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Biomedical subjects

I Hafström

Publications and source records attributed to I Hafström.

At least 19 recordsLinked to original sources
PubMed2006

Sex: a major predictor of remission in early rheumatoid arthritis?

BACKGROUND: The treatment goal of early rheumatoid arthritis is remission. This study reports remission rates in clinical practice using a cohort of patients with early rheumatoid arthritis. METHODS: 698 patients with early rheumatoid arthritis were included. Mean age at inclusion was 58 years and mean disease duration was 6.4 months; 64% of the patients were women, 56% were positive for antibodies to cyclic citrullinated peptide and 60% were positive for rheumatoid factor. Remission was defined as a disease activity score <2.6, with or without ongoing treatment with drugs for rheumatoid arthritis. RESULTS: After 2 years, 261 of 689 patients were in remission (37.9%), and after 5 years, the remission rate was 38.5%. However, only 26.1% were in remission at both these time points. Multiple logistic regression analyses found sex to be a main predictor for remission. Thus, significantly fewer women were in remission after 2 years (32.1% v 48%, p = 0.001) after 5 years (30.8% v 52.4%, p = 0.001) and at both these time points (19.1% v 39.3%, p = 0.001). Although disease activity was not with certainty more pronounced in women at onset of disease, the disease course became markedly worse in women. The disparity in remission frequency between women and men could not be explained by differences in disease duration, age or treatment with disease modifying antirheumatic drugs or glucocorticoids. CONCLUSIONS: Early remission of rheumatoid arthritis by 28-joint Disease Activity Score<2.6 was as frequent or more frequent in this study than in most previous reports. Importantly, women had more severe disease with a considerably lower remission rate than men, although the disease activity before treatment seemed similar.

Age of Onset↗
PubMed2004

Prediction of radiological outcome in early rheumatoid arthritis in clinical practice: role of antibodies to citrullinated peptides (anti-CCP).

OBJECTIVE: To investigate the role of anti-cyclic citrullinated peptide antibody (anti-CCP) for the prediction of radiological outcome in patients with early rheumatoid arthritis. METHODS: Anti-CCP was assessed at baseline in 379 patients with early rheumatoid arthritis (disease duration <1 year). Radiological joint damage and progression were assessed by Larsen score after two years of follow up (end point) and used as outcome variables. The prognostic value of anti-CCP and other demographic and disease related baseline variables were assessed by univariate and multivariate analyses, including calculation of odds ratios (OR), predictive values, and multiple logistic regression models. RESULTS: The presence of anti-CCP was associated with significantly higher Larsen score both at baseline and at end point. Univariate predictor analysis showed that anti-CCP had the highest significant OR for radiological joint damage and progression after baseline Larsen score, followed by rheumatoid factor, erythrocyte sedimentation rate (ESR), C reactive protein, age, smoking status, and sex. In stepwise multiple regression analyses, baseline Larsen score, anti-CCP, and ESR were selected as significant independent predictors of the radiological outcomes. CONCLUSIONS: There is good evidence for an association of anti-CCP with radiological joint changes in rheumatoid arthritis. Anti-CCP is an independent predictor of radiological damage and progression. Though prediction in early rheumatoid arthritis is still far from perfect, the use of anti-CCP in clinical practice should make it easier for rheumatologists to reach judicious treatment decisions.

Adult↗
PubMed2002

Bioavailable testosterone in men with rheumatoid arthritis-high frequency of hypogonadism.

OBJECTIVES: To study bioavailable testosterone (T) in men with rheumatoid arthritis (RA) by determining non-sex hormone-binding globulin (SHBG)-bound T (NST) under standardized conditions and to investigate if NST is related to disease variables. METHODS: Basal serum concentrations of total T, SHBG and luteinizing hormone (LH) were measured in 104 men with RA, and the levels of NST as well as the quotient T/SHBG were calculated. The data were compared with those of 99 age-matched healthy men. The results were analysed separately for the age groups 30-49, 50-59 and 60-69 yr. RESULTS: The RA men had lower NST levels than the healthy men in all age groups. T levels and the T/SHBG ratio were lower only in the age group 50-59 yr. SHBG did not differ significantly. LH was significantly lower in the patients than in the controls. Thirty-three of the 104 patients were considered to have hypogonadism compared with seven of the 99 healthy men. The only clinical variable apart from age that had a significant impact on NST was the Stanford Health Assessment Questionnaire (HAQ). CONCLUSION: Men with RA had lower levels of bioavailable T and a large proportion were considered hypogonadal. The low levels of LH suggested a central origin of the relative hypoandrogenicity.

