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Biomedical subjects

G B Scott

Publications and source records attributed to G B Scott.

At least 19 recordsLinked to original sources

Effect of corticosteroids on survival of children with acquired immunodeficiency syndrome and Pneumocystis carinii-related respiratory failure.

The medical records of patients with acquired immunodeficiency syndrome were reviewed to evaluate the effect of our adoption to the pediatric population of the National Institutes of Health recommendation for adjunctive corticosteroid therapy in adults with Pneumocystis carinii pneumonia. In 21 episodes of P. carinii-related respiratory failure, only adjunctive corticosteroids were associated with a significant improvement in survival to successful removal of the tracheal tube, from a historical rate of 11% to 91%.

AIDS-Related Opportunistic Infections

The effects of HIV on cognitive and motor development in children born to HIV-seropositive women with no reported drug use: birth to 24 months.

OBJECTIVE: This study documents delays in the mental and motor functioning of infants perinatally infected with human immunodeficiency virus (HIV) while controlling for confounding effects of prenatal drug exposure, ethnicity, socioeconomic status, and maternal separation and death. METHODS: The cognitive and motor development of 126 infants born to nondrug-using, HIV-seropositive Haitian women was assessed at 3-month intervals through 24 months of age using the Bayley Scales of Infant Development. By 18 months of age, 28 of the infants were diagnosed as HIV-infected, and the 98 uninfected infants served as a control group. The infected and uninfected infants did not differ with respect to mean gestational age, birth weight, ethnicity, or rates of maternal separation and death. RESULTS: By 3 months of age, the mean mental and motor scores of the infected infants were significantly lower than those of the uninfected controls. Furthermore, the initial differences between the two groups increased over time, as many of the infected infants became increasingly delayed. Although the infected infants tended to perform more poorly than the uninfected infants, nearly one third of the infected infants exhibited relatively normal cognitive development and half demonstrated relatively normal motor development. CONCLUSIONS: Over the first 24 months of life, the mean rate of development of HIV-infected infants is significantly slower than that of noninfected infants born to seropositive mothers. This occurs even when the effects are not confounded with those of prenatal drug exposure.

Adult

Functional evidence that the principal DNA replication origin of the Streptomyces coelicolor chromosome is close to the dnaA-gyrB region.

The degree of overrepresentation of selected chromosomal genes in rapidly growing cultures of Streptomyces coelicolor was assessed by quantitative DNA hybridization analysis. The results are consistent with the hypothesis that the principal origin of replication is close to the dnaA-gyrB region, in the center of the linear chromosome, and that replication proceeds bidirectionally.

Chromosome Mapping

Clinical and immunological correlates of immune-complex-dissociated HIV-1 p24 antigen in HIV-1-infected children.

It has been reported that HIV-1 p24 antigen (p24 Ag) detection is improved after dissociation of immune complexes using acid treatment (ICD assay). In order to evaluate the clinical significance of p24 Ag detected by the standard assay and by the ICD assay in pediatric patients, we related these measurements to clinical status, level of p24 antibody, and percentage of CD4+ lymphocytes. Fifty-nine plasma specimens from 20 symptomatic HIV-1-infected children, collected prospectively over a 1-year period, were tested for these markers. Plasma was collected at the beginning of zidovudine therapy and approximately 7 and 12 months thereafter. Compared with the standard assay, the ICD assay showed a higher number of samples positive for p24 Ag (78% versus 34%) and an increase in the levels of p24 Ag (median value of 129 versus 24 pg/ml). The anti-p24 antibody level was inversely correlated with the p24 Ag level measured by either assay. Four children negative for p24 Ag by both assays had a stable clinical course. In contrast, 50% of the children negative by the standard assay but positive for ICD p24 Ag and 75% of the children positive by both assays had progression of disease. No patients were positive by the standard assay but negative by the ICD assay. Children whose plasma tested positive by both assays had lower percentages of lymphocytes that were CD4+ by comparison with children who were negative by both assays; children whose plasma tested positive only by the ICD assay formed an intermediate group.(ABSTRACT TRUNCATED AT 250 WORDS)

Antigen-Antibody Complex

Prognostic significance of oral lesions in children with perinatally acquired human immunodeficiency virus infection.

