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Biomedical subjects

J Svensson

Publications and source records attributed to J Svensson.

At least 19 recordsLinked to original sources
PubMed2003

The effect of treatment with the oral growth hormone (GH) secretagogue MK-677 on GH isoforms.

Growth hormone (GH) consists of several isoforms. We have studied the proportion, expressed as percentage of total GH concentration, of non-22kDa (non-22K) GH isoforms and 20K GH during 8-week oral treatment with MK-677 25mg daily in 12 obese males. The proportion of non-22K GH isoforms in peak total GH samples after the initial MK-677 administration was higher than that after 2 and 8 weeks (p<0.01 and p<0.05, respectively). In selected non-peak total GH samples after the initial MK-677 administration, however, the proportion of non-22K GH isoforms was similar to that in the peak total GH samples after 2 and 8 weeks. The proportion of 20K GH in 2-h samples after the initial MK-677 administration was lower than that after 2 and 8 weeks (p<0.01 and p<0.05, respectively). We concluded that the proportion of non-22K GH isoforms was higher in peak, but not in non-peak, total GH samples after the initial MK-677 administration than that observed after multiple doses. The proportion of 20K GH in 2-h samples after the initial MK-677 administration was lower than that after 2 and 8 weeks. These moderate changes in the proportion non-22K GH isoforms are likely of small importance for the clinical response to MK-677 treatment.

Administration, Oral↗
PubMed2002

Influence of time pressure and verbal provocation on physiological and psychological reactions during work with a computer mouse.

The overall aim of this study was to investigate whether time pressure and verbal provocation has any effect on physiological and psychological reactions during work with a computer mouse. It was hypothesised that physiological reactions other than muscle activity (i.e. wrist movements, forces applied to the computer mouse) would not be affected when working under stressful conditions. Fifteen subjects (8 men and 7 women) participated, performing a standardised text-editing task under stress and control conditions. Blood pressure, heart rate, heart rate variability, electromyography, a force-sensing computer mouse and electrogoniometry were used to assess the physiological reactions of the subjects. Mood ratings and ratings of perceived exertion were used to assess their psychological reactions. The time pressure and verbal provocation (stress situation) resulted in increased physiological and psychological reactions compared with the two control situations. Heart rate, blood pressure and muscle activity in the first dorsal interosseus, right extensor digitorum and right trapezius muscles were greater in the stress situation. The peak forces applied to the button of the computer mouse and wrist movements were also affected by condition. Whether the increases in the physiological reactions were due to stress or increased speed/productivity during the stress situation is discussed. In conclusion, work with a computer mouse under time pressure and verbal provocation (stress conditions) led to increased physiological and psychological reactions compared to control conditions.

Adolescent↗
PubMed2002

Gradient echo imaging of flowing hyperpolarized nuclei: theory and phantom studies on 129Xe dissolved in ethanol.

The influence of flip angle and flow velocity on the signal intensity achieved when imaging a hyperpolarized substance with a spoiled gradient echo sequence was investigated. The study was performed both theoretically and experimentally using hyperpolarized xenon dissolved in ethanol. Analytical expressions regarding the optimal flip angle with respect to signal and the corresponding signal level are presented and comparisons with thermally polarized substances are made. Both experimentally and theoretically, the optimal flip angle was found to increase with increasing flow velocity. Numerical calculations showed that the velocity dependence of the signal differs between the cases of hyperpolarized and thermally polarized substances.

Echo-Planar Imaging↗
PubMed2002

An MLP training algorithm taking into account known errors on inputs and outputs.

A training algorithm is introduced that takes into account a priori known errors on both inputs and outputs in an MLP network. The new cost function introduced for this case is based on a linear approximation of the network function over the input distribution for a given input pattern. Update formulas, in the form of the gradient of the new cost function, is given for a MLP network, together with expressions for the Hessian matrix. This is later used to calculate error bars in a Bayesian framework. The error bars thus derived are discussed in relation to the more commonly used width of the target posterior predictive distribution. It will also be shown that the taking into account of known input uncertainties in the way suggested in this article will have a strong regularizing effect on the solution.

