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Biomedical subjects

R Berner

Publications and source records attributed to R Berner.

At least 19 recordsLinked to original sources

Evaluation of respiratory syncytial virus detection by rapid antigen tests in childhood.

BACKGROUND: Rapid and reliable diagnosis is crucial for clinical management of respiratory syncytial virus infection in childhood. We assessed the performance characteristics of respiratory syncytial virus antigen immunoassays in children hospitalized for respiratory infection. METHOD: A total of 1600 children up to three years of age hospitalized for diseases potentially caused by RSV were included in the study. Nasopharyngeal secretions were obtained in a standardized manner in the first 24 hours after hospital admission and tested in parallel by PCR and rapid antigen tests for RSV. The following parameters were recorded: recruitment center, gender, age, presence of fever, rhinitis, stridor, barking cough, cough, wheezing, vomiting, disturbed eating or sleep, tachypnea, tachycardia, increased body temperature, decreased oxygen saturation, C-reactive protein, erythrocyte sedimentation rate and chest X-ray results. RESULTS: Considering PCR testing as gold standard, rapid antigen testing had a specificity of 89.9% and a sensitivity of 66.2% for all samples tested. Logistic regression analysis revealed age and recruitment center as the only parameters influencing sensitivity whereas no such influence on specificity was found. Positive likelihood ratios ranged from 4,9 to 6.9 in different age groups. Negative likelihood ratio was 0.24 (95% CI: 0.18-0.42) in children aged up to 3 months but 0.67 (95% CI: 0.53-0.84) for children older than 2 years. CONCLUSION: Rapid detection of RSV antigen in this study was useful in detection of RSV mediated disease in younger infants but shows decreasing sensitivity in children older than three months.

Antigens, Viral↗

A comprehensive candidate gene study on bronchial asthma and juvenile idiopathic arthritis.

Bronchial asthma and juvenile idiopathic arthritis (JIA) are complex genetic diseases. As both represent chronic inflammatory diseases it is likely that they are at least partially influenced by the same genetic variants. One goal in dissecting the genetics of complex diseases is to identify a genetic risk profile. Therefore it is necessary to genotype polymorphisms in many different pathways. Thus we investigated 48 polymorphisms in 24 genes for association with asthma and/or JIA. Genotpying was performed on 231 asthmatic children, 86 children with JIA and 270 controls. Association analysis was performed by the Armitage's trend test. Furthermore haplotypes were calculated by FAMHAP. We found association of polymorphisms within IL-4, CTLA4 and TNFalpha with asthma and/or JIA. Furthermore, the polymorphisms showed an inverse distribution between children with asthma and JIA. However, we were not able to confirm association of most of the previously described candidate genes. We conclude from our data that it might be very difficult to identify genetic risk profiles for the development of asthma and/or JIA that would be valid across different populations. However, this study adds further evidence that the common genetic background of asthma and JIA is mainly based on polymorphisms in important TH1 and TH2 cytokines.

Adolescent↗

Identification and immunoreactivity of proteins released from Streptococcus agalactiae.

The aim of the present study was to identify released proteins of Streptococcus agalactiae and to investigate their immunoreactivity with human sera to determine whether such proteins might be viable as carrier proteins in conjugate vaccines. Infections with S. agalactiae are the leading cause of sepsis and meningitis in neonates. Vaccination of women of childbearing age would be a desirable alternative to intrapartum antibiotic prophylaxis, but factors that mediate S. agalactiae invasive disease and virulence are poorly defined. Capsule-based vaccines have shown only low immunogenicity to date, and interest has shifted towards S. agalactiae proteins, either as candidate vaccine antigens or as carrier proteins for serotype-specific S. agalactiae polysaccharides. In this study, some major released proteins of S. agalactiae could be identified, including molecules known to be present on the surface of bacterial cells but not previously described as released proteins, such as CAMP factor, a phosphocarrier protein, aldolase, enolase, PcsB, and heat-shock protein 70. Serotype-specific differences in the protein patterns of extracellular products and immunoreactivity with human sera could be detected by SDS-PAGE and Western blot. The identification of unexpected released proteins may indicate secondary functions for these proteins. In addition, the widespread immunoreactivity of these proteins with human sera as shown by Western blot indicates that released proteins may be promising candidates as carrier proteins in conjugate vaccines.

