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Biomedical subjects

J Svensson

Publications and source records attributed to J Svensson.

At least 55 records · Page 3Linked to original sources

Image artifacts due to a time-varying contrast medium concentration in 3D contrast-enhanced MRA.

The purpose of this work was to study image effects due to time-varying contrast medium concentration in contrast-enhanced three dimensional (3D) magnetic resonance angiography (MRA) images. Two different simulation models (1D and 3D) and two different contrast medium variation schemes were used. Phantom measurements were also performed. Experiments were performed for several different bolus timings. Similar sequence and image object parameters were used in both simulations and measurements (TE/TR 2. 1/7.8 mses, flip angle 30 degrees, T1/T2 1200-80/150-40 msec, flow velocity 100 cm/sec). A small variation in bolus timing yielded large variations in the appearance of the image effects, especially if the center of k-space was sampled in the vicinity of rapid contrast medium concentration variation. For a typical bolus injection in a patient, a severe signal loss but only minor ringing and edge artifacts appeared if the bolus injection was poorly timed. Effects of pulsatile flow were minor. The 3D model proved to be a useful tool in these studies. J. Magn. Reson. Imaging 1999;10:919-928.

Aorta↗

Screening for mutations in candidate genes for hypospadias.

Hypospadias. a condition with a frontally placed urethral orifice on the penis, is the most common malformation in males. During fetal development several components are necessary for normal male genital development. Testosterone and dihydrotestosterone act via the androgen receptor but a defective receptor function results in different degrees of genital malformations. Testosterone-5alpha-reductase converts testosterone to dihydrotestosterone, which is crucial for normal differentiation, and a total lack of this enzyme results, in syndromes with hypospadias. The Wilms' tumour 1 (WT1) gene is expressed in the fetal gonad and genital malformations can occur due to WT1 gene mutations. These genes are therefore strong candidate genes for hypospadias. We have analysed 35 boys with hypopadias and one girl diagnosed as with complete androgen insensitivity syndrome, using exon by exon polymerase chain reaction (PCR) amplification of the AR, WTI and 5alpha-reductase genes and screened for point mutations and performed subsequent DNA sequencing. No mutations in any of these genes were found in the 26 patients with isolated hypospadias. Two patients with severe hypospadias with cryptorchidism were found to carry mutations in the androgen receptor gene. Also the girl with clinically diagnosed complete androgen insensitivity was found to be homozygous for a splice mutation in the 5alpha-reductase gene. In summary, mutations in the WT1, AR and 5alpha-reductase genes are not common causes of isolated hypospadias.

Base Sequence↗

Discrepancy between serum leptin values and total body fat in response to the oral growth hormone secretagogue MK-677.

OBJECTIVE: Growth hormone (GH) treatment decreases total body fat while this effect has not yet been documented for the oral GH secretagogue MK-677. In the present study, the effects of MK-677 treatment on serum levels of leptin, thyroid hormones and testosterone were determined. DESIGN: This was a randomized, double-blind, and parallel study. Twenty-four healthy obese males, 19-49 years of age, with body mass index (BMI) > 30 kg/m2 and a waist:hip ratio > 0.95, were treated with MK-677 (25 mg/day; n = 12) or placebo (n = 12) for 8 weeks. RESULTS: MK-677 treatment increased serum leptin levels and leptin/body fat ratio at 2 weeks of treatment (P < 0.05 vs. placebo) but no significant change was observed at 8 weeks. An increase in serum free 3, 5, 3'-triiodothyronine (free T3) was not detected until 8 weeks of MK-677 treatment (P < 0.05 vs. placebo). Peak serum thyroid stimulating hormone (TSH) concentration after MK-677 administration was similar to that after placebo administration at initiation of treatment and at 2 weeks. At 8 weeks of MK-677 treatment, mean peak serum TSH concentration was increased (P < 0.05 vs. placebo) although it remained within the normal range. Serum peak values of luteinizing hormone (LH) and follicle stimulating hormone (FSH) were similar after MK-677 and placebo administration. MK-677 treatment reduced serum total testosterone (P < 0.05 vs. placebo) although total testosterone/sex hormone-binding globulin (SHBG) ratio (an index of free testosterone) was not changed. CONCLUSION: Treatment with the oral GH secretagogue MK-677 transiently increased serum leptin levels and leptin/body fat ratio at 2 weeks of treatment, and increased serum free T3 after 8 weeks. These results indicate that MK-677 treatment is able to affect circulating factors of importance for adipose tissue mass and fuel metabolism.

