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Biomedical subjects

D W Reynolds

Publications and source records attributed to D W Reynolds.

At least 37 records · Page 2Linked to original sources

Molecular epidemiology of cytomegalovirus infections in women and their infants.

We studied cytomegaloviruses (CMV's) isolated from mothers and their children to determine whether recurrent infections and transmission to the fetus in immune women are due to reinfection or reactivaton of endogenous virus. Twenty-one strains of CMV from six mother-baby pairs, from two congenitally infected siblings, and from repeat isolates from four women were examined for genetic relatedness, by means of restriction endonuclease analysis of purified viral DNA. Although CMV's from unrelated persons were always different, strains from five to six congenitally infected babies were identical or very closely related to those from their mothers. Strains from congenitally infected siblings were also concordant, as were repeat isolates form three of four women. Major differences in viral DNA were detected in strains recovered from the same woman or from a mother-baby pair in only two cases. Endogenous CMV appears to be most frequent source of recurrent infection and intrauterine transmission in immune women; reinfection also occurs, but less commonly.

Cytomegalovirus↗

Cytomegalovirus infection in patients with renal transplants: potentiation by antithymocyte globulin and an incompatible graft.

Fifty-six of 67 patients with antibody to cytomegalovirus before transplantation shed cytomegalovirus from urine and/or saliva postoperatively. Symptomatic reactivation occurred in 17 (25%) patients, five of whom had pneumonitis. The symptomatic patients were more likely to have received a cadaver kidney (P = 0.004) and high-dosage antithymocyte globulin (P = 0.003) and to be viremic (P < 0.0001), compared to patients with silent infection. Forty-eight of 49 patients treated with antithymocyte globulin received cadaver or parent donor kidneys. Twenty-four were given a low-dosage intramuscular regimen, and 25 received a higher dosage intravenously. In the latter group 48% experienced symptomatic reactivation adn 48% viremia, compared to 21% and 17%, respectively, in the former group (P < 0.05 for both comparisons). There were no symptomatic cytomegaloviral infections among 18 patients not treated with antithymocyte globulin, all of whom received related donor kidneys. Renal transplant patients who receive both a poorly matched graft and antithymocyte globulin are at increased risk of morbidity due to cytomegalovirus.

Antilymphocyte Serum↗

Oesophagitis--a complication of inhaled steroid therapy.

The hazards of steroid therapy, both inhaled and oral, in the asthmatic patient are well recognized. The following case report presents an unusual complication of steroid therapy, namely, that of a concomitant Candida and Herpes simplex oesophagitis occurring in a steroid-dependent 15-year-old asthmatic who had been maintained on inhaled beclomethasone for approximately 15 monts. Oesophagoscopy revealed a 'cottage cheese' appearance of the distal oesophagus. Cultures of the biopsy specimens obtained during oesophagoscopy grew Candida and Herpes simplex virus. Lymphocyte stimulation studies were consistent with a primary cellular response, although the neutralizing antibody titres to the Herpes simplex virus were initially high and remained stable throughout the illness and convalescent period. The patient responded well to oral nystatin therapy and developed no evidence of disseminated herpes. Eleven months after the initial episode, the patient's oropharynx cultured Herpes simplex virus but not Candida. Doctors who care for asthmatic patients need to be aware of the possibility of a herpetic as well as a candidal oesophagitis as a significant complication of inhaled steroid therapy.

Administration, Intranasal↗

Comparative study of diagnostic procedures for congenital cytomegalovirus infection.

In a prospective study the incidence of congenital cytomegalovirus (CMV) infection was 2.2% (31 OF 1,412) as evidenced by viruria during the first week of life. Among immunoserologic methods used to screen these neonates, the rheumatoid factor test, although non-specific, proved to be the most convenient; its sensitivity for identifying infants with CMV infection was 35% to 45% with no false-positives. The rates for correct and incorrect identification of neonates at risk was, respectively, 33% and 3.1% when testing for increased levels of IgM; 5% and 10% when testing for increased levels of IgA; 76% and 21% when testing for IgM anti-CMV (IgM immunofluorescent test) antibody, and 0% when testing for IgA anti-CMV antibody. Rapid virologic diagnosis was achieved by assessing urine specimens. Confirmation by electron microscopy was possible in less than one hour in 92% of cases. The detection of early induced CMV-specific nuclear antigens by anticomplement immunofluorescence was diagnostic in 91% of cases within one day of inoculation of specimens in tissue culture. Infectivity of CMV in urine was well preserved for a least seven days at 4 C. Thus, in order to achieve a rapid diagnosis of congenital CMV infection, in sick as well as asymptomatic neonates, urine specimens may, if necessary, be transported at 4 C to distant laboratories.

Child, Preschool↗

Development of adverse sequelae in children born with subclinical congenital Toxoplasma infection.

