Search PubMed⌕ Search

Biomedical subjects

T Fenton

Publications and source records attributed to T Fenton.

At least 19 recordsLinked to original sources
PubMed2002

Effect of soil compaction on organic carbon amounts and distribution, South-Central Iowa.

Soils on the Mormon Trail have been compacted for over 150 years. Bulk density, carbon, and nitrogen samples were taken in 5-cm increments to 20 cm. Bulk density was determined using rings of known volume; total carbon and nitrogen with a LECO CHN-600. Total above ground biomass (AGB) samples were collected by clipping vegetation within a 0.25 m2 frame and were analyzed for carbon. Statistical comparisons were made using a t-test (alpha = 0.05). Bulk density was higher in the on-trail soils from 5 to 20 cm; soil carbon and C/N ratios were higher in the off-trail soils from 10 to 20 cm. AGB and AGB carbon is significantly less on the trail. Results indicate the compacted layer on the trail alters the soil carbon pool by limiting additions of fresh organic matter to the soil, limiting vegetative production, and by "pooling" carbon additions in the upper 10 cm of the soil.

Carbon↗
PubMed2001

Human immunodeficiency virus type 1 (HIV-1) gp120-specific antibodies in neonates receiving an HIV-1 recombinant gp120 vaccine.

Infants born to human immunodeficiency virus type 1 (HIV-1)-infected mothers were immunized at birth and at ages 4, 12, and 20 weeks with low-, medium-, or high-dose recombinant gp120 vaccine with MF59 adjuvant (HIV-1(SF-2); n=52) or with MF59 alone as a placebo (n=9). An accelerated schedule (birth and ages 2, 8, and 20 weeks) was used for an additional 10 infants receiving the defined optimal dose and for 3 infants receiving placebo. At 24 weeks, anti-gp120 ELISA titers were greater for vaccine-immunized than for placebo-immunized infants on both schedules, and 87% of vaccinees had a vaccine-induced antibody response. At 12 weeks, antibody titers of infants on the accelerated vaccine schedule exceeded those of infants receiving placebo (4949 vs. 551; P=.01), and 63% of the vaccinees met the response criteria. Thus, an accelerated schedule of gp120 vaccinations generated an antibody response to HIV-1 envelope distinct from transplacental maternal antibody by age 12 weeks. These results provide support for further studies of vaccine strategies to prevent mother-to-infant HIV-1 transmission.

AIDS Vaccines↗
PubMed2001

Safety of 2 recombinant human immunodeficiency virus type 1 (HIV-1) envelope vaccines in neonates born to HIV-1-infected women.

To determine the safety of 2 candidate vaccines against human immunodeficiency virus type 1 (HIV-1), a randomized, placebo-controlled, multicenter trial compared low, medium, and high doses of the vaccines or an adjuvant among infants born to HIV-infected women. No local or systemic reactions of grade 2 or greater were reported 48 h after the subjects underwent immunization. Grade 3 or 4 chemistry toxicities occurred in 5 (3%) and grade 3 or 4 hematologic toxicities in 17 (11%) of 154 vaccinated subjects (not significantly different from 29 adjuvant recipients). CD4(+) cell percentages of < or = 20% occurred at least once in 9 vaccinated subjects and 1 control subject. Sustained CD4(+) cell percentages of < or = 20% occurred in 4 HIV-infected children. Fourteen infants (8%) were confirmed to be HIV-infected; median CD4(+) cell counts among these children were 2074, 1674, 1584, and 821 cells/mm(3) at birth and weeks 24, 52, and 104, respectively. Thus, both vaccines were safe and well tolerated in neonates, and there was no evidence of accelerated immunologic decline in HIV-infected infants.

AIDS Vaccines↗
PubMed2001

Nevirapine pharmacokinetics in pregnant women and in their infants after in utero exposure.

The safety, toxicity and pharmacokinetics of nevirapine were studied in HIV-infected pregnant women beginning chronic therapy late in the third trimester and in their infants. Initial dose pharmacokinetic profiles in the pregnant women were similar to those seen in nonpregnant adults. Serum nevirapine concentrations fell below the 100-ng/ml target concentration by Day 7 of life in four infants, suggesting that nevirapine elimination is accelerated in these infants compared with newborns whose mothers receive only a single intrapartum nevirapine dose.

Adult↗
PubMed2001

Dose-finding designs for HIV studies.

