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Biomedical subjects

K McIntosh

Publications and source records attributed to K McIntosh.

At least 163 records · Page 9Linked to original sources

Type A2 influenza viral infections in children.

We retrospectively reviewed the manifestations of influenza A2 in 83 hospitalized young children. Our purpose was to define the spectrum of clinical illness in this age group. Findings included fever (91%), vomiting or diarrhea (49%), pharyngitis (34%), pneumonitis (29%), otitis media (24%), conjunctivitis (13%), croup (13%), and bronchiolitis (6%). Neuromuscular manifestations occurred in 16 patients (19%) and included seizures, apnea, opisthotonos, and myositis. Three children had cerebrospinal fluid pleocytosis. Children younger than 3 months of age had fever less often and gastrointestinal symptoms more often than older children. Threee children died of progressive pneumonitis. We conclude that influenza A2 may cause a wide range of respiratory and neurologic findings in infancy and early childhood.

Child↗

Diagnosis of human coronavirus infection by immunofluorescence: method and application to respiratory disease in hospitalized children.

Rabbit antisera were prepared against coronavirus strains 229E and OC43 and used successfully to detect viral antigen in epithelial cells shed from the nasopharynx of symptomatic volunteers who had received coronavirus inocula three to four days before. The same serologic reagents were applied to nasopharyngeal secretion cells obtained from 106 infants and children hospitalized with respiratory tract disease and apparently not infected with conventional respiratory viruses. No coronavirus infections were detected by this method. It appears that coronavirus OC43 or 229E infections were not common in children in Tyneside hospitals during the period of study. However, fluorescence is a useful method for detection of coronavirus infections in symptomatic human subjects.

Adult↗

Interferon in nasal secretions from infants with viral respiratory tract infections.

Interferon levels in nasal secretions of infants under one year of age, and hospitalized with lower repiratory tract disease, were measured during two respiratory infection seasons. In the first year serial secretions from 50 infants with respiratory syncytial virus infection were examined. Undetectable or low levels of interferon were found in all samples, and mean levels did not fluctuate significantly in relation to disease and recovery. This was in contrast to anti-RSV IgA, which appeared and increased in concentration as virus shedding decreased and stopped. In the second year secretions were obtained from nine infants with influenza A virus infection as well as from 13 with RSV. All those with influenza developed measurable interferon in secretions (geometric mean titer 138 units/ml), which was acid and heat stable, and trypsin sensitive (type I interferon). RSV infection again stimulated very low levels (geometric mean 5 units/ml). The lack of correlation of interferon concentration with cessation of RSV shedding suggests either that it is not involved in recovery or that low levels are adequate. On the other hand, it appears that the young infant is fully capable of a brisk local interferon response, at least to infection by influenza A.

Antibodies, Viral↗

The immunologic response to infection with respiratory syncytial virus in infants.

Fifty infants younger than six months, hospitalized for infection with respiratory syncytial virus (RSV), were studied by examination of serial samples of nasal secretion. Secretory neutralizing activity was measured by plaque reduction and secretory antibody by indirect fluorescence using conjugated antiserum to human IgA, IgG, or IgM. Secretory neutralizing activity during infection rose or fell fourfold with approximately equal frequency (20% and 26%, respectively). In contrast, levels of IgA antibody to RSV in secretions rose fourfold in 56%--65% of the infants and fell in none. The frequency of such rises in titer of antibody was directly related to age. In individual secretions the correlation between neutralizing activity and IgA antibody to RSV was poor: neutralizing activity was often found in the absence of detectable antibody, and IgA antibody to RSV was often nonneutralizing. Nevertheless, the development of IgA antibody to RSV correlated in time with the disappearance of virus from the respiratory tract. The timing of this secretory response is consistent with the hypothesis that antibody contributes significantly to cure of infection.

Antibodies, Viral↗

Behavior of respiratory syncytial virus in piglet tracheal organ culture.

