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Biomedical subjects

T Persson

Publications and source records attributed to T Persson.

At least 37 records · Page 2Linked to original sources

Oral budesonide as maintenance therapy in Crohn's disease--results of a 12-month study. Global Budesonide Study Group.

BACKGROUND: Budesonide is a corticosteroid with high topical anti-inflammatory activity and low systemic activity due to rapid inactivation. We have assessed the efficacy and safety of an oral controlled ileal release (CIR) preparation of budesonide for maintenance of remission in patients with ileal or ileocaecal Crohn's disease. METHODS: In a double-blind, multicentre trial, 75 patients in clinical remission (Crohn's Disease Activity Index, CDAI, < or = 150) were randomly assigned to receive placebo, budesonide 3 mg or budesonide 6 mg daily for 12 months. Trial drugs were given at a fixed dose and without concomitant medication. The primary outcome measure was relapse, defined as a CDAI > 150 together with an increase of at least 60 units from entry. A patient was also considered to have a relapse if withdrawn from the study due to clinical deterioration, whether or not a CDAI value could be calculated at that time. RESULTS: There were no statistically significant differences in the relapse rate at any time-point throughout the study. By 12 months the proportion of patients having relapsed were 48, 46 and 60% in those patients treated with budesonide 6 mg, 3 mg and placebo, respectively (N.S.). Treatments were well tolerated, and the proportion of patients with suppressed adrenal function (according to predetermined criteria) were 50% (6 mg), 26% (3 mg) and 17% (placebo) (P = 0.096). CONCLUSIONS: In the present study, relapse rate and time to relapse were similar in the patients treated with budesonide CIR, 6 mg daily or 3 mg daily or with placebo, throughout 12 months. This is in contrast to the two previous trials with identical design, where a significant effect of budesonide CIR in prolonging the median time to relapse was found. Possible reasons for the negative results of the present study include small sample size, and the fact that there was a high placebo response.

Adolescent↗

The ankle strategy for postural control--a comparison between a model-based and a marker-based method.

When analysing postural control statistical characteristics of the centre of pressure or the ground reaction force are often used. A complement would be to analyse movement strategies as well. The purpose of this study was to determine to what extent the ankle strategy is used to maintain the balance in standing. One important question is if it is sufficient to use only force plate data in this determination, or if markers have to be used. To answer this question we studied two different methods--a marker-based method and a model-based method. The latter needs force plate data only as input to an inverted pendulum model. Different measures were calculated and used to draw conclusions of to what extent the ankle strategy was used. Experiments demonstrated that the data from the two methods provided the same general conclusions, although there were some differences in the estimated measures. By using the model-based method instead of tracking markers we can increase the clinical effectiveness considerably, get a lesser amount of data, and still get results comparable to the marker-based method.

Ankle↗

Estimation of the knee joint location using colour video.

Analysis of the knee joint moment might be useful for predicting the risk of prosthetic loosening. The moment can be estimated if the location of the centre of pressure in the knee joint and the ground reaction force vector are known. Usually, skin mounted markers are used to locate the knee joint centre. Since marker based methods have several drawbacks investigations of alternative methods are needed. A new method for location of the knee joint is outlined in this paper. The subject is video filmed during gait with an elastic blue band wrapped around the knee. The band is located by splitting the video images into the RGB-components, and the centroid of the band is used as an estimate of the knee joint centre location. The band is easier to mount than markers, and it is not sensitive for axial leg rotation like markers are, which simplifies the analysis. If desired, the axial leg rotation can be determined by attaching a circular cyan marker on the band. The centroid of the marker relative to the band centroid gives an approximation of the leg rotation. In this study, the band could easily be located in the images and the leg axial rotation estimated in the frontal and the sagittal view showed the same trend. Further, the band-based results were found to be comparable to results where a marker was used to locate the knee joint centre.

Adult↗

Oral budesonide is as effective as oral prednisolone in active Crohn's disease. The Global Budesonide Study Group.

