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Biomedical subjects

D Richman

Publications and source records attributed to D Richman.

At least 19 recordsLinked to original sources

A measure of food seeking in individuals with Prader-Willi syndrome.

BACKGROUND: Individuals with Prader-Willi syndrome (PWS), a chromosome 15 genetic disorder, often have a significant preoccupation with food and problem behaviour related to food seeking is often prevalent. METHODS: In the present study, we compared how individuals with PWS responded on a survey regarding the acceptability of food in various locations that varied according to degree of appropriateness for human consumption (e.g. food on a plate, food in a garbage can). For a subgroup of participants, we observed how they actually responded when placed in a room with food items placed in the same locations depicted in the survey. In the first part of the study, three groups (25 typically developing individuals, 7 individuals with intellectual disability (ID), and 19 individuals with PWS) responded to a visual survey to determine the degree of acceptability of food items in various locations (e.g. on a table near a hairbrush, on the floor behind a toy box, in a trash can). In the second part of the study, these food items (popcorn, jelly beans) were placed in the 12 locations described above. Nine individuals diagnosed with PWS (deletion type) and three individuals with ID were given some break time in the room for 15 min. The amount of food consumed, the time spent food seeking, and time spent interacting with materials were measured. RESULTS: Results of the survey indicated that the PWS group differed significantly with regard to how they responded on the survey from the typically developing group, but did not differ significantly from the ID group. Results of the food seeking observations indicated that only three individuals with PWS ate a significant number of items. The three individuals did not differ from the rest of the group according to IQ or compulsivity score; however, they had significantly lower body mass index (BMI) scores and were younger than the other participants. CONCLUSIONS: The findings from the survey indicate that individuals with PWS are able to discriminate the appropriateness of eating items in more or less contaminated areas; however, the amount of time spent seeking food and the amount of food covertly consumed appeared to depend more directly on age and BMI.

Adolescent↗

Patterns of plasma human immunodeficiency virus type 1 RNA response to antiretroviral therapy.

Early identification of treatment failure among human immunodeficiency virus (HIV) type 1--infected patients receiving antiretroviral therapy could enable clinicians to modify inadequate regimens and to improve treatment response. Clinical definitions of treatment failure, however, may not be ideally suited for this purpose. This study empirically characterizes the patterns of HIV-1 RNA response to antiretroviral therapy in patients in 4 AIDS clinical trials. The approach assumed 2 patterns of HIV-1 response: "on track," for eventual suppression to HIV-1 RNA levels below the limit of quantification, and "off track," for deviation from this response. The results of this on- or off-track classification generally agreed with the protocol-defined outcomes of virologic success and failure, thus validating these commonly used definitions. Overall, only a minority of patients went off track because of suboptimal HIV-1 RNA response by the first follow-up visit. Most patients who went off track did so at later time points and had sharp unexpected rebounds without prior indication of a suboptimal response.

Antiretroviral Therapy, Highly Active↗

Sequencing of protease inhibitor therapy: insights from an analysis of HIV phenotypic resistance in patients failing protease inhibitors.

OBJECTIVE: To characterize the pattern of HIV-1 susceptibility to protease inhibitors in patients failing an initial protease inhibitor-containing regimen. DESIGN: A cross-sectional analysis of antiretroviral susceptibility. SETTING: HIV clinics in six metropolitan areas. PATIENTS: Eighty-eight HIV-infected adults with HIV RNA > 400 copies/ml after > or = 6 months of antiretroviral therapy, including the use of one protease inhibitor for > or = 3 months. MEASUREMENTS: The frequency and magnitude of decreased susceptibility, measured with a phenotypic assay using recombinant constructs, to five protease inhibitors. Decreased susceptibility was defined as > 2.5-fold increase in the 50% inhibitory concentration (IC50) compared with drug sensitive control virus. RESULTS: At study entry, patients were being treated with nelfinavir (63%), indinavir (25%), or another protease inhibitor (11%). HIV isolates from these patients were susceptible (fold change < 2.5) to all five protease inhibitors in 18% of patients and to none in 8%. Isolates from patients receiving nelfinavir were less likely to have reduced susceptibility to other protease inhibitors than isolates from patients treated with indinavir (P < 0.001) or one of the other three agents (P < 0.001), even after adjustment for the duration of prior protease inhibitor use. Reduced susceptibility to saquinavir and amprenavir was observed significantly less frequently than for the other protease inhibitors. CONCLUSION: The frequency of protease inhibitor cross-resistance and the magnitude of changes in susceptibility varied according to the initial protease inhibitor used in the failing treatment regimen. Significantly less protease inhibitor cross-resistance was demonstrated for isolates from patients failing a nelfinavir-containing regimen compared with those from patients receiving other protease inhibitors.