Piglet tracheal organ cultures were infected with respiratory syncytial virus (RSV) and observed for 21 days. Light and immunofluorescence microscopy demonstrated destruction of the ciliated epithelial cells and the presence of viral antigens in the epithelium. Virus was shed in high titer for 12--19 days. Ciliostasis could be quantitated, and it was shown that several strains of RSV grew and damaged tracheal organ cultures in a similar fashion. A temperature-sensitive mutant of RSV, ts-1, was examined at permissive (33 C) and restrictive (37 C) temperatures. This mutant, although somewhat attenuated at 37 C, was still found to cause damage to the ciliated epithelium and to replicate at both temperatures. THIS BEHAVIOR IS SIMILAR TO THAT AFTER INOCULATION OF TS-1 INTO VOLUNTEERS. This in vitro model may prove useful in the study of RSV disease and in the evaluation of candidate live virus vaccines.

Animals↗

Decreased lymphocyte transformation to vaccinia virus in multiple sclerosis.

Lymphocyte transformation to vaccinia virus was measured in multiple sclerosis (MS) patients and normal controls. There was a significant reduction of lymphocyte transformation to vaccinia virus in multiple sclerosis patients compared with the control group. In addition, a positive correlation existed between the degree of disability of the multiple sclerosis patients and the extent of lymphocyte transformation in the presence of vaccinia virus. There was no correlation between cell-mediated immunity to vaccinia virus and either serum or cerebrospinal fluid (CSF) antibody levels to vaccinia in multiple sclerosis patients or controls, all of whom had been previously vaccinated. In conjunction with other studies, all of whom had been previously vaccinated. In conjunction with other studies that have demonstrated elevated antibody titers to vaccinia virus in the CSF of multiple sclerosis patients, these results support the possibility that vaccinia virus may play a role in the pathogenesis of multiple sclerosis.

Adolescent↗

Apnea associated with respiratory syncytial virus infection in young infants.

The hospital charts of 274 infants under 6 months of age with culture-proved respiratory syncytial virus infections were reviewed. Fifty-six infants (20.4%) demonstrated apnea in association with RSV infection. Predisposing factors significantly correlated with apnea included premature birth and young chronologic age at the time of virus infection. The clinical implications of this association are discussed.

Apnea↗

Clinical and serologic study of four smallpox vaccines comparing variations of dose and route of administration. Basic study and laboratory standardization.

The present four-center collaborative study was undertaken in an attempt to define the best vaccine and/or vaccination procedure for use in areas of the world that are free of smallpox. The study was designed to compare the effect of different vaccinial strains, viral concentrations, and routes of administration on the morbidity and antibody response associated with primary vaccination and standard challenge revaccination. Primary vaccinations were performed on 1,585 children; 49.6% of the children were vaccinated by the percutaneous route, and 50.4% received vaccine subcutaneously. The overall age and sex distributions of percutaneous and subcutaneous vaccinees were comparable, but there were marked differences in participants among the four study centers. Vaccines in Kentucky had a greater mean age; the greatest number of Negroid children were enrolled in St. Louis, and more of them were vaccinated by the subcutaneous route; and the dropout rate was much greater in San Diego and Colorado. An analysis of comparative interlaboratory serologic procedures with the use of 20 coded duplicate samples of serum revealed good agreement in the hemagglutination-inhibition test; results of neutralization tests had greater variability of mean titers. On duplicate samples of serum from study participants there was generally good correlation between each of the four study centers and the Center for Disease Control's reference laboratory in titers of hemagglutination-inhibiting antibody. In contrast, 38% of the neutralization titers determined at the four study centers were greater than or equal to 0.67 log10 higher than the respective titers noted at the Center for Disease Control.

Black or African American↗

Clinical and serologic study of four smallpox vaccines comparing variations of dose and route of administration. Primary percutaneous vaccination.