BACKGROUND: The use of corticosteroids in active Crohn's disease often becomes limited by side effects. Budesonide is a potent corticosteroid with low systemic bioavailability due to an extensive first pass liver metabolism. AIMS: To compare the efficacy and safety of two dosage regimens of budesonide and prednisolone in patients with active Crohn's disease affecting the ileum and/or the ascending colon. PATIENTS AND METHODS: One hundred and seventy eight patients were randomised to receive budesonide controlled ileal release (CIR) capsules 9 mg once daily or 4.5 mg twice daily, or prednisolone tablets 40 mg once daily. The treatment period was 12 weeks. The primary efficacy variable was clinical remission, defined as a Crohn's Disease Activity Index (CDAI) of 150 or less. RESULTS: After eight weeks of treatment, remission occurred in 60% of patients receiving budesonide once daily or prednisolone and in 42% of those receiving budesonide twice daily (p = 0.062). The presence of glucocorticoid associated side effects was similar in all groups; however, moon face was more common in the prednisolone group (p = 0.0005). The highest frequency of impaired adrenal function, as measured by a short ACTH test, was found in the prednisolone group (p = 0.0023). CONCLUSIONS: Budesonide CIR, administered at 9 mg once daily or 4.5 mg twice daily, is comparable to prednisolone in inducing remission in active Crohn's disease. The single dose administration is as promptly effective as prednisolone and represents a simpler and safer therapeutic approach, with a considerable reduction in side effects.

Acute Disease↗

A marker-free method for tracking human lower limb segments based on model matching.

A 2D marker-free method for tracking the human lower limb segments has been developed and tested. The method is based on model matching using distance transformations, and is intended for use in analysis of human gait. The model used consists of five line segments, which are matched to the contours of the lower limb segments. Experiments have been made on two different kinds of objects: a rigid model of a leg and a human leg. Only movement in the sagittal plane has been considered. An image sequence of the moving object was captured, and the method was used for tracking the segments of the object in each image. The results were then compared to data obtained using markers mounted at the ankle joint, the knee joint and the hip joint. The experiments on the rigid body were done to assess the accuracy of the method under perfect conditions. The average difference between the estimated joint positions and the reference positions was found to be less than 2 mm for all three joints, with a standard deviation of less than 1 mm. To test the method in a more realistic situation, it was applied to a human leg during the stance phase of walking. Measurements were made on three healthy male subjects. The average differences between the estimated joint positions and the reference marker positions were less than 6 mm, 10 mm and 22 mm, for the ankle joint, the knee joint, and the hip joint, respectively. The corresponding standard deviations were less than 4 mm, 7 mm and 9 mm, respectively. The satisfying results, though obtained controlled laboratory conditions, show that this method might be useful in gait analysis.

Adult↗

Synthesis of 2'-deoxyuridine 5'-(alpha,beta-imido) triphosphate: a substrate analogue and potent inhibitor of dUTPase.

The dUDP analogue, 2'-deoxyuridine 5'-(alpha,beta-imido)diphosphate (dUPNP) was synthesized. The corresponding triphosphate analogue (dUPNPP) was prepared by enzymic phosphorylation of dUPNP using the enzyme pyruvate kinase and phosphoenolpyruvate as the phosphate donor. This method was successful in phosphorylating the imidodiphosphate analogue of 2'-deoxythymidine (dTPNP) to 2'-deoxythymidine 5'-(alpha, beta-imido)triphosphate (dTPNPP), in contradiction to a previous report. The properties of dUPNPP have been tested using the enzyme dUTPase from Escherichia coli. This enzyme, having a crucial role in nucleotide metabolism, is strictly specific for its substrate (dUTP) and catalyzes the hydrolysis of the alpha, beta-bridge, resulting in dUMP and pyrophosphate. Replacement of the alpha, beta-bridging oxygen in dUTP with an imido group resulted in a nonhydrolyzable substrate analogue and a potent competitive inhibitor of dUTPase (Ki = 5 microM). The analogue prepared (dUPNPP) may be utilized in crystallographic studies of the active site of dUTPase to provide knowledge about specific interactions involved in substrate binding and as a parental compound in design of dUTPase inhibition for medical purposes.

