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Biomedical subjects

E Svensson

Publications and source records attributed to E Svensson.

At least 73 records · Page 4Linked to original sources

Expression of functional leptin receptors in the human ovary.

The size of body fat stores is known to influence fertility, indicating a link between adipose tissue and the reproductive system. Studies in mice have identified the adipocyte-derived hormone, leptin (Ob protein), as a possible mediator of this effect. The aim of this study was to investigate the possibility that leptin may have direct effects on the human ovary. To probe this hypothesis we first analyzed the expression of leptin receptors in the human ovary. Transcripts encoding both the long and short isoforms of the leptin receptor were present in human granulosa cells and thecal cells; however, the short isoforms were expressed at much higher levels. Immunoreactive leptin was present in follicular fluid at levels similar to those found in serum. ob gene expression, however, was undetectable in the ovary, as determined by reverse transcription-PCR, whereas it was easily detected in adipose tissue. To determine whether leptin could induce a biological response in ovarian cells, we examined the effect of leptin on estradiol production in cultured granulosa cells. Leptin (100 ng/mL) inhibited LH (0.1 ng/mL)-stimulated estradiol production. In contrast, leptin had no effect on estradiol production in the absence of LH. In conclusion, this study has demonstrated that the leptin receptor is expressed in the human ovary, that leptin is present in follicular fluid, and that leptin can induce a biological response in ovarian cells. These results suggest that leptin may have a direct effect on the human ovary.

Adult↗

Measures of individual and group changes in ordered categorical data: application to the ADL staircase.

The aim was to describe the application of a non-parametric method to a study of changes in activities of daily living (ADL) measured by a 10-level ordinal scale, the Staircase of ADL, in a population of 70-year-old persons followed to the age of 76 (n = 371). The statistical method takes account of the fact that change cannot be defined by differences and can separately measure the level of change for the group and for the individuals. This is demonstrated step by step. Measures of change for the subgroups, men and women, are also given. As a group, there was a systematic increase in ADL dependence between the ages of 70 and 76 years. The individual pattern of change was more dispersed between 73 and 76 years of age. Individual variations in ADL changes with increasing age were small compared to the systematic change for ADL for the subgroups of men and women. The systematic change in ADL follows a pattern with "one step at a time" for women and "many steps at a time" for men. In conclusion, this new statistical method provides a valuable tool for detailed information of individual as well as group changes in longitudinal studies.

Activities of Daily Living↗

Prostanoid biosynthesis in patients with cystic fibrosis.

The urinary excretion rate (ng/h/1.73 m2) of prostanoids was determined with a capillary gas-liquid chromatographic mass spectrometric method in 19 patients with cystic fibrosis (CF) aged 1-29 years. Patients with CF showed an increased excretion of prostaglandin E2 metabolites (PGE-M) and thromboxane B2 and its metabolites at all ages. An imbalance in the excretion pattern of thromboxane B2 metabolites also suggested a relative impairment of beta-oxidation. There was no increased excretion of dinor-6-keto-PGF1 alpha, indicating normal prostacyclin biosynthesis. No correlation was found to genotype, clinical score, lung function or bacterial colonization but a significant negative relation was found between the main prostanoids in the urine and serum phospholipid levels of essential fatty acids. The results show that, contrary to the generally accepted decrease of prostanoid excretion in essential fatty acid deficiency, patients with CF increase their production parallel to the development of the deficiency. Since prostanoid synthesis is rate limited by arachidonic acid release, our data support a previously presented hypothesis about a pathological regulation of the release of arachidonic acid in CF.

Adolescent↗

Analysis of interobserver disagreement in the assessment of subarachnoid blood and acute hydrocephalus on CT scans.

The purpose of this study was to analyse factors for interobserver disagreements in two scales used for the assessments of the amount of blood in subarachnoid space (Fisher grading) and of acute hydrocephalus on computerized tomographic (CT) scans. The assessments made by four neuroradiologists on 59 CT scans obtained in the acute stage after subarachnoid hemorrhage were analysed by a statistical method by Svensson and Holm. This method permits the separation of the inter-observer disagreements in their random and systematic components. The overall consistency of the assessments was significant (p < 0.0005) but the neuroradiologists disagreed on half of the CT-scans. The kappa values were 0.50-0.63. The analysis showed that the main reason for disagreements was systematic inter-observer differences in their use of the clinically most important parts of staging, i.e. subarachnoid clot or intraventricular blood (Fisher grading) and too low categories (hydrocephalus). The main conclusion from this study is that the proper remedy for Fisher grading and for grading of hydrocephalus is a sharpening of the criteria of specific category levels and given this improvement both grading systems will show a high level of reliability.