Algorithms↗
PubMed2002

Echo-planar MR imaging of dissolved hyperpolarized 129Xe.

PURPOSE: The feasibility of hyperpolarized 129Xe for fast MR angiography (MRA) was evaluated using the echo-planar imaging (EPI) technique. MATERIAL AND METHODS: Hyperpolarized Xe gas was dissolved in ethanol, a carrier agent with high solubility for Xe (Ostwald solubility coefficient 2.5) and long relaxation times. The dissolved Xe was injected as a bolus into a flow phantom where the mean flow velocity was 15 cm/s. Ultrafast EPI images with 44 ms scan time were acquired of the flowing bolus and the signal-to-noise ratios (SNR) were measured. RESULTS: The relaxation times of hyperpolarized Xe in ethanol were measured to T1=160+/-11 s and T2 approximately 20 s. The resulting images of the flowing liquid were of reasonable quality and had an SNR of about 70. CONCLUSION: Based on the SNR of the obtained Xe EPI images, it was estimated that rapid in vivo MRA with 129Xe may be feasible, provided that an efficient, biologically acceptable carrier for Xe can be found and polarization levels of more than 25% can be achieved in isotopically enriched 129Xe.

Echo-Planar Imaging↗
PubMed2001

Stress-induced accumulation and tissue-specific localization of dehydrins in Arabidopsis thaliana.

Stress-induced accumulation of five (COR47, LTI29, ERD14, LTI30 and RAB18) and tissue localization of four (LTI29, ERD14, LTI30 and RAB18) dehydrins in Arabidopsis were characterized immunologically with protein-specific antibodies. The five dehydrins exhibited clear differences in their accumulation patterns in response to low temperature, ABA and salinity. ERD14 accumulated in unstressed plants, although the protein level was up-regulated by ABA, salinity and low temperature. LTI29 mainly accumulated in response to low temperature, but was also found in ABA- and salt-treated plants. LTI30 and COR47 accumulated primarily in response to low temperature, whereas RAB18 was only found in ABA-treated plants and was the only dehydrin in this study that accumulated in dry seeds. Immunohistochemical localization of LTI29, ERD14 and RAB18 demonstrated tissue and cell type specificity in unstressed plants. ERD14 was present in the vascular tissue and bordering parenchymal cells, LTI29 and ERD14 accumulated in the root tip, and RAB18 was localized to stomatal guard cells. LTI30 was not detected in unstressed plants. The localization of LTI29, ERD14 and RAB18 in stress-treated plants was not restricted to certain tissues or cell types. Instead these proteins accumulated in most cells, although cells within and surrounding the vascular tissue showed more intense staining. LTI30 accumulated primarily in vascular tissue and anthers of cold-treated plants. This study supports a physiological function for dehydrins in certain plant cells during optimal growth conditions and in most cell types during ABA or cold treatment. The differences in stress specificity and spatial distribution of dehydrins in Arabidopsis suggest a functional specialization for the members of this protein family.

Arabidopsis↗
PubMed2001

Effects of oral administration of ibutamoren mesylate, a nonpeptide growth hormone secretagogue, on the growth hormone-insulin-like growth factor I axis in growth hormone-deficient children.

