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Biomedical subjects

H Valdimarsson

Publications and source records attributed to H Valdimarsson.

At least 91 records · Page 5Linked to original sources

Long-term cyclosporin for psoriasis.

Thirteen patients with severe persistent psoriasis, intolerant of, or unresponsive to, other current treatments have been treated with cyclosporin (Cys) for periods varying from 12-25 (mean 18) months. The dose ranged from 1-4 mg/kg/day (mean 2.8 mg). There was a 72% reduction in the mean PASI score at 4 weeks, and at the end of the study, an 81% reduction. Adjuvant therapy with topical steroids was used in 11 of the 13 patients after the first 3 months of Cys treatment to persistent patches on an intermittent basis with beneficial effect. Six patients developed mild to moderate hypertension, in three this was controlled by a reduction in the dose of Cys, and in the other three by hypotensive agents. The mean serum creatinine rose from 72 to 90 microM/l during the study. Hypertrichosis occurred in seven of the 13 patients. Low dosage Cys is an effective treatment for clearing psoriasis and maintaining improvement on a long-term basis.

Adult↗

Successful plasma infusion treatment of a patient with C2 deficiency and systemic lupus erythematosus: clinical experience over forty-five months.

We describe a patient with C2 deficiency and severe systemic lupus erythematosus (SLE) that did not respond to conventional therapy. Over a period of 45 months, she was given 22 cycles of plasma therapy. For 6-8 weeks after each plasma infusion, there was a full clinical remission of the SLE, and a brief restoration of hemolytic complement activity. However, there were more prolonged increases in the activities of the complement components that are believed to be more directly involved in the clearance of immune complexes. Because of the theoretical risk that the infused complement might enhance inflammatory tissue damage, there has been some reluctance to try plasma replacement therapy in SLE patients with complement deficiency. We have not observed any adverse effects with the long-term use of this treatment, and our experience indicates that this therapeutic approach can be beneficial.

Adult↗

An altered response by psoriatic keratinocytes to gamma interferon.

To determine whether psoriatic keratinocytes differ from normal keratinocytes in their response to gamma interferon, epidermal cell suspensions from normal and from lesional and uninvolved psoriatic skin were cultured in the presence of gamma interferon and the induction of HLA-DR expression and inhibition of cell growth were measured. The addition of 10(2) units of gamma interferon/ml during a 7-day culture period significantly increased mean HLA-DR+ cell numbers in 21 epidermal suspensions of normal from 3.9 to 24.1% (P less than 0.0001), uninvolved psoriatic from 8.4 to 33.1% (P less than 0.0001), and to a lesser extent lesional psoriatic biopsies from 12.6 to 18.3% (P less than 0.01). However, the increase in HLA-DR+ cell numbers in these latter cultures was significantly less than that observed in either normal or uninvolved psoriatic epidermal cell cultures (P less than 0.0001). Furthermore, [3H]thymidine incorporation was substantially decreased by gamma interferon in 16 out of 22 (73%) cultures of normal epidermal cells; this decrease was statistically significant (P less than 0.01). In contrast, only 4 out of 11 (36%) lesional and 9 out of 21 (43%) uninvolved psoriatic epidermal cultures showed comparable inhibition of proliferation. These findings suggest that psoriatic keratinocytes have an altered response to gamma interferon; this could explain the infrequency of keratinocyte HLA-DR expression in psoriatic plaques in vivo and may also contribute to the increased epidermal proliferation that characterizes this disease.

Adult↗

Rheumatoid factors in Yersinia-triggered reactive arthritis.

Total rheumatoid factor (RF) activity and RF isotypes were measured in the sera of 33 patients with Yersinia infection using enzyme-linked immunosorbent assay. Twenty out of 33 patients developed reactive arthritis as a postinfectious complication. Yersinia infection does not seem to stimulate formation of RFs. The serum samples were practically negative, except two consecutive samples of one patient with Yersinia enterocolitica 0:3 triggered reactive arthritis which were strongly positive for all RFs tested. Although in Yersinia triggered reactive arthritis continuous response against Yersinia is seen, especially in the form of persisting IgA response, RF do not seem to be involved.

Adolescent↗

Epidermal DR+T6- dendritic cells in inflammatory skin diseases.

T lymphocyte and dendritic cell subpopulations were counted in three biopsies each of endogenous eczema and pityriasis rosea and two of lichen planus and compared with previous findings in psoriatic lesions. In common with psoriasis, proportionately more CD4 T cells than CD8 T cells were DR+ in both epidermis and dermis of all lesions. In addition, total numbers of epidermal dendritic cells were significantly increased in endogenous eczema and pityriasis rosea, and variably in lichen planus lesions. Interestingly, a DR+T6- subpopulation of dendritic cells was present in varying proportions in all three skin lesion types. Electron microscopy of DR+T6- dendritic cells from psoriatic lesions, using an immunogold staining technique, showed the cells to be of the Langerhans' cell lineage. DR+T6- dendritic cells are a subpopulation of Langerhans' cells which are not specific to psoriasis, but present in the lesions of other benign, inflammatory skin conditions in which CD4 T cells are preferentially activated.

Antigens, Differentiation, T-Lymphocyte↗

A prospective study of the Koebner reaction and T lymphocytes in uninvolved psoriatic skin.

T lymphocyte and dendritic cell subpopulations were counted in untraumatized, uninvolved skin of 27 patients with psoriasis. Eight of the patients proved to be Koebner-positive, as determined by tape stripping and punch biopsy, and 19 Koebner-negative. In the epidermis the CD4/CD8 T cell ratio was significantly higher in the Koebner-positive vis-à-vis Koebner-negative patients (median CD4/CD8 = 1.68 and 0.75, respectively: p less than 0.05). This resulted from a small increase in CD4 and a larger decrease in CD8 epidermal T cells in the Koebner-positive group. However, numbers of epidermal dendritic cells did not differ significantly between the two groups. In the dermis the CD4/CD8 T cell ratio was also higher in the Koebner-positive than in Koebner-negative patients (median of 3.56 and 2.57, respectively). These findings demonstrate that the tendency of uninvolved skin of psoriatic individuals to become lesional after trauma is associated with a predominance of CD4 over CD8 T cells in the epidermis.

Dendritic Cells↗

Preferential activation of CD4 T lymphocytes in the lamina propria of gluten-sensitive enteropathy.

The distribution and activation of T-lymphocyte subsets in the small intestinal mucosa of coeliac disease and dermatitis herpetiformis subjects on a normal diet has been studied and compared to normal controls. Double-labelling immunofluorescence techniques with monoclonal antibodies were used on cryostat tissue sections. Intestinal epithelial cells demonstrated staining for HLA-DR, the intensity being proportional to the degree of enteropathy. In both patients and controls nearly all (97%) intra-epithelial lymphocytes were of the CD8 subset and not activated as judged by HLA-DR expression. In the lamina propria there was an approximate 50-fold increase in T cells in the patients as compared with the controls. Whilst the ratio of total CD4 to total CD8 cells was unchanged, the CD4 subset was preferentially activated in the patients. Thus in the normal controls the median ratio of activated CD4 cells to activated CD8 cells was 1.67 whilst for dermatitis herpetiformis and coeliac disease it was 3.42 and 6.07 respectively. These findings suggest that the lamina propria is a site of vigorous T-cell activity in gluten-sensitive individuals and is consistent with the view that the enteropathy of dermatitis herpetiformis and coeliac disease is the result of a delayed-type hypersensitivity against gliadin.

Adolescent↗