Administration, Oral↗

Five homologous repeats of the protein G-related protein MIG cooperate in binding to goat immunoglobulin G.

Protein MIG, from Streptococcus dysgalactiae, binds alpha2-macroglobulin and immunoglobulin G (IgG). MIG-derived fusion proteins with one to five IgG-binding repeats differed up to 72,000- fold in avidity for goat IgG, indicating a considerable cooperativity of the repeats. Significant sequence variation in the IgG-binding repeats was recognized. Protein MIG interacted with goat IgG1 via both the Fc and Fab parts.

Animals↗

Treatment of obese subjects with the oral growth hormone secretagogue MK-677 affects serum concentrations of several lipoproteins, but not lipoprotein(a).

Obesity is associated with blunted GH secretion and an unfavorable lipoprotein pattern. The objective of this study was to investigate the effects of treatment with the oral GH secretagogue MK-677 on lipoproteins in otherwise healthy obese males. The study was randomized, double blind, and parallel. Twenty-four obese males, aged 18-50 yr, with body mass index greater than 30 kg/m2 and waist/hip ratio above 0.95 were treated with 25 mg MK-677 (n = 12) or placebo (n = 12) daily for 8 weeks. MK-677 treatment did not significantly change serum lipoprotein(a) [Lp(a)] levels. Serum apolipoprotein A-I and E (apoA-I and apoE) were increased at 2 weeks (P < 0.001 and P < 0.01 vs. placebo, respectively), but were not changed at study end. Serum total cholesterol and low density lipoprotein (LDL) cholesterol (LDL-C) levels were not significantly changed by MK-677 treatment. Serum high density lipoprotein (HDL) cholesterol (HDL-C) was increased at 2 weeks of MK-677 treatment (P < 0.01 vs. placebo), but not at 8 weeks. The LDL-C/HDL-C ratio was reduced after 8 weeks of MK-677 treatment (P < 0.05 vs. placebo). Mean LDL particle diameter was decreased at 2 weeks (P < 0.05 vs. placebo), but was unchanged compared with baseline values at 8 weeks (P = NS vs. placebo). The level of serum triglycerides was increased at 2 (P < 0.05 vs. placebo), but not at 8, weeks. Lipoprotein lipase activity in abdominal and gluteal sc adipose tissue was not affected by active treatment. In conclusion, treatment with the oral GH secretagogue MK-677 affected circulating lipoproteins. The effects on serum apoA-1, apoE, triglycerides, and mean LDL particle diameter were transient. At study end, the LDL-C/HDL-C ratio was decreased. MK-677 treatment did not significantly affect serum Lp(a) concentrations at the present dose and administration protocol.

Adipose Tissue↗

Acromegaly and Cushing's syndrome due to ectopic production of GHRH and ACTH by a thymic carcinoid tumour: in vitro responses to GHRH and GHRP-6.

A 50-year-old male presented with diabetes mellitus and Cushing's syndrome associated with a large mediastinal mass. The levels of serum cortisol were high (1500-1800 nmol/l) without diurnal variation. Plasma ACTH levels (200-250 ng/l) and urinary excretion of cortisol were also increased. The levels of these hormones did not change in response to stimulation with corticotrophin releasing hormone (CRH) or suppression with high doses of dexamethasone. The patient had an elevated baseline GH level (7.3 mU/l), and the levels of immunoreactive GH-releasing hormone (GHRH) in eight plasma samples were markedly increased (600-1500 ng/l). Circulating levels of IGF-1, chromogranin A and neuropeptide Y (NPY) were also increased. Computer-assisted tomography and octreotide scintigraphy revealed a large mediastinal tumour and metastases in the left supraclavicular fossa. During treatment with octreotide, the baseline GH level was decreased (to 4.4 mU/l), while the GH pulse height was unchanged. Surgical removal of most of the tumour tissue resulted in a further decrease in the baseline serum GH level to a value (1.6 mU/l) about 20% of that before treatment, while the pulse height and mean GH were affected to a lesser extent. Postoperatively, circulating levels of cortisol and IGF-1 decreased, and the patient exhibited clinical improvement. Histological examination showed a neuroendocrine tumour with characteristics consistent with a foregut carcinoid of thymic origin. Immunoreactive GHRH, ACTH and NPY, but not immunoreactive GH, were detected in 80-90% of the tumour cells and the three peptides appeared to be co-localized. In primary culture, cells from this tumour displayed calcium influx in response to GHRH or GH releasing peptide-6 (GHRP-6), while there were not such responses by cells from another carcinoid not producing GHRH, ACTH or NPY. These results demonstrate a rare case of ectopic production of GHRH, ACTH and NPY, and indicate that the tumour cells were responsive to GHRH and GHRP-6 as well as octreotide.