Ibutamoren mesylate (MK-0677), an orally active nonpeptide growth hormone (GH) secretagogue, stimulates GH release through a pituitary and hypothalamic receptor that is different from the GH-releasing hormone receptor. We evaluated the safety and tolerability and the GH-insulin-like growth factor (IGF) responses to two dosages of oral ibutamoren mesylate given to children with GH deficiency for 7 to 8 days. The patients, 18 prepubertal children (15 male, 3 female) with idiopathic GH deficiency, had a chronologic age of 10.6 +/- 0.8 years (mean +/- SD), bone age of 7.4 +/- 0.7 years, growth velocity < 10th percentile for age, height < 10th percentile for age, and a maximum GH response of < or = 10 microg/L to two different GH stimulation tests. The children were assigned as follows to one of three treatment groups with ibutamoren mesylate: 0.2 mg/kg per day for 7 days (days 1-7 or 8-14) and matching placebo for the alternate 7 days (groups I and II, respectively) or 0.8 mg/kg per day for 7 days (days 8-14, group III). On day 15 all patients received an 0.8-mg/kg dose of ibutamoren mesylate. Patients in groups I and II were studied first to assess safety at the low dose before advancement to the high dose. Hormonal profiles were evaluated on day -1 (baseline) and day 15, and the results were expressed as the change from baseline within each group. After administration of ibutamoren mesylate 0.8 mg/kg for 8 days (group III), the median increases (on day 15) from baseline were as follows: 3.8 microg/L (range, 0 to 34.3) for serum GH peak concentration (P = .001), 4.3 microg x h/L (range, 1.3 to 35.6) for the GH area under the concentration-time curve from time zero to 8 hours (AUC(0-8)) (P < .001), 12 microg/L (range, -4 to 116) for serum IGF-I (P = .01), and 0.4 microg/L (range, -0.9 to 1.5) for serum IGF-binding protein 3 (IGFBP-3) (P = .01). There was no change in serum prolactin, glucose, triiodothyronine, thyroxine, thyrotropin, peak serum cortisol, and insulin concentrations or 24-hour urinary free cortisol after administration of 0.8 mg/kg per day of ibutamoren mesylate for 8 days. We conclude that short-term administration of ibutamoren mesylate can increase GH, IGF-I, and IGFBP-3 levels in some children with GH deficiency. Thus this compound is applicable for testing its effect on growth velocity.

Administration, Oral↗
PubMed2001

Changes in biochemical markers of bone metabolism and BMD during the first year after a hip fracture.

We measured the levels of biochemical markers of bone formation and bone resorption in hip fracture patients preoperatively and after 6 and 12 months. Bone densitometry was done with quantitative computer tomography (QCT), dual-energy X-ray absorptiometry (DXA) and heel ultrasound. After 6 months, the biochemical markers of bone formation and bone resorption had increased. The levels remained high after 1 year and no change occurred between 6 and 12 months. We found no correlations between biochemical bone markers and bone density/stiffness on admission and change in bone mineral density (BMD) during the first postoperative year, despite the changes in bone markers and bone density. In our opinion, biochemical bone markers can not be used to predict bone loss in the individual patient after a hip fracture.

Absorptiometry, Photon↗
PubMed2001

Comparison of some different methods for analysis of thyroid autoantibodies: importance of thyroglobulin autoantibodies.

Blood samples from 141 children and adolescents were used to evaluate differences between commercial kits and radioimmunoassay (RIA) methods for detecting thyroid autoantibodies. Thyroglobulin autoantibodies (Tg-Ab) were analyzed with a hemagglutination kit and a RIA; thyroid peroxidase autoantibodies (TPO-Ab) were measured with a gelagglutination assay and a RIA. The results of the antibody tests were compared with thyroid function tests (triiodothyronine [T3], thyroxine [T4], thyrotropin [TSH]) and with the results of ultrasound of the thyroid in antibody-positive patients. The correlation of antibody levels between the two methods was higher for TPO-Ab than for Tg-Ab. Moderate to high levels of TPO-Ab correlated to elevated TSH levels. Autoimmune thyroiditis (AIT) was found in 6 of the 141 children. The RIA-based thyroglobulin assay was the only test that identified autoantibodies in all 6 cases. In contrast, the hemagglutination kit thyroglobulin assay failed to identify 4 of the 6 AIT cases.

Adolescent↗
PubMed2001

Body composition and quality of life as markers of the efficacy of growth hormone replacement therapy in adults.

Growth hormone (GH) replacement therapy in GH-deficient adults should be initiated with a low dose, independent of body weight or body surface area. Measurements of serum insulin-like growth factor I (IGF-I) concentrations, as well as clinical examinations aimed at detecting signs of fluid excess, are important as safety markers to avoid overtreatment with GH. At present, there is no optimal marker for the long-term efficacy of GH replacement therapy. The long-term maintenance dose of GH should, therefore, be titrated in each individual based on the clinical response, with the aim of normalizing body hydration, other measurements of body composition, quality of life and well-being, and biochemical indices such as serum IGF-I concentration.

Adult↗
PubMed2001

A prospective study of 5 years of GH replacement therapy in GH-deficient adults: sustained effects on body composition, bone mass, and metabolic indices.