Adult↗
PubMed2002

Long term efficacy and safety of cyclosporin versus parenteral gold in early rheumatoid arthritis: a three year study of radiographic progression, renal function, and arterial hypertension.

OBJECTIVE: To compare the three year safety and efficacy of cyclosporin and parenteral gold in the treatment of early, active, severe rheumatoid arthritis (RA), and to study the reversibility of cyclosporin associated renal dysfunction in patients who discontinued cyclosporin treatment. METHODS: The patients continued to receive cyclosporin or parenteral gold in an 18 month open extension to an 18 month randomised, parallel group study. The main efficacy variable was blinded evaluation of radiographic progression of joint damage. Safety variables included serum creatinine, calculated creatinine clearance, and blood pressure. RESULTS: Radiographic progression during follow up was similar in both groups. About 60% of the patients in the intention to treat groups (n=272) and about half of the patients in the completer groups (n=114) had definite radiographic progression in joint damage (increases >6 in the Larsen-Dale score), and about one in three also had substantial progression (>18 increase in Larsen-Dale score). Both systolic and diastolic blood pressure were significantly increased in the cyclosporin group compared with the gold group, and 12/139 (9%) versus 3/139 (2%) (p=0.03) had notably raised blood pressure. The mean serum creatinine increased by 28% at the treatment end point in the cyclosporin group as compared with 7% in the gold group. The mean calculated creatinine clearance was reduced by 16% and increased by 1% in the cyclosporin and gold groups, respectively, at the end of the study. At the final follow up visit after discontinuation of cyclosporin (at least three months after treatment was stopped) the mean serum creatinine was increased by 15% and creatinine clearance reduced by 16%. Sustained increases in serum creatinine at this post-treatment end point were mostly seen in patients with a raised serum creatinine during treatment of at least 50%. CONCLUSION: Three year changes in radiographic damage during cyclosporin and parenteral gold were similar in patients with early, active RA. Abnormal renal function and raised blood pressure were often seen in the cyclosporin treated patients.

Activities of Daily Living↗
PubMed2001

Bone mineral density in women and men with early rheumatoid arthritis.

OBJECTIVE: To study bone mineral density (BMD) in patients with early rheumatoid arthritis. METHODS: Dual x-ray absorptiometry was performed in 227 patients, 149 women and 78 men, with rheumatoid arthritis (RA) of no more than 12 months duration. RESULTS: Women, as well as men above 60 years of age, had a BMD at spine and hip comparable with age and sex matched reference populations. Men younger than 60 years had a tendency to lower BMD. Although the proportion of female patients with osteoporosis was not higher than in the reference, population the proportion of patients with reduced bone mass was increased, and this was found also in men. There was no significant association between BMD and disease duration, disease activity or disability. CONCLUSION: Untreated patients with early RA have a BMD in spine and hip not significantly different from that of normal reference populations. However, an increased number of the patients had reduced bone mass already at disease onset.

Absorptiometry, Photon↗
PubMed2001

A vegan diet free of gluten improves the signs and symptoms of rheumatoid arthritis: the effects on arthritis correlate with a reduction in antibodies to food antigens.

