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Biomedical subjects

J F Modlin

Publications and source records attributed to J F Modlin.

At least 37 records · Page 2Linked to original sources
PubMed1993

Phase I evaluation of zidovudine administered to infants exposed at birth to the human immunodeficiency virus.

This study evaluated the safety, tolerability, and pharmacokinetics of zidovudine administered intravenously and orally to infants born to women infected with the human immunodeficiency virus. Thirty-two symptom-free infants were enrolled before 3 months of age. The pharmacokinetics of zidovudine were evaluated in each infant after single intravenously and orally administered doses of zidovudine on consecutive days, and during long-term oral administration of the drug for 4 to 6 weeks. As new patients were enrolled, doses of zidovudine were progressively increased from 2 to 4 mg/kg. Therapy was continued for up to 12 months in 7 of the infants proved to be infected with human immunodeficiency virus. Zidovudine was generally well tolerated; 20 children (62.5%) had anemia (hemoglobin level < 10.0 gm/dl) during therapy and 9 (28.1%) had neutropenia (neutrophil count < or = 750 cells/mm3); these hematologic abnormalities usually resolved spontaneously. The total body clearance of zidovudine increased significantly with age, from an average of 10.9 ml/min per kilogram in infants < or = 14 days of age to 19.0 ml/min per kilogram in older infants (p < 0.0001). Concurrently, there was a significant decrease in serum half-life from 3.12 hours in infants < or = 14 days to 1.87 hours in older infants (p = 0.0002). Oral absorption was satisfactory and bioavailability decreased significantly with age, from 89% in infants < or = 14 days to 61% in those > 14 days of age (p = 0.0002). Plasma concentrations of zidovudine were calculated to be in excess of 1 mumol/L (0.267 micrograms/ml) for 4.12 +/- 1.86 hours and 2.25 +/- 0.78 hours after oral doses of 2 mg/kg in infants younger than 2 weeks and 3 mg/kg in older infants, respectively. We conclude that zidovudine administered at oral doses of 2 mg/kg every 6 hours to infants aged less than 2 weeks and 3 mg/kg every 6 hours to infants older than 2 weeks resulted in plasma concentrations that are considered virustatic against human immunodeficiency virus. Zidovudine was well tolerated by infants at these doses.

Administration, Oral↗
PubMed1993

Aseptic meningitis in infants < 2 years of age: diagnosis and etiology.

Standard virologic methods were used to characterize the relative contribution of each of the enterovirus classes to the etiology of aseptic meningitis during a prospective study of this disease among children < 24 months old. Viruses were isolated in cell culture from 164 (60%) of 274 cases identified over 5 years and in newborn mice from only 2 of 104 remaining cell culture-negative cases. Serologic tests identified the viral pathogen in 3 additional cases. The group B coxsackieviruses and the echoviruses were implicated in 156 (92%) of the 169 laboratory-diagnosed cases. Forty-eight percent of all diagnosed cases were due to group B coxsackievirus serotypes 2, 4, and 5; 78% of all cases were attributable to only 8 of the 67 known enterovirus serotypes. Polioviruses were the only viruses isolated from 7 children, including a cerebrospinal fluid isolate from 1 child and a urine isolate from another. Disease was attributable to the group A coxsackie-viruses for only 3 cases.

Adenoviruses, Human↗
PubMed1993

Shedding of virulent poliovirus revertants during immunization with oral poliovirus vaccine after prior immunization with inactivated polio vaccine.

Fecal shedding of virulent revertant polioviruses was examined in isolates from infants previously immunized with > or = 1 dose of orally administered live attenuated polio vaccine (OPV) alone, enhanced-potency inactivated polio vaccine (EIPV) alone, or a combination of both. After administration of OPV alone, vaccine poliovirus serotypes were recovered in feces within 1 week and for as long as 31-60 days in 30%-80% of subjects after 1 or 2 doses and in 30%-50% after immunization with > or = 3 doses. No revertant poliovirus shedding was observed after OPV challenge in subjects immunized previously with > or = 3 doses of OPV. However, fecal shedding of revertant poliovirus after OPV challenge was observed in 50%-100% of subjects previously immunized with > or = 3 doses of the EIPV. These findings suggest that prior immunization with EIPV does not prevent fecal shedding of revertant polioviruses after subsequent reexposure to OPV.

