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H Valdimarsson

Publications and source records attributed to H Valdimarsson.

At least 19 recordsLinked to original sources
PubMed1992

Rheumatoid factor isotypes and cancer prognosis.

The relationship between rheumatoid factor (RF) and cancer was studied during a long-term health survey done in the Reykjavik area of Iceland since 1967. A total of 16,299 blood samples from 13,858 persons attending this health survey between 1974 and 1983 were screened for the presence of RF. In 1987, RF-positive participants in this study (n = 270) and matched RF-negative control subjects (n = 223) were evaluated for incidence and prognosis of cancer with information obtained from the comprehensive Icelandic Cancer Registry. The average observation time for this cohort was 9.3 years. Participants with raised immunoglobulin A RF in their original blood sample showed an increased risk of having cancer compared with both other members of the cohort and the national cancer incidence. Their total mortality was also higher during the study period. By contrast, patients with cancer and elevated immunoglobulin M RF before the diagnosis of cancer were more likely to survive than those who were immunoglobulin M RF negative. Cancer incidence in the RF-negative control group was not different from the expected national incidence of cancer in Iceland for that age group. It is suggested that elevation of immunoglobulin A RF is an adverse phenomenon in relation to cancer; elevation of immunoglobulin M RF is associated with a favorable prognosis.

Agglutination Tests↗
PubMed1992

Clinical significance of rheumatoid factor isotypes in seropositive arthritis.

In this cross-sectional study a comparison was made of rheumatoid factor (RF) isotypes in 203 RF positive patients with arthritis. Of these, 129 had rheumatoid arthritis (RA) and 74 a milder disease that would formerly have been classified as probable RA. The majority (74%) of the RA patients had elevations of two or three RF isotypes compared with only 34% of the patients with the milder form of arthritis. A striking feature was that combined elevation of IgM RF and IgA RF was found in 67% of the RA patients compared to only 20% of the patients with milder arthritis who most frequently had an isolated elevation of IgM RF (41%). RA patients with an isolated elevation of IgA RF were younger and had a shorter disease history than RA patients with an isolated elevation in IgM RF or a combined elevation of IgA RF and IgM RF. The prevalence of raised IgM RF was, furthermore, found to increase with age and disease duration. We conclude that a raised level of IgA RF is an adverse phenomenon in patients with seropositive arthritis while patients with an isolated increase in IgM RF may be expected to experience a relatively mild disease course.

Adolescent↗
PubMed1992

Correlation between serum immunoglobulin A concentrations and allergic manifestations in infants.

We studied the relationship of serum levels of IgA and IgE to allergic manifestations and otitis media in a cohort of 179 Icelandic children, aged 18 to 23 months. Only one of the infants had IgA deficiency (less than 50 micrograms/ml); all the others had IgA levels that were normal for their age. The children were divided into three groups according to their IgA levels (lowest 25%, intermediate 50%, highest 25%) and the clinical findings analyzed accordingly. The cumulative incidence of definite allergic manifestations was 37%. Asthma and otitis media were significantly more common among the infants with low normal IgA levels than among those with intermediate to high IgA levels. There was also a significant association between the severity of allergic manifestations and low IgA levels (p = 0.002). Children with detectable IgE (greater than or equal to 0.23 kilounit/L) had a higher incidence of atopic manifestations than did children in whom IgE was not detectable, but only a weak correlation was found between the occurrence and extent of allergic symptoms and increasing amounts of IgE beyond the 0.23 kilounit/L level. These findings suggest that atopic manifestations in infants may be more dependent on delayed maturation of IgA production than on overproduction of IgE.

Asthma↗
PubMed1992

Expression of interferon-gamma receptors in normal and psoriatic skin.

Psoriatic keratinocytes have a reduced antiproliferative response to interferon (IFN)-gamma, and HLA-DR expression is usually not observed on keratinocytes in psoriatic plaques despite the presence of activated T cells. We have therefore compared the expression of IFN-gamma receptors in psoriatic skin with that of normal human skin. Using mouse monoclonal antibodies and immunoperoxidase staining on cryostat cut sections, we detected IFN-gamma receptors on keratinocytes throughout the epidermal layers except stratum corneum in normal skin (n = 11). Biopsy specimens from involved psoriatic skin (n = 17) consistently showed a staining pattern that differed from that of normal skin in that only the lower part of epidermis reacted with the antibodies to IFN-gamma receptors, whereas the upper layers showed no or minimal staining. Expression of IFN-gamma receptors in uninvolved psoriatic skin (n = 16) did not differ from that of healthy controls. Forty-five percent of the biopsies from lesional psoriatic skin displayed ICAM-1 positive keratinocytes, and only two specimens had a limited expression of HLA-DR reactive keratinocytes. The decreased binding of antibodies against the IFN-gamma receptors in the upper part of psoriatic epidermis might be secondary to abnormal maturation of psoriatic keratinocytes or a primary defect involving abnormal modulation of IFN-gamma receptors.

