Program review of community residential care.

This article provides an overview of the Department of Veterans Affairs Community Residential Care Program and summarizes key literature about programs developed in the United States. Descriptive data for 1995 and 1996 are provided to assist program planners in comparing and contrasting client characteristics and services. The authors conclude that, in addition to being cost effective, the residential care program strengthens relationships between the health care facility and the community it serves.

A fully human antibody neutralising biologically active human TGFbeta2 for use in therapy.

Phage display provides a methodology for obtaining fully human antibodies directed against human transforming growth factor-beta (TGFbeta) suitable for the treatment of fibrotic disorders. The strategy employed was to isolate a human single chain Fv (scFv) fragment that neutralises human TGFbeta2 from a phage display repertoire, convert it into a human IgG4 and then determine its TGFbeta binding and neutralisation properties and its physical characteristics. Several scFv fragments binding to TGFbeta2 were isolated by panning of an antibody phage display repertoire, and subsequent chain shuffling of the selected V(H) domains with a library of V(L) domains. The three most potent neutralising antibodies were chosen for conversion to IgG4 format. The IgG4 antibodies were ranked for their ability to neutralise TGFbeta2 and the most potent, 6B1 IgG4, was chosen for further characterisation. 6B1 IgG4 has a high affinity for TGFbeta2 with a dissociation constant of 0.89 nM as determined using the BIAcore biosensor and only 9% cross-reactivity with TGFbeta3 (dissociation constant, 10 nM). There was no detectable binding to TGFbeta1. 6B1 IgG4 strongly neutralises (IC50 = 2 nM) the anti-proliferative effect of TGFbeta2 in bioassays using TF1 human erythroleukaemia cells. Similarly, there was strong inhibition of binding of TGFbeta2 to cell surface receptors in a radioreceptor assay using A549 cells. 6B1 IgG4 shows no detectable cross-reactivity with related or unrelated antigens by immunocytochemistry or ELISA. The 6B1 V(L) domain has entirely germline framework regions and the V(H) domain has only three non-germline framework amino acids. This, together with its fully human nature, should minimise any potential immunogenicity of 6B1 IgG4 when used in therapy of fibrotic diseases mediated by TGFbeta2.

Case managed residential care for homeless addicted veterans. Results of a true experiment.

OBJECTIVES: The effectiveness of case-managed residential care (CMRC) in reducing substance abuse, increasing employment, decreasing homelessness, and improving health was examined. METHODS: A five-year prospective experiment included 358 homeless addicted male veterans 3, 6, and 9 months during their enrollment and at 12, 18, and 24 months after the completion of the experimental case-managed residential care program. The customary control condition was a 21-day hospital program with referral to community services. RESULTS: The experimental group averaged 3.4 months in transitional residential care with ongoing and follow-up case management for a total of up to 1 year of treatment. The experimental group showed significant improvement compared with the control group on the Medical, Alcohol, Employment, and Housing measures during the 2-year period. An examination of the time trends indicated that these group differences tended to occur during the treatment year, however, and to diminish during the follow-up year. CONCLUSIONS: Within groups, significant improvements were observed with time from baseline to all posttests on the four major outcomes. We learned, however, that veterans had access to and used significant amounts of services even without the special case-managed residential care program. This partially may account for improvements in the control group and may have muted the differences between groups.

Human antibodies with sub-nanomolar affinities isolated from a large non-immunized phage display library.

To generate a stable resource from which high affinity human antibodies to any given antigen can be rapidly isolated, functional V-gene segments from 43 non-immunized human donors were used to construct a repertoire of 1.4 x 10(10) single-chain Fv (scFv) fragments displayed on the surface of phage. Fragments were cloned in a phagemid vector, enabling both phage displayed and soluble scFv to be produced without subcloning. A hexahistidine tag has been incorporated to allow rapid purification of scFv by nickel chelate chromatography. This library format reduces the time needed to isolate monoclonal antibody fragments to under two weeks. All of the measured binding affinities show a Kd < 10 nM and off-rates of 10(-3) to 10(-4) s-1, properties usually associated with antibodies from a secondary immune response. The best of these scFvs, an anti-fluorescein antibody (0.3 nM) and an antibody directed against the hapten DTPA (0.8 nM), are the first antibodies with subnanomolar binding affinities to be isolated from a naive library. Antibodies to doxorubicin, which is both immunosuppressive and toxic, as well as a high affinity and high specificity antibody to the steroid hormone oestradiol have been isolated. This work shows that conventional hybridoma technology may be superseded by large phage libraries that are proving to be a stable and reliable source of specific, high affinity human monoclonal antibodies.

Pleuroperitoneal shunt for pneumonectomy cavity malignant effusion.

Delayed mediastinal shift toward the remaining lung is an unusual cause of postpneumonectomy dyspnea. We report a patient who developed severe dyspnea when a malignant effusion occurred in the pneumonectomy cavity and caused a contralateral mediastinal shift. Repeated thoracentesis was needed until insertion of a pleuroperitoneal shunt effected palliation.