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Biomedical subjects

K Sandström

Publications and source records attributed to K Sandström.

15 recordsLinked to original sources

Descriptions of functioning and health and relations to a gross motor classification in adults with cerebral palsy.

PURPOSE: The aim of this study was to describe functioning and health, and explore the use of the Gross Motor Function Classification System (GMFCS) in an adult population with cerebral palsy (CP). METHODS: From a cohort of 199 persons, 48 persons were selected for structured interviews and functional assessments regarding activities of daily living, motor function, range of motion, pain and general health. RESULTS: A third of the population had deteriorated in function from adolescence to adulthood according to the GMFCS. The majority were independent in personal ADL, but many of those were dependent in instrumental ADL. Motor function scores reflected problems in walking ability, and limited ROM and pain were common in all functional levels. General health was lower than in a general population. GMFCS seems valid for classifying adults with CP since it is correlated with instruments measuring motor function and ADL in terms of dependence. CONCLUSION: Decreased functional ability and secondary musculoskeletal problems are common in adults with CP and general health can be associated with those problems. It is important to further explore health aspects and relations between health status and self-perceived health. The GMFCS is a useful tool, especially for comparisons throughout the life span, but in order to use in an adult population further development is needed.

Activities of Daily Living↗

Inhibition of the CD28-CD80 co-stimulation signal by a CD28-binding affibody ligand developed by combinatorial protein engineering.

CD28 is one of the key molecules for co-stimulatory signalling in T cells. Here, novel ligands (affibodies) showing selective binding to human CD28 (hCD28) have been selected by phage display technology from a protein library constructed through combinatorial mutagenesis of a 58-residue three-helix bundle domain derived from staphylococcal protein A. Analysis of selected affibodies showed a marked sequence homology and biosensor analyses showed that all investigated affibodies bound to hCD28 with micromolar affinities (KD). No cross-reactivity towards the related protein human CTLA-4 could be observed. This lack of cross-reactivity to hCTLA-4 suggests that the recognition site on hCD28 for the affibodies resides outside the conserved MYPPPYY motif. The apparent binding affinity for hCD28 could be improved through fusion to an Fc fragment fusion partner, resulting in a divalent presentation of the affibody ligand. For the majority of selected anti-CD28 affibodies, in co-culture experiments involving Jurkat T-cells and CHO cell lines transfected to express human CD80 (hCD80) or LFA-3 (hLFA-3) on the cell surface, respectively, pre-incubation of Jurkat cells with affibodies resulted in inhibition of IL-2 production when they were co-cultured with CHO (hCD80+) cells, but not with CHO (hLFA-3+) cells. For one affibody variant denoted Z(CD28:5) a clear concentration-dependent inhibition was seen, indicating that this affibody binds hCD28 and specifically interferes in the interaction between hCD28 and hCD80.

Amino Acid Sequence↗

Specific metal-ion binding sites in a model of the P4-P6 triple-helical domain of a group I intron.

Divalent metal ions play a crucial role in RNA structure and catalysis. Phosphorothioate substitution and manganese rescue experiments can reveal phosphate oxygens interacting specifically with magnesium ions essential for structure and/or activity. In this study, phosphorothioate interference experiments in combination with structural sensitive circular dichroism spectroscopy have been used to probe molecular interactions underlying an important RNA structural motif. We have studied a synthetic model of the P4-P6 triple-helical domain in the bacteriophage T4 nrdB group I intron, which has a core sequence analogous to the Tetrahymena ribozyme. Rp and Sp sulfur substitutions were introduced into two adjacent nucleotides positioned at the 3' end of helix P6 (U452) and in the joining region J6/7 (U453). The effects of sulfur substitution on triple helix formation in the presence of different ratios of magnesium and manganese were studied by the use of difference circular dichroism spectroscopy. The results show that the pro-Sp oxygen of U452 acts as a ligand for a structurally important magnesium ion, whereas no such effect is seen for the pro-Rp oxygen of U452. The importance of the pro-Rp and pro-Sp oxygens of U453 is less clear, because addition of manganese could not significantly restore the triple-helical interactions within the isolated substituted model systems. The interpretation is that U453 is so sensitive to structural disturbance that any change at this position hinders the proper formation of the triple helix.

Animals↗

A method to study apoptosis in eosinophils by flow cytometry.

