Viral-specific immunization in AIDS-related complex by photopheresis.

The potential for therapeutic intervention in 7 patients with AIDS-related complex (ARC) was evaluated through the use of photopheresis. The rationale for the study was based on: 1. the demonstration that psoralen and UVA could inactivate HIV/virus in vitro; 2. CD4 cells are the primary target population effected by HIV and photopheresis; and 3. reinfusion of inactivated virus and cell-associated virus might serve to engender an immune response. Preliminary results in 7 patients with ARC over 6 to 18 months revealed a virus-specific response with an elevation of HIV antibodies, while EBV and CMV titers remained unchanged. The immunologic results revealed an increase in the CD8 lymphocyte population, stable activation markers (B2 microglobulin neopterin), a decrease in p24 antigen titers and inability to culture HIV virus in 3 patients. All of these results were in the context of a stable or increasing CD4+ percent. Six patients did not reveal a generalized inhibition of other immune responses as demonstrated by recovery of DTH. In addition, the resolution of lymphadenopathy, night sweats, fever and weight loss, paralleled the immunologic response.

Production of hydrogen peroxide by cutaneous T-cell lymphoma following photopheresis with psoralens and ultraviolet light.

Treatment of peripheral blood mononuclear cells with 8-methoxypsoralen (8-MOP) and ultraviolet light, a procedure known as PUVA, has been found to be useful in the management of systemically disseminated cutaneous T-cell lymphoma (CTCL). In the present study we used a highly sensitive flow cytometric assay in conjunction with the hydroperoxide-sensitive dye 2',7'-dichlorofluorescein diacetate to measure intracellular hydrogen peroxide in normal lymphocytes and CTCL following PUVA treatment. Based on their laser light-scattering properties, lymphocytes were separated into three major subpopulations. We found that ultraviolet light alone caused an increase in the hydrogen peroxide content of each of the subpopulations, a response that was augmented when the cells were pretreated with 8-MOP (50 ng/ml). Cells from CTCL patients were more sensitive to the effects of 8-MOP than were normal lymphocytes. In both cell types, the production of hydrogen peroxide was found to be inhibitable by catalase. We noted an increase in hydrogen peroxide production following photopheresis; however, this was observed only 24 h after treatment. In addition, a further increase in hydrogen peroxide production was observed in lymphocytes isolated from peripheral blood that had been obtained from patients at 15 min after a second photopheresis treatment. Hydrogen peroxide is known to modulate the action of cytokines as well as the immunological responses of leukocytes. Our data suggest that the production of hydrogen peroxide by lymphocytes may be important in the action of PUVA in CTCL.

Photopheresis for the treatment of cutaneous T cell lymphoma.

We investigated the use of extracorporeal chemotherapy (photopheresis) in eight patients with cutaneous T cell lymphoma. Initially described by Edelson et al. for the treatment of erythrodermic cutaneous T cell lymphoma, we have expanded the treatment to include patients with extensive patch/plaque disease as well as tumor-stage disease. Four of five patients with erythrodermic stage disease had either a complete or a partial clinical remission with photopheresis alone. One patient with extensive patch/plaque disease continued to have a partial clinical remission of 7 months' duration with photopheresis alone. Of the two patients with tumor-stage disease, one remained without evidence of clinical disease at 10 months with photopheresis alone, whereas the second patient had a partial clinical remission of 5 months with a combination of local radiation therapy followed by monthly photopheresis. The skin biopsy specimen obtained from the patient with tumor-stage disease in complete clinical remission did not show cutaneous T cell lymphoma. We conclude that photopheresis is an effective modality alone or in combination with adjunctive therapy for erythroderma, extensive patch/plaque disease, and some tumor-stage disease.

Aphasic and non-brain-damaged adults' knowledge of scripts for common situations.

This study was designed to determine whether script knowledge (mental representations of event sequences for situations that have been experienced in daily life) is compromised by aphasia. Aphasic and non-brain-damaged adults participated in several tasks designed to test their knowledge of scripts for common situations. The tasks included discrimination, in which subjects separated printed phrases identifying test scripts from phrases identifying foil scripts, centrality judgment, in which subjects identified the most typical and frequently occurring events in test scripts, and sequencing, in which subjects arranged the central events from test scripts in the order in which they would be expected to occur in the scripts. Error rates for both non-brain-damaged and aphasic subjects were low in all three tasks, and aphasic subjects generally performed as well as non-brain-damaged subjects did, except that aphasic subjects were significantly poorer at sequencing central events from scripts. However, the actual differences between groups in the sequencing task were quite small. These results suggest that knowledge of scripts is not seriously compromised by aphasia, at least when the aphasia is mild to moderate.