Unusual cause of dyspnea: Cardiac fusiform cells carcinoma.

This manuscript illustrates an unusual cause of dyspnea. Cardiac tumor are uncommon, especially fusiform cells carcinoma.

Markers of a recent bocavirus infection in children with Kawasaki disease: "a year prospective study".

BACKGROUND: Retrospective studies and case-reports have suggested the possible role of various viruses in the pathogenesis of the Kawasaki disease. OBJECTIVES: To determine prospectively the incidence of Kawasaki diseases associated with a recent bocavirus infection in the course of a year. STUDY DESIGN: Thirty-two children with Kawasaki disease were enrolled in a 13 months prospective study to assess the frequency of human bocavirus type 1 infections. Seasonal shedding of virus, markers of recent infection such as viraemia, viral load, and serum interferon alpha were analyzed. RESULTS: Three of 32 (9%) children had HBoV-DNA in the serum suggesting a recent infection. HBoV-DNA was detected in naso-pharyngeal aspiration of 7/32 (21.8%) children with Kawasaki Disease and six of them (18%) had an increased viral load. No common respiratory viruses were isolated from the 32 patients with the exception of one adenovirus. The seven bocaviruses were identified during the winter-spring season. In addition, 4 of 7 of Kawasaki disease patients shedding bocavirus had detectable interferon alpha in the blood, indicating a possible active or recent viral infection. CONCLUSIONS: This study shows that a recent bocavirus infection is concomitant with the onset of some cases of Kawasaki disease. Bocavirus may be a cofactor in the pathogenesis of this disease as previously reported for other infectious agents.

Low immunogenicity of seasonal trivalent influenza vaccine among patients receiving docetaxel for a solid tumour: results of a prospective pilot study.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Epidemiology and clinical features of gastroenteritis in hospitalised children: prospective survey during a 2-year period in a Parisian hospital, France.

Rotavirus is recognised as the most important agent of severe acute gastroenteritis (AGE) in young children. In a 2-year prospective survey, we investigated the epidemiology and clinical features of the viral and bacterial pathogens in children hospitalised for AGE. The study was performed in a Parisian teaching hospital from November 2001 to May 2004. Clinical data were prospectively collected to assess the gastroenteritis severity (20-point Vesikari severity score, the need for intravenous rehydration, duration of hospitalisation). Stools were systematically tested for group A rotavirus, norovirus, astrovirus and adenovirus 40/41, sapovirus and Aichi virus and enteropathogenic bacteria. A total of 457 children (mean age 15.9 months) were enrolled. Viruses were detected in 305 cases (66.7%) and bacteria in 31 cases (6.8%). Rotaviruses were the most frequent pathogen (48.8%), followed by noroviruses (8.3%) and adenoviruses, astroviruses, Aichi viruses and sapoviruses in 3.5%, 1.5%, 0.9% and 0.4%, respectively. Cases of rotavirus gastroenteritis were significantly more severe than those of norovirus with respect to the Vesikari score, duration of hospitalisation and the need for intravenous rehydration. Rotaviruses were the most frequent and most severe cause in children hospitalised for AGE, and noroviruses also account for a large number of cases in this population.

Chilblains as a diagnostic sign of aicardi-goutières syndrome.

Aicardi-Goutières syndrome (AGS) is a genetically heterogeneous disorder showing variability in age of onset and clinical features. Chilblain lesions have been described in AGS patients and recent papers have discussed the clinical, molecular and cutaneous histopathological overlap with chilblain lupus. Here we report on 2 unrelated children with AGS and chilblain lesions, whose clinical histories and examination findings well illustrate the wide phenotypic variability that can be seen in this pleiotropic disorder. Although both patients show remarkable similarity in the histopathology of their associated skin lesions, with thrombi formation, fat necrosis and hyalinization of the subcutaneous tissue, we note that the histopathology reported in other AGS cases with chilblains does not necessarily demonstrate this same uniformity. Our findings highlight the significant role of the characteristic chilblain skin lesions in the diagnosis of AGS, and variability in the associated histopathology which may relate to the stage and severity of the disease.

[Polyomavirus newly discovered]. / Virus Polyoma nouvellement découverts.

Three new polyoma viruses have been recently identified; two of them, the KI et WU viruses are present in nasopharyngeal aspirates during the course of acute respiratory infections. The incidence of these viruses is low compared to other respiratory viruses and the disease has not shown a high severity of clinical signs. The physiopathology of the diseases and the mode of cultivation of these viruses remain unknown. The third virus was discovered from cutaneous biopsies of Merkel tumours with a higher incidence than in tissue from healthy patients. Its mode of transmission and its role in the cancerogenesis need more studies. However, as the virus can integrate into the cellular DNA, it signifies that the virus may have a role in various human tumors.