Feces↗
PubMed1993

Aseptic meningitis in infants younger than 2 years of age: acute illness and neurologic complications.

OBJECTIVE: We report the clinical features and cerebrospinal fluid (CSF) laboratory values for 277 children younger than 24 months of age with aseptic meningitis who were prospectively evaluated at three Baltimore hospitals between July 1986 and December 1990. A major objective was to define the incidence, etiology, and outcome of neurologic complications occurring during the acute illness. METHODS: Cases were identified by surveillance in the ambulatory care departments of each of the three hospitals, pertinent historical and clinical data were obtained by interview of the parents and by review of the medical records, initial CSF laboratory values were recorded, and appropriate specimens were submitted to determine the viral etiology. A subset of 216 children who participated in a long-term natural history study were followed periodically with neurologic examinations and formal neurodevelopmental testing. RESULTS: Most cases occurred in very young infants; 63.5% of patients were 8 weeks of age or younger, and 84.1% were younger than 16 weeks of age. In this very young cohort, the dominant symptoms were fever and irritability; only 8.7% had evidence of meningeal irritation at the initial examination. The acute illness was complicated by either complex seizures, physical evidence of increased intracranial pressure, or coma in 25 (9.0%) cases. Within the age group under study, these complications were each significantly more likely to occur in patients older than 12 weeks of age than in younger infants. The risk of neurologic complications was similar among infants infected with group B coxsackieviruses and echoviruses, the two major enterovirus classes observed to cause disease. Acute central nervous system (CNS) complications could not be correlated with extremely abnormal CSF laboratory indices. Importantly, there was no risk of long-term neurologic sequelae attributable to acute CNS complications. CONCLUSIONS: While approximately 9% of infants and children younger than 2 years of age with aseptic meningitis experience acute CNS complications in the form of complex seizures, increased intracranial pressure, or coma, the prognosis for long-term cognitive development appears to be as favorable as the prognosis for children with aseptic meningitis who do not experience these complications.

Acute Disease↗
PubMed1992

Localization of human immunodeficiency virus core antigen in term human placentas.

Evidence of human immunodeficiency virus (HIV) replication was sought in human placentas obtained at term from pregnancies complicated by maternal HIV infection. Placentas were obtained from the pregnancies of 19 HIV-seropositive women, 4 women who were seronegative, and 4 untested women with no risk factors for HIV infection. These placentas were each examined by immunoperoxidase immunocytochemistry using monoclonal anti-p24/55 antibodies. In addition, minced placental tissue from 11 of the seropositive pregnancies and the 3 seronegative pregnancies were co-cultivated with stimulated human peripheral blood mononuclear cells. The clinical status of the infants born to the HIV-seropositive women was assessed when the infants were 8 to 28 months of age. P24/55 antigen was detected in 5 of the 19 placentas of the HIV-seropositive pregnancies and in none of the 8 placentas of seronegative or low-risk pregnancies. This HIV core viral antigen was located exclusively in the cytoplasm of villous cells with morphological characteristics of macrophages. The HIV antigen-containing cells were very sparsely distributed. Staining of the trophoblast was not observed in any placental specimen. Human immunodeficiency virus was isolated in culture from 3 of the 11 placentas from seropositive pregnancies. Clinical follow-up has not revealed a relationship between infection of the infant and either p24/55 antigen identification or isolation of virus from the placenta. Virological and histological evidence of HIV replication is found in approximately one fourth of placentas obtained at term from pregnancies complicated by maternal HIV infection. Replicating virus appears localized to sparse macrophages located within the chorionic villi, but specifically not within the trophoblastic layer.(ABSTRACT TRUNCATED AT 250 WORDS)

Acquired Immunodeficiency Syndrome↗
PubMed1991

Early diagnosis of perinatal HIV infection by detection of viral-specific IgA antibodies.