Adult↗

Association study of polymorphisms within interleukin-18 in juvenile idiopathic arthritis and bronchial asthma.

BACKGROUND: Interleukin-18 (IL-18) plays an important role in the regulation of TH1 as well as TH2 immunologic responses and thus in the development of chronic inflammatory diseases. Positive association studies of polymorphisms in IL-18 with different diseases have underlined the involvement of IL-18 in the pathogenetics processes. Our interest was to test polymorphisms of IL-18 for association with a typical TH1-mediated disease--juvenile idiopathic arthritis--and the TH2-mediated disease bronchial asthma in Caucasian children. METHODS: We genotyped five polymorphisms that were in association with chronic inflammatory diseases (-607C, -137C, 113G, 127T, and -133G). This was performed by restriction fragment length polymorphism in populations of asthmatic children, control individuals, and children with antinuclear antibodies (ANA)-positive juvenile idiopathic arthritis. Statistical analysis was performed by the Armitage trend test; haplotypes were calculated by the Arlequine program. RESULTS: No significant association was found between any single nucleotide polymorphism or any haplotype and bronchial asthma or ANA-positive juvenile idiopathic arthritis. CONCLUSION: We conclude that the effect of IL-18 in the immunologic context of diseases like bronchial asthma or juvenile arthritis might be too complex to be reflected in a simple one-way association study. Furthermore, the polymorphisms under investigation might be nonfunctional.

Adolescent↗

Late onset group B streptococcal disease manifested by isolated cervical lymphadenitis.

Sepsis and meningitis are the major clinical manifestations of group B streptococcal (GBS) infections in neonates, but GBS can cause a wide spectrum of presentations ranging from asymtomatic bacteraemia to fulminate septicaemia and shock. To our knowledge this is the first report of isolated neonatal lymphadenitis as a manifestation of late onset GBS disease.

Humans↗

[PFAPA Syndrome: Current Standard of Knowledge and Relevance for the ENT Specialist].

BACKGROUND: The symptoms fever, aphthous stomatitis, pharyngitis and cervical lymph node enlargement are among the most frequent complaints that particularly make children and adolescents consult an ENT specialist. In cases where these symptoms occur periodically, a PFAPA syndrome may be present. PATIENTS AND METHODS: We report on an atypical process in a 22 year old woman in whom the PFAPA syndrome first occurred during early infancy with recurrences since adolescence. RESULTS: Since the age of eight months the patient suffered from periodically occurring fever and pharyngitis with cervical lymph node enlargement. Therefore, by age four a tonsillectomy was performed and the symptoms disappeared. At age 15 similar symptoms occurred again with fever thrusts over approximately four to five days with temperatures up to 39.8 degrees C associated with pharyngitis, weakness and cervical lymphadenitis. Those symptoms relapsed periodically every four weeks. Treatment regimens with different antibiotics, Dimepranol and Inosin did not show any effect. Hyper-IgD syndrome and cyclic neutropenia were excluded. There were no signs for a humoral or cellular immune defect or a juvenile idiopathic arthritis. CONCLUSIONS: It is often very difficult to make the right diagnosis in a child or a young adolescent presenting with periodically occurring fever. So far the PFAPA syndrome is relatively unknown. Nevertheless, we think that it should be considered in the differential diagnosis by the ENT specialist patients with periodic fever, aphthous stomatitis, pharyngitis and cervical lymphadenopathy.

Adult↗

Respiratory syncytial virus infection of the lower respiratory tract: radiological findings in 108 children.

For years the typical appearance of respiratory syncytial virus (RSV)-induced infection of the lower respiratory tract has been discussed. All available studies have led to different results. The aim of this study was to control these results, with 108 children. The age range was 1 day to 10 years (median 7 months). Within 72 h of admission, all children developed an RSV infection of the lower respiratory tract. Chest X-rays (pa-view) of 55 children under, and 53 children over, the age of 6 months (10/53>24 months) were evaluated. The diagnosis of RSV and the chest X-ray were mostly done on the same day. The major radiological findings of the two age-groups were compared by Wilcoxon's unpaired rank sum test. Major radiological findings were: normal chest X-ray (30%), central pneumonia (32%) or peribronchitis (26%). There was no statistical significance between the age-groups. Other findings were emphysema (11%), pleural effusion (6%), lobar- or broncho-pneumonia (each 6%), atelectasis (5%) or pneumothorax in one case. Therefore, the most common radiological findings in RSV-induced infection of the lower respiratory tract, supported by our results (RSV infection without bacterial superinfection) are central pneumonia, peribronchitis or normal chest X-ray. Thus an age-group separation into under or over 6 months is no longer necessary.