OBJECTIVE: To assess the prevalence and prognostic significance of oral lesions in children with human immunodeficiency virus infection. DESIGN: Clinical cohort study. SETTING: Children's Hospital Center at Jackson Memorial Hospital, Miami, Fla. PARTICIPANTS: Ninety-nine children with perinatally acquired human immunodeficiency virus infection examined longitudinally for oral lesions. INTERVENTIONS: None. MEASUREMENTS/MAIN RESULTS: Presence of oral lesions was determined by a pediatrician who had been trained in the diagnosis of oral lesions. The cumulative prevalence of lesions was 72% for oral candidiasis, 47% for parotid enlargement, and 24% for herpes simplex. The median time from birth to development of a lesion was 2.4 years for candidiasis, 4.6 years for parotid enlargement, and 5 years for herpes simplex. The median time from lesion to death was 3.4 years for patients with candidiasis, 5.4 years for patients with parotid enlargement, and 4.3 years for patients with herpes simplex. In a time-dependent proportional-hazards model, oral candidiasis was associated with a more rapid rate of progression to death (relative hazard, 14.2; 95% confidence interval, 4.8 to 41.8), while parotid enlargement was associated with a less rapid rate of progression to death (relative hazard, 0.38; 95% confidence interval, 0.16 to 0.88) and herpes simplex was unrelated to the rate of progression (relative hazard, 1.3; 95% confidence interval, 0.5 to 3.1). CONCLUSIONS: The presence of oral candidiasis and parotid enlargement confer important prognostic information and should be incorporated into decisions regarding therapy for HIV-infected children.

Child

The pharmacokinetics and safety of zidovudine in the third trimester of pregnancy for women infected with human immunodeficiency virus and their infants: phase I acquired immunodeficiency syndrome clinical trials group study (protocol 082). Zidovudine Collaborative Working Group.

OBJECTIVES: We measured the pharmacokinetics and safety of zidovudine in pregnant women infected with human immunodeficiency virus and their offspring. STUDY DESIGN: Asymptomatic human immunodeficiency virus-infected women with uncomplicated singleton gestations (28 to 36 weeks) underwent parenteral and oral zidovudine treatment during pregnancy and labor. Maternal and neonatal drug levels were measured at delivery and sequentially for 48 hours. Infants were followed up for 18 months. RESULTS: The total body clearance (26.3 +/- 10.1 ml/min/kg), mean terminal elimination phase zidovudine half-life (1.3 +/- 0.2 hours), and urinary zidovudine recovery were similar to values in nonpregnant adults. Essentially equivalent zidovudine levels in the mother and neonate at delivery implied little, if any, fetal zidovudine metabolism. The half-life of zidovudine in the neonates was tenfold that of the mother. No significant adverse effects were noted in the infant at birth or on follow-up. CONCLUSIONS: In both mothers and infants the drug appeared safe and well tolerated with no significant hematologic abnormalities.

Acquired Immunodeficiency Syndrome

Thermal stress on chickens in transit.

1. An artificial chicken, 'Gloria', was constructed to simulate heat exchanges of poultry during transport. Tests of the instrument in a wind tunnel showed it to have insulation properties similar to that of a live bird. 2. Gloria accompanied chickens in two types of transport modules, A (enclosed) and B (open). The average temperature difference between inside and outside the loaded vehicles when stationary and in motion were 14.0 and 7.6 for Type A and 8.8 and 6.0 for Type B. Average air movement while vehicles were in motion was 0.5 m/s for Type A and 3.3 m/s for Type B. 3. Measurements of sensible heat loss from Gloria at different temperatures and wind speeds were compared with published estimates of thermoneutral heat production and thermal insulation for well and poorly feathered chickens to estimate the range of thermal stresses likely to be experienced by chickens in transit. 4. The results showed that the combination of circumstances necessary to ensure thermal comfort for birds both at rest and in motion is very rare (e.g. only between 7 and 8 degrees C for well feathered birds in enclosed vehicles). It is, however, possible to ensure thermal comfort over a wide range of ambient air temperatures by appropriate control of air movement within the vehicle whether at rest or in motion.

Animals

Retinal antigen specific lymphocytes, TCR-gamma delta T cells and CD5+ B cells cultured from the vitreous in acute sympathetic ophthalmitis.

CD5+ B lymphocytes and TCR gamma-delta T lymphocytes, phenotypes implicated in the pathogenesis of autoimmune disease, were isolated from the vitreous in a case of acute sympathetic ophthalmitis. These cells were obtained using a method which allows the selective maintainance in vitro of in vivo activated T lymphocytes. Dual colour flow cytometry showed that after 3 days culture in IL-2 containing medium 61% of cells were CD5/CD19 + ve and 41% CD3/TCR gamma delta + ve. Of the total CD3 + ve population, 15% were gamma/delta negative. These cells formed a population which also responded in a proliferation assay to retinal antigens. Histologically the eye showed a marked mononuclear cell infiltration of the retina, ciliary body and choroid. Granulomatous lesions within the choroid contained lymphocytes, plasma cells and multinucleate giant cells. Immunocytochemistry showed lymphocyte populations to be predominantly CD2 + ve CD3 + ve T lymphocytes of the CD4 sub-set. Distribution of monocytes/macrophages throughout the lesions and restriction of B-lymphocytes to granulomata were all consistent with a DTH type reaction. Despite immunosuppressive therapy, the expression of activation antigens HLA-DR and ICAM-1 on infiltrating and resident ocular tissue cells was high, although IL-2 receptor (CD25) expression was virtually absent. Flow cytometric analysis of peripheral blood cells prior to treatment with Cyclosporin-A showed systemic activation of lymphocytes, with high levels of HLA-DR and CD25 expression and a raised CD4/CD8 ratio.