Adult↗

Productive infection of T cells in lymphoid tissues during primary and early human immunodeficiency virus infection.

Current models suggest that during human immunodeficiency virus type 1 (HIV-1) transmission virions are selected that use the CCR5 chemokine receptor on macrophages and/or dendritic cells. A gradual evolution to CXCR4 chemokine receptor use causes a shift in the proportion of productively infected cells to the CD4 cell population. Productively infected cells during acute and early infection in lymphoid tissue were assessed, as well as the impact of productive infection on the T cell population in 21 persons who had biopsies performed on days 2-280 after symptoms of acute HIV-1 seroconversion. Even in the earliest stages of infection, most productively infected cells were T lymphocytes. There were sufficient infected cells in lymphoid tissue (LT) to account for virus production and virus load in plasma. Despite the relatively high frequency of productively infected cells in LT, the impact on the size of the T cell population in LT at this stage was minor.

CD4-Positive T-Lymphocytes↗

The effect of highly active antiretroviral therapy on binding and neutralizing antibody responses to human immunodeficiency virus type 1 infection.

The effect on humoral immune responses of highly active antiretroviral therapy (HAART) commenced during primary or chronic human immunodeficiency virus type 1 (HIV-1) infection was investigated. HAART inhibited the development of anti-gp120 antibodies when initiated during primary infection and could sometimes reduce antibody titers in patients treated within 2 years of HIV-1 infection. Conversely, antibody responses in patients infected for several years were less sensitive to HAART. Administering HAART during primary infection usually did not substantially affect the development of weak neutralizing antibody responses against autologous virus. However, 2 patients treated very early after infection did not develop neutralizing responses. In contrast, 3 of 4 patients intermittently adherent to therapy developed autologous neutralizing antibodies of unusually high titer, largely coincident with brief viremic periods. The induction of strong neutralizing antibody responses during primary HIV-1 infection might require the suppression of virus replication by HAART, to allow for the recovery of immune competency, followed by exposure to native envelope glycoproteins.

Anti-HIV Agents↗

Rapid accumulation of human immunodeficiency virus (HIV) in lymphatic tissue reservoirs during acute and early HIV infection: implications for timing of antiretroviral therapy.

The follicular dendritic cell network (FDC) in lymphoid tissues (LTs) is the major site of human immunodeficiency virus (HIV) storage in presymptomatic and late stages of disease. However, little is known about the rate of virus accumulation during the acute and early stages. In situ hybridization and quantitative image analysis were used to determine the amount of virus bound to the FDC network during the first year of infection. The FDC pool was already >7.0 log10 copies of HIV RNA/g LT in the first year, and 2 patients biopsied within 2-4 days of symptom onset had 7.3 and 8.2 log10 copies of HIV RNA/g LT, respectively. There was no correlation between duration of infection and accumulation of HIV into the FDC network. These data suggest that a large pool of infectious virus is established soon after infection and that initiation of antiretroviral therapy when symptoms of primary HIV infection are recognized is unlikely to prevent substantial accumulation of virus in the FDC network.

Acute Disease↗

Functional analysis of aberrant behavior through measurement of separate response topographies.

Functional analysis results for multiple topographies of aberrant behavior were graphed in an aggregate fashion and then separately for 48 clients. The results indicated that multiple topographies of behavior may be maintained by different contingencies. These results indicate that graphing functional analysis data in an aggregate fashion and then separately may improve the accuracy of their interpretation.