OBJECTIVES: To evaluate the clinical utility of a human immunodeficiency virus (HIV)-IgA serological assay for diagnosis of perinatally acquired HIV infection. DESIGN: Coded serum samples prospectively collected from children born to HIV-infected mothers and uninfected mothers were analyzed by HIV-IgA immunoblot. SETTING: A university hospital in Baltimore, Md, and an outpatient clinic in Port-au-Prince, Haiti. POPULATION: Five hundred thirty-nine serum samples were obtained sequentially from 278 children born to HIV-infected women (116 from The Johns Hopkins Hospital and 62 from Port-au-Prince) and from 42 control children born to HIV-seronegative children in Port-au-Prince. OUTCOME MEASURES: Results from the HIV-IgA serological assays were compared with the known infection status of the child at 15 months of age as determined by the standard IgG Western blot and the clinical classification of the Centers for Disease Control. Sensitivity, specificity, and predictive values were calculated at different ages and collectively for children 3 months of age or older. RESULTS: The HIV-IgA assay was positive in one of six specimens from HIV-infected children under 1 month of age, six of nine specimens from infected children at 3 months of age, and 160 of 161 specimens from 47 HIV-infected children 6 months of age or older. Of 334 specimens from 243 uninfected children, 333 were negative by the HIV-IgA assay. The overall sensitivity and the specificity of the IgA assay for children older than 3 months of age were 97.6% and 99.7%, and the positive and negative predictive values were 99.4% and 98.7%, respectively. CONCLUSION: Although the HIV-IgA assay had a low sensitivity within the first months of life, the high sensitivity, specificity, and predictive values of this assay demonstrate its utility for the diagnosis of perinatally acquired HIV infection after the third month of age. Early diagnosis with this relatively simple and inexpensive serological assay should aid in the implementation of antiviral therapy and provide useful information for the care of children born to HIV-infected mothers in both developing and developed countries.

Blotting, Western↗
PubMed1991

A multicenter trial of oral zidovudine in children with advanced human immunodeficiency virus disease. The Protocol 043 Study Group.

BACKGROUND AND METHODS: Zidovudine has been shown to be an effective antiretroviral treatment in adults with human immunodeficiency virus (HIV) infection. We examined the safety of zidovudine and the tolerance of and therapeutic response to the drug in 88 children with advanced HIV disease. During a 24-week outpatient trial, zidovudine (180 mg per square meter of body-surface area per dose) was given by mouth every six hours and serial measurements were made of clinical, immunologic, and virologic indexes. Children who completed 24 weeks of treatment were permitted to continue receiving zidovudine. RESULTS: Of the 88 children (mean age, 3.9 years; range, 4 months to 11 years), 61 completed the initial 24-week trial, and 49 continued to receive zidovudine for up to 90 weeks (median follow-up, 56 weeks). The patients generally tolerated zidovudine well. One or more episodes of hematologic toxicity occurred in 54 children (61 percent)--anemia (hemoglobin level, less than 75 g per liter) in 23 children (26 percent) and neutropenia (neutrophil count, less than 0.75 x 10(9) per liter) in 42 (48 percent). Many of these abnormalities resolved spontaneously, but 30 children required transfusions or a modification of the dose of zidovudine. Only three children had to stop receiving the drug because of hematologic toxicity. Kaplan-Meier analysis demonstrated that the probability of survival was 0.89 after 24 weeks and 0.79 after 52 weeks. There was marked improvement in weight gain, cognitive function (mainly in children less than 3 years old), serum and cerebrospinal fluid concentrations of p24 antigen, and the proportion of cerebrospinal fluid cultures negative for HIV. CD4+ lymphocyte counts (mean at base line, 0.263 x 10(9) per liter) improved during the first 12 weeks, although the improvement was not sustained through the 24th week. CONCLUSIONS: Zidovudine in a dose of 180 mg per square meter every six hours can be safely administered to children with advanced HIV disease. The resultant clinical, immunologic, and virologic improvements in children are similar to those reported with zidovudine in adults.

Acquired Immunodeficiency Syndrome↗
PubMed1991

Microbiology of chronic sinusitis in children.

