PubMed Health⌕ Search

Biomedical subjects

E E Morgan

Publications and source records attributed to E E Morgan.

9 recordsLinked to original sources

Utility of the HIV dementia scale in assessing risk for significant HIV-related cognitive-motor deficits in a high-risk urban adult sample.

Considerable literature reflects the range of HIV-related neurocognitive complications, including relatively poor performance on tests of: movement and coordination; attention and concentration; reaction time; and mental flexibility. Efforts to develop appropriate screening techniques include the HIV Dementia Scale (HDS), a brief measure that has demonstrated promise but is lacking extensive independent evaluation. The present study examines the utility of the HDS in a sample of HIV-seropositive adults with a co-morbid history of psychiatric and substance use disorders. Forty subjects (65% male; mean age 41 years; mean education 12.2 years; 55% African American, 30% Caucasian) recruited for a study of the impact of brief psychotherapy on adherence to medications and medical appointments, relapse prevention, and/or enhancement of mental health functioning completed a battery of neuropsychological measures, including the HDS. Forty percent were identified as at high risk for significant cognitive-motor disorder (HDS total score < or =10). After controlling for age, education, illness (absolute CD4), and depressed mood, high-risk participants performed significantly worse on measures of simple and sustained divided attention, psychomotor speed, and working memory. However, only 25 of 40 (63%) were correctly classified based on their performance on traditional tests of neuropsychological functioning. Implications and limitations of the study are discussed.

AIDS Dementia Complex↗

Understanding the interface of HIV, trauma, post-traumatic stress disorder, and substance use and its implications for health outcomes.

Many individuals living with HIV have been exposed to some type of traumatic event during their lives and may be living with symptoms of post-traumatic stress disorder (PTSD). A substantial number of these individuals are also likely to show evidence of a co-morbid substance use disorder (SUD). There is reason to believe that the co-occurrence of HIV and PTSD or co-morbid PTSD and SUD (PTSD/SUD) may predict poorer health outcomes. There are several pathways through which PTSD or PTSD/SUD might adversely impact the health of individuals living with HIV, including participation in negative health behaviours, low levels of adherence to antiretroviral medications, and/or a direct, deleterious effect on immune function. Psychological interventions are needed to treat PTSD and PTSD/SUD in HIV-positive individuals, and reduce the negative impact of these conditions on health outcomes. This article will explore data on the prevalence of trauma exposure, PTSD, and PTSD/SUD among individuals living with HIV, the pathways through which these conditions might affect health, possible interventions for PTSD and PTSD/SUD for individuals living with HIV, and methods for integrating care for individuals with these disorders. Future directions for research related to HIV, PTSD, and PTSD/SUD will also be discussed.

Attitude to Health↗

Vaccination with a CDR2 BV6S2/6S5 peptide in adjuvant induces peptide-specific T-cell responses in patients with multiple sclerosis.

Earlier studies from several groups including ours have documented that patients with multiple sclerosis (MS) have over-expression of activated T-cells from specific TCR V beta families, including BV6S2/S5 (Kotzin et al. [1991] Proc. Natl. Acad. Sci. USA 88:9161--9165; Gold et al. [1997] J. Neuroimmunol. 76:29--38). It has also been established in the rat EAE model that peptide vaccines to the over-expressed V beta 8.2 TCR can prevent MBP induced disease (Vandenbark et al. [1989] Nature 341:541--544). In the current clinical study, 10 patients were vaccinated with 300 microg of BV6S2/6S5 peptide emulsified in incomplete Freund's adjuvant (IFA) and monitored for safety and immunogenicity in a 48-week multicenter, open-label trial. The peptide vaccine was well tolerated and no serious adverse events were observed. Vaccinations induced cell-mediated immunity to the immunizing peptide in eight of 10 patients as demonstrated by lymphocyte proliferation assay (LPA) and delayed-type hypersensitivity (DTH) skin test responses. In summary, these results demonstrate that immunization with TCR BV6S2/6S5 peptide vaccine in MS patients is safe and immunogenic, and supports a larger double-blind placebo controlled trial to determine the clinical efficacy of this approach.

Adult↗

T cell receptor peptide vaccination in rheumatoid arthritis: a placebo-controlled trial using a combination of Vbeta3, Vbeta14, and Vbeta17 peptides.