Two further cases of spondyloenchondrodysplasia (SPENCD) with immune dysregulation.

Although the diagnosis of spondyloenchondrodysplasia (SPENCD) can only be made in the presence of characteristic metaphyseal and vertebral lesions, a recent report has highlighted the pleiotropic manifestations of this disorder which include significant neurological involvement and variable immune dysfunction. Here we present two patients, one of whom was born to consanguineous parents, further illustrating the remarkable clinical spectrum of this disease. Although both patients demonstrated intracranial calcification, they were discordant for the presence of mental retardation, spasticity and white matter abnormalities. And whilst one patient had features consistent with diagnoses of Sjögren syndrome, polymyositis, hypothyroidism and severe scleroderma, the other patient had clinical manifestations and an autoantibody profile of systemic lupus erythematosus. These cases further illustrate the association of SPENCD with immune dysregulation and highlight the differential diagnosis with Aicardi-Goutières syndrome and other disorders associated with the presence of intracranial calcification. Undoubtedly, identification of the underlying molecular and pathological basis of SPENCD will provide important insights into immune and skeletal regulation.

[Different human cytomegalovirus glycoprotein B (gB) genotype distribution]. / Distribution de différents génotypes de la glycoprotéine B (gB) du cytomégalovirus humain.

The glycoprotein B (gB) is the major glycoprotein of the envelope of the human cytomegalovirus, it is encoded by UL55 open reading frame, implicated in host cell, entry cell to cell virus transmission and fusion of infected cells and a significant is an important target for immuno-reactions humoral and cellular. A prospective analysis of cytomegalovirus glycoprotein B genotype was conducted on 31 immunodepressed (transplant recipients and AIDS patients). The DNA was extracted directly from the bronchoalveolar liquid (BAL) of these patients. The gB genotypes of CMV was determined by using the polymerase chain reaction, followed by the digestion of two enzymes of restriction HinfI and RsaI. The distribution of the gB genotype of the CMV was: gB1 38,70%; gB2 25,80%; gB3 16,12% and gB4 19,35%. The analysis of the peptide sequence of this region (codons 437-520), indicate the variation was more frequent between codons 448-480.

Single-stranded RNA viruses inactivate the transcriptional activity of p53 but induce NOXA-dependent apoptosis via post-translational modifications of IRF-1, IRF-3 and CREB.

To characterize the mechanisms underlying apoptosis induced by viral infection, transcriptional activation of genes encoding members of the 'BH3-only' family of proteins was analysed during the course of virus infection. Among these genes, only NOXA is transcriptionally activated by vesicular stomatitis virus (VSV), sendai virus (SV), measles virus, herpes simplex virus, or dsRNA and required for efficient apoptosis of cells. Transcriptional activation of NOXA by VSV or SV is independent of p53, but requires the presence of interferon regulatory factor 1 (IRF-1), IRF-3 and cAMP-responsive element binding protein (CREB). Binding to and transactivation of the NOXA promoter by each of these transcription factors is governed by post-translational modification involving different pathways for each factor. Thus, SV infection activates IRF-3 and CREB by phosphorylation triggered by Toll like receptor 3 signalling, and a pathway involving calcium-independent phopholipase A2, respectively. In addition transactivation induced by IRF-1 during viral infection correlates with a 10 kDa increase in its molecular weight, suggesting a covalent linkage with a previously unknown regulatory polypeptide.

A second locus for Aicardi-Goutieres syndrome at chromosome 13q14-21.

BACKGROUND: 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 alpha metabolism. The disorder is genetically heterogeneous with approximately 50% of families mapping to the first known locus at 3p21 (AGS1). METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

The natural history of Aicardi-Goutières syndrome: follow-up of 11 Italian patients.

Described are the outcomes of 11 Italian patients with Aicardi-Goutières syndrome. Neurologic symptoms progressed in the first year of life and stabilized by the end of the second year in 10 patients. White matter abnormalities remained stable; cerebral atrophy was stable in four patients and progressive in two. Calcifications increased (in number and size) in two of six patients. Serial CSF and serum interferon-alpha measurements (three patients) showed reduced CSF interferon-alpha levels.

Cerebral thrombotic microangiopathy and antiphospholipid antibodies in Aicardi-Goutieres syndrome--report of two sisters.

