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Biomedical subjects

U Tarp

Publications and source records attributed to U Tarp.

At least 19 recordsLinked to original sources
PubMed2005

Routine database registration of biological therapy increases the reporting of adverse events twentyfold in clinical practice. First results from the Danish Database (DANBIO).

OBJECTIVE: To present from the Danish Database for Biological Therapies in Rheumatology (DANBIO) the frequencies and types of adverse events as well as risk factors during treatment with biological agents in clinical practice. METHODS: Adverse events during the first 2 years of clinical use of biological agents in Denmark were reported to the nationwide DANBIO and compared to the mandatory reports to the Danish Medicines Agency. RESULTS: Almost 90% of the patients treated with biological agents were registered in the DANBIO, and the database picked up 20 times as many adverse events as the Danish Medicines Agency. Infections and hypersensitivity reactions were the most prevalent adverse events. Age, disease duration, and previous number of disease-modifying anti-rheumatic drugs (DMARDS) were found to be risk factors for bacterial infections. CONCLUSION: A routine-based Danish database for biological therapies covers approximately 90% of patients and improves the reporting of adverse events.

Adult↗
PubMed2002

Autoantibodies against interleukin 1alpha in rheumatoid arthritis: association with long term radiographic outcome.

OBJECTIVES: To investigate the possible association of interleukin 1alpha autoantibodies (IL1alpha aAb) with the long term course of joint erosion in patients with rheumatoid arthritis (RA). METHODS: Serum samples from 176 patients with RA included in a prospective study over 30 years were analysed for IL1alpha aAb by binding to human [(125)I]IL1alpha. Erosions of 19 diarthrodial joints were radiographically scored by the Larsen method. RESULTS: The relative risk (RR) of early IL1alpha aAb positive patients developing at least 30% of maximum radiographic joint destruction was significantly lower than for IL1alpha aAb negative patients, RR=0.29 (p=0.04). In rheumatoid factor positive patients RR was only 0.18 (p=0.02). Patients who seroconverted more than two years after the onset of RA showed the most aggressive development of joint erosion, with a relative risk of at least 40% of maximum radiographic joint destruction of 2.56 (p=0.048) CONCLUSIONS: The progression of radiographic joint destruction in patients with RA is associated with, and perhaps modified by, circulating IL1alpha aAb, suggesting that IL1alpha or IL1alpha aAb, or both, have a role in the erosive processes. IL1alpha aAb appear to be of prognostic significance in RA.

Adolescent↗
PubMed2001

Effect of early vocational intervention in a rheumatological outpatient clinic--a randomized study.

This study aims to explore the effect of vocational intervention in a rheumatological outpatient clinic. The study is designed as a randomized study with intervention in 108 patients and with 93 patients serving as controls. The study population comprises patients referred for non-inflammatory diseases of the locomotor system who are all active members of the workforce and whose vocational status is threatened by their disease. Intervention consisted of sociomedical examination, multidisciplinary assessment and individual sociomedical rehabilitation plans. The study shows that intervention was an important instrument in the process of clarifying patients' future maintenance situation as assessed 1 year after intervention (relative risk (RR) = 1.2 (CI 1.0-1.5)). The effect was particularly prominent among well-educated women. A non-significant effect was established for vocational status in general (RR = 1.1 (CI 0.8-1.4)). This effect was significant and positive for well-educated patients with a short-term sick leave (maximum 6 months). The verified effect of early sociomedical intervention in the secondary healthcare sector warrants the permanency of routine intervention.

Adolescent↗
PubMed2000

The association of variant mannose-binding lectin genotypes with radiographic outcome in rheumatoid arthritis.