Adult↗
PubMed1992

Is epidermal cell proliferation in psoriatic skin grafts on nude mice driven by T-cell derived cytokines?

Plasminogen activity and DNA synthesis by epidermal cells have been reported to be doubled in psoriatic skin grafts compared with grafts of normal skin 6 weeks after transplantation to nude mice. In our study human lymphocytes disappeared from such grafts within 48 h whilst some DR-positive human dendritic cells were retained in the grafts for up to 4 weeks. However, the grafts were infiltrated by Thy 1.2+ mouse lymphocytes within 6 days and this infiltration persisted at a moderate level throughout the observation period. It consisted of perivascular aggregates, scattered dermal and papillary T cells, and some mouse T cells were also found in the epidermal compartment. Grafts of psoriatic and non-psoriatic control skin were infiltrated to a similar extent, suggesting a low-grade rejection response against the human xenografts. These findings raise the possibility that psoriatic keratinocytes are responding abnormally to inflammatory cytokines released by mouse lymphocytes reacting against the skin grafts.

Animals↗
PubMed1992

Population study of the importance of rheumatoid factor isotypes in adults.

Blood samples collected from 13,858 randomly selected subjects participating in a health survey in Iceland from 1974 to 1983 were tested for rheumatoid factor. Samples that were positive in a sensitive RF screening test were analysed further by the Rose-Waaler technique and an isotype specific enzyme linked immunosorbent assay (ELISA). In 1987 the 173 available participants who were RF positive and 156 matched RF negative controls were evaluated clinically for rheumatoid diseases. RF levels and isotype patterns were more persistent in the patients with rheumatoid arthritis (RA) than in RF positive subjects who did not have overt RA. The prevalence of RA was only 19% in the participants who were RF positive in 1987. Forty per cent of the participants who had a persistent (four to 13 years) increase of IgA RF combined with either IgM or IgG RF were diagnosed as having RA. A positive correlation was found between RF levels and various manifestations of RA. This association was stronger for the IgA and IgG RF isotypes than for IgM RF. Excluding RF positivity as a diagnostic parameter, RA was diagnosed in 33 of the participants and 20 (61%) of these patients had increased levels of IgM and IgA RF. Patients with RA with bone erosions in their hands had higher levels of IgA RF than patients without erosions, but an association was not found between bone erosions and other RF isotypes. None of the RF negative participants who were symptom free when the original blood sample was taken developed RA during the four to 13 year follow up period. In contrast, five symptom free RF positive participants developed RA during this period. These five patients had all had increased levels of at least two RF isotypes before the onset of their symptoms. It is concluded that the IgA and IgG RF isotypes have a closer association with the clinical parameters of RA than IgM RF. Furthermore, increases in RF can precede clinical manifestations of RA and this applies in particular to the IgA and IgG RF isotypes.

Adult↗
PubMed1992

Do adults with high gliadin antibody concentrations have subclinical gluten intolerance?

Gliadin antibodies of the IgG and IgA isotypes and IgG subclasses were measured in 200 adults who were randomly selected from the Icelandic National Register. Those with the highest gliadin antibody concentrations were invited with negative controls to participate in a clinical evaluation. Neither the study subjects nor the physicians who recorded and evaluated the clinical findings were aware of the antibody levels. Significantly higher proportion of the gliadin antibody positive individuals reported unexplained attacks of diarrhoea (p = 0.03), and IgA gliadin antibodies were associated with increased prevalence of chronic fatigue (p = 0.0037). The gliadin antibody positive group also showed significantly decreased transferrin saturation, mean corpuscular volume and mean corpuscular haemoglobin compared with the gliadin antibody negative controls. Serum folic acid concentrations were significantly lower in the IgA gliadin antibody positive individuals. On blind global assessment 15 of the 48 participants were thought to have clinical and laboratory features that are compatible with gluten sensitive enteropathy, and 14 of these were in the gliadin antibody positive group (p = 0.013). Complaints that have not been associated with gluten intolerance had similar prevalence in both groups with the exception of persistent or recurrent headaches that were more common in the gliadin antibody positive group. These findings raise the possibility that a subclinical form of gluten intolerance may be relatively common.