Adolescent↗

The effects of presession exposure to attention on the results of assessments of attention as a reinforcer.

The effects of presession exposure to attention on responding during subsequent assessments of attention as a reinforcer were evaluated across three behavioral assessments. In Experiment 1, a contingent attention assessment condition was preceded by either a noncontingent attention condition (free play) or a contingent escape condition. In Experiment 2, a diverted attention with extinction condition was preceded by either an alone or a free-play condition. In Experiment 3, a two-choice preference assessment was preceded by either 10 min of free play or 10 min of playing alone. In each experiment, the participant responded differentially within the test condition according to the presence or absence of dense schedules of attention immediately prior to that condition. The results of this study show that events occurring immediately prior to an assessment condition can influence behavior within the assessment.

Attention↗

A phase II safety and efficacy study of amprenavir in combination with zidovudine and lamivudine in HIV-infected patients with limited antiretroviral experience. Amprenavir PROAB2002 Study Team.

OBJECTIVE: To determine the safety and efficacy of amprenavir (APV) in combination with lamivudine (3TC) and zidovudine (ZDV). DESIGN: Multicenter, randomized, partially blinded trial. SETTING: Nine study sites in the United States and Europe. PATIENTS: A group of 84 HIV-infected subjects with no prior 3TC or protease inhibitor therapy experience, CD4 cell count > or = 150 x 10(6) cells/l, and plasma HIV RNA > 10000 copies/ml. INTERVENTIONS: 3TC/ZDV with one of three doses of APV (900, 1050, or 1200 mg) versus 3TC/ZDV with 1050 mg placebo. All medications were dosed twice daily. The 1050 mg placebo and the APV 1050 mg dose were administered blinded. After 12 weeks, APV 1050 mg was substituted for 1050 mg placebo in the control group and the blind was maintained. MAIN OUTCOME MEASURES: Reduction in plasma HIV RNA from baseline; proportion of subjects with plasma HIV RNA < 400 copies/ml; and an increase in CD4 cell count from baseline. RESULTS: During the initial 12-week study period, APV/3TC/ZDV-treated subjects had greater viral suppression than the group receiving two nucleosides. By 48 weeks, 89% of subjects in the group taking the highest APV dose (1200 mg) had plasma HIV RNA < 400 copies/ml while 42% of the 900 mg group and 60% of the 3TC/ZDV group (1050 mg APV added at week 12) had plasma HIV RNA < 400 copies/ml using an as-treated analysis. By 60 weeks, 86% of subjects in the APV 1200 mg group had plasma HIV RNA < 400 copies/ml in the as-treated analysis, while 25% (900 mg), 43% (1050 mg), and 20% (1200 mg) of subjects had viral load <400 copies/ml in a strict intent-to-treat analysis owing to treatment discontinuations. Median CD4 cell count increases at week 60 were highest for the three treatment groups who received APV throughout the study, by intent-to-treat and as-treated analyses. The most common adverse events considered to be possibly drug related were nausea, rash, oral paresthesia, diarrhea, and fatigue. CONCLUSIONS: Treatment with APV, dosed at 1200 mg twice daily in combination with 3TC/ZDV, resulted in sustained viral suppression. This combination represents a potent alternative initial antiretroviral regimen for protease inhibitor-naive individuals.

Adult↗

Aberrant and unstable expression of immunoglobulin genes in persons infected with human immunodeficiency virus.

We examined the IgM VH gene subgroup use-distribution in serial blood samples of 37 human immunodeficiency virus (HIV)-infected patients and a group of HIV-seronegative healthy adults. The IgM VH gene repertoires of healthy adults were relatively similar to one another and were stable over time. In contrast, individuals infected with HIV had IgM VH gene repertoires that were significantly more heterogeneous and unstable. Persons at early stages of HIV infection generally had abnormal expression levels of Ig VH3 genes and frequently displayed marked fluctuations in the relative expression levels of this VH gene subgroup over time. In contrast, persons with established acquired immunodeficiency syndrome (AIDS) had a significantly lower incidence of abnormalities in Ig VH3 expression levels, although continued to display abnormalities and instability in the expression levels of the smaller Ig VH gene subgroups. Moreover, the skewing and/or fluctuations in the expressed-IgM VH gene repertoire appeared greatest for persons at earlier stages of HIV infection. These studies show that persons infected with HIV have aberrant and unstable expression of immunoglobulin genes suggestive of a high degree humoral immune dysregulation and ongoing humoral immune responses to HIV-associated antigens and superantigens.