OBJECTIVE: Whether food intake can modify the course of rheumatoid arthritis (RA) is an issue of continued scientific and public interest. However, data from controlled clinical trials are sparse. We thus decided to study the clinical effects of a vegan diet free of gluten in RA and to quantify the levels of antibodies to key food antigens not present in the vegan diet. METHODS: Sixty-six patients with active RA were randomized to either a vegan diet free of gluten (38 patients) or a well-balanced non-vegan diet (28 patients) for 1 yr. All patients were instructed and followed-up in the same manner. They were analysed at baseline and after 3, 6 and 12 months, according to the response criteria of the American College of Rheumatology (ACR). Furthermore, levels of antibodies against gliadin and beta-lactoglobulin were assessed and radiographs of the hands and feet were performed. RESULTS: Twenty-two patients in the vegan group and 25 patients in the non-vegan diet group completed 9 months or more on the diet regimens. Of these diet completers, 40.5% (nine patients) in the vegan group fulfilled the ACR20 improvement criteria compared with 4% (one patient) in the non-vegan group. Corresponding figures for the intention to treat populations were 34.3 and 3.8%, respectively. The immunoglobulin G (IgG) antibody levels against gliadin and beta-lactoglobulin decreased in the responder subgroup in the vegan diet-treated patients, but not in the other analysed groups. No retardation of radiological destruction was apparent in any of the groups. CONCLUSION: The data provide evidence that dietary modification may be of clinical benefit for certain RA patients, and that this benefit may be related to a reduction in immunoreactivity to food antigens eliminated by the change in diet.

Adult↗
PubMed2000

[New drugs against rheumatoid arthritis. Improved treatment options place new demands on health care organization].

During the present year more new drugs will be introduced for the treatment of rheumatoid arthritis than have been for several decades. In order to make the widening range of therapeutic options truly available in daily clinical care, certain changes will be required in the organization of treatment resources for rheumatic patients. Several articles in the present issue of Läkartidningen describe the new drugs. Besides introducing these new drugs, it is shown that combinations of "old" antirheumatic drugs (DMARD's) given in high doses and in an earlier phase of disease than previously also exert positive effects on disease course. Taken together, new strategies have been developed for the treatment of patients with RA. One such strategy, endorsed by the Swedish Rheumatology Association, is described in this paper, together with a description of a new national surveillance system for the new drugs.

Antirheumatic Agents↗
PubMed1998

Progression of joint damage in early active severe rheumatoid arthritis during 18 months of treatment: comparison of low-dose cyclosporin and parenteral gold.

OBJECTIVE: This study compared the progression of joint damage in patients with early active severe rheumatoid arthritis (RA) treated with cyclosporin or parenteral gold. METHODS: In this open, randomized, multicentre study with a blinded radiological endpoint, 375 patients who had suffered from active severe RA for <3 yr were randomized to be treated for 18 months with low-dose cyclosporin or parenteral gold. The groups were stratified with regard to corticosteroid use. Primary efficacy variables were numbers of erosions, erosion score and the Larsen-Dale joint damage score. RESULTS: Joint damage progressed at similar rates in both treatment arms. In both groups, patients receiving corticosteroids had less X-ray progression. Rheumatoid factor positivity, high swollen joint count, high erythrocyte sedimentation rate and pre-existing X-ray abnormalities predicted progression of joint damage. Although numbers of serious adverse events were similar, more gold patients (n = 65) than cyclosporin patients (n = 45) withdrew from study medication because of adverse events. CONCLUSION: Cyclosporin was comparable to parenteral gold in retarding progression of joint damage and was better tolerated in terms of adherence to therapy. The open label design should be kept in mind when assessing this difference.

Adolescent↗
PubMed1997

Availability of iron and degree of inflammation modifies the response to recombinant human erythropoietin when treating anemia of chronic disease in patients with rheumatoid arthritis.

Forty-six patients with rheumatoid arthritis (RA) and documented anemia of chronic disease (Hb < 100/110 g/l) were randomized to receive either human recombinant erythropoietin (r-HuEPO, n = 36, 300 U/kg body weight) or placebo (n = 10) for 12 weeks in a multicenter study. An adequate response was defined as elevation of Hb > or = 120 g/l. Relevant clinical and laboratory assessments were made to evaluate efficacy and secure safety. A significant elevation in Hb from week 10 onwards was noted in twenty-six patients (five drop-outs) out of nine patients receiving placebo (one drop-out) (12 +/- 1.2 g/l vs 4 +/- 0.5 g/l; Hb elevation from 95 g/l to 107 g/l vs 93 g/l to 97 g/l, P < 0.05). Only 14.6%, however, were considered responders according to preset criteria. In the responders a lower initial CRP, a significant reduction in ESR but not in CRP was seen compared to the remaining r-HuEPO group. A significant elevation of energy level was noted in the r-HuEPO group; otherwise, no differences in clinical variables were seen. No serious adverse effects were noted. When analyzing patients receiving oral iron in combination with r-HuEPO and adding five additional, openly selected patients receiving both adequate iron supplementation and r-HuEPO, there was a significant weekly elevation of Hb from week 8 onwards in favor of combination therapy over the ones only receiving r-HuEPO (18 +/- 1.1 g/l vs 7 +/- 1.1 g/l, P < 0.05). The initial six responders had now reached ten of whom seven belonged to the combination therapy group. Response to r-HuEPO in RA patients appears to be dependent on availability of iron and on the degree of inflammation. If r-HuEPO treatment is considered, iron deficiency should always be corrected and strenuous efforts should have been made to control the disease itself.