Adult↗
PubMed1991

Altered cell-mediated immunity to group A haemolytic streptococcal antigens in chronic plaque psoriasis.

The proliferative lymphocyte response to sonicated group A, beta-haemolytic streptococci (Strep-A) was measured by thymidine incorporation in 78 patients with psoriasis (guttate, chronic plaque or both). Lymphocytes from 72 of these patients were also cultured with streptokinase/streptodornase (SK/SD), and 20 of the patients with chronic plaque psoriasis were further tested with PPD, Candida albicans and sonicated Streptococcus mutans, a bacterial type not associated clinically with psoriasis. The median stimulation index (SI) of the psoriasis group to the Strep-A preparation was significantly higher than that of a group of 27 non-psoriatic individuals (P less than 0.05). Within this group, only the patients with chronic plaque psoriasis (n = 42) showed a significantly increased proliferative response compared to the non-psoriatic controls (median SI = 123.8 and 31.9, respectively, P less than 0.01). Although the lymphocyte response of the chronic plaque group to SK/SD was also markedly higher than that of the control group, this difference did not reach statistical significance. In addition, these patients did not show significantly increased responses to any of the other antigens tested, including S. mutans. No correlation was observed between the degree of proliferation to Strep-A and disease extent or activity. Similarly, ASO titres, which were raised in 11 out of 23 guttate and three out of nine chronic plaque psoriasis patients tested, did not correlate with the proliferative responses observed.

Adolescent↗
PubMed1991

Cross-reactivity between streptococcal M surface antigen and human skin.

Psoriasis can be triggered by haemolytic streptococcal infections. As M protein is a major pathogenic surface antigen in these streptococci, the cross-reactivity between streptococcal M protein surface antigens and human epidermis was investigated. The conserved component common to the few M proteins investigated consists of an alpha-helical 'coiled-coil' configuration, similar to sub-units of human keratin. The amino acid sequence of protein M6, one of the M proteins that has been fully sequenced, was compared with that of 4721 ubiquitous peptides, by computer-assisted analysis using a protein-sequence data bank. Of all human proteins in the data bank 50-kDa keratin type 1 showed the closest homology with protein M6. Further evaluation revealed that this homology mainly involved the heptapeptide repeat patterns, which form the alpha-helical 'coiled-coil' structure, in both M6 and 50-kDa keratin. Cryostat sections of normal, involved and uninvolved psoriatic skin were studied for cross-reactivity with rabbit antisera raised against 10 different M proteins. All these antisera reacted with the stratum corneum of normal and psoriatic epidermis to a variable extent. Staining of keratinocyte cytoplasm was also observed, but this tended to be more prominent in lesional than in uninvolved and normal skin. Some of the M antisera also stained dendritic cells in the upper dermis as well as endothelium and smooth muscle. These cross-reactivities might be relevant to the pathogenesis of post-streptococcal psoriasis.

Amino Acid Sequence↗
PubMed1990

Immunity during cyclosporine therapy.

Cyclosporine is not cytotoxic but it inhibits the production of immunologic memory-building growth factors by CD4+ T lymphocytes. It also may have inhibitory effects on the effector phase of certain immune reactions. These inhibitory effects are largely reversible and when treatment is stopped, the immune competence of cyclosporine-treated patients returns to normal. In contrast, conventional cytotoxic immunosuppressive agents tend to exterminate the lymphocyte clones that are activated during therapy, and such clonal deletions may cause permanent loss of immunologic memory to those antigens because T lymphocytes are not readily restored in adults with involuted thymus. Most transplant patients have received cyclosporine in combination with various other immunosuppressive agents, and reports suggest that a combination of this drug and conventional immunosuppressive agents may be associated with increased early appearance of non-Hodgkin's lymphoma and, possibly, endocrine-related tumors. An increase in cancers has not been observed in patients treated with cyclosporine alone for such conditions as psoriasis and autoimmune diseases. Treatment of adults with cytotoxic immunosuppressive drugs may permanently delete T-lymphocyte clones that are required for control of latent oncogenic viruses or certain malignant cells. Because of this, when such patients are treated with cyclosporine, further suppression of T-cell function combined with impairment of cytokine-mediated stimulation of natural killer cells and cytotoxic macrophages may facilitate tumor growth. Consequently, it is predicted that if cyclosporine monotherapy is associated with an increased incidence of tumors, it would primarily affect psoriasis patients who are treated with cyclosporine after PUVA or methotrexate therapy. Eventually, comparison of cancer incidence in different categories of patients should resolve this issue.