Most infants born with congenital Toxoplasma infection are asymptomatic in the newborn period, and therefore their infection is not recognized. We performed follow-up evaluations on 24 such children. The mean age of these children at least examination was 8.5 years. In group I (13 children), the diagnosis was made prospectively. In group II (11 children), no symptoms or signs were noted in the newborn period and the diagnosis was made only after the first sign developed. Eighty-five percent of the children in group I and all of the children in group II have developed chorioretinitis. In group I, three children (23%) have unilateral blindness; in group II, three children (27%) and five children (45%) have unilateral and bilateral blindness, respectively. One child (8%) in group I and two children (18%) in group II developed severe, permanent neurologic sequelae after they initially presented with eye disease. Two of the children in each group are now retarded (IQ score range, 36 to 62). Six of the children in group I who were tested sequentially have had lower IQ scores (mean change from 97 to 74) on repeat tests performed an average of 5.5 years later. Less severe neurologic, intellectual, and audiologic deficits were observed in other children in each group. Treatment of some children may have had a beneficial effect on their outcome.

Adolescent↗

Transfer of measles, mumps, and rubella antibodies from mother to infant. Its effect on measles, mumps, and rubella immunization.

Sera from 42 mother-infant pairs were examined to determine the effect of passively acquired enhanced neutralizing (ENt) antibody on immunization. The ENt antibodies to measles, mumps, and rubella were greater in term newborns than in their mothers, with mean ratio of 1.8:1, 1.3:1, and 1.2:1, respectively. In 21% to 25% of the children, these antibodies persisted until 12 months of age. When immunized with trivalent measles-mumps-rubella vaccine, children who had persisting ENt measles and rubella titers had significantly lower mean antibody responses than children without detectable antibodies to the two viruses. Persisting ENt mumps antibodies did not affect the postimmunization titers. Seroconversion rates to any of the three viruses were not different in children with or without preexisting ENt antibody.

Antibodies, Viral↗

Progressive hearing impairment in children with congenital cytomegalovirus infection.

Audiological assessment of 86 children with congenital cytomegalovirus infection revealed progressive hearing loss in four of 12 subjects with sensorineural hearing impairments. Case descriptions are presented documenting the progression of the hearing loss. In view of the findings, children with congenital cytomegalovirus should be monitored closely to insure detection of possible delayed or progressive hearing impairment and delivery of appropriate habilitative services.

Auditory Threshold↗

Comparative prevalence of subclinical cytomegalovirus and herpes simplex virus infections in the genital and urinary tracts of low-income, urban women.

The prevalence of subclinical infections caused by cytomegaloviruses (CMV) and herpes simplex viruses (HSV) was assessed simultaneously in the genital and urinary tracts of 1,101 indigent women. Shedding of CMV from the genital and urinary tracts exceeded that of HSV by ninefold (8.89% vs. 0.95) and sevenfold (3.8% vs. 0.51%), respectively. Pregnancy, regardless of gestational age, had no discernible influence on productive infection with either virus in either the genital or the urinary tract. In contrast, age was a significant variable, especially with CMV. The prevalence of CMV shedding decreased steadily with age, from peak values of 15% and 8% in the genital and urinary tracts, respectively, of females 11-14 years of age to undetectable levels in females 31 years of age and older. Productive HSV infection was more prevalent in postmenopausal than in premenopausal women: 2.4% vs. 0.8% and 3.1% vs. 0.2% in the genital and urinary tracts, respectively. Likewise, HSV infection of both the genital and the urinary tract combined was more common in older than in younger females.

Adolescent↗

Identification of patients with increased risk of infection with herpes simplex virus after renal transplantation.

Forty-nine recipients of renal allografts were studied for infection with herpes simplex virus (HSV) before and at sequential intervals after transplantation. Forty-four (90%) of the patients studied were initially seropositive for neutralizing antibody to HSV type 1. HSV was not shed prior to transplantation nor by any of the five seronegative recipients after transplantation. Twenty-nine (66%) of the 44 seropositive patients shed virus postoperatively: 23 in saliva, three in urine, and three in both sites. Twenty (63%) of 32 seropositive patients examined developed herpetic mucocutaneous lesions. Both viral shedding and lesions were most prevalent during the first four weeks after transplantation. Twenty-nine (85%) of 34 patients with antibody titers of 1:256-1:4,096 and zero of 10 with titers of 1:8-1:128 shed HSV postoperatively (P less than 0.0001). The group with high antibody titers before transplantation were also more likely to develop lesions after transplantation (P = 0.002) as were those with a positive history (P = 0.017). The ability to predict symptomatic HSV recurrences in renal transplant patients could be a valuable aid in identifying individuals with which to evaluate antiviral compounds.