OBJECTIVE: To investigate the possible association of mannose-binding lectin (MBL) genotypes with the outcome of rheumatoid arthritis (RA). METHODS: MBL genotypes and plasma concentrations were retrospectively determined in 140 RA patients who were selected from a major cohort followed up prospectively for up to 32 years. RESULTS: MBL-insufficient patients (those with 2 defective structural MBL alleles or with 1 defective allele combined with a low-expression variant of the normal allele) had unfavorable outcomes. The relative risk of a severe radiographic outcome event (30% of maximum radiographic destruction, or an RE30) was 3.1 (95% confidence interval 1.8-5.1) in the MBL-insufficient group versus the MBL-competent group (P < 0.0001). An RE30 occurred in 50% of MBL-competent patients within 17 years, while such an event occurred 9 years earlier in MBL-insufficient patients (i.e., within 8 years) (P < 0.0001). During the first 15 years, there was a significant trend toward lower hemoglobin levels (P < 0.04), higher erythrocyte sedimentation rates (P < 0.02), and a higher number of swollen joints (P < 0.05) in the MBL-insufficient group. CONCLUSION: MBL genotypes giving rise to MBL insufficiency are highly significant risk factors for fast progression of radiographic joint destruction.

Adolescent↗
PubMed2000

Inflammatory patterns in rheumatoid arthritis estimated by the number of swollen and tender joints, the erythrocyte sedimentation rate, and hemoglobin: longterm course and association to radiographic progression.

OBJECTIVE: To investigate the association of individual plots and time-integrated values of repeated measures of inflammatory variables with radiographic outcome in rheumatoid arthritis (RA). METHODS: In 112 patients with RA, examinations of joint swelling and joint tenderness of 68 joints, and measurement of hemoglobin (Hb) and erythrocyte sedimentation rate (ESR) were performed each year for up to 22 years after the first visit. For each of these 4 variables, the patients were divided arbitrarily into 5 characteristic subgroups by means of inspection of individual plots of longitudinal observations of the variables and divided into 5 other subgroups according to 20% percentiles of the cumulative mean values of the variables. The outcome of the subgroups was evaluated by varying degrees of radiographic events estimated by Larsen scoring of consecutive radiographs of 46 joints. RESULTS: An increasing number of radiographic events in subgroups with increasing severity (increasing values of joint swelling, joint tenderness, and ESR, decreasing values of Hb) was seen for both the arbitrary subgroups and the percentile subgroups of joint swelling, Hb, and ESR, whereas the association of joint tenderness to radiographic progression was weak. CONCLUSION: A highly significant association between inflammatory variables and radiographic outcome could be observed, indicating that the degree of inflammation is important for the development of destructive joint damage in RA.

Adolescent↗
PubMed1999

Mortality and causes of death of 513 Danish patients with systemic lupus erythematosus.

A multicentre cohort of 513 clinic attenders with systemic lupus erythematosus (SLE) was retrospectively identified, representing 4185 patient-years of follow-up. Expected numbers of death were calculated by means of age- and sex-specific mortality rates of the general Danish population. The observed number of deaths was 122. The survival rates were 97%, 91%, 76%, 64% and 53% after 1, 5, 10, 15, and 20 years respectively. The overall mortality rate was 2.9% per year (95% CI 2.4-3.5), and the standardized mortality rate (SMR) was 4.6 (95% CI 3.8-5.5). The causes of death included active SLE (n = 19), end stage organ failure due to SLE (n = 16), infections (n = 25), malignancy (n = 9), cardiovascular disease (n = 32), and other causes (n = 21). SLE was directly related to one third of the excess mortality. In conclusion, SLE patients in the present cohort had a 4.6-fold increased mortality compared with the general population and half of the deaths were caused by SLE manifestations or infections, especially in young patients during the early period of the disease.

Adolescent↗
PubMed1999

Prognostic value of renal biopsy and clinical variables in patients with lupus nephritis and normal serum creatinine.

OBJECTIVE: To evaluate factors with possible influence on the renal outcome in patients with lupus nephritis but without chronic renal insufficiency (CRI). METHODS: Renal biopsies from 94 patients were re-assessed with regard to WHO class, activity, chronicity and tubulointerstitial indices without knowledge of clinical features. The outcome parameters were CRI defined as irreversibly increased serum creatinine and renal end stage disease. RESULTS: The risk ratios (RR) of developing CRI were 2.6 for active urinary sediment, 3.1 for hyaline thrombi and 7.3 for glomerular leukocyte exudation. The RR of renal end stage disease was 5.0 when the duration of renal disease exceeded one year at the time of biopsy and 4.3 when biopsy disclosed a class IV lesion. Glomerular sclerosis was also associated to renal end stage disease. CONCLUSION: Early renal biopsy and the abovementioned signs of active renal disease carry prognostic information that may have significant therapeutic implications.