Bronchitis↗

Serodiagnosis of cat scratch disease: response to Bartonella henselae in children and a review of diagnostic methods.

In this study, sera from 116 children without clinical evidence of cat scratch disease (CSD) and sera from 19 children with CSD were investigated by two different immunofluorescent assays (test A and test B) to evaluate the seroprevalence of Bartonella henselae antibodies in this population. Antibodies against Bartonella henselae were found in noninfected children only in low titers: 13% and 3.5% of serum samples were positive by test A and test B, respectively. IgG titers as determined by test A ranged from 1:64 to 1:256, whereas test B did not yield titers >1:64. Of the 19 children with CSD, 7 (37%) and 5 (26%) had low antibody titers (1:64-1:256) on admission by test A and test B, respectively. In such cases, IgM antibodies against Bartonella henselae and/or a titer increase in the following weeks are required to prove suspected CSD. The results indicate that the seroprevalence of Bartonella henselae antibodies in children without evidence of CSD is low, and that the results may differ depending on the tests being used. Low antibody titers, however, were found not only in healthy children but also among patients with CSD, which could be indicative of the beginning or of the end of an illness. Currently, only few data are available concerning the seroprevalence of antibodies to Bartonella spp. among children. Although children are often affected by CSD, the specificity of most tests has been evaluated by investigating blood donors, who are usually adults. Several different serological tests are used for the diagnosis of CSD, including the immunofluorescence assay, the enzyme-linked immunosorbent assay, and Western blot (WB) analysis. The sensitivities of different IFAs range from 14 to 100%, depending on the antigen used, the cut-off chosen, and the test procedures. The current diagnostic value of different serological tests for diagnosis of CSD is reviewed.

Adolescent↗

Community and nosocomially acquired respiratory syncytial virus infection in a German paediatric hospital from 1988 to 1999.

UNLABELLED: Respiratory syncytial virus (RSV) is the major cause of lower respiratory tract infections in infants. Since epidemiological data from Germany are scarce, a large retrospective hospital based analysis was performed. In the first part of the study, laboratory records were checked for RSV positive specimens from January 1988 to December 1997. A total of 1664 specimens were positive corresponding to 1171 episodes in 1064 patients; 88% were up to 4 years old and 47% up to 3 months old. The percentage of premature newborns from all patients 0-4 years old was 24%. The rate of nosocomial infection was 38%. The core RSV season began in December, lasted until April, and peaked in January and February. In the second part of the study, from April 1, 1997 to March 31, 1999, which encompassed two RSV winter seasons, patients with the ICD-9 coded discharge diagnoses of lower respiratory tract infections, bronchopulmonary dysplasia (BPD) and prematurity were analysed. Of the premature newborns, 25% were tested RSV positive at least once up to the age of 1 year, as were 52% of those with BPD. The rehospitalisation rate due to RSV infection was 22% in patients with BPD, and 8.9% in all premature newborns. Of patients with community acquired RSV infection, 12% required intensive care and 6% had to be ventilated mechanically. The mortality rates in both parts of the study were 0.8% and 0.7%, respectively. CONCLUSION: Respiratory syncytial virus infection in young children is also of major importance in Germany. Although the mortality rate is low, the high incidence and the severity of the disease in the particular risk group of premature infants with chronic lung disease contribute to a very high disease burden.

Child, Preschool↗

Cord blood levels of interleukin-6 and interleukin-8 for the immediate diagnosis of early-onset infection in premature infants.