We present a class of simple designs that can be used in early dose-finding studies in HIV. Such designs, in contrast with Phase I designs in cancer, have a lot of the Phase II flavor about them. Information on efficacy is obtained during the trial and is as important as that relating to toxicity. The designs proposed here sequentially incorporate the information obtained on viral reduction. Initial doses are given from some fixed range of dose regimens. The doses are ordered in terms of their toxic potential. At any dose, a patient can have one of three outcomes: inability to take the treatment (toxicity), ability to take the treatment but insufficient reduction in viral load (viral failure), and ability to take the treatment as well as a sufficient reduction of viral load (success). A clear goal for some class of designs would be the identification of the dose leading to the greatest percentage of successes. Under certain assumptions, which we identify and discuss, we can obtain efficient designs for this task. Under weaker, sometimes more realistic assumptions, we can still obtain designs that have good operating characteristics in identifying a level, if such a level exists, having some given or greater success rate. In the absence of such a level, the designs will come to an early closure, indicating the ineffectiveness of the new treatment.

Anti-HIV Agents↗
PubMed2000

Recombinant CD4-IgG2 in human immunodeficiency virus type 1-infected children: phase 1/2 study. The Pediatric AIDS Clinical Trials Group Protocol 351 Study Team.

The use of recombinant CD4-IgG2 in pediatric human immunodeficiency virus type 1 (HIV-1) infection was evaluated by single and multidose intravenous infusions in 18 children in a phase 1/2 study. The study drug was well tolerated, and dose proportionality was observed in terms of area under time-concentration curve and peak serum concentration. Acute decreases of >0.7 log(10) copies/mL in serum HIV-1 RNA concentration were seen in 4 of the 6 children treated with 4 weekly 10 mg/kg doses. At 14 days after treatment, 3 children had sustained reductions in serum HIV-1 RNA; the other children had rebounded to baseline levels or above. By 28 days after therapy, the peak HIV-1 cellular infectious units was reduced in all 6 children, including the 2 who had experienced an earlier transient increase in values. Thus, recombinant CD4-IgG2 treatment of HIV-1-infected children appears to be well tolerated and capable of reducing HIV-1 burden.

Adolescent↗
PubMed2000

Patterns of plasma human immunodeficiency virus type 1 RNA response to highly active antiretroviral therapy in infected children.

This study examined the rate of decline in plasma human immunodeficiency virus type 1 (HIV-1) RNA levels to <400 and <50 copies/mL in children receiving highly active antiretroviral therapy (HAART) consisting of efavirenz, nelfinavir, and 1 or 2 nucleoside reverse-transcriptase inhibitors. Children receiving HAART achieved a plasma HIV-1 RNA level <400 copies/mL by a median of 4 weeks after initiation of therapy and a decline to <50 copies/mL by 20 weeks. Baseline plasma HIV-1 RNA levels affected the likelihood of achieving potent and sustained virus suppression, and children whose CD4 lymphocyte counts increased >70 cells/microL by 20 weeks on therapy were more likely to achieve durable virological and immunological benefit. These data provide time frames for virus suppression after the initiation of HAART that should be useful in evaluating the potential efficacy and durability of response of newly instituted combination antiretroviral therapy in HIV-1-infected children.

Adolescent↗
PubMed2000

Use of human immunodeficiency virus (HIV) human hyperimmune immunoglobulin in HIV type 1-infected children (Pediatric AIDS clinical trials group protocol 273).

The clinical, immunologic, and virologic effects and the pharmacokinetics of human immunodeficiency virus (HIV) human hyperimmune immunoglobulin (HIVIG) were assessed in 30 HIV-infected children aged 2-11 years. All had moderately advanced disease with an immune complex-dissociated (ICD) p24 antigen >70 pg/mL and were on stable antiviral therapy. Three groups of 10 children received 6 monthly infusions of 200, 400, or 800 mg/kg of HIVIG, and serial immunologic and virologic assays were performed. HIVIG doses as high as 800 mg/kg were safe and well tolerated. The half-life of HIVIG, determined by serial p24 antibody titers, was 13-16 days, the volume of distribution was 102-113 mL/kg, and clearance was 5.6-6.0 mL/kg/day. Plasma ICD p24 decreased during the infusions, but CD4 cell levels, plasma RNA copy number, cellular virus, immunoglobulin levels, and neutralizing antibody titers were minimally affected by the infusions. Clinical status did not change during the 6-month infusion and 3-month follow-up periods.

Cells, Cultured↗
PubMed2000

Lymphoproliferative responses to recombinant HIV-1 envelope antigens in neonates and infants receiving gp120 vaccines. AIDS Clinical Trial Group 230 Collaborators.