Creatine Kinase↗

Oral budesonide as maintenance treatment for Crohn's disease: a placebo-controlled, dose-ranging study. Canadian Inflammatory Bowel Disease Study Group.

BACKGROUND & AIMS: Budesonide is a corticosteroid with high topical anti-inflammatory activity and low systemic activity due to rapid hepatic metabolism. The efficacy and safety of an oral controlled-release preparation of budesonide for maintenance of remission was evaluated in patients with ileal or ileocecal Crohn's disease. METHODS: In a double-blind, multicenter trial, 105 patients were randomly assigned to receive placebo or budesonide at doses of 3 or 6 mg daily for 1 year. The primary outcome measure was relapse defined by a Crohn's Disease Activity Index score of > 150 and a minimum increase of 60 points. RESULTS: Patients receiving 6 mg of budesonide had a median time to relapse or discontinuation of therapy of 178 days compared with 124 days in those receiving 3 mg of budesonide and 39 days in those receiving placebo. However, at 1 year, the rate of relapse in the group receiving 6 mg of budesonide was similar to the rates in the 3-mg and placebo groups. Basal plasma cortisol levels and incidence of corticosteroid-associated effects were similar in the three groups. CONCLUSIONS: Oral controlled-release budesonide (6 mg/day) was well tolerated and prolonged remission in Crohn's disease of the ileum and proximal colon, but this effect was not sustained at 1-year follow-up.

Administration, Oral↗

Oral budesonide versus prednisolone in patients with active extensive and left-sided ulcerative colitis.

BACKGROUND & AIMS: Systemic glucocorticosteroids (GCSs) have proven efficacy in active ulcerative colitis but cause undesired systemic side effects. Therefore, new GCSs with high topical activity and a high rate of metabolism may be of clinical value in this condition. The aim of this study was to explore the efficacy and safety of the topically acting GCS budesonide in an oral controlled-release formulation in extensive or left-sided, mild to moderately active ulcerative colitis. METHODS: A 9-week, randomized, double-blind, controlled trial was performed, and treatments with 10 mg budesonide or 40 mg prednisolone daily, both gradually tapered, were compared. Endoscopic improvement and effect on endogenous plasma cortisol were assessed. RESULTS: Thirty-four patients were administered budesonide, and 38 patients were administered prednisolone. Mean endoscopic scores improved significantly in both groups but without difference between the groups. Five patients in the budesonide group and 7 patients in the prednisolone group deteriorated and were withdrawn from the study. Morning plasma cortisol levels were suppressed in the prednisolone group (entry, 449 nmol/L; 2 weeks, 116 nmol/L; 4 weeks, 195 nmol/L) but were unchanged in the budesonide group. CONCLUSIONS: The GCS budesonide administered in an oral controlled-release formulation seems to give an overall treatment result in active ulcerative colitis approaching that of prednisolone but without suppression of plasma cortisol levels. This concept merits further evaluation.

Administration, Oral↗

Budesonide prolongs time to relapse in ileal and ileocaecal Crohn's disease. A placebo controlled one year study.