Data Interpretation, Statistical↗

Cytotoxicity, pH, and glucose degradation products in four different brands of PD fluid.

This study was undertaken in order to evaluate differences in pH, cytotoxicity, and concentration of glucose degradation products between different peritoneal dialysis (PD) fluids. Four brands of commercial PD fluids were selected: Gambrosol, Bieffe, Dianeal, and Lock-olys, with a glucose concentration between 3.86% and 4.25%. The cytotoxicity of unused PD fluid was measured as inhibition of cell growth after three days' exposure of a fibroblast cell line using neutral red vital stain. The concentration of 2-furaldehyde, 5-hydroxymethyl-furaldehyde (5-HMF), acetaldehyde, formaldehyde, glyoxal, and methylglyoxal was analyzed by high-performance liquid chromatography technique. All the investigated PD fluids were cytotoxic and contained noticeable amounts of aldehydes. No major differences were observed in pH, although one fluid with a slightly lower pH was found to be less cytotoxic. This fluid also contained less formaldehyde, acetaldehyde, methylglyoxal, and glyoxal but instead contained more 5-HMF. We conclude that all brands of PD fluid are cytotoxic due to glucose degradation products and that they contain noticeable concentrations of low-molecular aldehydes. Our results also demonstrate that the concentration of 5-HMF, used as a regulatory control of PD fluids, does not correlate well with cytotoxicity.

Acid-Base Equilibrium↗

A comparison of six weeks with six months of oral anticoagulant therapy after a first episode of venous thromboembolism. Duration of Anticoagulation Trial Study Group.

BACKGROUND: The optimal duration of oral anticoagulant therapy after a first episode of venous thromboembolism is still a matter of debate. METHODS: We performed a multicenter trial comparing six weeks of oral anticoagulant treatment with six months of such therapy in patients who had a first episode of venous thromboembolism. Anticoagulant therapy consisted of warfarin or dicumarol. Of the 902 patients enrolled, 5 were later excluded because they had congenital protein C deficiency; 443 were randomly assigned to receive six weeks of oral anticoagulant therapy with a targeted international normalized ratio (INR) of 2.0 to 2.85, and 454 were randomly assigned to receive six months of such therapy. The initial diagnoses were confirmed by means of venography in cases of deep-vein thromboses (n = 790) and with perfusion-ventilation scanning or angiography in cases of pulmonary embolism (n = 107); recurrences were confirmed in the same way. RESULTS: After two years of follow-up, there had been 123 recurrences of venous thromboembolism that met the diagnostic criteria, 80 in the six-week group (18.1 percent; 95 percent confidence interval, 14.5 to 21.6) and 43 in the six-month group (9.5 percent; 95 percent confidence interval, 6.8 to 12.2). The odds ratio for recurrence in the six-week group was 2.1 (95 percent confidence interval, 1.4 to 3.1). There was no difference in mortality or the rate of major hemorrhage between the six-week and six-month groups. CONCLUSIONS: Six months of prophylactic oral anticoagulation after a first episode of venous thromboembolism led to a lower recurrence rate than did treatment lasting for six weeks. The difference between the two groups occurred between 6 weeks and 6 months after the start of treatment, and the rates of recurrence remained nearly parallel for 1 1/2 years thereafter.

Anticoagulants↗

Pharmacodynamic effects of meropenem on gram-negative bacteria.

The in vitro initial killing and post-antibiotic effect (PAE) of meropenem on five gram-negative reference strains were evaluated by bioluminescence assay of bacterial adenosine triphosphate (ATP) and viable count. Morphology studies were performed in parallel. Meropenem showed concentration-dependent long (2-5 h) PAEs on Enterobacter cloacae, Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa and Serratia marcescens when assayed by bioluminescence and induced spheroplasts at almost all concentrations. The bioluminescence PAEs reached a maximum response at 4 x MIC. These PAEs of meropenem on Escherichia coli, Klebsiella pneumoniae and Serratia marcescens were longer than corresponding PAEs of imipenem shown in previous studies. The higher affinity of meropenem than imipenem for PBP 3 might explain the longer PAEs obtained with meropenem. However, there was only a very short PAE, no PAE or even a negative PAE when viable count was used as the initial value for the PAE calculation. A strong initial decrease in viability but a less pronounced change in intracellular ATP was registered. Since this initial change in cell numbers is the initial value for the PAE calculation, the length of PAE was highly method dependent. In summary, a strong initial killing and no PAE were shown using viable count as the initial value for the PAE calculation, but a weak initial killing and long PAEs were shown when bioluminescence was used throughout the experiments.