Acromegaly↗

Hypospadias is related to birth weight in discordant monozygotic twins.

PURPOSE: Hypospadias is a common urogenital malformation in boys. The etiology is unknown but genetic and environmental factors are involved. Because monozygotic twins have the same genetic constitution, we studied disease discordant twin pairs to evaluate environmental risk factors while controlling for genetic effects. MATERIALS AND METHODS: We used questionnaires to identify 28 male twins discordant for hypospadias at 4 pediatric surgical clinics in Sweden. Using deoxyribonucleic acid fingerprinting, and histopathological examination of the placenta and fetal membranes 18 twin pairs were diagnosed as monozygotic. RESULTS: In 16 of the 18 monozygotic pairs discordant for hypospadias the twin with the lowest birth weight has hypospadias. Mean difference in birth weight was 498 gm. (t = 3.8, p <0.01). CONCLUSIONS: Environmental factors associated with low birth weight are involved in the etiology of hypospadias.

Birth Weight↗

Two-month treatment of obese subjects with the oral growth hormone (GH) secretagogue MK-677 increases GH secretion, fat-free mass, and energy expenditure.

Obesity is associated with blunted GH secretion, unfavorable body composition, and increased cardiovascular mortality. The objective of this study was to investigate the effects of oral treatment with the GH secretagogue MK-677 on GH secretion and body composition in otherwise healthy obese males. The study was randomized, double blind, parallel, and placebo controlled. Twenty-four obese males, aged 18-50 yr, with body mass indexes greater than 30 kg/m2 and waist/hip ratios greater than 0.95, were treated with MK-677 25 mg (n = 12) or placebo (n = 12) daily for 8 weeks. Serum insulin-like growth factor I (IGF-I) increased approximately 40% with MK-677 treatment (P < 0.001 vs. placebo). Serum IGF-binding protein-3 was also significantly increased (P < or = 0.001 vs. placebo). GH and PRL (peak and area under the curve values) were significantly increased after the initial dose of MK-677. Significant increases, with the exception of peak PRL, persisted at 2 and 8 weeks of treatment. The increases in GH and PRL after the initial dose were significantly greater than the increase seen after multiple doses. Serum and urinary concentrations of cortisol were not increased at 2 and 8 weeks (P = NS, vs. placebo). Fat-free mass increased significantly in the MK-677 treatment group when determined with dual energy x-ray absorptiometry (P < 0.01) or using a four-compartment model (P < 0.05). Total and visceral fat were not significantly changed with active therapy. The basal metabolic rate was significantly increased at 2 weeks of MK-677 treatment (P = 0.01) but not at 8 weeks (P = 0.1). Fasting concentrations of glucose and insulin were unchanged, whereas an oral glucose tolerance test showed impairment of glucose homeostasis at 2 and 8 weeks. We conclude that 2-month treatment with MK-677 in healthy obese males caused a sustained increase in serum levels of GH, IGF-I, and IGF-binding protein-3. The effects on cortisol secretion were transient. Changes in body composition and energy expenditure were of an anabolic nature, with a sustained increase in fat-free mass and a transient increase in basal metabolic rate. Further studies are needed to evaluate whether a higher dose of MK-677 or a more prolonged treatment period can promote a reduction in body fat.

Adult↗

Treatment with the oral growth hormone secretagogue MK-677 increases markers of bone formation and bone resorption in obese young males.