Antibodies, Viral↗

Specific cell-mediated immunity in children with congenital and neonatal cytomegalovirus infection and their mothers.

Cell-mediated immunity (CMI) to cytomegalovirus (CMV) and herpes simplex virus type 1 (HSV-1) was examined in 35 mothers and 30 of their offspring with congenital or neonatal CMV infection by means of the lymphocyte transformation assay. Eleven offspring did not respond to CMV antigen, and 15 of the 19 positive children displayed lower responses than those of normal immune adults. Productive infection in the younger children at the time of assay and the presence of disease correlated strongly with the absence of responses. The mothers as a group also demonstrated impaired CMI to CMV while reacting normally to HSV-1 antigen. Neither time after transmission of infection nor viral excretion was significantly associated with impaired CMI, although a trend toward diminished responses was evident among women who were shedding virus. Mitogen stimulation was normal in all test subjects. These findings imply that deficient specific CMI may play a role in the genesis of persistent CMV infection and fetal pathology.

Adolescent↗

A longitudinal study of the serological and virological status of 18 women infected with cytomegalovirus.

18 women, of known seropositivity, have been followed for between 18 and 66 months (mean 50.2 months) for viral excretion and serological changes. CMV was isolated from 58/146 (39.7 per cent) cultures from various sites, mostly cervix. A total of 129 sera were obtained and each was titrated in the late antigen, early antigen and anti-complement immunofluorescence assays, as well as the complement fixation and microneutralisation tests. From 3 women virus was consistently re-isolated, from 3 others virus was never re-isolated and the remaining 12 women excreted virus intermittently during the period of study. No significant changes in antibody titres could be detected by any of the 5 serological assays in any woman during periods of viral excretion. This suggests that local reactivation of latent CMV infection is not associated with a demonstrable systemic antibody response. Inter-assay correlations were sought for each of the 10 possible combinations of pairs of tests. Significant correlations were found for most pairs of tests, with the notable exception fo those involving the early antigen test. This confirms that antibodies detected in this assay are distinct from those detected by the other 4 serological assays.

Adult↗

Antibody response to live virus vaccines in congenital and neonatal cytomegalovirus infections.

When 42 infants with congenitally or neonatally acquired cytomegalovirus infections were one year of age, they were given live attenuated measles-mumps-rubella combined vaccine to determine what effect, if any, the existence of chronic CMV infection has on the antibody response to measles and rubella antigens. When the infected infants were compared with 60 healthy non-CMV-infected control infants, no significant difference in the seroconversion rates or ultimate antibody levels was observed with either measles or rubella antigens. Persistence of antibody, when measured three years after vaccination, was likewise similar in each group; levels had waned only slightly. These results demonstrate the intactness of humoral immunity in children with pre- and perinatal CMV infection.

Antibodies, Viral↗

Productive infection with cytomegalovirus and herpes simplex virus in renal transplant recipients: role of source of kidney.

Forty patients were prospectively studied for infection with cytomegalovirus (CMV) and herpes simplex virus (HSV) after renal transplantation. Although 85% had antibody to CMV and 95% had antibody to HSV prior to transplantation, excretion of CMV was found in 92.5%, usually as viruria, and HSV was recovered from 70%, most often from the oropharynx. Shedding of HSV reached a peak within the first month after transplantation when immunosuppression was most intense and then rapidly declined. In contrast, excretion of CMV was found in a greater proportion of patients during each interval up to about six months after transplantation and subsequently persisted in the majority of patients. Both serologic responses and viral isolation rates indicated more rapid activation of CMV but not of HSV in recipients of kidneys from cadavers than in patients who received kidneys from living related donors. At 60 days after transplantation, 76% of the recipients of kidneys from cadavers and only 33% of the recipients of kidneys from living, related donors had shed CMV (P = 0.003). These differences could not be accounted for by immunosuppressive treatment. Excretion of HSV was clearly associated with the time of most intense immunosuppression, but the major factor in initiation and maintenance of productive infection with CMV appeared to be the host vs. graft reaction.

Antibodies, Viral↗

Perinatal cytomegalovirus infection: influence of placentally transferred maternal antibody.

The kinetics of the response to passively transferred maternal neutralizing antibody were studied for determination of whether this antibody offered protection against primary cytomegalovirus (CMV) infection in the offspring. Antibody response was determined in 17 infants infected in the immediate perinatal period and in 18 appropriate control subjects. Levels of neutralizing antibody in serum obtained at birth and at one month of age were similar in infected and in exposed, uninfected neonates. In addition, the quantity of neutralizing antibody did not influence the time of onset of viruria. Clearly, passive humoral immunity failed to prevent naturally acquired primary CMV infection in a significant number of young infants exposed to virus during and shortly after delivery.

Antibodies, Viral↗