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Biomedical subjects

O Ruuskanen

Publications and source records attributed to O Ruuskanen.

At least 19 recordsLinked to original sources

Shedding of infectious virus and virus antigen during acute infection with respiratory syncytial virus.

Shedding of respiratory syncytial virus (RSV) in nasopharyngeal aspirates (NPA) of hospitalized children with acute respiratory infection was studied using direct antigen detection by time-resolved fluoroimmunoassay, rapid identification of infectious virus in centrifugally inoculated cell cultures by immunoperoxidase staining and conventional virus culture. Sequential NPAs, in which also local RSV-specific IgA response was measured, were collected from children with proven RSV infection. The shedding pattern was similar for both infectious virus and viral antigen. The overall agreement of the three methods was good (81%) in diagnostic specimens collected on admission, but markedly reduced (46%) in follow-up specimens. Secretory IgA was abundant in specimens giving discrepant or negative results only. The proportion of patients who shed RSV was high (> or = 87%) in the first week after onset of symptoms, and decreased sharply in the second week. An opposite temporal pattern was found in the proportion of patients with detectable RSV-IgA in their secretions. Sequentially isolated strains were antigenically stable as determined by their reactivity with a large panel of monoclonal antibodies. The findings suggest that RSV shedding should be monitored by using more than one method for virus detection.

Acute Disease

Pneumonia in childhood: etiology and response to antimicrobial therapy.

A prospective eight-month study was carried out in 50 children admitted to hospital for radiologically confirmed community-acquired pneumonia. A potential causative agent of infection was identified in 44 (88%) cases. Using virus isolation, virus antigen detection and enzyme immunoassay serology, respiratory virus infection was diagnosed in 30 (60%) patients. Antibody assays for seven bacteria and antigen detection from serum and urine for Streptococcus pneumoniae produced evidence of bacterial infection in 31 (62%) cases. Streptococcus pneumoniae (38%), respiratory syncytial virus (30%) and Mycoplasma pneumoniae (20%) were the most common causative agents. A mixed infection was diagnosed in 25 (50%) episodes. Nine patients failed to respond to antibiotics within 24 h after onset of treatment. Three of them had a pure viral infection, three a mixed viral-bacterial infection, two a Mycoplasma pneumoniae infection mixed with other bacteria and one a pure Mycoplasma pneumoniae infection. All three Mycoplasma pneumoniae infections were initially treated with penicillin.

Adolescent

Influenza vaccination in the prevention of acute otitis media in children.

We studied a new approach to the prevention of acute otitis media through the administration of influenza vaccine to 187 day-care center children aged 1 to 3 years before the influenza A epidemic of 1988-1989. The control group consisted of 187 unvaccinated children of similar age and background. During the 6-week study period, influenza A infection was diagnosed in five (3%) of 187 vaccinees and in 29 (16%) of 187 controls. Acute otitis media developed in three (60%) of five vaccinees with an influenza A infection compared with 18 (67%) of 27 controls (excluded were two children with a double viral infection). The incidence of acute otitis media associated with influenza A was reduced by 83% in the vaccinees. The total number of children with acute otitis media in the vaccine group was 35, compared with 55 in the control group, disclosing a 36% reduction among the vaccinees. We conclude that influenza vaccination decreases the incidence of acute otitis media in children during an influenza A epidemic, suggesting also that other vaccines against respiratory viruses may be an effective way to reduce the incidence of acute otitis media.

Causality

Development of an acellular pertussis vaccine and its administration as a booster in healthy adults.

An acellular pertussis vaccine which contains highly purified pertussis toxoid (PT) and filamentous haemagglutinin (FHA) has been developed. These proteins have been shown to be stable, with essentially no significant reversion of the pertussis toxoid after a new detoxification procedure. Two clinical trials using this vaccine as a booster in 45 healthy adults have been performed. Results show that the vaccine was well tolerated, causing essentially mild, transient symptoms after administration. It induced an increase in anti-PT and anti-FHA antibody titres in all vaccinees.

Adult

Recurrent wheezy bronchitis and viral respiratory infections.

Fifty four patients aged from 1 to 6 years who had had recurrent attacks of wheezy bronchitis were prospectively followed up for three months to find out if there was an association between different viral respiratory infections and episodes of wheezing. Of the 115 episodes of upper or lower respiratory tract symptoms, virus or Mycoplasma pneumoniae infection were diagnosed in 52 (45%). Thirty four of rhinoviruses. The patients had an average of 2.1 episodes of respiratory tract symptoms the total mean (SD) duration of which was 30 (2) days of the 92 days that followed. Wheezing occurred during 76 (66%) of the 115 episodes and during a third of these the patient was admitted to hospital because of severe dyspnoea. Wheezing started a mean (SD) of 43 (7) hours after the first symptoms of respiratory infection and persisted for 3.8 (4.2) days in patients in whom virus infection was diagnosed. The incidence of wheezing was not associated with IgE mediated atopy, with positive virological tests, or with fever during virus infection, but was associated with parental smoking and more than one sibling.

