ABSTRACT
OBJECTIVE: This pilot phase II, double-blind, placebo-controlled trial of 1 month duration, with a 2-3-month open-label extension, evaluated the safety, tolerability, biologic effects, and efficacy of interleukin-2 diphtheria fusion protein (DAB486IL-2) in refractory rheumatoid arthritis (RA). METHODS: Forty-five RA patients were enrolled in the trial, and were randomized, after a 3-4-week disease-modifying antirheumatic drug washout, to receive a daily intravenous dose of either DAB486IL-2 or placebo (saline) for 5 days. A blinded, third-party observer evaluated arthritis activity. Clinical response was defined as > or = 25% improvement in swollen and tender joints and > or = 25% improvement in at least 2 of 6 additional parameters. The double-blind phase was 4 weeks; placebo patients could cross over to receive open-label treatment for a maximum of 3 monthly DAB486IL-2 cycles. RESULTS: In the double-blind phase, 4 of 22 patients (18%) in the treated group and none in the placebo group (P = 0.05) met the criteria for clinical response. During the open-label treatment phase, 11 of 36 patients (31%) and 11 of 33 patients (33%) had a clinical response after completing 2 and 3 courses of DAB486IL-2, respectively. Adverse events included transient fever/chills (45%), nausea/vomiting (50%), elevated (< or = 3 x normal) transaminases (55%), and increased joint pain (45%). Twelve patients (8 placebo, 4 DAB486IL-2) did not complete 3 treatment cycles. No apparent differences were noted in CD4+ CD25+ cells of responders versus nonresponders, or of DAB486IL-2-treated versus placebo-treated patients. CONCLUSION: Clinical responses were noted in patients treated with DAB486IL-2 (18%) compared with placebo (0%) in the double-blind phase. In the open-label phase, 33% of patients completing 3 monthly DAB486IL-2 cycles had improvement in arthritis activity. Further studies of IL-2 diphtheria fusion proteins are warranted to elucidate factors that may predict clinical response and define mechanism(s) of action.
Subject(s)
Arthritis, Rheumatoid/drug therapy , Diphtheria Toxin/therapeutic use , Interleukin-2/therapeutic use , Adolescent , Adult , Aged , Antibodies/analysis , Antigens, CD/analysis , Antirheumatic Agents/therapeutic use , Biomarkers , Diphtheria Toxin/adverse effects , Double-Blind Method , Female , Humans , Interleukin-2/adverse effects , Lymphocytes/immunology , Male , Middle Aged , Pilot Projects , Recombinant Fusion Proteins/therapeutic useABSTRACT
Alpha-2a-interferon (IFN) has been shown to provide important local defense against some viral infections. In vitro, IFN inhibits the growth of respiratory syncytial virus in bovine monolayer cultures, but respiratory syncytial virus is known to be a poor inducer of IFN in infected infants. When IFN was administered by daily intramuscular injection in a double blind, placebo-controlled study of 22 infants with bronchiolitis caused by respiratory syncytial virus, there was no statistically significant difference in clinical course, duration of oxygen requirement or physical assessment between the treatment and control groups. Likewise viral isolation showed no difference between the groups. Further studies are needed to determine whether higher dosing or aerosol or other alternative route of delivery of IFN might lead to therapeutic benefit.
Subject(s)
Bronchiolitis, Viral/therapy , Interferon-alpha/therapeutic use , Respiratory Syncytial Virus Infections/therapy , Respiratory Syncytial Virus, Human , Bronchiolitis, Viral/microbiology , Double-Blind Method , Humans , Infant , Interferon alpha-2 , Nasal Lavage Fluid/microbiology , Nasal Mucosa/metabolism , Nasal Mucosa/microbiology , Recombinant Proteins , Respiratory Syncytial Virus, Human/isolation & purification , Treatment OutcomeSubject(s)
Arthritis, Rheumatoid/surgery , Adrenal Cortex Hormones/administration & dosage , Adrenal Cortex Hormones/adverse effects , Anti-Bacterial Agents/administration & dosage , Anti-Bacterial Agents/adverse effects , Contraindications , Dose-Response Relationship, Drug , Humans , Intubation, Intratracheal , Joint Prosthesis , Methotrexate/administration & dosage , Methotrexate/adverse effects , PremedicationABSTRACT
Family life and a definition of the family are frequent topics of discussion in 1980. Catholic health care institutions have a special opportunity and obligation to advocate a sense of family on three levels: among their own staffs, between patients and their families, and in outreach to the global community.
Subject(s)
Catholicism , Family , Pastoral Care , Community-Institutional Relations , Holistic HealthSubject(s)
Abortion, Legal , Catholicism , Attitude , Female , Humans , Interpersonal Relations , Pregnancy , Quality of Life , Social Change , United StatesABSTRACT
Equations have been derived that allow differences in reflectometer readings of the same sample with various reflectometers to be minimized by placing all reflectances on an absolute basis. For pigmented vehicle films the Fresnel reflectances and transmittances at the air-vehicle interface can be calculated for an arbitrary incident angular light distribution. The form of the reflected and transmitted angular distributions can also be calculated. The equations have been used to determine absolute reflectances of titanium dioxide pigmented films from meter readings of two reflectometers-the General Electric Recording and the Colormaster.