Gram-Negative Bacteria↗

Control-related effective regrowth time and post-antibiotic effect of meropenem on gram-negative bacteria studied by bioluminescence and viable counts.

A study was performed to compare viable counts and bioluminescence for determining control related effective regrowth time (CERT) and postantibiotic effect (PAE) on Gram-negative bacteria after two hours of exposure to meropenem. There was a good correlation between bioluminescence and viable counts in determining the cell numbers in growing cultures of Escherichia coli. CERT was defined as the time required for the resumption of logarithmic growth and an increase of 1 log10 to occur over the pre-exposure inoculum in the test culture minus corresponding time for the control culture. PAE and CERT were studied on reference strains of Enterobacter cloacae, E. coli, Klebsiella pneumoniae and Pseudomonas aeruginosa. At 4 x MIC of meropenem the CERTs of these four Gram-negative strains were 4.1, 4.9, 4.2, and 3.6 h, respectively, when assayed by bioluminescence. Corresponding CERTs using viable counts were 4.2, 5.0, 5.1 and 3.8 h, respectively. In contrast to this good agreement between the methods in assessing CERT, the corresponding PAEs were highly method dependent. At 4 x MIC of meropenem the PAEs on E. cloacae, E. coli, K. pneumoniae and P. aeruginosa were 3.9, 4.8, 4.7, and 3.5 h, respectively, when assayed by bioluminescene. However, the corresponding and simultaneously determined viable count PAEs were -0.4, 0.5, -0.1, and 0.7 h, respectively. The poor correlation between these methods in assessing the PAE is caused by greater initial decrease in viability compared with the less prominent initial change in cell density as measured by bioluminescence.(ABSTRACT TRUNCATED AT 250 WORDS)

Colony Count, Microbial↗

In vitro biocompatibility of a heat-sterilized, low-toxic, and less acidic fluid for peritoneal dialysis.

OBJECTIVE: The aim of this study was to investigate a peritoneal dialysis (PD) fluid (PD-Bio), produced with the intention of reducing the amount of glucose degradation products and to increase the final pH. The heat sterilization of the fluid was performed with the glucose separated from the electrolytes. After sterilization the two solutions were combined. METHODS: The in vitro biocompatibility of PD-Bio was measured as the inhibition of cell growth of a cultured fibroblast cell line and as the stimulated release of interleukin-1 beta from cultured human mononuclear cells. The glucose degradation products were measured as UV absorbance at 228 nm or 284 nm and the concentration of aldehydes was estimated with high-performance liquid chromatography and gas chromatography. RESULTS: Our results demonstrate that in comparison to conventional PD fluids the pH of PD-Bio was increased, to about 6.5. Due to less contaminating glucose degradation products in PD-Bio, basal cytotoxicity was significantly decreased for both 1.5% and 4% glucose-containing fluids, and the stimulated release of interleukin-1 beta was normalized compared to sterile filtered controls with the same pH. UV absorbance measured at 228 nm was decreased, whereas the absorbance at 284 nm was equal to that of a conventional fluid. In PD-Bio the concentrations of formaldehyde, acetaldehyde, methylglyoxal, and 2-furaldehyde were found to be below the detection limit, whereas glyoxal was present in the same and 5-hydroxymethylfurfural (5-HMF) in higher concentrations than in conventionally produced PD fluid. CONCLUSIONS: The results demonstrate that it is possible to improve biocompatibility of PD fluids by simply changing the way the fluid is produced.

Acetaldehyde↗

Severity of mutation in the phenylalanine hydroxylase gene influences phenylalanine metabolism in phenylketonuria and hyperphenylalaninaemia heterozygotes.