Adolescent↗
PubMed1998

A multicentre study of 513 Danish patients with systemic lupus erythematosus. I. Disease manifestations and analyses of clinical subsets.

A Danish multicentre study was undertaken of the manifestations, infections, thrombotic events, survival and predictive factors of survival in 513 Danish patients with systemic lupus erythematosus (SLE) according to the 1982 classification criteria of the American College of Rheumatology. The mean duration of follow-up was 8.2 years from diagnosis and 12.8 years from first symptom. This paper describes the most common clinical and laboratory manifestations and their relationship to sex and age at the time of onset and diagnosis. Cluster analysis revealed three clinically defined clusters at the time of disease onset. Cluster 1 (57% of patients) consisted of relatively elderly patients without nephropathy or malar rash, but with a high prevalence of discoid lesions. Cluster 2 (18%) consisted of patients with nephropathy, a third of whom also developed serositis and lymphopenia. The patients of the third cluster (25%) all had malar rash and half were photosensitive. Follow-up showed that the patients of cluster 2 developed azotaemia, large proteinuria, arterial hypertension and myositis significantly more often than did the rest of the patients, but the mortality was not increased. The risk of developing renal end-stage disease was highest in men with early-onset disease.

Adolescent↗
PubMed1998

A multicentre study of 513 Danish patients with systemic lupus erythematosus. II. Disease mortality and clinical factors of prognostic value.

In this Danish multicentre study, predictive clinical factors of mortality and survival were calculated for 513 patients with systemic lupus erythematosus (SLE), 122 of whom died within a mean observation period of 8.2 years equalling a mortality rate of 2.9% per year. Survival rates were 97%, 91%, 76% and 64% after 1, 5, 10 and 15 years, respectively. The direct causes of death included SLE (n = 35), infections (n = 25), malignancy (n = 9), cardiovascular disease (n = 32) and other causes (n = 21). Uni- and multivariate analyses of survival and mortality were performed for all deaths and for SLE-related deaths. Azotaemia (one-fifth of the patients) was a strong predictor of increased overall and SLE-related mortality, but nephropathy per se (one-half of the patients) and large proteinuria (one-sixth of the patients) were unrelated to survival. Haemolytic anaemia had a significant negative influence on survival related to mortality caused by infections. Diffuse central nervous system disease and myocarditis were related to increased SLE-related mortality, whereas photosensitivity predicted a decreased mortality. Non-fatal infections and thrombotic events predicted a decreased overall survival. Since 1980 the mortality caused by SLE manifestations has decreased significantly.

Adolescent↗
PubMed1998

Treatment of rheumatoid arthritis with a peptide diet: a randomized, controlled trial.

Elemental diets provide food in its simplest formulation and have been used in the treatment of rheumatoid arthritis (RA) and other chronic inflammatory diseases. Such a diet is supposed to be less antigenic to the human immune system than normal food. The aim of this study was to evaluate the clinical effect of an artificial peptide diet as a temporary supplement to conventional treatment. Patients with active RA were single-blindly randomized either to a liquid elemental peptide-diet for four weeks or to continuation of the usual food (control group). In the diet group all normal foods were renounced. Thirty patients were included and followed for six months. The outcome measurements were pain intensity, morning stiffness, HAQ-score, number of swollen joints, joint tenderness, erythrocyte sedimentation rate, and patient's global assessment of health. Two of the fifteen patients assigned to the diet dropped out. The diet resulted in a transient but statistically significant improvement in the average level of pain (P = 0.02), in HAQ-score (P=0.03), and a significant reduction in Body Mass Index (P=0.001). Only one patient in the diet group had a clear remission. Side-effects were frequent but compliance good. The study showed that the peptide diet can improve some subjective and objective disease parameters. Due to the low remission ratio the peptide diet is not a treatment of choice in unselected RA-patients. but the peptide diet might be beneficial to a subset of RA-patients, e.g. patients where foods aggravate disease activity.

