Subject(s)
Autobiographies as Topic , Conflict, Psychological , Mental Disorders , Symbolism , Depressive Disorder/ethnology , Depressive Disorder/history , Depressive Disorder/psychology , England/ethnology , History, 17th Century , Mental Disorders/ethnology , Mental Disorders/history , Mental Disorders/psychology , Mental Health/history , Social Problems/economics , Social Problems/ethnology , Social Problems/history , Social Problems/legislation & jurisprudence , Social Problems/psychology , Travel/history , Travel/psychologyABSTRACT
The aim of this phase II study was to evaluate the safety, immunogenicity and tolerability of the yeast-derived virus-like particle immunogen, Ty.p24.VLP (p24-VLP), in HIV-antibody-positive asymptomatic volunteers. Fifteen informed and consented volunteers, with p24 Antibody titres >1/100, p24 Antigen <20 pg/l, and CD4>350 x 10(9)/l were enrolled. Five were immunized with aluminium hydroxide placebo, five with 25 microg, and five with 100 microg p24-VLP in Alum adjuvant at weeks 0 and 4 by the intramuscular route. Patients were followed for 16 weeks post vaccination and the main outcome assessments were CD4 and CD8 lymphocyte counts, p24 antigen and antibody, Ty antibody and quantitative viral cultures. No serious adverse events were observed in any of the groups. There were increases in CD4 counts in the treated groups but not in the controls, although these changes were not statistically significant. There were no significant intrasubject or intergroup changes in the other parameters, such as p24 antigen and antibody. No pattern of change in plasma viraemia was detected, and most cultures were negative. Therefore we conclude that p24-VLP immunizations of 25 microg and 100 microg are well tolerated, and the CD4 changes are encouraging, but higher doses and larger numbers are required to see if there are significant humoral or cellular responses, and extended phase II studies are now in progress.
Subject(s)
AIDS Vaccines/therapeutic use , HIV Core Protein p24/therapeutic use , HIV Seropositivity/therapy , HIV/immunology , Immunotherapy, Active , Adolescent , Adult , CD4 Lymphocyte Count , Double-Blind Method , Enzyme-Linked Immunosorbent Assay , HIV Antibodies/biosynthesis , HIV Core Protein p24/immunology , HIV Core Protein p24/pharmacology , HIV Seropositivity/immunology , Humans , Male , Middle Aged , Pilot Projects , Vaccines, Synthetic/immunology , Vaccines, Synthetic/therapeutic use , Viral Load , Viremia/therapyABSTRACT
In this Phase I study, immunisation with the yeast-derived p24 virus-like particles Ty p24-VLP (3 x 100 or 3 x 500 micrograms subcutaneously) in 16 healthy male subjects elicited p24 antibody responses in 4 of 16 (25%) subjects. After a fourth, intramuscular, immunisation (500 micrograms), p24 antibody responses were detected in 11 of 15 (70%) subjects. In addition to p24 antibody responses, T cell proliferative responses were also observed, although no HLA restricted p24-specific cytotoxic T cell responses were detected. The results demonstrate that Ty p24-VLP is immunogenic and well-tolerated in healthy male subjects.
Subject(s)
AIDS Vaccines/immunology , Gene Products, gag/immunology , HIV Antigens/immunology , HIV Core Protein p24/immunology , HIV Infections/prevention & control , HIV/immunology , Viral Proteins , AIDS Vaccines/genetics , AIDS Vaccines/therapeutic use , Adult , Blotting, Western , Enzyme-Linked Immunosorbent Assay , HIV Antibodies/biosynthesis , HIV Core Protein p24/genetics , HIV Core Protein p24/therapeutic use , Humans , Male , Middle Aged , Reference Values , Saccharomyces cerevisiae/genetics , T-Lymphocytes, Cytotoxic/cytology , T-Lymphocytes, Cytotoxic/immunology , Vaccines, Synthetic/genetics , Vaccines, Synthetic/immunology , Vaccines, Synthetic/therapeutic use , gag Gene Products, Human Immunodeficiency VirusABSTRACT
The diagnostic vocabulary of a clinician appears to be specific and measurable for each clinical discipline. The diagnostic vocabulary of 11 primary care physicians over four-years' work has been analyzed. For every 1,000 patients cared for, each physician made, on average, 2,691 diagnoses every year, representing a diagnostic vocabulary of 475 different clinical entities. This vocabulary has been analyzed according to frequency of usage and clinical decision making. The clinical, teaching, and administrative implications of this analysis are discussed.