To better understand the factors involved in chronic sinusitis in childhood, we cultured the sinuses, middle meatus, and nasopharynx in 39 children requiring surgical intervention. Sixty-nine percent of these patients had other medical problems, including asthma (49%) and immunologic compromise (18%). We cultured coagulase-negative staphylococcus in 18 patients, Streptococcus viridans in 14 patients, normal flora in 10 patients, Staphylococcus aureus in nine patients, group D streptococcus in five patients, Corynebacterium in five patients, Haemophilus influenzae in three patients, Neisseria in three patients, and Streptococcus pneumoniae, group A streptococcus, Escherichia coli, Pseudomonas aeruginosa, Klebsiella oxytoca, Propionibacterium acnes, Actinomyces, and an anaerobic gram-negative bacillus in one patient each. Cultures yielded no growth in nine patients. A strong association between cultures of the middle meatus obtained ipsilaterally and cultures of the maxillary (83%) and ethmoid sinuses (80%) occurred. A poor correlation was found between cultures of the nasopharynx and maxillary (45%) and ethmoid sinuses (49%). All seven patients who had both maxillary and ethmoid sinus cultures showed the same organisms in both sinuses. Only 41% of organisms were found on both sides when procedures were performed bilaterally. Cultures of the middle meatus appear to be sensitive and specific for organisms within sinuses. The presence of predominantly nonvirulent organisms in low titers suggests that additional factors other than bacterial overgrowth contribute to the pathogenesis of chronic sinusitis in children.

Adolescent↗
PubMed1991

Mucosal immunity induced by enhance-potency inactivated and oral polio vaccines.

Oral polio vaccine (OPV) is recommended for routine immunization in the United States in part because of its ability to induce intestinal and pharyngeal immunity to reinfection. Mucosal immunity produced by OPV and enhanced-potency inactivated polio vaccine (E-IPV) was compared by challenging vaccines with type 1 OPV. Fewer OPV (25%) than E-IPV (63%) vaccinees excreted OPV virus in stool after challenge. The mean stool virus titer was higher and the duration of shedding longer among E-IPV excreters. Only one E-IPV and three OPV vaccinees shed virus in the pharynx after challenge. Prechallenge serum neutralizing antibody levels were not statistically different among E-IPV vaccinees who did and did not shed virus; these levels were much higher than those of OPV vaccinees. Poliovirus-specific IgA levels in stool did not correlate with viral excretion. E-IPV was less effective than OPV in preventing and limiting intestinal infection, even though it induced higher postvaccination serum antibody levels.

Antibodies, Viral↗
PubMed1991

Mucosal immunity following oral poliovirus vaccine and enhanced potency inactivated poliovirus vaccine immunization.

Mucosal immunity is considered to be an important barrier for inhibiting person-to-person transmission of naturally occurring (wild type) poliovirus infection. This review briefly summarizes the results of a previously published study in which 79 oral poliovirus vaccine (OPV) vaccinated children and 93 enhanced-potency inactivated poliovirus vaccine (IPV) children were challenged with one of two doses of type 1 OPV virus to test the oropharyngeal and gastrointestinal mucosal immunity conferred by each type of poliovirus vaccine. Although both OPV and IPV produced excellent oropharyngeal immunity, OPV was clearly superior in decreasing fecal shedding of the challenge virus.

Child, Preschool↗
PubMed1991

Focal encephalitis with enterovirus infections.

We report on four pediatric patients with Enterovirus infections who were admitted to the hospital with signs or symptoms of acute, focal encephalitis. All four experienced focal seizures. Each had a cerebrospinal fluid pleocytosis at the initial lumbar puncture. In all four patients the diagnosis of herpes simplex encephalitis was entertained. Each child improved spontaneously within a few days of admission to the hospital, and only one had residual neurologic abnormalities at the time of discharge. A brief review of these cases, and three additional cases from the literature, indicate that the enteroviruses, particularly the group A Coxsackieviruses, are rare causes of acute focal encephalitis in children and adolescents.

Adolescent↗
PubMed1990

The humoral immune response to type 1 oral poliovirus vaccine in children previously immunized with enhanced potency inactivated poliovirus vaccine or live oral poliovirus vaccine.