BACKGROUND: Cytokine plasma levels are suggested to be sensitive indicators of neonatal sepsis, but conventional assays are time consuming. This study aimed at evaluating the significance of cord blood levels of interleukin (IL)-6 and IL-8 determined by a fully automated random access assay within 90 min of admission to predict systemic bacterial infection. PATIENTS AND METHODS: Cord blood levels of IL-6 and IL-8 were determined in 71 mature and 100 premature infants by a chemiluminescence assay (Immulite). Patients were divided into four groups according to a clinical and laboratory scoring system. Group A: documented early-onset infection; group B: infection possible; group C: infection unlikely, and group D: healthy newborns. RESULTS: Median IL-6 levels in the subgroup of premature newborns were as follows: group A, 1,920 pg/ml (5-95% confidence interval 308-4,660 pg/ml); group B, 50 (15-102) pg/ml; group C, 21 (12-71) pg/ml, and group D, 8 (6-11) pg/ml. For IL-8, median levels for groups A-D were 289 (226-514) pg/ml, 87 (40-107) pg/ml, 44 (33-98) pg/ml and 21 (16-25) pg/ml, respectively. The difference between group A and the other groups was highly significant (IL-6 p < 0.0001, IL-8 p < 0.001). At a cut-off of 80 pg/ml, the sensitivity of IL-6 for the diagnosis of sepsis was 96% (specificity 95%). For IL-8 (cut-off 90 pg/ml), the sensitivity was 87% (specificity 94%). CONCLUSION: In premature infants, the diagnosis of an early-onset infection can be established or ruled out with a high level of confidence by measuring IL-6 or IL-8 levels from cord blood using a random access chemiluminescence assay.

Apgar Score↗

Different cytokine expression in cord blood mononuclear cells after stimulation with neonatal sepsis or colonizing strains of Streptococcus agalactiae.

Streptococcus agalactiae (group B streptococcus, GBS) is the major pathogen of neonatal sepsis. In some newborns, GBS sepsis may have a severe course, including septic shock with a high mortality rate, whereas other newborns are colonized with GBS on their surfaces without any clinical signs of bacterial infection. The reason for this discrepancy is far from clear. We sought, in this study, to compare cytokine expression in cord blood mononuclear cells after stimulation with GBS strains isolated from newborns with sepsis, and strains isolated from newborns without any symptoms of invasive infection. Cord blood mononuclear cells were incubated with either heat-killed bacteria of different strains or lipopolysaccharide, respectively. After 6 and 24 h, cells were harvested and cytokine mRNA-expression was analyzed by reverse-transcriptase PCR. Likewise, supernatants were tested for IL-6 and tumor necrosis factor-alpha concentrations by enzyme immunoassay. When comparing IL-6 and tumor necrosis factor-alpha secretion, there were significantly higher IL-6 levels after stimulation with sepsis than with colonizing isolates. Likewise, mRNA expression of IL-6, IL-1 beta, and IL-12p40 was significantly higher after stimulation with sepsis isolates. This was also true when normalizing to cytokine expression after stimulation with lipopolysaccharide. These findings indicate that the different clinical pictures in response to GBS, either septic infection or colonization, might reflect strain-specific properties. If the respective characteristics can be defined, it might become possible to distinguish by molecular methods potentially "dangerous" from "harmless" strains. Moreover, our findings underline the essential role of these cytokines in the pathogenesis of neonatal GBS sepsis.

Base Sequence↗

The knee joint in early juvenile idiopathic arthritis. An ROC study for evaluating the diagnostic accuracy of contrast-enhanced MR imaging.

PURPOSE: Diagnosis of juvenile idiopathic arthritis (JIA) remains difficult due to unspecific clinical and laboratory findings, especially in early stages of the disease. The purpose of our study was to determine the sensitivity and specificity of MR imaging in diagnosing JIA of the knee joints. MATERIAL AND METHODS: Forty children (3-17 years old) clinically diagnosed with JIA (follow-up > 1 year) of a knee joint and a control group of 40 children with painful knee joints (MR diagnosis: bone bruise of the knee (n = 7), normal knee joint (n = 12), osteomyelitis (n = 6), septic arthritis (n = 2), bone tumor (n = 7) and miscellaneous bone lesions (n = 6)) were examined using a 1.5 T MR unit. T1-weighted spin-echo (SE), T2-weighted fast SE, contrast-enhanced T1-weighted SE and 2D gradient echo sequences were performed. The receiver operating characteristic (ROC) curves evaluation was conducted by 5 independent radiologists. RESULTS: The positive criteria for diagnosing JIA were joint effusions (n = 40), contrast-enhancing synovitis (n = 39), cartilage lesions (n = 15), subchondral erosions and bony destruction (n = 1). Sensitivity and specificity were 93.5% and 92.5%, respectively. Both cases of septic arthritis were misdiagnosed as JIA by all radiologists. CONCLUSION: Contrast-enhanced MR imaging seems to be a highly sensitive tool in establishing the diagnosis of JIA.

