogeneity logarithm of the odds (LOD) score of 5.75 at D13S768. The AGS2 locus lies within a 4.7 cM region as defined by a 1 LOD‐unit support interval.
We have identified a second AGS disease locus and at least one further locus. As in a number of other conditions, genetic heterogeneity represents a significant obstacle to gene identification in AGS. The localisation of AGS2 represents an important step in this process.
PMCID: PMC2649012  PMID: 15908569
AGS2; Aicardi‐Goutières syndrome; interferon α; intracranial calcification; 13q14–21
3.  Prevalence and Genetic Diversity of Aichi Virus Strains in Stool Samples from Community and Hospitalized Patients▿  
Journal of Clinical Microbiology  2008;46(4):1252-1258.
Aichi virus has been proposed as a causative agent of gastroenteritis. A total of 457 stool specimens from children hospitalized with acute diarrhea and 566 stool specimens from adults and children involved in 110 gastroenteritis outbreaks were screened for the presence of Aichi virus by reverse transcription-PCR (RT-PCR) amplification of the genomic region of the 3C and 3D (3CD) nonstructural proteins. Our results show a low incidence of Aichi virus in pediatric samples and the existence of mixed infections with other microbiological agents in some cases. From the outbreak survey, it appears that the presence of Aichi virus is an indicator of mixed infections causing gastroenteritis outbreaks and that it could be involved in half of the oyster-associated outbreaks. A second RT-PCR was developed to amplify a part of the VP1 gene. The phylogenetic analysis showed a good correlation between the two classifications based on 3CD and VP1 gene sequences and revealed the prevalence of genotype A in France. It also allowed us to partially describe an Aichi virus strain that could represent a new genotype, thus suggesting the existence of a certain diversity.
PMCID: PMC2292896  PMID: 18256215
5.  Real-Time PCR Quantification of Human Cytomegalovirus DNA in Amniotic Fluid Samples from Mothers with Primary Infection 
Journal of Clinical Microbiology  2002;40(5):1767-1772.
A real-time PCR assay was developed to quantify human cytomegalovirus (HCMV) DNA in amniotic fluid (AF) samples collected from 30 pregnant women with primary HCMV infection as detected either from HCMV-immunoglobulin G (IgG) seroconversion or by the presence of HCMV-specific IgG and IgM associated with a low IgG avidity. Clinical information available for each case included ultrasonographic examination and fetal or newborn outcome. HCMV infection of fetuses or newborns was confirmed for the 30 studied cases. AF samples were subdivided into three groups. In group A (n = 13), fetuses presented major ultrasound abnormalities, and pregnancy was terminated. In group B (n = 13), fetuses had normal ultrasound findings, the pregnancy went to term, and the newborns were asymptomatic at birth. In group C (n = 4), fetuses had no or minor ultrasonographic signs, and pregnancy was terminated. The HCMV DNA load values in AF samples were significantly higher in group A (median, 2.8 × 105 genome equivalents [GE]/ml) than in group B (median, 8 × 103 GE/ml) (P = 0.014). Our findings suggest that HCMV load level in AF samples correlates with fetal clinical outcome but might also be dependent on other factors, such as the gestational age at the time of AF sampling and the time elapsed since maternal infection.
PMCID: PMC130652  PMID: 11980958
7.  Multicenter Evaluation of the Amplicor Enterovirus PCR Test with Cerebrospinal Fluid from Patients with Aseptic Meningitis 
Journal of Clinical Microbiology  1998;36(9):2652-2657.