OBJECTIVE: Restricted T cell receptor (TCR) gene usage has been demonstrated in animal models of autoimmune disease and has resulted in the successful use of TCR peptide therapy in animal studies. This clinical trial was undertaken to determine the safety and efficacy of a combination of Vbeta3, Vbeta14, and Vbeta17 TCR peptides in Freund's incomplete adjuvant (IFA) in patients with rheumatoid arthritis (RA). METHODS: A double-blind, placebo-controlled, multicenter, phase II clinical trial was undertaken using IR501 therapeutic vaccine, which consists of a combination of 3 peptides derived from TCRs (Vbeta3, Vbeta14, and Vbeta17) in IFA. A total of 99 patients with active RA received either 90 microg (n = 31) or 300 microg (n = 35) of IR501 or IFA alone (n = 33) as a control. The study medication and placebo were administered as a single intramuscular injection (1 ml) at weeks 0, 4, 8, and 20. RESULTS: Treatment with IR501 was safe and well tolerated. None of the patients discontinued the trial because of treatment-related adverse events. Efficacy was measured according to the American College of Rheumatology 20% improvement criteria. Using these criteria, patients in both IR501 dosage groups showed improvement in disease activity. In the most conservative analysis used to evaluate efficacy, an intent-to-treat analysis including all patients who enrolled, the 90-microg dosage group showed a statistically significant improvement compared with control patients at the 20-week time point after the third injection. Trends toward improvement were shown in both the 90-microg and the 300-microg dosage groups at week 24 after the fourth injection. CONCLUSION: IR501 therapeutic vaccine therapy was safe and well tolerated, immunogenic, and demonstrated clinical improvement in RA patients. Additional clinical trials are planned to confirm and extend these observations.

Adult↗

Results of a phase I clinical trial of a T-cell receptor vaccine in patients with multiple sclerosis. II. Comparative analysis of TCR utilization in CSF T-cell populations before and after vaccination with a TCRV beta 6 CDR2 peptide.

We report here the results of a phase I trial of a T-cell receptor (TCR) V beta 6 CDR2 region peptide vaccine in 10 patients with multiple sclerosis who showed biased over-representations of V beta 6 mRNA among T-cells in their cerebrospinal fluids (CSF). One group of 5 patients was immunized twice during a four week period with 100 micrograms of the TCRV beta 6 peptide 39-LGQGPEF LTYFQNEAQLEKS-58 emulsified in incomplete Freund's adjuvant (IFA); the second group of 5 MS patients received 300 micrograms of the same peptide in IFA over a similar time period. Patients were monitored for adverse events, immunogenicity of the peptide and changes in their CSF T-cell populations. The results indicate that this peptide was immunogenic (T-cell proliferation assays and recall DTH responses) in some of the patients, although none of the immunized patients produced detectable anti-peptide antibodies. More importantly, we show that the 5 patients treated with higher doses of the vaccine displayed a slight decrease in CSF cellularity, a lack of growth of CSF cells in cytokine supplemented expansion cultures that implies a significant absence of a subset of activated CD4 T-cells and a marked diminution in V beta 6 mRNA levels among T-cells in these cultures. By comparison, in 5 patients receiving the lower dosage of the vaccine, CSF cellularity was the same or slightly increased over pre-vaccination levels, CSF cells from 1 patient failed to grow in expansion cultures and cultured CSF cells from 2 patients underwent a change from an oligoclonal V beta 6 pattern to one that was more polyclonal. These results justify a more through exploration of the use of TCR peptide vaccines as a possible therapeutic treatment for MS.

Adult↗

V beta 17 T cell receptor peptide vaccination in rheumatoid arthritis: results of phase I dose escalation study.

OBJECTIVE: To determine whether modulation of activated T cells occurs in patients with rheumatoid arthritis (RA) after immunization with T cell receptor (TCR) V beta 17 peptides, a phase I trial was initiated to investigate the safety and feasibility of TCR peptide immunization as a therapeutic approach in RA. METHODS: 15 patients with moderate to severe RA were given an intramuscular injection of one of 4 doses (10, 30, 100, and 300 micrograms) of the V beta 17 peptide vaccination, followed by a booster injection of the same dose of vaccine 3 weeks later. Patients were followed for 48 weeks. RESULTS: The product was well tolerated and no serious adverse events attributable to the vaccine were observed. This was an uncontrolled phase I trial, however; decreases in patients joint scores were observed at all followup visits starting at 4 weeks after primary immunization. Activated V beta 17 T cells (IL-2R+) in peripheral blood were decreased (> or = 20%) in 3/5 patients in the 100 micrograms group after initial measurement at Week 2 and 3/4 patients in the 300 micrograms group 3 weeks after immunization. Lymphocyte proliferation in response to the V beta 17 peptide was detected at 6 weeks or later after primary inoculation in 6/15 patients (40%) immunized. CONCLUSION: Further controlled studies are required to assess the biologic and clinical efficacy of this treatment approach.

Adult↗

Variability of voice fundamental frequency in elderly female speakers.

Three groups of women, of mean age 21, 72, and 84 yr. (ns = 34, 17, 17), were tape-recorded while describing the "Cookie Thief" picture of the Boston Diagnostic Aphasia Test. Voice fundamental frequency (fo) was measured for a 30-sec. sample from the middle of their descriptions. Analysis showed that the two elderly groups' mean fo was significantly lower than the younger females', but no differences between means were significant for the older groups. Similar findings were obtained for variability of performance. Also, the older groups were more restricted in their vocal maneuvering below their average fo. Compared to past findings showing greater fo variability during reading, the current data suggest that the magnitude of variability of fo in elderly women is dependent upon both the vocal parameters measured and the method used to obtain the data.

Adult↗