BACKGROUND AND AIMS: To evaluate the efficacy and safety of the topical corticosteroid budesonide, given in an oral controlled release formulation for maintenance of remission in patients with ileal and ileocaecal Crohn's disease (CD). PATIENTS AND METHODS: Out of 176 patients with active CD who had achieved remission (CD activity index score < or = 150) after 10 weeks' treatment with either budesonide or prednisolone, 90 were randomised to continue with once daily treatment of 6 mg budesonide, or 3 mg budesonide or placebo for up to 12 months in a double blind, multicentre trial. Time to symptomatic relapse was calculated using Kaplan-Meier estimates. Morning plasma cortisol was measured at clinic visits and a corticotropin stimulation test was performed after three months of treatment. RESULTS: Thirty two patients were allocated to the 6 mg budesonide group, 31 to the 3 mg group, and 27 to the placebo group. After three months, 19 per cent of the patients in the 6 mg group had relapsed, compared with 45 per cent in the 3 mg group and 44 per cent in the placebo group (p = 0.047). The corresponding results after 12 months was 59 per cent in the 6 mg budesonide group, 74 per cent in the 3 mg group, and 63 per cent in the placebo group (p = 0.44). The median time to relapse or discontinuation was 258 days in the 6 mg group, 139 days in the 3 mg group, and 92 days in the placebo group (p = 0.021). Mean morning plasma cortisol values increased from entry in all three groups with no statistically significant differences at 12 months. All 13 patients remaining in the placebo group after three months had a normal corticotropin stimulation response, compared with 18 of 23 patients in the 6 mg, and 19 of 21 in the 3 mg budesonide groups (p = 0.14). Acne and moon face were slightly more common in the budesonide groups. CONCLUSION: 6 mg budesonide once daily is significantly more efficacious than placebo in prolonging time to relapse in CD, and causes only minor systemic side effects.

Administration, Oral↗

Magnetic-field Exposures in the Workplace: Reference Distribution and Exposures in Occupational Groups.

Exposures to extremely-low-frequency magnetic fields were assessed by taking personal measurements with a dosimeter calibrated at 50 Hz with a bandwidth of 40-400 Hz. The study group was a population-based random sample of 1,098 Swedish men. Exposures were determined as workday mean, median, maximum, and standard deviation, and the time fraction of the day when exposures exceeded 0.20 µT. For workday means, the 50th percentile was 0.17 µT, and the 75th percentile was 0.27 µT. For median values, the 50th percentile was 0.11 µT and the 75th percentile was 0.16 µT. The strongest correlation (Spearman rank correlation = r&infs;) found was between the workday mean and the fraction of time above 0.20 µT (r&infs; = 0.89). The authors used the same data to estimate exposures for the 100 most common occupations according to the 1990 Swedish census. A minimum of four independent measurements for each occupation was required. Among occupations with low workday mean values were earth-moving machine operator, health care worker, and concrete worker. Among occupations with high workday mean exposures were welder and electrical or electronics engineer or technician. High exposure levels were also found in occupations outside the study base, such as train engine driver and glass, ceramic, or brick worker. Exposures to magnetic fields vary widely, since levels of exposure are strongly affected by factors such as duration of exposure and distance from the source. Large variations often found between individuals within occupations could reflect variations in tasks across different workdays for the particular occupations and/or local conditions such as tools and installations, and/or how the work is organized and performed.

Journal Article↗

Can overconfidence be used as an indicator of reconstructive rather than retrieval processes?

In a recent paper Wagenaar (1988) suggested that overconfidence can be used as an indicator of reconstructive processes which allow responses based on inference to be distinguished from responses based on retrieval. The ecological models (Björkman, in press; Gigerenzer, Hoffrage, & Kleinbölting, 1991; Juslin, 1993a, 1993b, 1994) provide a more positive view of the calibration of reconstructive responses. In this paper we compare these two views and argue that overconfidence cannot be considered a reliable indicator of reconstructive processes since people may be well calibrated for tasks that require inference, provided that tasks are selected in offunbiased manner. Instead, we discuss two different models: the response-independence model which is appropriate to retrieval, and the response-dependence model which applies to inference. These two models predict different distributions of solution probabilities and they therefore provide a criterion by which we can distinguish between direct retrieval and reconstruction. In two empirical studies modelled after Experiment 1 in Wagenaar's (1988) paper it is shown that calibration can be very similar and quite reasonable both for tasks that are dominated by inference and tasks that are dominated by retrieval processes. In Experiment 2 we show that the two conditions nevertheless differ in regard to the distributions of solution probabilities in the manner predicted by the two response models presented in the paper. It is proposed that the issue of which is the most appropriate interpretation of solution probabilities is neglected, and that the criterion should be of interest also to applications outside the domain of calibration research.

Adult↗

A marker-free method to estimate joint centre of rotation by video image processing.