Adult↗
PubMed1994

Evidence of a local intestinal immunomodulatory effect of sulfasalazine in rheumatoid arthritis.

OBJECTIVE: To analyze whether the intestinal mucosa in rheumatoid arthritis (RA) is immunologically abnormal and whether sulfasalazine (SSZ) possesses any local intestinal immunoregulatory effect. METHODS: Lymphocyte subpopulations and HLA-DR expression were evaluated in biopsy specimens from the duodenal-jejunal mucosa and in peripheral blood samples obtained from 17 patients with RA, both before and after 16 weeks of SSZ treatment. The same mucosal assays were also performed in 7 controls. RESULTS: The mucosa of the small intestine in RA patients showed no differences in morphology, HLA-DR expression, or the amounts and distribution of CD3+, CD4+, CD8+, and gamma/delta + lymphocytes compared with the control group. However, there was a reduction in mucosal CD3+ and gamma/delta + lymphocyte numbers after SSZ therapy, which did not correspond to a change in peripheral blood CD3+ lymphocyte number. SSZ treatment also tended to diminish the peripheral blood CD4+:CD8+ cell ratio (P = 0.05). CONCLUSION: No signs of inflammation or immunologic abnormalities were seen in RA duodenal-jejunal mucosa. In this part of the intestine, however, SSZ exerted immunoregulatory effects that were not encountered in the peripheral blood.

Adjuvants, Immunologic↗
PubMed1994

Effect of sulphasalazine on gastrointestinal microflora and on mucosal heat shock protein expression in patients with rheumatoid arthritis.

This study was performed in order to elucidate a possible association between mucosal heat shock protein expression, the gastrointestinal microflora and disease activity in 17 patients with RA before and after 16 weeks of sulphasalazine (SASP) treatment. The duodenal-jejunal mucosal binding of the monoclonal antibody ML30, recognizing the 65 kDa heat shock protein of mycobacteria, was increased (P = 0.048) in the untreated RA patients compared to controls, but did not correlate to disease, activity or microflora and was not altered by SASP therapy. There was no convincing evidence for bacterial overgrowth in the jejunum and the faecal microflora was normal. SASP treatment altered the faecal microflora, with significant reductions of the total aerobic bacteria, Escherichia coli and Bacteroides, and increased numbers of Bacillus. SASP had only minor effects on the jejunal microflora. A high carriage frequency of Candida albicans was found in saliva and the counts correlated negatively with the unstimulated whole salivary secretion rate. These results suggest that the gut may be involved in the aetiopathogenesis of RA but do not substantiate the hypothesis that the anti-rheumatic effects of SASP are mediated via its anti-microbial properties. However, the possibility that a micro-organism, not detected in this study, may be of crucial importance in RA, cannot be ruled out.

Adult↗
PubMed1993

The effect of endothelin, neuropeptide Y, calcitonin gene-related peptide and substance P on neutrophil functions.

Neuropeptides are putative mediators of inflammation. At physiological concentrations substance P has been shown to prime polymorphonuclear neutrophil granulocyte (PMN) chemiluminescence (CL). In the present study we show also that both endothelin and neuropeptide Y (NPY), but not calcitonin gene-related peptide (CGRP) are able to prime PMN oxidative metabolism. At similar nanomolar concentrations SP and endothelin (but not NPY) also primed formyl-methionyl-leucyl-phenylalanine (fMLP)-induced rises of cytosolic calcium. On the other hand, NPY caused a direct and dose-related increase of cytosolic calcium concentrations. None of the mentioned neuropeptides primed PMN aggregation or directly induced CL, aggregation or chemotaxis over a wide range of concentrations (1 fM-1 microM).