Bronchitis

Respiratory virus infection as a cause of prolonged symptoms in acute otitis media.

We studied respiratory viruses in 22 children with acute otitis media who had failed to improve after at least 48 hours of antimicrobial therapy. The mean duration of preenrollment antimicrobial therapy was 4.8 days. For comparison we studied 66 children with newly diagnosed acute otitis media. Respiratory viruses were isolated from middle ear fluid or from the nasopharynx, or both, significantly more often in the patients unresponsive to initial antimicrobial therapy than in the comparison patients (68% vs 41%, p less than 0.05). Viruses were recovered from the middle ear fluid in 32% of the study patients and from 15% of the comparison group. Bacteria were isolated from the middle ear fluid of four (18%) children in the study group; one child had an isolate resistant to initial antimicrobial therapy. All four children with bacteria in the middle ear fluid had evidence of concomitant respiratory virus infection. Our results indicate that respiratory virus infection is often present in patients with acute otitis media unresponsive to initial antimicrobial therapy, and may explain the prolongation of symptoms of infection. Resistant bacteria seem to be a less common cause of failure of the initial treatment.

Acute Disease

Serologic diagnosis of pertussis: evaluation of pertussis toxin and other antigens in enzyme-linked immunosorbent assay.

IgM, IgA, and IgG antibodies to Bordetella pertussis were measured in paired sera from 34 patients who were culture-positive for pertussis by enzyme-linked immunosorbent assay (ELISA) with disrupted B. pertussis bacteria, purified pertussis toxin, or outer membrane proteins (OMP) as antigens. Paired sera from 50 patients with other respiratory infections were used as controls. The sensitivities of the assays from paired sera were 61%, 90%, and 90% and specificities were 98%, 92%, and 72%, respectively. Of the patients culture-positive for pertussis, 68% had positive levels of antibody to pertussis toxin antigen in their first serum samples, obtained at the same time as samples for culture. Infants had antibody responses to pertussis toxin antigen, in contrast to weak antibody responses measured by B. pertussis antigen. The results from this study indicate that ELISA, especially measuring pertussis toxin IgA, is a valuable additional tool for diagnosing pertussis and can be used as a complementary test with cultures.

Adolescent

Rapid detection of respiratory syncytial virus and influenza A virus in cell cultures by immunoperoxidase staining with monoclonal antibodies.

Peroxidase-labeled monoclonal antibodies against respiratory syncytial virus (RSV) and influenza A virus were used for immunoperoxidase staining (IPS) of cell cultures inoculated with nasopharyngeal aspirates. Cells were grown in 24-well plates, and specimens were inoculated by low-speed centrifugation. Cultures were incubated for 2 days at 37 degrees C and then fixed, stained, and observed by light microscopy. IPS was compared with standard virus isolation by using cultures of human diploid fibroblasts and Vero, HEp-2, and HeLa cell lines for RSV and Madin-Darby canine kidney cells for influenza A virus; these cultures were inoculated with specimens that were previously stored at -70 degrees C. Of 40 known RSV-positive specimens, 30 were found to be positive on reinoculation by both methods, and an additional 5 specimens were found to be positive by IPS only. Of 190 specimens tested for influenza A virus, 14 were positive by IPS and in tubes, and a further 8 specimens were positive by IPS only. IPS was also compared with direct detection of viral antigens in nasopharyngeal aspirates by a time-resolved fluoroimmunoassay (TR-FIA). Fresh nasopharyngeal aspirates were inoculated into human diploid fibroblasts and Madin-Darby canine kidney cells and tested for RSV and influenza A virus, respectively, by IPS. Of 110 specimens tested for RSV, 37 were positive in total, 32 were positive by IPS, and 33 were positive by TR-FIA. Of 150 specimens tested for influenza A virus, 39 were positive in total, 35 were positive by IPS, and 34 were positive by TR-FIA. IPS of cultures inoculated by centrifugation and incubated for 2 days is a sensitive method for the diagnosis of respiratory virus infections, and 24-well plates allow for the easy processing of a large number of specimens.

Animals

Rhinovirus in otitis media with effusion.

We studied rhinovirus in the middle ear fluid of 61 children with subacute or chronic otitis media with effusion. Rhinovirus was recovered from the middle ear fluid of 5 children with subacute otitis media with effusion. The minimum duration of effusion was 32 to 60 days. Additionally, 1 patient had middle ear fluid that was positive for adenovirus. Bacterial pathogens were cultured from the middle ear fluid of 20 of 61 patients. Our finding that rhinovirus can be isolated from middle ear fluid after an asymptomatic period of several weeks suggests its possible role in the development of otitis media with effusion.