GH replacement therapy has proved its efficacy and safety in short-term trials and in a few long-term trials with limited number of subjects. In this 1-center study, including 118 consecutive adults (70 men and 48 women; mean age, 49.3 yr; range, 22-74 yr) with adult-onset GH deficiency, the effects of 5 yr of GH replacement on body composition, bone mass, and metabolic indices were determined. The mean initial GH dose was 0.98 mg/d. The dose was gradually lowered, and after 5 yr the mean dose was 0.48 mg/d. The mean IGF-I SD score increased from -1.73 at baseline to 1.66 at study end. A sustained increase in lean body mass and a decrease in body fat were observed. The GH treatment increased total body bone mineral content as well as lumbar (L2-L4) and femur neck bone mineral contents. BMD in lumbar spine (L2-L4) and femur neck were increased and normalized at study end. Total cholesterol and low density lipoprotein cholesterol decreased, and high density lipoprotein cholesterol increased. At 5 yr, serum concentrations of triglycerides and hemoglobin A(1c) were reduced compared with baseline values. The treatment responses in IGF-I SD score, body fat as estimated by four- and five-compartment body composition models, total body protein and nitrogen, and lumbar bone mineral content and BMD were more marked in men than in women. One patient died during the period, four patients discontinued the study due to adverse events, and one dropped out due to lack of compliance. Four patients were lost to follow-up. However, all patients were retained in the statistical analysis according to the intention to treat approach used. In conclusion, 5 yr of GH substitution in GH-deficient adults is safe and well tolerated. The effects on body composition, bone mass, and metabolic indices were sustained. The effects on body composition and low density lipoprotein cholesterol were seen after 1 yr, whereas the effects on bone mass, triglycerides, and hemoglobin A(1c) were first observed after years of treatment.

Adult↗
PubMed2001

Baseline characteristics and the effects of five years of GH replacement therapy in adults with GH deficiency of childhood or adulthood onset: a comparative, prospective study.

The consequences of GH deficiency may differ if the disease is childhood onset or adulthood onset. In this single-center, prospective study, 21 consecutive adults with childhood onset GH deficiency and 21 adults with adulthood onset GH deficiency, matched for age, gender, body mass index, and number of anterior pituitary hormonal deficiencies, were included. Baseline differences and differences in the responses in body composition, muscle strength, bone mass, and metabolic indices during 5-yr GH replacement were determined. The duration of GH deficiency was longer and serum IGF-I level and body height were lower in the childhood onset patients than in the adulthood onset patients. Body fat (observed/predicted ratio) was increased, and lean mass and muscle strength were decreased, in the childhood onset patients. Total body and lumbar (L2-L4) bone mineral content and bone mineral density were lower in the childhood onset patients. Serum total cholesterol level was higher in the adulthood onset patients. The childhood onset and adulthood onset patients received a similar dose of GH. After adjustment for body weight, however, the dose of GH was higher in the childhood onset patients. The treatment responses were more marked in the childhood onset patients in lean mass, knee extensor strength, left-hand grip strength, and in total body and lumbar (L2-L4) bone mineral content and bone mineral density. The reduction in serum total cholesterol concentration was more marked in the adulthood onset patients. At study end, no differences remained between the two study groups after the correction for body height in the statistical analysis. In conclusion, the baseline analysis suggests more decreased lean mass, muscle strength, and bone mass in the childhood onset patients whereas the lipid profile was more disturbed in the adulthood onset patients. The 5-yr GH replacement eliminated all the anthropodometric and metabolic differences between the two groups.

Adolescent↗
PubMed2001

Effects of growth hormone and its secretagogues on bone.

The growth hormone (GH)/insulin-like growth factor-1 axis is not only of importance for linear body growth during childhood, but it is also one of the major determinants of adult bone mass. Studies show that GH treatment increases bone mass in rodents as well as in adult GH-deficient humans, but the effect of GH treatment on bone mass in healthy humans has so far not been impressive. Recently, a new class of GH secretagogues (GHSs) has been developed. In humans, GHS treatment affects biochemical markers of bone turnover and increases growth velocity in selected short children with or without GH deficiency. In rodents, GHS treatment increase bone mineral content, but it has not yet been shown that GHS treatment can affect bone mass in adult humans.

