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Biomedical subjects

J L Sever

Publications and source records attributed to J L Sever.

At least 19 recordsLinked to original sources

Perinatal 'TORCH' infections identified by serology: correlation with abnormalities in the children through 7 years of age.

A matched case-control methodology was used to assess the risk for a wide range of abnormalities in children associated with serological evidence for 'TORCH' infections in the mothers. Specimens were selected from the large bank of sera from the approximately 54,000 pregnant women who participated in the Collaborative Perinatal Project. There was no clear association between any of the antigens studied and any specific damage to the child. These 'negative' findings are consistent with the absence of frequent significant effects due to these agents in the second and third trimesters of pregnancy.

Case-Control Studies

Detection of human immunodeficiency virus type 1 infection in young pediatric patients by using polymerase chain reaction and biotinylated probes.

Polymerase chain reaction (PCR) testing using up to four primer pairs and biotinylated probes was 97.9% sensitive (188 of 192 specimens positive) and 100% specific (267 of 267 specimens negative) for detecting the presence or absence of human immunodeficiency virus (HIV) DNA in peripheral blood mononuclear cells from pediatric patients whose HIV status has been confirmed. SK38/39 and SK145/150 were the most sensitive primer pairs, respectively detecting HIV DNA in 95.6 and 95.9% of peripheral blood mononuclear cell specimens from HIV-infected children and collectively detecting all adequately tested PCR-positive specimens. Primer pairs SK29/30 and SK68/69 respectively detected HIV DNA in only 76.4 and 76.6% of HIV-positive specimens. Among infants born to HIV-seropositive mothers, 30 who subsequently were confirmed to be infected were sampled when they were less than or equal to 6 months of age; in all but one infant, HIV DNA was found in the first specimen collected. Among the nine youngest infected infants tested, all were PCR positive by 38 days of age. PCR methods thus have reliably detected vertically transmitted HIV infection early in life.

Acquired Immunodeficiency Syndrome

Toxoplasmosis.

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Adult

Limitations in the laboratory diagnosis of vertically acquired HIV infection.

At present, the only well-standardized and widely available diagnostic techniques for HIV infection are detection of IgG HIV antibodies and HIV antigen. The antibody detection is sensitive, but is useful only in infants and children older than 15 months because of the presence of maternal antibodies. The utility of HIV antigen testing in neonates and young infants has not been established. A number of sensitive techniques, such as PCR, ELISPOT, and detection of HIV-specific IgM and IgA antibodies, are under development and promise to be very useful in the early diagnosis of vertical HIV infection. However, we will be able to accurately establish the sensitivity or specificity of the individual tests only when we have results of large prospective studies. These studies should compare different diagnostic methods and correlate the results of tests performed sequentially in neonates and young infants with the natural history of their disease process and eventual clinical outcome.

AIDS Serodiagnosis

Perinatally acquired infections and screening.

For hepatitis B, universal screening of pregnant women for HBsAg along with the combined use of hepatitis B vaccine and HBIG in infants of infected mothers appears to be the best way to detect and prevent vertically transmitted infection. Cytomegalovirus is the most common congenital viral infection, but the lack of a good screening test precludes its accurate and rapid diagnosis. For HPV-B19, larger and more controlled studies are needed to confirm the safety and effectiveness of fetal blood transfusions in the management of hydrops fetalis caused by this infection. Finally, the fact that most mothers of HSV- and toxoplasma-infected neonates have no history of infection, and are asymptomatic at the time of delivery, underscores the need for a high index of clinical suspicion in sick neonates.

Cytomegalovirus Infections

CSF viral antibodies. Evaluation in amyotrophic lateral sclerosis and late-onset postpoliomyelitis progressive muscular atrophy.