Bacteria

A randomised comparison of ceftazidime and piperacillin, both in combination with flucloxacillin for treatment of febrile episodes in neutropenic children. Finnish Three-Centre Study.

111 febrile episodes in 98 neutropenic children were randomly treated with either ceftazidime (CAZ) 150 mg/kg/day or with piperacillin (PIP) 200 mg/kg/day, both combined with flucloxacillin (FLUC) 50 mg/kg/day. A total of 37/47 (79%) eligible episodes in the CAZ group and 41/53 (77%) in the PIP group were cured without needing to stop the initial therapy. The success without modification of the treatment in the verified septicaemias in the CAZ group was 8/18 (44%) and in the PIP group 5/18 (28%). Of the bacteriologically documented infections, 13/24 (54%) in the CAZ group and 11/24 (46%) in the PIP group were cured without modification of the therapy. Similarly, 17/31 (55%) of all the isolated bacteria in the CAZ group and 14/33 (42%) in the PIP group were eradicated with the initial therapy. Overall there were 13 deaths of which 4 in the CAZ group and 5 in the PIP group occurred during the infection. An increasing granulocyte count exceeding 0.25 x 10(9)/l at the end of the therapy was a good prognostic sign for the outcome of the infection. This study indicates that CAZ is as effective as PIP in the treatment of infections in neutropenic children.

Adolescent

Clinical role of respiratory virus infection in acute otitis media.

The clinical characteristics of acute otitis media in relation to coexisting respiratory virus infection were studied in a 1-year prospective study of 363 children with acute otitis media. Respiratory viruses were detected using virus isolation and virus antigen detection in nasopharyngeal specimens of 42% of the patients at the time of diagnosis. Rhinovirus (24%) and respiratory syncytial virus (13%) were the two most common viruses detected. Adenovirus, parainfluenza viruses, and coronavirus OC43 were found less frequently. The mean duration of preceding symptoms was 5.9 days before the diagnosis of acute otitis media. Ninety-four percent of the children had symptoms of upper respiratory tract infection. Fever was reported in 55% and earache in 47% of cases. Patients with respiratory syncytial virus infection had fever, cough, and vomiting significantly more often than patients with rhinovirus infection or virus-negative patients. No significant differences were found in the appearance of the tympanic membrane and outcome of illness between virus-negative and virus-positive patients with acute otitis. Most patients respond well to antimicrobial therapy despite the coexisting viral infection. If the symptoms of infection persist, they can be due to the underlying viral infection, and viral diagnostics preferably with rapid methods may be clinically useful in these patients.

Acute Disease

Acute otitis media and respiratory virus infections.

We studied the association of acute otitis media with different respiratory virus infections in a pediatric department on the basis of epidemics between 1980 and 1985. Altogether 4524 cases of acute otitis media were diagnosed. The diagnosis was confirmed by tympanocentesis in 3332 ears. Respiratory virus infection was diagnosed during the same period in 989 patients by detecting viral antigen in nasopharyngeal mucus. There was a significant correlation between acute otitis media and respiratory virus epidemics, especially respiratory syncytial virus epidemics. There was no significant correlation between outbreaks of other respiratory viruses and acute otitis media. Acute otitis media was diagnosed in 57% of respiratory syncytial virus, 35% of influenza A virus, 33% of parainfluenza type 3 virus, 30% of adenovirus, 28% of parainfluenza type 1 virus, 18% of influenza B virus and 10% of parainfluenza type 2 virus infections. These observations show a clear association of respiratory virus infections with acute otitis media. In this study on hospitalized children Haemophilus influenzae strains were the most common bacteriologic pathogens in middle ear fluid, occurring in 19% of cases. Streptococcus pneumoniae was present in 16% and Branhamella catarrhalis in 7% of cases. There was no association between specific viruses and bacteria observed in this study.

Female

Regulatory T-cell function in primary humoral immunodeficiency states.

The function of B cells and highly purified T-cell subpopulations was studied in patients with various primary humoral immunodeficiencies. In the presence of normal T4+ cells B cells of the patients with X-linked agammaglobulinemia (XLA) were not capable either for IgM or IgG synthesis, whereas B cells of the patient with hyper-IgM syndrome and three of eight patients with common variable immunodeficiency (CVI) could produce normal amounts of IgM, but not IgG. All patients with XLA and the patient with hyper-IgM syndrome exhibited normal helper function by T4+ cells for both IgG and IgM synthesis of normal B cells. The function of CVI T4+ cells was variable. When the function of the patients' T8+ cells was tested against normal B cells, one CVI patient had overactive suppression capacity; in other patients the suppressor cell activity was normal. The findings indicate considerable heterogenicity in the function of lymphocyte subpopulations of the CVI patients.

Adolescent