In an investigation of the antigenicity and reactogenicity of four smallpox vaccines, 786 children received primary percutaneous vaccination with vaccine in one of three concentrations, 10(6), 10(7), or10(8) pock-forming units/ml. Dose-response curves indicated that the three licensed vaccines (New York City Board of Health strains grown in calf lymph or chorioallantoic membrane, and the Lister vaccine) had similar potencies, but the CV-1 strain was about 10-fold less infectious. CV-1 also produced smaller skin lesions than the other three vaccines, and the incidence of fever in CV-1 vaccines who developed either "major reactions" or serum antibody was not significantly different from that in children in all vaccine groups with no evidence of "take." Hemmagglutination-inhibiting antibody was consistently seen in individuals who received potent New York City and Lister vaccines, and neutralizing antibody was induced in 82%-85% of children in this group who had some evidence of take (production of hemagglutination-inhibiting antibody or or major reaction). Only 30% of CV-1 vaccines with takes produced neutralizing antibody. Minor complications occurred in all groups, but most often in children who received the New York City strains."

Animals↗

Clinical and serologic study of four smallpox vaccines comparing variations of dose and route of administration. Standard percutaneous revaccination of children who receive primary percutaneous vaccination.

A standard challenge with percutaneous smallpox vaccine was administered to 629 children six to 12 months after percutaneous primary inoculation with one of four vaccines (New York City Board of Health strains grown in calf lymph or chorioallantoic membranes, the Lister vaccine, or the CV-1 strain). Of those who had had major reactions on primary vaccination, 8%-21% responded to revasccination with a typical primary-type skin response. In contrast, such a primary-type response occurred in 50% of those who on primary vaccination had developed serum antibody in the absence of major reactions and in 83% of those who had had no serologic or clinical evidence of primary "take." Skin lesions on revaccination tended to be largest in thosewhose primary vaccination was with CV-1, although fever and minor complications were not more frequent. Moreover, even in children who had received CV-1 vaccine, skin responses to challenge vaccine were clearly attenuated when compared with responses of children who had not had takes on primary vaccination. Sizes of lesions and acceleration of skin erytherma after challenge were related in most children to titers of both hemagglutination-inhibiting and neutralizing antibody at the time of revaccination. One month after revaccination, neutralizing antibody was present in 93%-96% of those with takes onprimary vaccination with New York City or Lister vaccines, but only 75% of CV-1 vaccines.

Antibody Formation↗

Clinical and serologic study of four smallpox vaccines comparing variations of dose and route of administration. Primary subcutaneous vaccination.

As part of a large study designed to develop schedules for smallpox immunization with reduced morbidity, 799 children received primary immunization with subcutaneous vaccine. Four vaccines (New York City Board of Health calf lymph, New York City chorioallantoic membrane, CV-1 and Lister) at three dosages (l0(3), 10(4), 10(5) pock-forming units) were administered. Eighty-two percent responded with hemagglutination-inhibiting antibody at one month, and only 22% with neutralizing antibody. There was no correlation between concentration of vaccine and antibody response. The CV-1 strain was slightly but significantly less likely to induce antibody than the other three vaccines. Subcutaneous vaccination was not associated with significant temperature elevation in general. However, some children developed erythema at the vaccination site or a swollen arm, and fever did tend to occur in this small group. Four children developed nonspecific vaccinia-related rashes, and one had generalized vaccinia.

Antibody Formation↗

Clinical and serologic study of four smallpox vaccines comparing variations of dose and route of administration. Standard percutaneous revaccination of children who receive primary subcutaneous vaccination.

Six months after subcutaneous vaccination with one of four smallpox vaccines, 655 children were challenged with a standard percutaneous smallpox vaccine. Response to reimmunization was characterized by a significant acceleration and diminution of skin response, but not to the degree seen in an equivalent group who had received their primary immunization percutaneously. Fever after revaccination was absent if there had been a "take" with primary subcutaneous vaccination. The overall incidence of minor vaccine-related complications with revaccination was 2-1/2%. The neutralizing antibody response to revaccination was markedly reduced, as compared to that of children who received either one or two successful percutaneous vaccinations. Subcutaneous vaccination followed by percutaneous vaccination is not recommended as a schedule for smallpox immunization, because complications are not avoided, and the incidence and mean titer of resultant neutralizing antibody are low.

Antibody Formation↗