Adult↗
PubMed2000

[Drug addicts with severe mental disorders can be helped by programs using moderate means. Good results when psychiatric, social and drug abuse services cooperate].

Dependency disorders are more common than expected in psychiatric populations. Untreated, dual diagnosis leads to severe social and psychiatric deterioration. Nine treatment resistant, homeless, drug addicts suffering from chronic psychotic disorders were selected to take part in a case management program, integrating social services with regular psychiatric treatment. All but one were greatly improved in general terms as well as regarding their ability to maintain an ordered life style. The need for institutional care decreased dramatically.

Community Mental Health Services↗
PubMed2000

Purification of recombinant Arabidopsis thaliana dehydrins by metal ion affinity chromatography.

In this study we describe a novel method for purification of Arabidopsis thaliana dehydrins overproduced in Escherichia coli. The cDNAs corresponding to the four dehydrin genes RAB18, LTI29, LTI30, and COR47 were inserted into a bacterial expression vector under an isopropyl beta-d-thiogalactopyranoside (IPTG) inducible bacterial promoter. After IPTG induction all four proteins accumulated in high amounts. The recombinant proteins were efficiently purified to over 95% purity with a three-step purification scheme: heat fractionation, immobilized metal ion affinity chromatography (IMAC), and ion exchange chromatography. In this study we introduce the novel use of IMAC as an efficient purification method for native dehydrins. Characterization of the purified proteins was done by Edman degradation, mass spectrometry, reverse-phase chromatography, and analytical gel filtration under native and denaturing conditions. Yields of purified proteins were between 2.8 and 12.5 mg per liter of bacterial culture, sufficient for further biochemical studies.

Arabidopsis↗
PubMed2000

Growth hormone and ageing.

The proportion of elderly people is steadily growing in Western societies. The result is a disproportionate accumulation of the oldest and most vulnerable sector of the population, suffering from frailty-associated disorders and cardiovascular diseases. Growth hormone (GH) secretion declines progressively during adulthood. In ageing and severe GH deficiency, an individual's muscle mass, muscle strength and bone mass are decreased, and the relative proportion of total and visceral fat is increased. An association between reduced GH levels and the catabolism of ageing has been suggested. GH or GH secretagogue treatment could be of value to minimize the health-related consequences associated with the ageing process.

Aged↗
PubMed2000

The activity of the hypothalamic-pituitary-adrenal axis and the sympathetic nervous system in relation to waist/hip circumference ratio in men.

OBJECTIVE: To investigate possible differences, between generally and abdominally obese men, in activity and regulation of the hypothalamic-pituitary-adrenal (HPA) axis and the sympathetic nervous system. RESEARCH METHODS AND PROCEDURES: Fifty non-diabetic, middle-aged men were selected to obtain two groups with similar body mass index (BMI) but different waist/hip circumference ratio (WHR). Measurements were performed of the activity of the HPA axis and the sympathetic nervous system, as well as metabolic and endocrine variables. RESULTS: Men with a high WHR, in comparisons with men with a low WHR, had higher insulin, glucose, and triglyceride values in the basal state and higher glucose and insulin after an oral glucose tolerance test. Men with high WHR had elevated diurnal adrenocorticotropic hormone (ACTH) values but similar cortisol values, except lower cortisol values in the morning. Diurnal growth hormone concentrations showed reduced peak size. Stimulation of the HPA axis with corticotropin-releasing hormone (CRH) and laboratory stress showed no difference in ACTH values between groups, but cortisol values were lower in men with high WHR. In comparison with men with a low WHR, men with a high WHR had elevated pulse pressure and heart rate in the basal state and after challenges by CRH and laboratory stress. They also had increased urinary excretion of catecholamine metabolites. DISCUSSION: These results suggest a mild dysregulation of the HPA axis, occurring with elevated WHR independent of the BMI. The results also indicate a central activation of the sympathetic nervous system, such as in the early phases of hypertension, correlating with insulin resistance.

Adipose Tissue↗