Serum and CSF from 48 patients with amyotrophic lateral sclerosis and six patients with late-onset postpoliomyelitis progressive muscular atrophy were investigated for the presence of antibody to poliovirus types 1, 2, and 3, coxsackie viruses B3 and B4, influenza A, measles, rubella, mumps, herpes simplex types 1 and 2, cytomegalovirus, varicella-zoster, and Toxoplasma gondii. These results were compared with those from 53 control patients with neuromuscular disease matched for age, sex, race, and poliovirus vaccine exposure. There was no difference either in distribution of serum or CSF antibody titers or the geometric-mean antibody titers. There was no evidence suggesting the presence of locally produced specific viral antibody within the CNS to any of the agents studied. In particular, there was no serological evidence to suggest an association between persistent infection with any poliovirus type and amyotrophic lateral sclerosis or late-onset postpoliomyelitis progressive muscular atrophy.

Adult

Subacute sclerosing panencephalitis in only one of identical twins. A seven-year follow-up.

We report a seven-year follow-up of identical twins, in one of whom subacute sclerosing panencephalitis (SSPE) developed. Primary measles infection occurred simultaneous in both twins at age 4. The affected twin sustained a grade 1 closed head injury within six months of her primary measles infection. At age 13, SSPE was diagnosed following the onset of personality change and myoclonic seizures. Measles antibody level was elevated in the serum and CSF. After remaining in stage 2 for five years, rapid mental and neurological deterioration occurred. Measles antibody level remained elevated, and oligoclonal IgG was present in both serum and CSF. Results of neurological examination as well as virological and immunological tests were normal in the unaffected twin. Besides the occurrence of head injury, factors known to be associated with SSPE were not obviously different in the twins. We have been unable to determine a difference that would easily explain the occurrence of SSPE in only one of two identical twins.

Adolescent

Induction of congenital hydrocephalus with mumps virus in rhesus monkeys.

Rhesus monkey fetuses were inoculated intracerebrally with wild-type mumps virus near the beginning of the last third of the gestation period. Within three days after inoculation, mumps virus was isolated from many fetal tissues. Thirteen animals receiving virus were delivered at term. Five of these showed slight to severe hydrocephalus. Hydrocephalus was most prominent in the posterior horns of the lateral ventricles, but other lesions occurred at various levels of the ventricular system. Virus was isolated from three animals at one day of age (two months after inoculation). However, mumps virus was not recovered from one-month-old monkeys. The recovery of mumps virus from newborn rhesus monkeys two months after inoculation suggests that attempts should be made to document similar persistence of the virus in humans. Furthermore, this model indicates that mumps virus infection in humans may result in hydrocephalus.

Amniotic Fluid

HLA types and immunity in multiple sclerosis.

HLA types and levels of humoral and cell-mediated immune responses to several antigens were studied in a large group of patients with multiple sclerosis, and in controls. Patients were more likely than controls to have the DRw2 antigen. They had higher mean antibody titers to measles but not to cytomegalovirus, herpes 1, or herpes 2, and had less competent cell-mediated responses. Antibody titers to measles were lower and cell-mediated immune responses were more effective in patients with the DRw2 antigen in patients than in patients without it. This apparent specificity for measles suggests that the etiology of multiple sclerosis is related to the immune response to measles or related viruses.

Antibodies, Viral

Congenital rubella.

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Antibodies, Viral

Experimental group B streptococcal infection in the rhesus monkey. I. Disease production in the neonate.

Group B streptococci (GBS) are responsible for serious infections of newborn infants. An experimental model for GBS infection was developed in the newborn rhesus monkey in order to obtain more information concerning the pathogenesis of such infections. A series of 29 newborn monkeys were inoculated with either type Ic or type III GBS or sterile broth. Fatal neonatal meningitis without associated pneumonia was produced consistently following intracerebral inoculation with either type Ic or type III; intracerebral inoculation with sterile broth produced no apparent disease. Variable disease production followed intravenous or intra-amniotic GBS inoculation, and clinical manifestations ranged from no apparent disease to fatal meningitis and pneumonia. This monkey model may be useful for further investigation of treatment and prevention of neonatal GBS infection.

Animals