Children of mothers infected with human immunodeficiency virus type 1 (HIV-1) were immunized at birth and at 1, 3, and 5 months with 1 of 3 doses of recombinant gp120 vaccines prepared from SF-2 or MN strains of HIV-1. A total of 126 children were not infected; 21 received adjuvant only. Vaccine recipients developed lymphoproliferative responses on >/=2 occasions, responding more often to homologous HIV-1 antigens than did adjuvant recipients (56% vs. 14%; P<.001). Responses were appreciated after 2 immunizations and were maintained for >84 weeks after the last immunization. An accelerated immunization schedule (birth, 2 weeks, 2 months, and 5 months) with the lowest dose of the SF-2 vaccine produced responses in all 11 vaccinees by 4 weeks. Responses to heterologous envelope antigens were also detected. Immune responses to vaccination are achievable at an age when some infection (perinatal or breast milk exposure related) may be prevented.

AIDS Vaccines↗
PubMed1999

Combination therapy with efavirenz, nelfinavir, and nucleoside reverse-transcriptase inhibitors in children infected with human immunodeficiency virus type 1. Pediatric AIDS Clinical Trials Group 382 Team.

BACKGROUND: Consistent long-term viral suppression has been difficult to achieve in children with human immunodeficiency virus type 1 (HIV-1) infection. We tested the safety and antiviral efficacy of a novel combination consisting of efavirenz, nelfinavir, and one or more nucleoside reverse-transcriptase inhibitors in 57 children previously treated with only nucleoside reverse-transcriptase inhibitors. METHODS: The children were monitored for 48 weeks after the initiation of therapy. We assessed plasma concentrations of efavirenz and nelfinavir, plasma HIV-1 RNA levels, and lymphocyte subpopulations. RESULTS: At base line, the 57 HIV-1-infected children (age range, 3.8 to 16.8 years) had a median of 699 CD4 cells per cubic millimeter and 10,000 copies of HIV-1 RNA per milliliter of plasma. The most common treatment-related effects of at least moderate severity were rash (in 30 percent of children), diarrhea (in 18 percent), neutropenia (in 12 percent), and biochemical abnormalities (in 12 percent). Serious side effects were uncommon. The mean values for the area under the curve for efavirenz and nelfinavir corresponded to expected values. In an intention-to-treat analysis, 76 percent of children had plasma HIV-1 RNA levels of less than 400 copies per milliliter after 48 weeks of therapy and 63 percent had levels of less than 50 copies per milliliter. A high plasma HIV-1 RNA level at base line significantly decreased the likelihood that plasma levels of HIV-1 RNA would become undetectable during treatment. CONCLUSIONS: In HIV-1-infected children who were previously treated with nucleoside reverse-transcriptase inhibitors, the combination of efavirenz, nelfinavir, and nucleoside reverse-transcriptase inhibitors was generally well tolerated and had a potent and sustained antiviral effect.

Adolescent↗
PubMed1999

Axonal cytoskeletal responses to nondisruptive axonal injury and the short-term effects of posttraumatic hypothermia.

In human diffuse axonal injury (DAI), axons are exposed to transient tensile strain. Over the ensuing several hours, injured axons enter a "pathological cascade" of events that lead to secondary axotomy. Use of animal models of traumatic axonal injury (TAI) has allowed description of a number of pathological changes before axotomy occurs, including structural and functional changes in the axolemma, disorientation, and/or loss of microtubules, either compaction and/or dispersion of neurofilaments together with focal compaction at sites where continuity of the axolemma is lost. Recent literature suggests that use of hypothermia may improve behavioral outcomes or reduce the number/density of injured axons in which axonal transport is altered after TAI. But there is presently no ultrastructural, pathological explanation as to how hypothermia may act at the level of the axon to reduce posttraumatic loss of axoplasmic transport. In this study, we tested the hypothesis that posttraumatic hypothermia may ameliorate (a) alteration of axonal transport and (b) early pathological changes in the axonal cytoskeleton prior to secondary axotomy. We have undertaken a pilot study within 4 h of stretch injury to adult guinea pig optic nerve axons as a model of TAI and applied stereological techniques to assess differences in pathology in animals either maintained at 37.5 degrees C or cooled to 32-32.5 degrees C for 2 or 4 h after injury. We provide quantitative evidence that posttraumatic hypothermia significantly reduces the number of axons labelled for beta-APP, a marker for disruption of fast axonal transport, and reduces the loss of microtubules and compaction of neurofilaments, which occurs in normothermic animals over the first 4 h after injury.

Amyloid beta-Protein Precursor↗
PubMed1999

A nationwide survey of financing health-related services for special education students.