Calcitonin Gene-Related Peptide↗
PubMed1991

Antirheumatic effects of fasting.

Total fasting induces within a few days a substantial reduction of joint pain, swelling, morning stiffness, and other arthritic symptoms in patients with rheumatoid arthritis. This remission subsides slowly after discontinuation of fasting. Its mechanisms are complex and involves diminished activation of neutrophils and lymphocytes and decreased generation of leukotrienes and of concentrations of serum complement factors, as well as of other proinflammatory systems. Moreover, ketosis and other metabolic and endocrine changes may be of significance for symptom expression and recognition.

Arthritis, Rheumatoid↗
PubMed1990

Effect of sulphasalazine and sulphapyridine on neutrophil superoxide production: role of cytosolic free calcium.

As the neutrophil granulocyte plays an important part in rheumatoid inflammation the effect of sulphasalazine on neutrophil function was studied. The results show that sulphasalazine, and its metabolite sulphapyridine, inhibit neutrophil superoxide production elicited by the receptor mediated stimulus N-formyl-methionyl-leucyl-phenyl-alanine (fMLP) and by the calcium ionophore A23187. This effect seems to be dependent on inhibition of intracellular Ca++ increase as both substances reduce this increase upon cell activation with fMLP and A23187. Sulphasalazine and sulphapyridine do not inhibit superoxide production after stimulation with the ester phorbol myristate acetate, a stimulus response coupling which is independent of intracellular Ca++ increase. The reported inhibition of superoxide generation may explain, at least partly, the antirheumatic property of sulphasalazine.

Calcimycin↗
PubMed1990

Dietary linoleate supplementation modulates formyl-peptide receptor expression and functional responses of rat neutrophils.

We studied effects of dietary supplementation with the essential fatty acid (EFA) linoleic acid (LA) to see if neutrophil responses would be modulated. Neutrophils from rats maintained on a diet supplemented with EFA to 10% of the energy content--the high EFA (HEFA) group--showed a significantly higher LA concentration (but similar arachidonic acid content) compared with neutrophils from control rats maintained on a standard diet with 3% of the energy content as EFA. The HEFA group showed a significantly higher neutrophil oxidative metabolism compared with controls in response to N-formyl-methionyl-leucyl-phenylalanine (FMLP), but this response was equal to control values when stimulated by ionophore A23187, sodium fluoride, or phorbol myristate acetate. Similarly, FMLP conferred a more pronounced increase of intracellular Ca2+ in HEFA neutrophils, whereas this response to ionomycin was equal to that in controls. In contrast, HEFA rat neutrophil migration was decreased to 71% of the value in controls in response to FMLP. Similar results were observed for aggregation responses. On A23187 stimulation, HEFA and control neutrophils generated equal amounts of leukotriene B4 and other 5-lipoxygenase products as well as thromboxane B2 and 6-keto-prostaglandin F1 alpha. However, assessment of binding of FMLP labeled with tritium revealed an increase of the low affinity state of the FMLP receptor population. Thus an increased intake of one unsaturated fatty acid, LA, leading to its accumulation in neutrophils, conferred alterations in formyl-peptide-elicited responses, not associated with the formation of the assessed arachidonate-derived mediators, but most likely through the observed modulation of FMLP receptor subpopulations.

6-Ketoprostaglandin F1 alpha↗
PubMed1989

Substance P activates and modulates neutrophil oxidative metabolism and aggregation.

The substance P (SP) fragment SP(7-11) induced chemiluminescence (CL) and aggregation in human neutrophils at high concentrations (greater than or equal to 10 microM), whereas the entire molecule SP(1-11) was less potent and the SP(1-4) fragment was inactive. At these concentrations SP and its fragments also inhibited CL and aggregation evoked by subsequent addition of formyl-methionyl-leucyl-phenylalanine (fMLP), an effect that may depend on desensitization. However, at lower concentrations (1-10 nM) SP was able to prime human neutrophils to enhanced CL and enzyme release stimulated by fMLP. These findings indicate that, in addition to direct activation of CL and aggregation, SP also modulates neutrophil function and can thus amplify the release of potentially cytotoxic substances, a possible mechanism for nervous system involvement in rheumatoid arthritis.

Cell Aggregation↗