We examined whether the degree of residual activity from the mutant phenylalanine hydroxylase (PAH) allele affected phenylalanine metabolism in heterozygotes for phenylketonuria (PKU) or non-PKU hyperphenylalaninaemia (HPA). Discriminant analysis was carried out to find the function of fasting plasma concentrations of phenylalanine (PHE) and tyrosine (TYR) that best separated carriers from non-carriers. This function (0.103TYR -0.214-PHECORR -4.499) was subsequently used as the dependent variable, with the in vitro activity of the expressed mutant PAH as the independent variable, in a regression analysis performed on heterozygotes for mutations that had been studied in a eukaryotic cell expression system. This analysis showed a significant correlation (r = 0.40, n = 140, p < 0.001), although there was a wide spread of values within each of the two major groups of carriers and a considerable overlap between the groups. We conclude that the severity of the mutation, as determined by in vitro expression analysis, in the mutant PAH gene is reflected in the biochemical phenotype of heterozygotes. This result emphasizes the relevance of the cell expression system used for establishing the relative severities of most mutations at the PAH locus. Differences in the activities from the carried mutant PAH allele on phenylalanine metabolism in heterozygotes are, however, small compared to the activity from the normal PAH allele and are easily obscured by other factors leading to inter- or intra-individual variation in phenylalanine metabolism. Fasting plasma concentrations of phenylalanine and tyrosine thus can not be used to predict the severity of the carried PAH mutation in individual PKU or HPA heterozygotes.

Adult↗

Perceived exertion during submaximal G exposures before and after physical training.

Ratings of perceived exertion (RPE) were registered at submaximal levels in G endurance tests of a combined strength and endurance training program in 17 pilots. After 12 months of physical training, the endurance G tolerance (time to exhaustion during simulated aerial combat maneuver), increased by a mean of 40% (p < 0.001), while the mean RPE at 5 min submaximal G exposure decreased by 1.2 units (p < 0.02). Following 12 months of physical training, a significant relationship was observed between the improvement of the endurance G tolerance and the decrease of the RPE at 5 min (p = 0.05). Mean SaO2 at 5 min increased from 84 to 90% (p < 0.01) after training, while heart rate responses to G stress did not change. It is concluded that mean RPE and, to some extent, mean SaO2 during submaximal G exposures may be used as indicators of shifts in endurance G tolerance. The procedure may reduce the need for exhaustive G tolerance tests with associated risks and discomfort.

Aerospace Medicine↗

The phenylketonuria G272X haplotype 7 mutation in European populations.

We have compiled data on the frequencies of the phenylketonuria G272X mutation in European populations. This mutation occurs north of the Alps. It has a particularly high frequency in the Oslo Fjord region of Norway with the adjacent Bohuslän region of Sweden. An intermediate frequency was noted in a separate area, the eastern part of Germany with the adjacent western part of Czechoslovakia. The G272X mutation was associated with phenylalanine hydroxylase haplotype 7, except for one case with haplotype 3. Genealogical studies going back eight to nine generations revealed no common source for this mutation, but there was some geographical convergence to the Bohuslän region. These findings suggest a single origin for this mutation, with at least one founding population in south-eastern Norway/adjacent Sweden.

Europe↗

Relation between genotype and phenotype in Swedish phenylketonuria and hyperphenylalaninemia patients.

Phenylketonuria (PKU) and hyperphenylalaninemia (HPA) are caused mostly by an inherited (autosomal recessive) deficiency in hepatic phenylalanine hydroxylase (PAH) activity. More than 50 PAH mutations have ben reported. The goal of the present study was to examine the molecular basis for the clinical heterogeneity of Swedish PKU and HPA patients. Mutations were identified through allele-specific oligonucleotide hybridization or DNA sequencing on 128 of the 176 mutant alleles (73%). Three mutations (R408W, Y414C and IVS12) together accounted for 56% of all mutant alleles and ten relatively infrequent mutations were found on another 17% of all mutant alleles. Patients from 50 of the 88 families (57%) had identified mutations in both PAH genes and allowed use to compare the clinical effects of different combinations of PAH mutations. The in vitro activity of all of these mutations, including the newly identified G272X and delta L364, have been tested in a eukaryotic expression system. There was a strong relationship between the average in vitro PAH activity of the two mutant enzymes and both the phenylalanine tolerance and the neonatal pretreatment serum phenylalanine concentration. This confirms previous observations in Danish and German PKU patients that disease phenotype is a consequence of the nature of the mutations at the PAH locus and not significantly influenced by other loci. The sample population in the previous study did not, however, include mild HPA patients, and the observed correlation is thus restricted to severe and moderate mutant alleles. Since a comparatively high proportion of the Swedish patients were mildly affected, we have provided additional evidence that this correlation is valid throughout a continuous spectrum of clinical varieties.(ABSTRACT TRUNCATED AT 250 WORDS)

Base Sequence↗

Effects of imipenem on Escherichia coli studied using bioluminescence, viable counting and microscopy.