A marker-free video measurement and image processing method that provides numerical estimation of the 2-D centre of rotation of one rigid segment is tested. The algorithm is based on binary region moment features. A comparison is made between this method and a marker-based one, where the location of the markers has been calculated in two ways. The algorithm is also extended to handle two rigid segments. The method is to be applied in human locomotion analysis in order to calculate the centre of rotation of the hip joint. It's accuracy has been tested by a comparison with in vivo radiological measurements on humans.

Adult↗

Synthesis and antiviral effects of 2-heteroaryl substituted adenosine and 8-heteroaryl substituted guanosine derivatives.

2-(2"- and 3"-Thienyl)adenosine and the corresponding furyl derivatives were prepared though Pd(0)-catalyzed coupling of 2',3',5'-tri-O-(t-butyldimethylsilyl)-2-iodoadenosine with the appropriate tributyltin derivatives followed by deprotection. Preparation of the 8-(2"- and 3"-thienyl)guanosines and 8-(2"- and 3"-furyl)guanosines followed a similar route. Antiviral properties of these compounds and the related 2,6-diaminopurine ribofuranosides were of no pharmacological interest.

Adenosine↗

Oral budesonide for active Crohn's disease. Canadian Inflammatory Bowel Disease Study Group.

BACKGROUND: Corticosteroids are the most efficacious drugs for inducing remission in active Crohn's disease, but their benefits are frequently offset by serious side effects. Budesonide is a corticosteroid with high topical antiinflammatory activity but low systemic activity because of extensive hepatic metabolism. We investigated the efficacy and safety of an oral controlled-ileal-release preparation of budesonide in patients with active Crohn's disease involving the ileum or ileum and proximal colon. METHODS: In a double-blind, multicenter trial, 258 patients were randomly assigned to receive placebo or one of three doses of budesonide--3, 9, or 15 mg daily. The primary outcome measure was clinical remission, as defined by a score of 150 or less on the Crohn's disease activity index. RESULTS: After eight weeks of treatment, remission occurred in 51 percent of the patients in the group receiving 9 mg of budesonide (95 percent confidence interval, 39 to 63 percent), 43 percent of those receiving 15 mg (95 percent confidence interval, 31 to 55 percent), and 33 percent of those receiving 3 mg (95 percent confidence interval, 21 to 44 percent), as compared with 20 percent of those receiving placebo (P < 0.001, P = 0.009, and P = 0.13, respectively). Improvements in the quality of life, as measured by the patients' responses to the inflammatory bowel disease questionnaire, paralleled these remission rates. Location of disease, prior surgical resection, and previous use of corticosteroids did not affect the outcome. A total of 119 patients (46 percent) were withdrawn from the study before the trial ended, 96 because of insufficient therapeutic effects, 13 because of adverse reactions, and 10 because of noncompliance. Budesonide caused a dose-related reduction in basal and corticotropin-stimulated plasma cortisol concentrations but was not associated with clinically important corticosteroid-related symptoms or other toxic effects. CONCLUSIONS: In an eight-week trial, an oral controlled-release preparation of budesonide at an optimal daily dose of 9 mg was well tolerated and effective against active Crohn's disease of the ileum and proximal colon.

Administration, Oral↗

Effects of reducing or discontinuing inhaled budesonide in patients with mild asthma.