The effect of 2 months of treatment with the oral growth hormone (GH) secretagogue MK-677 on markers of bone metabolism was determined in healthy obese male subjects. This was a randomized, double-blind, parallel, placebo-controlled study. Twenty-four healthy obese males, 19-49 years of age, with body mass index > 30 kg/m2 were treated with MK-677 (25 mg/day; n = 12) or placebo (n = 12) for 8 weeks. MK-677 increased markers of bone formation; a 23% increase in the carboxy-terminal propeptide of type I procollagen levels and a 28% increase in procollagen III peptide levels were seen with as little as 2 weeks of MK-677 treatment (p < 0.01 and p = 0.001 vs. placebo, respectively) while a 15% increase in serum levels of osteocalcin was not detected until 8 weeks of treatment (p < 0.01 vs. placebo). Markers of bone resorption were induced within 2 weeks of treatment with MK-677; serum levels of the carboxy-terminal cross-linked telopeptide of type I collagen were increased 26% at 8 weeks (p = 0.001 vs. placebo), and urine hydroxyproline/creatinine and calcium/creatinine ratios at 8 weeks were increased by 23% (p < 0.05 vs. placebo) and 46% (p < 0.05 vs placebo), respectively, MK-677 increased serum insulin-like growth factor binding protein-5 (IGFBP-5) by 43-44% after 2-8 weeks of treatment (p < 0.01 vs. placebo). Serum IGFBP-4 was increased by 25% after 2 weeks of treatment (p < 0.001 vs. placebo) but no significant change from baseline was observed after 8 weeks of treatment. Plasma interleukin-6 was not significantly changed by active treatment. In conclusion, short-term treatment of healthy obese male volunteers with the GH secretagogue MK-677 increases markers of both bone resorption and formation. Large increases in serum levels of IGF-1 and IGFBP-5 and a transient increase in serum IGFBP-4 were found. Future long-term studies are needed to investigate if prolonged treatment with MK-677 increases bone mass.

Administration, Oral↗

Insulin-like growth factor-I in growth hormone-deficient adults: relationship to population-based normal values, body composition and insulin tolerance test.

BACKGROUND: Although an insulin tolerance test (ITT) is the most commonly used method for detecting growth hormone (GH) deficiency (GHD) in adults, measurements of serum insulin-like growth factor-I (IGF-I) may also be of value. OBJECTIVE: To validate the use of serum IGF-I concentration in the diagnosis of GHD in adults. DESIGN: A cross-sectional study. PATIENTS: One hundred and four patients, 60 men and 44 women, with known pituitary disease and verified GHD based on ITT. MEASUREMENTS: Serum IGF-I was determined by radioimmunoassay after acid-ethanol extraction. Body composition was estimated with total body potassium combined with total body water assessments. RESULTS: According to age- and sex-adjusted population-based references values, 51 patients had serum IGF-I concentrations below -2 SD of the predicted values and 53 had concentrations within 2 SD. Fifty-seven per cent of the patients aged 41 years (25th percentile) or below and 39% of the patients aged 57 years (75th percentile) or above had serum IGF-I concentrations below -2 SD. Women had lower mean IGF-I SD scores than men (P < 0.01). Serum IGF-I was correlated with peak GH response during ITT (r = 0.40; P < 0.001), age (r = -0.27; P < 0.01), duration of hypopituitarism (r = -0.52; P < 0.001), number of pituitary hormonal deficiencies (r = -0.35; P < 0.001), body cell mass (r = 0.30; P < 0.01) and serum insulin (r = 0.21; P < 0.05). The peak GH response during ITT correlated with spontaneous GH secretion, duration (P = -0.48; P < 0.001) and number of deficiencies (r = -0.50; P 0.001). CONCLUSION: The measurement of serum IGF-I concentrations is not suitable as a single diagnostic test for growth hormone deficiency in adults. Even as a screening test, its use appears to be limited, especially in elderly subjects. The serum level of IGF-I was influenced by several factors in addition to GH, such as age, gender, anthropodometry and serum insulin level. The peak GH response during the insulin tolerance test appears to be influenced to a lesser degree by these factors.

Adolescent↗

Bladder exstrophy in Sweden--a long-term follow-up study.

A retrospective review of all new cases of bladder exstrophy in Sweden in 1970 through 1989 is presented. The aim was to evaluate management of the malformation in Sweden and possibly identify factors that might improve the outlook. The incidence was 1:33,500 births. Records were reviewed of the 61 children (37 males and 24 females) treated at Sweden's four specialist centers of pediatric surgery. There was one perinatal death. Primary management was mainly early bladder closure (within 72 hours), late closure or perinatal urinary diversion. Subsequent measures included augmentation cystoplasty, bladder neck reconstruction, provision of continent urinary reservoir and penile reconstruction. The follow-up time was 4-19 years. In 15 cases renal scarring developed, though with impairment of total function in only three. Ten patients achieved continence, defined as 3-hour dry intervals, of whom four had urinary reservoirs with continent stoma. Urinary tract infections were recorded during follow-up in 43% of the surviving patients, though the true incidence of infection presumably was higher. To improve management of bladder exstrophy in sparsely populated Sweden, a nation-wide strategy of ongoing interhospital collaboration has been adopted. Results will be continuously presented.