Sixty-one children who had previously received three doses of enhanced potency inactivated poliovirus vaccine (epIPV) at 2, 4, and 18 months of age and 56 children who had previously received oral poliovirus vaccine (OPV) according to the same schedule were challenged with a single dose of monovalent, type 1 oral poliovirus vaccine (OPV1) between 19 and 52 months of age. Before the OPV1 challenge, the previously epIPV-immunized recipients had a geometric mean poliovirus type 1 microneutralization antibody titer (geometric mean titer [GMT]) of 11.1 IU, which was significantly higher than the prechallenge GMT of 2.2 IU among the children who had previously received OPV. Three weeks after the OPV1 challenge, the GMTs for the epIPV-immunized recipients and the OPV-immunized recipients were 35.3 IU and 5.1 IU, respectively. For the epIPV-immunized recipients, both the prechallenge GMT and the postchallenge GMT were dependent on the D antigen content of the vaccine that they had previously received. A fourfold or greater rise in poliovirus type 1 antibody occurred after the OPV1 challenge in 50.9% of the epIPV-immunized children and in 28.6% of the OPV-immunized children; this difference was statistically significant. For both groups, antibody boosts were inversely correlated with the pre-challenge serum antibody titer. However, the epIPV-immunized children consistently were more likely to boost than the OPV-immunized children at equivalent levels of prechallenge antibody. This experience indicated that OPV1 administration effectively raises the level of serum antibody in children previously immunized with three doses of epIPV, especially in children with lower levels of preexisting antibody. This booster response was superior to the booster response of children who received three doses of OPV.

Antibodies, Viral↗
PubMed1990

Comparative evaluation of immunization with live attenuated and enhanced-potency inactivated trivalent poliovirus vaccines in childhood: systemic and local immune responses.

Serum neutralizing, nasopharyngeal neutralizing, and IgA antibodies were determined in 123 infants immunized with one of four schedules containing live oral vaccine (OPV), inactivated vaccine (IPV), or combinations of the two trivalent poliovirus vaccines: OPV-OPV-OPV, IPV-IPV-IPV, IPV-OPV-OPV, or IPV-IPV-OPV. Nearly 100% of individuals formed serum neutralizing antibodies. The highest geometric mean titer (GMT) of antibody to polioviruses 1, 2, and 3 occurred in groups IPV-IPV-OPV, IPV-OPV-OPV, and IPV-IPV-IPV, respectively. Local neutralizing and IgA antibody responses were detected in 41%-88% and 75%-100%, respectively. Peak GMT of nasopharyngeal antibodies differed minimally between immunization groups. The data suggest that incorporation of at least one dose of IPV at the start of the immunization schedule tends to increase systemic as well as local antibody production.

Antibodies, Viral↗
PubMed1988

Prevalence of enteric pathogens in homosexual men with and without acquired immunodeficiency syndrome.

We studied 388 homosexual or bisexual men from the Baltimore-Washington area to define the spectrum of enteric pathogen carriage in a population at high risk for "gay bowel syndrome" in association with human immunodeficiency virus infection. Seventy-seven patients with acquired immunodeficiency syndrome, 68 gay men with symptoms of acute diarrhea or proctitis, and 243 gay men without gastrointestinal symptoms and participating in a natural history study of human immunodeficiency virus infection were selected for study. Approximately 12% of the asymptomatic men harbored at least one enteric pathogen; the most frequently recovered were Chlamydia trachomatis, herpes simplex virus, and Giardia lamblia. Men carrying a pathogen were more likely to be human immunodeficiency virus seropositive (48%) than men without a pathogen (25%) (p = 0.018), more likely to have fewer T helper cells (p = 0.015), and more likely to have a mucopurulent exudate (p = 0.014). We recovered an agent of enteric disease from 68% of gay men presenting with diarrhea or proctitis. Campylobacter species, herpes simplex virus, Neisseria gonorrhoeae, C. trachomatis, G. lamblia, and Shigella species were identified most frequently. The most common pathogen associated with diarrhea in acquired immunodeficiency syndrome was Cryptosporidium (16% of 49 cases). Other agents identified were Clostridium difficile, Vibrio parahemolyticus, Campylobacter species, G. lamblia, Isospora, and cytomegalovirus. Approximately half of the identifiable etiologic agents of diarrhea in acquired immunodeficiency syndrome patients were treatable with antibiotics, but these agents required special culture procedures for detection.

Acquired Immunodeficiency Syndrome↗