Acquired Immunodeficiency Syndrome↗

Interlaboratory concordance of DNA sequence analysis to detect reverse transcriptase mutations in HIV-1 proviral DNA. ACTG Sequencing Working Group. AIDS Clinical Trials Group.

Thirteen laboratories evaluated the reproducibility of sequencing methods to detect drug resistance mutations in HIV-1 reverse transcriptase (RT). Blinded, cultured peripheral blood mononuclear cell pellets were distributed to each laboratory. Each laboratory used its preferred method for sequencing proviral DNA. Differences in protocols included: DNA purification; number of PCR amplifications; PCR product purification; sequence/location of PCR/sequencing primers; sequencing template; sequencing reaction label; sequencing polymerase; and use of manual versus automated methods to resolve sequencing reaction products. Five unknowns were evaluated. Thirteen laboratories submitted 39043 nucleotide assignments spanning codons 10-256 of HIV-1 RT. A consensus nucleotide assignment (defined as agreement among > or = 75% of laboratories) could be made in over 99% of nucleotide positions, and was more frequent in the three laboratory isolates. The overall rate of discrepant nucleotide assignments was 0.29%. A consensus nucleotide assignment could not be made at RT codon 41 in the clinical isolate tested. Clonal analysis revealed that this was due to the presence of a mixture of wild-type and mutant genotypes. These observations suggest that sequencing methodologies currently in use in ACTG laboratories to sequence HIV-1 RT yield highly concordant results for laboratory strains; however, more discrepancies among laboratories may occur when clinical isolates are tested.

Codon↗

Quality improvement in neurology residency programs. Report of the Quality Improvement Committee of the Association of University Professors of Neurology.

The neurology residency programs in the United States are facing a crisis of quality. The Association of University Professors of Neurology (AUPN) approved the Quality Improvement Committee to examine this situation and make recommendations, which have been accepted by the AUPN. The recommendations are (1) that the educational goals of neurology residency training be dissociated from patient-care needs in academic medical centers and (2) that minimum levels of quality be applied to residents in neurology residency programs and to these programs themselves. These minimum criteria should include minimum educational criteria for entry into the program, minimum criteria for advancement from one year to the next in the program, and minimum criteria for performance of the graduates of neurology residency programs for program accreditation. The implementation of these recommendations will require a shift of funding of the care of indigent patients from the graduate medical education budget to direct patient-care sources. These recommendations will significantly improve the quality of neurologists and neurologic care in the United States.

Academic Medical Centers↗

Choice-making treatment of young children's severe behavior problems.

The choice-making behavior of 5 young children with developmental disabilities who engaged in aberrant behavior was studied within a concurrent operants framework. Experimental analyses were conducted to identify reinforcers that maintained aberrant behavior, and functional communication training packages were implemented to teach the participants to gain reinforcement using mands. Next, a choice-making analysis, in which the participants chose one of two responses (either a mand or an alternative neutral response) to obtain different durations and qualities of reinforcement, was conducted. Finally, treatment packages involving choice making via manding were implemented to decrease inappropriate behavior and to increase mands. The results extended previous applications of choice making to severe behavior disorders and across behaviors maintained by positive and negative reinforcement.

Behavior Therapy↗

Brief experimental analysis of stimulus prompts for accurate responding on academic tasks in an outpatient clinic.

Brief multielement designs were used to examine the effects of specific instructional strategies on accuracy of academic performance during outpatient evaluations of 4 children with learning disorders. Instructional strategies that improved accuracy on academic tasks were identified for all participants. These results suggest that the application of experimental analysis methodologies to instructional variables may facilitate the identification of stimulus prompts that are associated with enhanced academic performance.

Ambulatory Care Facilities↗