Antigens

Clinical manifestations, management and therapy of HIV infection in children.

Perinatal infection accounts for the majority of cases of HIV infection in children both in developed and developing countries. Transmission may occur in utero, intrapartum or postpartum as a result of breast-feeding. The actual risk of transmission through breast-feeding is unknown. The majority of infants reported to be infected through breast milk have been infected as a result of a recently acquired HIV infection in the mother. Infants with HIV infection frequently present with clinical symptoms early in life. There is a broad spectrum of clinical findings in paediatric HIV infection, with opportunistic infections and multiorgan system involvement being common. The management of infants born to seropositive mothers includes routine paediatric care as well as careful clinical and laboratory monitoring for evidence of HIV infection. Infants who are seronegative with normal clinical and immunological findings at 18 months of age are considered uninfected. The prognosis and outcome of infants with HIV infection have improved considerably with earlier diagnosis and the availability of specific antiviral therapy. Modalities of therapy include frequent medical evaluation, aggressive diagnosis and treatment of infection, prophylaxis for Pneumocystis carinii infection, the use of intravenous gamma-globulin and specific antiviral therapy, such as zidovudine, didanosine or other drugs in development through clinical trials. HIV infection in children is a chronic illness and requires a comprehensive, family-oriented approach to care. With longer survival, children require support systems and an atmosphere of care and understanding to give them a good quality of life as well as prolonged survival.

Child

Quantitative analysis of human immunodeficiency virus type 1 antibody reactivity by western immunoblots: evaluation of relative antibody levels in seropositive individuals and mothers.

A quantitative analysis of antibody responses to human immunodeficiency virus type 1 (HIV-1) proteins using Western immunoblots and 125I-labeled protein A is reproducible and can be validated. The antibody levels obtained by Western immunoblots were compared with stoichiometric p24 radioimmunoassay over a wide range of antibody (correlation coefficient, .94; P less than .001). Antibody levels to gp160 and gp120 were validated using purified antigens. Analysis of antibody levels from 31 seropositive individuals revealed a statistically significant correlation between antibody levels to p24 and the other viral proteins except gp120. Anti-gag p24 antibody was strongly correlated with antibodies to other env products, specifically gp41 and gp160. Using the validated assay, HIV-1-infected mothers of infants were found to have highly variable levels of antibody to all viral proteins. Mothers of infected infants did not differ significantly from mothers of uninfected infants in antibody pattern or levels to any viral protein including gp120.

Adult

Mycobacterium tuberculosis in children with human immunodeficiency virus type 1 infection.

A retrospective study was conducted at the Childrens Hospital Center at Jackson Memorial Hospital in Miami, FL, to evaluate the natural history of Mycobacterium tuberculosis infection in nine children with vertically acquired human immunodeficiency virus type 1 infection. The patients' ages ranged from 6 months to 7 years (median age, 42 months). Common presenting symptoms included prolonged fever, cough and anorexia. Only one patient had a positive tuberculin test. Five patients evidenced only pulmonary disease, three patients had pulmonary and extrapulmonary disease and one patient developed extrapulmonary tuberculosis (mastoiditis) and pulmonary interstitial disease that could not be attributed to mycobacterial infection because of lack of information. Organisms isolated before January, 1989, were susceptible to isoniazid and rifampin whereas isolates from three patients cultured after that time were resistant to multiple antituberculosis drugs. The median survival time after M. tuberculosis diagnosis for all children was 20 months. Our study suggests that children with human immunodeficiency virus type 1 infection who have tuberculosis have an increased risk for extrapulmonary disease. A high index of suspicion for the diagnosis of M. tuberculosis should be maintained in human immunodeficiency virus type 1-infected children with prolonged fever and respiratory symptoms. In areas of high endemicity of multidrug-resistant organisms, therapy with a broader panel of drugs may need to be instituted until susceptibility testing becomes available.

AIDS-Related Opportunistic Infections

Pediatric HIV-1 infection: a clinical overview.