BACKGROUND: In a previous study, we found that two years of treatment with an inhaled corticosteroid, budesonide, was more effective than treatment with an inhaled beta 2-agonist, terbutaline, in patients with newly diagnosed, generally mild asthma. We continued this study for a third year to investigate whether the steroid dose could be reduced or discontinued and what effect crossover of patients from beta 2-agonist therapy to corticosteroid therapy would have. METHODS: A total of 37 patients treated for two years with inhaled budesonide at a dose of 1200 micrograms per day were randomly assigned to treatment with 400 micrograms of budesonide per day (19 patients) or placebo (18 patients) in a double-blind manner. Another 37 patients, who had received terbutaline during the first two years, were crossed over in an open-label manner to treatment with 1200 micrograms of budesonide per day during the third year. RESULTS: Treatment with the reduced dose of budesonide was sufficiently effective in 74 percent of the patients to maintain bronchial responsiveness at a level similar to that achieved with the higher dose. In contrast, improvement was maintained in only 33 percent of the patients receiving placebo, and the differences in pulmonary function between the steroid and placebo groups were significant (for forced expiratory volume in one second, P = 0.007; for bronchial responsiveness to histamine, P = 0.025; and for peak expiratory flow in the morning, P = 0.040). The condition of patients who were crossed over from terbutaline therapy to treatment with 1200 micrograms of budesonide per day improved. However, the degree of improvement in these patients appeared to be less than in those who were treated with budesonide at the beginning of the three-year study. CONCLUSIONS: Early treatment with inhaled budesonide results in long-lasting control of mild asthma. Maintenance therapy can usually be given at a reduced dose, but discontinuation of treatment is often accompanied by exacerbation of the disease.

Administration, Inhalation↗

Occupational exposure to electromagnetic fields in relation to leukemia and brain tumors: a case-control study in Sweden.

Occupational exposure to low-frequency electromagnetic fields (EMF) was studied in 250 leukemia patients and 261 brain-tumor cases, diagnosed in 1983-87 and compared with a control group of 1,121 randomly selected men, from the mid-region of Sweden, 1983-87. We based the exposure assessment on measurements from 1,015 different workplaces. On the basis of the job held longest during the 10-year period before diagnosis, we found an association between the average, daily, mean level of EMF and chronic lymphocytic leukemia (CLL). The risk increased with increasing level of exposure. The odds ratios (OR) and the 95 percent confidence interval (CI) for three consecutive levels of exposure were: 1.1 (CI = 0.5-2.3); 2.2 (CI = 1.1-4.3); 3.0 (CI = 1.6-5.8), respectively. No association was observed for acute myeloid leukemia (OR = 1.0, CI = 0.5-1.8; OR = 0.8, CI = 0.4-1.6; OR = 1.0, CI = 0.6-1.9). For brain tumors, the corresponding risk estimates were 1.0 (CI = 0.7-1.6); 1.5 (CI = 1.0-2.2); 1.4 (CI = 0.9-2.1). Different EMF indices were tested. Tasks with frequent or large variations between high and low field-densities (high standard deviation) were more common among CLL subjects. For brain tumors, a prolonged high level (high median values) showed the strongest association. Confounding by place of residence, smoking, benzene, ionizing radiation, pesticides, and solvents was evaluated, and these factors did not seem to have a decisive influence on the associations. We also analyzed other potential sources of bias. For CLL, there were indications of an excess number of low-exposure subjects among non-responders, which, to some extent, may have enhanced but not caused the risk estimates obtained. Our conclusion is that the study supports the hypothesis that occupational EMF exposure is a hazard in the development of certain cancers.

Acute Disease↗

A steroid enema, budesonide, lacking systemic effects for the treatment of distal ulcerative colitis or proctitis.

The aim of this study was to evaluate whether budesonide enema (2 mg/100 ml) had a significantly better effect than placebo in the treatment of distal ulcerative colitis or proctitis. The trial was of controlled, randomized, double-blind design and included 41 treated patients. The treatment time was 4 weeks, with revisits after 2 and 4 weeks. If no improvement was seen, the patient could be switched over to open-label therapy with budesonide enema. Sigmoidoscopy, histology, blood chemistry, and diary cards were used for estimating the effect of treatment. The results showed that budesonide was superior to placebo. Sigmoidoscopy and biopsy scores improved significantly (p less than 0.01) in budesonide-treated patients compared with placebo. Significantly more patients switched over to open budesonide treatment in the placebo group owing to lack of efficacy compared with budesonide (p less than 0.001). No drug-related adverse experiences occurred, and there was no decrease in endogenous morning plasma cortisol levels. It is concluded that budesonide enema appears to be an effective and safe treatment for distal ulcerative colitis and proctitis.

Administration, Topical↗