Cerebral thrombotic microangiopathy was found at autopsy in one of two sisters with Aicardi-Goutieres syndrome, whereas the other revealed increased serum levels of anticardiolipin IgG antibodies (measured only in the living sister); both typical features of systemic lupus erythematosus. These findings add support to the suggestion that Aicardi-Goutieres syndrome and systemic lupus erythematosus are closely related disorders in which dysregulated production of interferon-alpha might play a crucial role.

[Community acquired pneumonia and influenza in children]. / Pneumonies communautaires et infection grippale.

UNLABELLED: Children without chronic or serious medical conditions are at increased risk for hospitalization during influenza seasons, mainly with respiratory tract infections. But influenza virus infections frequently remain undiagnosed, even in hospitalized patients. We prospectively studied the rate of concomitant and preceding influenza infections in children hospitalized with a community acquired pneumonia (CAP). POPULATION AND METHODS: All 1-15-year-old children with CAP requiring hospitalization between 1st April 2000 and 2002 had nasopharyngeal aspirate for viruses, immunofluorescence and serologies for respiratory pathogens. The peak of influenza IgG measured by complement fixation (CF) is transient, and a titer of 1/64 or more indicates an acute influenza infection in the preceding weeks. Children with chronic disease were excluded and a control group of patients from outpatient clinic was measured. RESULTS: Among 33 previously healthy children (age 4.9 years, range 1.2-14 years), 8 had a pneumococcal pneumonia, 10 a pneumonia caused by Mycoplasma pneumoniae (MP), 1 by Chlamydia pneumonia, and 8 of unknown origin. In six patients immunofluorescence was positive: Respiratory Syncitial Virus, 2, Adenovirus, 1 and Influenza A, 3 (including a patient with concomitant MP infection). Thirteen of the 33 children (39.4%) had evidence of a recent influenza A infection with CF ab > or = 1/64: with pneumococcal pneumonia, 5/10 with MP pneumonia, 3/8 with unknown origin pneumonia, 9/13 of these previous influenza infections being clinically inapparent. Only 1/30 children of control group (3.3%) had CF ab > or = 1/64. CONCLUSION: In this study, influenza infection is the direct cause of CAP of children in 12% of cases. In other children with CAP, 39.4% of patients had an influenza infection in the preceding weeks which leads to secondary infection caused by Streptococcus pneumoniae or by MP or other pathogens.

Cree encephalitis is allelic with Aicardi-Goutiéres syndrome: implications for the pathogenesis of disorders of interferon alpha metabolism.

Aicardi-Goutiéres syndrome (AGS) is an early onset, progressive encephalopathy characterised by calcification of the basal ganglia, white matter abnormalities, and a chronic cerebrospinal fluid (CSF) lymphocytosis. Cree encephalitis shows phenotypic overlap with AGS although the conditions have been considered distinct because of immunological abnormalities observed in Cree encephalitis. We report that levels of interferon alpha (IFN-alpha), a marker of AGS, are raised in Cree encephalitis. Moreover, linkage analysis indicates that the disorders are allelic and refines the AGS1 locus to a 3.47 cM critical interval. Our data show that a CSF lymphocytosis is not necessary for the diagnosis of AGS and strongly suggest that AGS and pseudo-TORCH syndrome are the same disorder. Recognition of immunological dysfunction as part of the AGS phenotype provides further evidence of a primary pathogenic role for abnormal IFN-alpha production in AGS.

[Diarlex LA and Diarlex MB: study for direct detection of rotaviruses and adenoviruses in stools]. / Etude des réactifs Diarlex LA et Diarlex MB pour la détection directe des rotavirus et des adénovirus dans les selles.

Gastro-enteritis have an important frequency in clinician consultation especially in pediatric department. Viral responsible for these diseases are, in most cases rotaviruses and adenoviruses. From the use of electronic microscopy, the identification of these viruses has advanced : Elisa methods are now usually used in that area. More recently, easier methods using sensitized latex particles (Diarlex LA Orion Diagnostica) and immunochromatography (Diarlex MB , Orion Diagnostica) appeared and,in that study, their accuracy is compared to the electronic microscopy (for Adenoviruses) and Elisa method IDEIA Rotavirus trade mark (Dako) (for rotaviruses). Reliability, easy use, immediate results and moderate cost may assure to these new tests a leader place in all kinds of clinical laboratories.

Plasma exchange and interferon-alpha pharmacokinetics in patients with hepatitis C virus-associated systemic vasculitis.