Adolescent↗

Identification of a novel insertion sequence element in Streptococcus agalactiae. bspeller@imib.rwth-aachen.de.

Gain and loss of bacterial pathogenicity is often associated with mobile genetic elements. A novel insertion sequence (IS) element designated ISSa4 was identified in Streptococcus agalactiae (group B streptococci). The 963bp IS element is flanked by 25bp perfect inverted repeats and led to the duplication of a 9bp target sequence at the insertion site. ISSa4 contains one open reading frame coding for a putative transposase of 287 aa and exhibits closest similarities to insertion elements of the IS982 family which has previously not been identified in streptococci. Analysis of different S. agalactiae strains showed that the copy number of ISSa4 in S. agalactiae varies significantly between strains. The S. agalactiae strain with the highest copy number of ISSa4 was nonhemolytic and harbored one copy inserted in cylB, which encodes the membrane-spanning domain of the putative hemolysin transporter (Spellerberg et al., 1999. Identification of genetic determinants for the hemolytic activity of Streptococcus agalactiae by ISS1 transposition. J. Bacteriol. 181, 3212-3219). Determination of the distribution of ISSa4 in different S. agalactiae strains revealed that ISSa4 could be detected only in strains isolated after 1996, which might indicate a recent acquisition of this novel insertion element by S. agalactiae.

Amino Acid Sequence↗

Elevated gene expression of interleukin-8 in cord blood is a sensitive marker for neonatal infection.

Bacterial infection is a major cause of neonatal morbidity and mortality. Early diagnosis is essential for a successful treatment and outcome. Cytokine plasma levels are suggested to be sensitive parameters for the diagnosis of neonatal sepsis. The aim of this study was to assess cytokine mRNA expression in cord blood cells as a marker for neonatal infection. In a prospective study, cord blood samples of neonates with septic bacterial infection were analyzed qualitatively and semiquantitatively by reverse transcriptase-polymerase chain reaction (RT-PCR) for mRNA expression of tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, IL-6, IL-8, as well as for IL-8 cord plasma levels. Results were compared to those of non-septic neonates. A method was used requiring only a microvolume (25 microl or less) of cord blood. Cord plasma levels of IL-8 were significantly elevated in septic infants (n = 9) when compared to infants with not confirmed sepsis (n = 22) and healthy infants that served as controls (n = 68) (median 1,686 vs 262.7 vs 33.1 pg/ml, P < 0.001). The presence of IL-6 and TNF-alpha gene expression was observed more frequently in septic than in non-septic patients; sensitivity, however, reached only 56 and 67%, respectively. When using a semiquantitative approach for analyzing IL-8 mRNA levels, a high sensitivity (86%) and specificity (96%) for the detection of sepsis was achieved. A new method for the early diagnosis of neonatal infection is described measuring cytokine mRNA in neonatal cord blood cells. With this molecular approach only a microvolume of blood is required for analysis.

Bacterial Infections↗

Streptococcus pyogenes meningitis: report of a case and review of the literature.

UNLABELLED: Streptococcus pyogenes is a very uncommon cause of bacterial meningitis beyond the neonatal period. A case report and a review of the recent literature is presented. We report on a previously healthy 7-year-old boy who developed S. pyogenes meningitis following a 2-day history of otitis media. A CT scan revealed right-sided mastoiditis as a possible focus of infection. The patient was treated with penicillin G for 14 days. The clinical course was uneventful, and the recovered without sequelae. By means of the polymerase chain reaction, the presence of streptococcal pyrogenic exotoxin (SPE) B and SPE C, but not SPE A genes was discovered from the bacterial DNA. CONCLUSION: Streptococcus pyogenes is a rare cause of bacterial meningitis but has to be considered as the causative pathogen beyond the neonatal period.

Bacterial Proteins↗