Several questions remain unanswered including the timing of perinatal transmission, maternal factors predisposing to perinatal transmission of HIV-1, the best methods for early diagnosis in the neonate, and means of preventing perinatal HIV-1 infection. Significant advances have been made in the early diagnosis of HIV-1 infection, and now it is possible to make a diagnosis in most infants by 6 months of age. Unfortunately, not all these techniques are commercially available, so this capability is limited to certain institutions and laboratories. The natural history of HIV-1 infection in children continues to evolve, particularly with increased prophylaxis of P. carinii pneumonia and the availability of antiretroviral therapy. Our challenges for the future are to prevent perinatal transmission, to develop new and better therapies for opportunistic infections and HIV-associated complications, and to improve outcome and prognosis.

Child, Preschool

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

A hospital-based prospective study of perinatal infection with human immunodeficiency virus type 1.

Most infants with pediatric acquired immunodeficiency syndrome and infections with human immunodeficiency virus type 1 (HIV-1) are infected perinatally by their mothers. To determine the proportion of exposed infants who are infected, we conducted a hospital-based prospective study in HIV-1-infected women whose infants were delivered at a single metropolitan hospital in Miami, Fla. A population of uninfected women and their infants was also enrolled and followed longitudinally for 2 years to assess laboratory and clinical measurements. The median follow-up is now 18 months for 82 infants born to HIV-1-infected mothers. The proportion of infected infants in this group is 0.30 (25/82). None of the infants born to 110 HIV-1-seronegative mothers were seropositive. Infected infants were easily distinguished from noninfected infants by virus isolation. No single immunologic or hematologic measure was predictive of infection for all infants at risk for HIV-1 infection who were 6 months of age or younger. As a group, however, infected infants could be distinguished from uninfected index infants by a number of immunologic measures by 6 months of age; the absolute number of CD4+ lymphocytes and the CD4+/CD8+ lymphocyte ratio were the variables most predictive of infection. As in retrospective studies, clinical disease developed in 80% of infected infants within the first 24 months of life. This study provides documentation of HIV-1 perinatal transmission risk and early correlates of infection in young infants from a single hospital.

Acquired Immunodeficiency Syndrome

Aversiveness of motion and noise to broiler chickens.

1. The aversiveness of motion and noise to broiler chickens was examined using a passive avoidance technique. Birds were initially trained to peck a key a fixed number of times to obtain food. After training, food could still be obtained by key pecking, but feeding was immediately followed by 1 min exposure to noise or motion. Birds could delay or avoid exposure by delaying or avoiding key pecking, hence foregoing food. Reduced pecking rate was therefore taken as a measure of aversion. 2. In experiment 1, simultaneous motion and noise, but not noise alone, resulted in a significant decrease in pecking rate in comparison with baseline rates obtained after training. 3. In experiment 2 there was no significant difference in the pecking rates of 4 groups of broilers during training. However, after exposure to 1 of 4 types of motion, strongly significant differences in pecking rates were found between the groups. The mean latency to peak 3 times was significantly greater for birds exposed to gentle vibration, with a single jolt after 55 s, than for birds exposed to simple harmonic motion in either the horizontal or vertical plane. Birds exposed to circular motion in the horizontal plane had a significantly greater mean pecking latency than birds exposed to simple harmonic motion in the vertical plane. 4. Baseline latencies to keypeck in experiments 1 and 2 were longer than expected. In experiment 3 a direct comparison of baseline pecking was made between broilers and laying hens. The hens had significantly shorter pecking latencies.

Animals

Pediatric HIV infection. An update.

Human immunodeficiency virus infection is a leading cause of immunodeficiency in children. The epidemic in children parallels that in women since most infected women are in the child-bearing age groups. The risk of vertical transmission of HIV from an infected mother to her infant ranges from 13% to 39%. Diagnosis of infection in the infant is complicated by the passive transfer of antibody across the placenta, making the use of standard serologic tests to confirm infection difficult. In children less than 15 months of age, a positive p24 core antigen test, a positive viral culture or AIDS defining criteria with immune abnormalities are required for diagnosis. HIV infection in children is chronic and multisystem characterized by immunologic and clinical deterioration with a higher incidence of serious bacterial infections, neurologic disease, and lymphoid interstitial pneumonitis. The cornerstones of management include close medical follow-up, good nutrition, and prompt diagnosis and treatment of infections. Certain children will benefit from therapeutic modalities such as Pneumocystis carinii pneumonia prophylaxis and/or intravenous gamma globulin. The antiretroviral drugs have improved the quality of life and increased survival. Several newer antiviral agents are presently in clinical trials.

Acquired Immunodeficiency Syndrome