Adult↗
PubMed1994

Selenium and the selenium-dependent glutathione peroxidase in rheumatoid arthritis.

Selenium is an essential component in the two antioxidant enzymes glutathione peroxidase (GSH-Px) and phospholipid hydroperoxide glutathione peroxidase (PLGSH-Px). Free oxygen radicals are involved in the inflammatory process seen in rheumatoid arthritis (RA) and are generated mainly through the phagocytic activity of the polymorphonuclear leucocytes. Several experimental studies indicate that selenium is important to the functioning of the immune system and to the inflammatory process. A low selenium status among patients with RA has been reported from areas with both high and low natural selenium intake. The reduction in the serum level is approx. 10%. This reduction is related to the clinical disease activity in arthritis patients in both cross-sectional and longitudinal studies, and selenium concentrations have been found to fluctuate during the disease. Reduced selenium concentrations have been reported in red blood cells, too, and concentrations have been found to be slightly reduced in the polymorphonuclear leucocytes. Studies do not agree on the activity of GSH-Px among RA patients. Thus activity levels have been reported to range from low to high. Those studies that have focused on the subgroup of patients with high persistent disease activity have reported reduced GSH-Px activities in both serum, red blood cells and polymorphonuclear leucocytes. Selenium supplementation using organic selenium compounds in doses of around 250 microgram/day increases the selenium concentration in serum and red blood cells considerably. However, supplementation is not reflected in the selenium level in polymorphonuclear leucocytes from RA patients as opposed to healthy subjects, in whom the level of selenium in polymorphonuclear leucocytes increases. Selenium supplementation increased GSH-Px activity in serum, red blood cells and platelets from RA patients, but in the polymorphonuclear leucocytes the increase was not sufficient to reach the levels of the controls. This apparent lack of de novo synthesis of GSH-Px in polymorphonuclear leucocytes from RA patients may be explained by their inability to increase their selenium content in spite of high levels of available extracellular selenium. this may be in accordance with the lack of anti-arthritic effect of selenium supplementation in controlled clinical studies among RA patients. Several experimental studies have reported inhibition of GSH-Px by antirheumatic drugs, in particular gold. In addition, gold has been found to reduce selenium in rat plasma. These interactions can, however, be modified by increasing the amount of selenium in the feed. Among RA patients there is no clear evidence of an interaction between gold, selenium and GSH-Px.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1993

[Effects of low concentrations of NO2 on alveolar permeability and glutathione peroxidase in healthy subjects].

Potential toxic effects of prolonged NO2 exposure below the current threshold limit value (TLV) were examined in 14 healthy, non-smoking adults. The subjects were exposed to 2,3 ppm NO2 and to clean air for five hours with a one week interval between exposures. Physiological and biochemical measurements were obtained during exposure and the following 24 hours after. A 14% decrease in serum glutathione peroxidase activity (GSH-Px) was observed 24 hours after the start of the NO2 exposure while indications of a 22% decrease in alveolar permeability were found 11 hours after the start. There were no indications of mucous membrane irritation or of decreased lung function during or after NO2 exposures. The results support the assumption that a delayed response is a feature of the human reaction to NO2 even below the current TLV of three ppm, and they stress the importance of an extended period of observation in future NO2 exposure studies.

Adult↗
PubMed1993

[Dental amalgam: a toxicological evaluation].