The Individuals with Disability Education Act (IDEA) requires state educational systems to provide school-based, health related services (RS). This survey determined the financing arrangements used by states for health-related services for school-aged children with disabilities. A survey was sent to directors of special education, Medicaid, and public health departments in each of the 50 states. Financial patterns for RS were sought at the state level for children ages 3-21 with disabilities for the 1993-1994 school year, the most recent year for which complete financial data were available. Univariate analyses probed the relationship between systems' variables and the extent of Medicaid usage by local education agencies. Respondents reported that schools tapped traditional health resources to supplement educational dollars in paying for related services in schools. Medicaid was by far the most common source with 29 states reporting established mechanisms for recouping Medicaid dollars and 10 states reporting phase-in activities. Seventeen states reported that departments of public health played some role in administration, training, and demonstrations, but only six states provided specific dollars for related services through the department. Use of private insurance was reported sporadically with only one state indicating a specific state-level program. Correlates of increased Medicaid usage were presence of interagency agreements (IAAs) (OR 11.1, p = 0.002), having specific personnel for school-based medical assistance (OR 17.7, p = 0.001), and utilizing school nursing services as a Medicaid optional service (OR 4.2, p = 0.048).

Adolescent↗
PubMed1999

Recombinant human gamma interferon in human immunodeficiency virus-infected children: safety, CD4(+)-lymphocyte count, viral load, and neutrophil function (AIDS Clinical Trials Group Protocol 211).

Nineteen children with human immunodeficiency virus (HIV) infection were treated with recombinant human gamma interferon (rIFN-gamma) (50 microg/m2 subcutaneously three times each week during weeks 1 through 12 and 100 microg/m2 subcutaneously three times each week during weeks 13 through 24) in a phase I/II clinical trial. All children continued to receive previously prescribed therapy with oral zidovudine or didanosine. Children were assessed clinically and with laboratory studies during 24 weeks of study treatment and for 12 weeks after completion of rIFN-gamma therapy. In general, rIFN-gamma therapy was well tolerated. There were two clinical or laboratory adverse events thought to be possibly or probably study drug associated. One child developed acute pancreatitis; another child developed granulocytopenia. Median CD4(+)-lymphocyte counts and plasma HIV RNA concentrations did not change significantly during therapy. In vitro neutrophil bactericidal activity against Staphylococcus aureus and superoxide production were not significantly affected by rIFN-gamma therapy. We conclude that rIFN-gamma therapy in HIV-infected children receiving single-agent antiretroviral therapy is safe and does not produce consistent changes in CD4(+)-lymphocyte count, plasma HIV RNA concentration, or in vitro neutrophil function.

Anti-HIV Agents↗
PubMed1998

Safety and immunogenicity of HIV recombinant envelope vaccines in HIV-infected infants and children. National Institutes of Health-sponsored Pediatric AIDS Clinical Trials Group (ACTG-218).

Study objectives were to evaluate the safety and immunogenicity of three HIV recombinant glycoproteins in HIV-infected infants and children between 1 month and 18 years of age with asymptomatic (P-1) infection. Using Chiron rgp 120 (SF-2) 15 or 50 microg; MicroGeneSys rgp 160 (IIIB) 40 or 320 microg; Genentech rgp120 (MN) 75 or 300 microg; or adjuvant control (Alum or MF-59), children were randomized to a double-blind, placebo-controlled, dose-escalating study of vaccine administered intramuscularly at entry and 1, 2, 3, 4, and 6 months later. No adverse events were attributed to study vaccines. Between 30% and 56% of volunteers exhibited a lymphoproliferative response as defined in terms of stimulation index (SI) to vaccine antigens; 65% of vaccinees but none of placebo recipients exhibited moderate or strong responses after enzyme immunoassay to HIV specific antigens. CD4 cell counts and quantitative HIV culture did not differ significantly among vaccine and control groups, nor were differences found among groups in HIV disease progression. The rgp160 and gp120 subunit vaccines were safe and immunogenic in this population.

AIDS Vaccines↗
PubMed1998

Pharmacokinetics of nevirapine in human immunodeficiency virus type 1-infected pregnant women and their neonates. Pediatric AIDS Clinical Trials Group Protocol 250 Team.

The safety, toxicity, and pharmacokinetics of intrapartum and early newborn nevirapine were evaluated in 17 human immunodeficiency virus type 1-infected women in labor and their newborns. No adverse effects of nevirapine were noted in any study mothers or infants. Following maternal dosing with 200 mg during labor, concentrations exceeding 100 ng/mL (10 times the in vitro IC50) were achieved in the newborns. Nevirapine elimination was prolonged in both mothers and infants, with median half-lives ranging from 36.8 to 65.7 h. Administration of 200 mg orally to the mothers in labor and of a single 2-mg/kg oral dose to the infants at 48-72 h after birth maintained serum concentrations in the infants > 100 ng/mL through 7 days of life.

Adult↗