UNLABELLED: Different types of vasculitis have been reported in association with hepatitis C virus (HCV) infection, i.e. type II mixed cryoglobulinemia and polyarteritis nodosa (PAN). Therapeutic approach of such severely symptomatic patients include interferon-alpha (IFN) plus plasma exchange (PE). There are no data on IFN pharmacokinetic changes related to PE. PATIENTS AND METHODS: We studied 7 HCV-infected patients (mean age: 57 years) presenting with symptomatic type II mixed cryoglobulinemia (n = 5) or biopsy-proven PAN (n = 2). All patients underwent subcutaneous IFN therapy with concomitant PE. Serum IFN concentration was measured in serial samples on days with and without PE. RESULTS: Without PE, IFN C(max )(range: 100-750 IU/ml) was obtained 3-6 h after subcutaneous injection, followed by a 3- to 9-hour plateau. IFN concentration declined subsequently reaching a residual concentration 24 h after injection, ranging from 20 to 40 IU/ml. PE performed 6 h after IFN administration resulted in increased IFN clearance in that the concentration-time IFN-alpha area under the curve decreased from 3,005 IU x h/ml (1,563-4,614) on days without PE to 2,142 IU x h/ml (973-4,123) on day with PE. CONCLUSIONS: In patients with HCV-associated vasculitis, PE increase IFN clearance. Combined IFN-alpha and PE therapy schedule have to be further studied to optimize its biological activity.

[Procalcitonin in pediatric emergencies: comparison with C-reactive protein, interleukin-6 and interferon alpha in the differentiation between bacterial and viral infections]. / Procalcitonine aux urgences pédiatriques. Comparaison avec la protéine C-réactive, l'interleukine-6 et l'interféron-alpha pour la différenciation des infections bactériennes et virales.

OBJECTIVE: Procalcitonin concentration increases in bacterial infections but remains low in viral infections and inflammatory diseases. The change is rapid and the molecule is stable making it a potentially useful marker for distinguishing between bacterial and viral infections. PATIENTS AND METHODS: Procalcitonin (PCT) was determined with an immunoluminometric assay on plasma collected at admission in 436 infants and children hospitalized for bacterial or viral infection. It was compared with C reactive protein, interleukin-6 and interferon-alpha measured on the same sample. RESULTS: PCT was 41.3 +/- 77.4 micrograms/l in children with septicemia or bacterial meningitis (n = 53), 0.39 +/- 0.57 microgram/l in children with viral infection (n = 274) and 3.9 +/- 5.9 micrograms/l in children with a localized bacterial infection who had a negative blood culture (n = 109). PCT was > 1 microgram/l in 126 children with a localized or systemic bacterial infection (sensitivity 78%). PCT was < 1 microgram/l in 258 children with a viral infection (specificity 94%). For differenciation between viral and bacterial infections, CRP value > or = 20 mg/l, IL-6 > 100 pg/ml and interferon-alpha > 0 Ul/ml have 85, 48 and 76% sensitivity and 73, 85 and 92% specificity respectively. CONCLUSIONS: In this study, a PCT value of 1 microgram/l or greater had better specificity, sensitivity and predictive value than CRP, IL-6 and interferon-alpha in children for distinguishing between viral and bacterial infections. PCT may be useful in pediatric emergency room for making decision about antibiotic treatments.

Inhibition of interferon-inducible MxA protein expression by hepatitis B virus capsid protein.

Chronic hepatitis B treatment has been significantly improved by interferon (IFN) treatment. However, some studies have suggested that hepatitis B virus (HBV) might have a direct effect on the resistance to IFN. Defective particles, generated by spliced HBV RNA and associated with chronic hepatitis B, have been previously characterized; expression of these particles leads to cytoplasmic accumulation of the capsid protein. The aim of this study was to investigate the role of these defective genomes in IFN resistance. The global antiviral activity of IFN was studied by virus yield reduction assays, the expression of three IFN-induced antiviral proteins was analysed by Western blotting and confocal microscopy, and the regulation of MxA gene expression was studied by Northern blotting and the luciferase assay, in Huh7 cells transfected with a complete or the defective HBV genome. Results showed that the expression of the defective genome reduces the antiviral activity of IFN and that this modulation involves a selective inhibition of MxA protein induction by the HBV capsid protein. Our results also show the trans-suppressive effect of the HBV capsid on the MxA promoter, which might participate in this phenomenon. In conclusion, this study shows a direct interplay between the IFN-sensitive pathway and the capsid protein and might implicate this defective HBV genome in virus persistence.