Adolescent↗

Autologous blood transfusion in hip replacement. No effect on blood loss but less increase of plasminogen activator inhibitor in a randomized series of 80 patients.

80 patients underwent total hip replacement (THR) for primary coxarthrosis. In a randomized study, half of them donated 2 units of blood before operation. One unit was collected 4 weeks and one 2 weeks before the scheduled THR. All except 1 patient tolerated the predonations well. Total blood losses were similar in both groups. Additional bank blood was given in 7/38 in the predonation group, compared to 29/40 in the control group. Hemostatic parameters were studied in 10 consecutive patients in each group. Plasminogen activator inhibitor 1 (PAI-1), a possible risk parameter for thromboembolism, was significantly more increased postoperatively in the control group, which received only homologous blood. Platelet count, prothrombin complex, antithrombin III and von Willebrand factor antigen were significantly reduced and C reactive protein increased after surgery in both groups. We recommend predonation of 2 autologous units before a primary THR. In most cases, such predonation makes homologous blood transfusion unnecessary. The use of predonated blood causes no reduction of blood loss in THRs, but the increase in PAI-1 seen after homologous transfusions is avoided.

Aged↗

Reconstruction of the standard 12-lead ECG from recordings using nonstandard activity-compatible proximal limb lead positions.

Proximal or torso placement of limb leads in the 12-lead electrocardiogram (ECG) has been shown to influence the appearance of QRS waveforms considerably. A method was developed for computer-based reconstruction of standard-like waveforms from nonstandard torso-recorded waveforms. Reconstruction coefficients required by the method were determined using ECG data obtained from 30 patients. The coefficients were then applied on an independent test set of 100 patients. In 21 of these patients, a second standard EGG was obtained the next day to determine the day-to-day variation in QRS waveforms. R wave amplitudes in leads I and II, and electrical axes in the frontal plane were measured in the standard ECG, the nonstandard ECG, and the reconstructed ECG. It is shown that the reconstruction method yields ECGs that differ less from standard than do two standard ECGs recorded on consecutive days. The performance of the reconstruction method was not influenced by age, sex, height, or weight.

Adult↗

Cervical fetal fibronectin correlates to cervical ripening.

AIM OF STUDY: It is well established that the cervical ripeness is of great prognostic value at labor induction. The available methods of measuring the cervical ripeness are not satisfactory. This study was therefore initiated to investigate if there is any correlation between cervical fetal fibronectin and cervical ripening at term. METHOD: Three groups were included in this study: women with unripe cervices, women with spontaneous cervical ripening and those with PGE2-induced cervical ripening. Fetal fibronectin was measured by ELIZA after sampling from the cervical canal. RESULTS: The cervical fetal fibronectin was low in women with unripe cervices. In women with favorable cervices a ten fold higher level was found. The fibronectin level was even higher after PGE2-induced ripening. CONCLUSION: Conclusively an increased amount of cervical fetal fibronectin is registered during the cervical ripening process. A level of > 0.80 microgram/ml of cervical fetal fibronectin seems to indicate a favorable cervix.

Adult↗

PEEP ventilation does not cause humorally mediated cardiac output depression in pigs.

OBJECTIVE: This study was designed to see if humorally mediated negative inotropism contributes to the cardiac output (CO) depression seen during positive end-expiratory pressure (PEEP) ventilation. DESIGN: 8 pairs of piglets were used and a combined blood circulation was established between the two animals in each pair. One animal was ventilated with a PEEP of 15 cmH20 (donor) and the other was ventilated without PEEP (recipient). MEASUREMENT AND RESULTS: CO and stroke volume deteriorated in the donors by 32% and 44%, respectively, while no change was seen in the recipients. CONCLUSION: As humorally mediated negative inotropism during PEEP ventilation has earlier been demonstrated in dogs, the results suggest that this mechanism might be species-dependent.

Analysis of Variance↗