The effects of imipenem on the growth of Escherichia coli ATCC 25922 were studied using a bioluminescence assay of bacterial ATP, microscopy and viable counting in iso-osmotic Mueller-Hinton broth (MHB) and hypo-osmotic nutrient broth (NB). Imipenem showed a post-antibiotic effect (PAE) of > 2 h for E. coli in both MHB and NB after 2 h exposure to 1 and 8 mg/L of imipenem when determined by bioluminescence and microscopy. The intracellular ATP level increased after 2 h exposure of E. coli to 1 mg/L of imipenem in MHB. In this culture there was a predominance of spheroplasts. These spheroplasts were large and osmotically fragile and a 10 min treatment in water-diluted MHB (hypo-osmotic) prior to the assays lysed the large spheroplasts. This reduced the intracellular ATP level and shortened the PAE when determined by bioluminescence, and caused more rapid initial killing and a negative PAE when determined by viable counting. At 8 mg/L imipenem in MHB and at all concentrations in NB there was a predominance of rods and only a small number of spheroplasts which all disappeared when the cultures resumed logarithmic growth. In these cultures there was a significant initial decrease in intracellular ATP. This study showed reasonable agreement between microscopy and bioluminescence, which are direct methods, for determining the initial killing and PAE of imipenem on E. coli. More rapid initial killing and shorter or no PAEs, were in general, obtained in both MHB and NB when determined by viable counting. However, the effective regrowth time, defined as the time for the bacterial density to increase 1 log10 from the pre-exposure inoculum, was independent of the method used for measuring regrowth in both MHB and NB.

Adenosine Triphosphate↗

Three polymorphisms but no disease-causing mutations in the proximal part of the promoter of the phenylalanine hydroxylase gene.

The proximal promoter region of the human phenylalanine hydroxylase (PAH) gene was analyzed for the presence of mutations in 122 European phenylketonuria (PKU) and hyperphenylalaninemia patients having altogether 187 uncharacterized mutant PAH alleles. This promoter fragment, which contained the most 5' transcription start site and about 300 bp upstream, was sequenced directly from polymerase-chain-reaction-amplified genomic DNA. No disease-causing mutations but three neutral nucleotide substitutions were found. A -195 T-to-C transition was present on 1% of 441 normal and 0.3% of 653 mutant chromosomes. All chromosomes that carried this transition and to which a restriction fragment length polymorphism (RFLP) haplotype had been assigned were of haplotype 1. A -71 G-to-A change and a +7 C-to-T change were always observed together and were found on 1% of 425 normal and 4% of 681 mutant chromosomes. In addition, these two transitions were found in seven heterozygote samples where the phase could not be established due to incomplete family samples. In individuals where RFLP haplotypes were known and phase could be established, these linked substitutions were associated with RFLP haplotype 9. The relatively high frequency (10-20%) of these two polymorphisms on PKU chromosomes from Great Britain, Ireland and France may reflect a relative concentration of haplotype 9 alleles among PKU chromosomes from these countries compared to the rest of Europe. The absence of disease-causing mutations within a region of the PAH gene that possesses basal promoter activity suggests that transcriptional mutations are not likely causes of PKU in Caucasian populations.

Base Sequence↗

Mission challenge, mental workload and performance in military aviation.

In modern military aircraft, complexity of information combined with time stress creates difficulties for the pilot under combat conditions. The first step to mitigate this problem is to measure mental workload. Several methods for doing so have been proposed. In this paper we develop an analysis of mental workload as distinguished from its prior flight mission parameters (risk, challenge) and subsequent effects (mission performance). A model is developed on the basis of extensive mission data, both ground attack and fighter missions, which exhibits a dual coping process as a response to challenge and risk: emotion coping, leading to tension and decreased performance, and problem solving, leading to increased mental energy and improved performance. The model implies a selection of optimal measures for constructing an index of mental workload which is demonstrated to yield a sensitive measure of the pilot's changing mental status over the course of a period of training.

Aerospace Medicine↗