Carcinogens↗
PubMed1990

IgG subclass response and opsonization of Streptococcus pneumoniae after vaccination of healthy adults.

Studies relating opsonization and IgG antibodies to Streptococcus pneumoniae have yielded contradictory results. This study compared changes in opsonization with IgG subclass response after vaccinating healthy subjects with a 23-valent pneumococcal vaccine. Total IgG and IgG subclass antibodies to pneumococcal polysaccharide types 8, 9, and 19 were measured by ELISA. Opsonic activity was assayed using 3H-labeled bacteria and polymorphonuclear leukocytes in different serum concentrations (5%-40%). A substantial postvaccination increase in total and subclass IgG antibody was observed in most subjects, although variations were seen. Postvaccination sera generally gave rise to enhanced opsonization, and a correlation was found between increases in antibody levels and opsonization. This correlation was closest for IgG1 and IgG4 and generally strongest at the lowest serum concentration, but weak or absent at the highest concentration. Thus, vaccination against S. pneumoniae stimulates a variable increase in specific opsonic activity in health persons that is best demonstrated when serum is a limiting factor in the opsonin assay.

Adult↗
PubMed1990

Four years of experience with cyclosporin A for psoriasis.

Forty-four patients with severe psoriasis have been treated with cyclosporin A (CyA) for 2-50 months (mean 17 months). During the study, 31 (70%) of these patients achieved a greater than 70% reduction in PASI score, 39 (88%) achieved a greater than 60% reduction and 42 (95%) a greater than 50% reduction. The mean initial dose of CyA was 3 mg/kg/day and the mean dose was 3.3 mg/kg/day throughout the study. Twenty-five (57%) patients were maintained on less than or equal to 3 mg and six (14%) required greater than 5 mg/kg/day for limited periods to obtain significant improvement. In three of these patients, this was achieved with 6 mg/kg/day but, of the remainder, one required 7 mg and two required 10 mg/kg/day. Of the 44 patients, 32 (73%) are still taking CyA. Patients were discontinued because of: side-effects directly attributable to treatment (n = 4); remission of psoriasis (n = 4); death (n = I); defaulting (n = I); infrequent attendance (n = I); high doses of NSAID were necessary for arthritis (n = I). Before starting CyA, 39 patients were normotensive; 21 (54%) developed mild hypertension. In 28 patients where the GFRs were estimated before and during treatment, there was a 16% reduction (P less than 0.0001) during a mean period of 8 months. Two patients developed malignancies. The incidence of hypertension and percentage decrease in GFR were strongly correlated with the dose required to control the psoriasis.

Adult↗
PubMed1990

Renal function after long-term low-dose cyclosporin for psoriasis.

Two groups of patients receiving cyclosporin A (CyA) for psoriasis had their renal function assessed by measurement of glomerular filtration rate (GFR) and effective renal plasma flow (ERPF). The first group comprised 13 patients who had taken low dose (average 3 mg/kg per day) CyA for an average period of 2.5 years. Seven of the 13 had a normal GFR of 108 (77-121) ml/min (median; range). In the other six patients the GFR was low at 63 (50-77) ml/min and CyA was discontinued for periods ranging from 3 to 17 weeks. The GFR rose in all six patients, to 79 (60-91) ml/min; this change was significant (P less than 0.05). The six patients restarted CyA because their psoriasis recurred and after a mean interval of 15 weeks the GFR had fallen in all six to 63 (46-80) ml/min (P less than 0.05) and the ERPF decreased from 339 (231-414) ml/min to 244 (177-321) ml/min (P less than 0.05). In the second group of 11 patients measurements were made prior to starting CyA and after taking CyA for a mean of 9 weeks. The GFR fell in eight out of 11 subjects, the GFR for the 11 patients being 117 (72-128) ml/min before taking CyA and 97 (51-122) ml/min after CyA (P less than 0.02). The ERPF was measured in nine of the 11 patients and fell in seven of the nine. The ERPF for the nine patients before CyA was 490 (296-642) ml/min and for the 11 patients after CyA was 410 (195-543) ml/min (P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

Cyclosporin A in psoriatic arthritis: an open study.