The Amplicor Enterovirus PCR test was compared with viral culture for the detection of enteroviruses in cerebrospinal fluid (CSF) specimens. In a multicenter study in which nine laboratories participated, a total of 476 CSF specimens were collected from patients with suspected aseptic meningitis. Sixty-eight samples were positive by PCR (14.4%), whereas 49 samples were positive by culture (10.4%), demonstrating that the Amplicor Enterovirus PCR test was significantly more sensitive than culture (P < 0.001). After discrepancy analysis the sensitivity and specificity of the Amplicor Enterovirus PCR test obtained by using viral culture as the “gold standard” were 85.7 and 93.9%, respectively. Our results with the CSF specimens collected in different countries demonstrate that the Amplicor test is capable of detecting a large variety of enterovirus serotypes and epidemiologically unrelated isolates in CSF specimens from patients with aseptic meningitis. The Amplicor Enterovirus PCR test is a rapid assay which can be routinely performed with CSF samples and is an important improvement for the rapid diagnosis of enteroviral meningitis.
PMCID: PMC105179  PMID: 9705409
8.  GEMHEP multicenter quality control study of PCR detection of GB virus C/hepatitis G virus RNA in serum. 
Journal of Clinical Microbiology  1997;35(12):3298-3300.
PCR is, to date, the only available tool for the detection of GB virus C (GBV-C) and hepatitis G virus (HGV) RNAs. Twenty-two French laboratories participated in a quality control study to assess the sensitivity and specificity of their procedures. The panel included 13 positive controls and 7 negative controls. The laboratories used either in-house PCR techniques adapted from the literature or partly standardized commercial tests. Three laboratories performed faultlessly with the entire panel. Most laboratories had excellent specificity (100% in 20 of 22 laboratories). Sensitivity was acceptable (85 to 100%) in 15 centers and insufficient (38 to 77%) in 7. As with nonstandardized in-house PCR, the commercial assays gave discrepant performances in different laboratories. These results suggest that laboratories willing to use PCR for detection of GBV-C/HGV RNA for research or diagnostic purposes should participate in multicenter quality control trials.
PMCID: PMC230166  PMID: 9399538
9.  Multicenter evaluating of a commercially available PCR assay for diagnosing enterovirus infection in a panel of cerebrospinal fluid specimens. 
Journal of Clinical Microbiology  1996;34(12):3002-3006.
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.
PMCID: PMC229449  PMID: 8940438
10.  Amplification and characterization of herpesvirus DNA in cerebrospinal fluid from patients with acute encephalitis. 
Journal of Clinical Microbiology  1991;29(11):2412-2417.
A single pair of oligonucleotide primers selected within a highly conserved region of the DNA polymerase gene of the herpesviruses was designed to amplify related viral genomes, i.e., herpes simplex virus type 1, herpes simplex virus type 2, Epstein-Barr virus, and cytomegalovirus, by the polymerase chain reaction. A simple restriction enzyme analysis of these amplified products allowed accurate characterization of the herpesvirus type. Ninety-nine cerebrospinal fluid samples from 36 patients (including newborns, children, and adults) with acute encephalitis were tested for the presence and identification of herpesvirus DNA by this approach. High levels of viral DNA, which were readily visualized by simple ethidium bromide staining, were found in all these patients from the first days of the disease and, in some cases, until the third week following the onset of acute encephalitis. The herpesvirus type was rapidly identified by enzymatic digestion in 33 patients' samples and by hybridization and direct sequencing in the last 3 patients' samples. Our results show that the polymerase chain reaction provides a highly sensitive and specific technique for the identification of herpesviruses DNA in cerebrospinal fluid that should be of value for early and rapid diagnosis, therapeutic decisions, prognostic evaluation, and epidemiological studies.
PMCID: PMC270348  PMID: 1663508
11.  Presence of gamma interferon in human acute and congenital toxoplasmosis. 
Journal of Clinical Microbiology  1990;28(6):1434-1437.
The production of gamma interferon in acute acquired and congenital toxoplasmosis was studied. Gamma interferon was produced at significant titers (P less than 0.001) in the course of both congenital toxoplasmosis and acquired toxoplasmosis at an early stage of infection, when Toxoplasma gondii was multiplying. Its presence in fetal blood was correlated with the positive inoculation of fetal blood or amniotic fluid into mice (95%). The data suggest that the fetus is able to synthesize gamma interferon as early as week 21 of pregnancy. This test, easily and rapidly performed, could be included among those useful for diagnosing fetal toxoplasmic disease.