During the latest decades the use of dental amalgam has been discussed with respect to potential toxic effects of the mercury component. In order to evaluate potential risks from this practice the recent literature is reviewed. Corrosion of fillings results in liberation of mercury. The absorption from this source in the Danish population can be estimated to be one to five micrograms/24 hrs. This exposure level is far below that accepted in occupational exposure and far below the minimum toxic level. Investigation of placental transfer of mercury has not provided any reason to avoid using amalgam during pregnancy. Micromercurialism or metal syndrome is claimed to be related to amalgam fillings. This syndrome consists mainly of complaints from the central nervous system, but also from muscles, joints and the gastrointestinal tract. The symptoms are non-specific and the documentation of the existence of such a syndrome related to mercury exposure is weak. The symptoms reported can be due to other chemical exposures, but psycho-social conditions may also play an important role. Information on disappearance of symptoms after removal of fillings may be a result of a placebo effect, which may be suggested until controlled experiments are performed. For this reason the use of chelating therapy is not indicated. Allergic contact eczema observed in few individuals is the only problem documented in connection with the use of amalgam fillings.

Brain↗
PubMed1992

Glutathione redox cycle enzymes and selenium in severe rheumatoid arthritis: lack of antioxidative response to selenium supplementation in polymorphonuclear leucocytes.

The antioxidant capacity of the glutathione redox cycle and the concentrations of selenium in serum, red blood cells or whole blood, and polymorphonuclear leucocytes was evaluated in nine patients with severe rheumatoid arthritis (RA) and eight healthy controls receiving daily supplementation with 250 micrograms selenomethionine for six months. Serum and whole blood concentrations of selenium and the activity of the selenium dependent enzyme glutathione peroxidase (GSH-Px) were low in the serum, red blood cells, and polymorphonuclear leucocytes of patients with RA before selenium supplementation. During supplementation serum and whole blood concentrations of selenium and the activity of GSH-Px in serum and red blood cells of patients with RA and serum GSH-Px in controls increased. Selenium and GSH-Px in polymorphonuclear leucocytes were unaffected in patients with RA in contrast with the controls where both were augmented. Glutathione reductase activity in the red blood cells and polymorphonuclear leucocytes of patients with RA was low but increased during selenium supplementation. Whole blood concentrations of glutathione were slightly lower in patients with RA than controls and no difference in the content in polymorphonuclear leucocytes was found between the groups. The activity in red blood cells of glucose-6-phosphate dehydrogenase was high in patients with RA, indicating sufficient function of the hexose monophosphate pathway. The reduced antioxidant activity of the glutathione redox cycle in patients with severe RA was mainly due to the low availability of selenium. This was further supported by the response to selenium supplementation in serum and red blood cells. In the polymorphonuclear leucocytes, however, no biochemical effects of selenium supplementation were seen. This lack of antioxidative response could play a pathogenetic part in inflammation in patients with RA.

Adult↗
PubMed1992

Delayed effects of NO2 exposure on alveolar permeability and glutathione peroxidase in healthy humans.

Potential toxic effects of prolonged NO2 exposure below the current threshold limit value (TLV) were examined in 14 healthy, nonsmoking adults. The subjects were exposed to 2.3 ppm NO2 and to clean air for 5 h with a 1-wk interval between exposures. Physiologic and biochemical measurements were obtained during the exposures and until 24 h after. A 14% decrease in serum glutathione peroxidase activity (GSH-Px) was observed 24 h after the start of the NO2 exposure, while indications of a 22% decrease in alveolar permeability were found 11 h after the start. There were no indications of mucous membrane irritation or of decreased lung function during or after NO2 exposures. The results support the assumption that a delayed response is a feature of the human reaction to NO2 even below the current TLV of 3 ppm, and they stress the importance of an extended period of observation in future NO2 exposure studies.

Adult↗
PubMed1991

Selenium in human mammary carcinogenesis: a case-referent study.

In a case-referent study on the possible role of selenium in human mammary carcinogenesis, serum selenium was found to be 79 +/- 12 micrograms/l in 66 cases and 81 +/- 12 micrograms/l in 93 referents. An internal trend in serum selenium was observed among cases (TNM stage I 81 +/- 11 micrograms/l and TNM stage II 76 +/- 13 micrograms selenium/l), indicating disease-mediated changes. The evaluation of selenium as a risk indicator in human breast cancer was therefore restricted to TNM stage I patients (n = 36). Multiple logistic regression analyses including variables associated with selenium levels revealed no association between selenium levels and breast cancer risk.

Adenocarcinoma↗