Eight patients with psoriatic arthritis entered an open study to determine the efficacy of oral cyclosporin A for their treatment. The starting dose was 3.5 mg/kg daily. Findings after the first six months are reported. One patient withdrew from the study after five months because of tremors, general malaise, and lack of improvement. Seven patients continued through the study, and marked improvement was found after two months in all clinical indices. The skin lesions improved in a parallel fashion. The cyclosporin A dose had to be reduced temporarily by 25% in three patients because of an increase in serum creatinine of more than 50%. A rise in diastolic blood pressure in three patients responded to treatment. The study suggests that cyclosporin A effectively treats arthritic manifestations of psoriasis as well as psoriatic skin lesions.

Adult↗
PubMed1990

Intradermal antigen tests in psoriasis.

To assess whether elicitation of delayed hypersensitivity may be superior to trauma in inducing the Koebner reaction in psoriasis, 12 affected patients and 9 control subjects were tested with 0.1 ml intradermal injections of streptokinase/streptodornase (20 mu/5 mu per 0.1 ml), PPD (1 in 1000) and saline control solutions in a double-blind study; Koebner status was also established in the psoriatic patients. Injected sites were examined at 48 h and 7, 14, 21 and 28 days for local development of psoriasis, erythema and induration (diameter). One patient was Koebner-positive and developed psoriasis at all three injection sites. The other, Koebner-negative psoriatic subjects did not develop psoriasis locally. However, compared with non-psoriatic controls they showed a marked delay in resolution of the delayed hypersensitivity reaction to the PPD antigen and a similar but less marked phenomenon was observed for streptokinase/streptodornase. These findings indicate that intradermal antigen, of the nature and amount used in this study, is no more effective in inducing the Koebner phenomenon than injury alone. However, the ability of psoriasis patients to switch off cell-mediated immune reaction appears to be impaired.

Adult↗
PubMed1990

Epidermal rupture is the initiating factor for the Koebner response in psoriasis.

The Koebner phenomenon was studied using low pressure suction and/or sellotape stripping. Each of 10 patients with psoriasis had 5 suction blisters induced and sellotape stripping. In each patient the roof of 4 of the 5 blisters was removed. In 6 of the 10 patients, psoriasis developed where the blister roof was removed, but not where the blister was left intact. However, only 3 of these 10 patients were also Koebner-positive at the tape-stripped site. Similarly, in a group of 37 psoriasis patients who were sellotape-stripped alone, only 8 (21.6%) were Koebner-positive at the tape-stripped site. In another experiment, 5 suction blisters were produced in each of 4 patients. The roof of 4 blisters was removed, one of which was occluded. Psoriasis developed in 3 of the 4 patients, but only where the blister roof had been removed and left unoccluded. These findings suggest that rupture of the epidermis can initiate the Koebner response, but that secondary dermal events are necessary for a psoriatic lesion to form.

Adult↗
PubMed1989

Intralesional cyclosporin in psoriasis: effects on T lymphocyte and dendritic cell subpopulations.

On each of 10 patients with untreated plaque psoriasis, two symmetrical plaques were injected with cyclosporin A or placebo on six occasions over 12 days, in a double-blind manner. Biopsies taken from these lesions at 14 days were examined for differences in cellular composition using a double-labelling immunofluorescent technique. The cyclosporin-injected plaques cleared significantly better than those injected with placebo (P less than 0.001). In the epidermis of the cyclosporin-injected plaques, total and HLA-DR+ CD4+ and CD8+ T cell numbers were significantly decreased compared to corresponding plaques treated with placebo (total CD4+, total CD8+, DR+ CD4+, P less than 0.01; DR+ CD8+, P less than 0.02). Similarly, T lymphocyte numbers in the dermis were decreased in the cyclosporin compared to placebo-treated plaques; the reduction in total CD4+ and DR+ CD8+ T cell numbers was statistically significant (P less than 0.05). Although total numbers of epidermal dendritic cells were not significantly altered, the DR+CD1- dendritic cell subpopulation was markedly decreased (P less than 0.01) and DR-CD1+ dendritic cells increased (P less than 0.05) in the plaques injected with cyclosporin compared to corresponding placebo-treated plaques. These findings show that cyclosporin injected in situ is effective in clearing psoriasis and probably exerts this beneficial effect by its action on T lymphocytes. A suitable topical preparation that allows penetration of the drug should prove helpful in the treatment of psoriasis.

Adult↗