PMCID: PMC267947  PMID: 2116447
12.  Interferon γ in acute and subacute encephalitis 
Intrathecal synthesis of interferon γ was shown in 14 out of 16 samples of cerebrospinal fluid collected in the first days of disease in adults, children, and newborn infants with herpes encephalitis. This synthesis was concomitant with that of interferon α and was switched off when the specific antibodies in the central nervous system increased. No endogenous interferon γ was detected in 11 serum samples or 13 samples of cerebrospinal fluid collected early in the course of the disease from patients with measles encephalitis and rubella encephalitis, or in serum and cerebrospinal fluid samples from seven patients with subacute sclerosing panencephalitis. In serum collected after the 10th day after the onset of neurological symptoms interferon γ was present at low concentrations in only three out of 11 serum specimens from patients with measles encephalitis or rubella encephalitis.
Interferon γ was present in patients with acute herpes encephalitis and there was active virus replication, but it was not present in postinfectious encephalitis. Possibly the local production of specific antibodies masks the viral antigens and switches off the induction of interferons.
PMCID: PMC2544642  PMID: 2827836
13.  Subacute sclerosing panencephalitis: detection of measles virus RNA in appendix lymphoid tissue before clinical signs. 
An appendix removed 15 days before onset of symptoms of subacute sclerosing panencephalitis was examined retrospectively for measles virus ribonucleic acid (RNA). Tissue sections hybridised in situ to a cloned measles virus probe of deoxyribonucleic acid specific for nucleocapsid protein showed that many cells of the lymphoid tissue contained measles virus RNA. In contrast, only a few infected lymphoid cells were detected in three out of six seropositive controls and none in three seronegative infants. A widespread chronic viral infection of the immune system, established after measles, may promote or even initiate nerve cell infection in subacute sclerosing panencephalitis.
PMCID: PMC1341304  PMID: 3092900
14.  Presence of an acid-labile alpha-interferon in sera from fetuses and children with congenital rubella. 
Journal of Clinical Microbiology  1985;21(5):775-778.
In congenital rubella an acid-labile alpha-interferon was present in sera collected from fetuses between weeks 21 and 29 of gestation and from children with active congenital rubella. This interferon was different from the interferon detected in normal amniotic fluid and was not found in sera from uninfected fetuses or from children with postnatally acquired rubella. The fetal interferon is of interest as a complementary marker to confirm the virus contamination of the fetuses during maternal rubella. The role of the prolonged synthesis of this interferon in congenital rubella disease and its immune defects are discussed.
PMCID: PMC271779  PMID: 3998109
15.  Synthesis of intrathecal interferon in systemic lupus erythematosus with neurological complications. 
Intrathecal synthesis of interferon in the absence of viral or bacterial infection was detected during the occurrence of neurological complications in two patients with systemic lupus erythematosus. The interferons displayed characteristics similar to those observed in the sera of patients with the disease. No interferon inducing activity was detected in the cerebrospinal fluid or serum of the two patients. These observations support the hypothesis of a localised mechanism of interferon induction in systemic lupus erythematosus which includes the interaction of lymphocytes with damaged tissues.
PMCID: PMC1549458  PMID: 6414612
16.  l-Arginine Elution of Measles Virus Adsorbed on Monkey Erythrocytes 
Infection and Immunity  1975;11(6):1407-1408.
l-Arginine (1 M) eluted measles virus adsorbed on monkey erythrocytes without affecting the infectious and hemagglutinating activities of the virus. This phenomenon was also observed for encephalomyocarditis virus and Newcastle disease virus.
PMCID: PMC415230  PMID: 166920
17.  Grafting for Alopecia 
British Medical Journal  1967;1(5536):367.
PMCID: PMC1840815
18.  Management of the Fat Child 
British Medical Journal  1966;2(5523):1200.
PMCID: PMC1944742
19.  Hormones and Hair 
British Medical Journal  1965;1(5440):996-997.
PMCID: PMC2165697

Results 1-19 (19)