The aim of this study was to develop a simple flow cytometric procedure to study eosinophil apoptosis. Eosinophils were isolated from the peripheral blood of healthy, non-allergic individuals and then cultured in basal culture medium. The cells were examined after 24, 48 and 72 h for forward- and side scatter (FS-SSC) pattern, staining with FDA, PI, and anti-CD95, and light microscopic appearance. After culture for >24 h, two populations with different FS-SSC-patterns appeared, referred to as A and B. Population A consisted of living, FDA-positive eosinophils. The eosinophils in population B showed a lower FS scatter than those in population A and a staining pattern with PI indicating the presence of hypodiploid DNA. Anti-CD95 demonstrated a significant staining of the eosinophils in population B, which increased after 2 days in culture. The cells were sorted using a FACS-Scan cell sorter and by Annexin V-coated magnetic beads to permit separate analyses of PI-staining pattern, DNA electrophoresis, and light microscopic examination of the cells in population B. The present study suggest that it is possible to discriminate between apoptotic and living eosinophils using the FS-SSC pattern and the PI-staining pattern obtained by flow cytometry.

Annexin A5↗

Effects of propofol on desipramine-sensitive [3H]-noradrenaline uptake kinetics in rat femoral artery.

BACKGROUND: The intravenous anaesthetic propofol inhibits the neuronal uptake of noradrenaline (uptake1) from the vascular sympathetic neuromuscular junction, resulting in an enhancement of the sympathetic neurotransmission. This could be important for maintenance of blood pressure during propofol anaesthesia. The aim of the present study was to determine how propofol influences the kinetics of uptake1. METHODS: Isolated segments of rat femoral arteries were incubated with [3H]-noradrenaline in the presence or absence of propofol and the radioactivity taken up was measured in a scintillation counter. The uptake1 inhibitor, desipramine, was used to delineate the specific neuronal uptake. RESULTS: Desipramine and 10 microM propofol significantly reduced the uptake in segments incubated with 0.1 microM [3H]-noradrenaline. Propofol at 1 microM and 100 microM did not affect the uptake. Non-linear regression analysis of specific uptake yielded Km 0.50 microM, Vmax 1.6 pmol mg(-1) 15 min(-1) and Hill coefficient 1.1. Propofol (1-10 microM) increased the Km value and propofol (10-100 microM) increased the Vmax value concentration-dependently, while the Hill coefficient was not affected. CONCLUSION: Propofol seems to have a biphasic effect on the uptake of noradrenaline in the vascular sympathetic neuromuscular junction. At lower propofol concentrations there is a decrease in the affinity of the noradrenaline transporters. The resulting uptake inhibition is counteracted at higher propofol concentrations by an increase in the efficacy of the uptake.

Adrenergic Uptake Inhibitors↗

Effects of propofol on substance P-induced relaxation in isolated human omental arteries and veins.

To elucidate if an effect of propofol on endothelium-dependent relaxation could contribute to propofol-induced vasodilation, smooth muscle relaxation of isolated human omental artery and vein segments precontracted by endothelin-1 were measured. Substance P induced a concentration-dependent relaxation (mean +/- SEM) in both artery (63 +/-8.4% of precontraction, n = 9) and vein (60+/-11%, n = 7). The relaxation was enhanced by 10(-6) M propofol (artery, 72+/-9.5%, n = 9; vein, 81+/-12%, n = 7) but not affected by 10(-7), 10(-5) and 10(-4) M propofol. In the presence of Nomega-nitro-L-arginine methyl ester (nitric oxide synthase inhibitor), 10(-6) M propofol still enhanced the substance P-induced relaxation in arteries but not veins, whereas 10(-4) M propofol inhibited the relaxation in both arteries (rightward shift of the concentration-response curve) and veins (28+/-7.5%, n = 8). In the presence of potassium chloride (to prevent hyperpolarization), the enhancement of substance P-induced relaxation by 10(-6) M propofol was abolished in both arteries and veins whereas 10(-5) and 10(-4) M propofol reduced the relaxation in arteries (38+/-13% at 10(-5) M, n = 6; 30+/-11% at 10(-4) M, n = 6) but not in veins. These results demonstrate that propofol, at lower, clinically relevant concentrations, promotes endothelium-dependent relaxation mediated via hyperpolarization in human omental arteries and via both nitric oxide and hyperpolarization in human omental veins.

Adult↗

Increased levels of S-100 protein after cardiac surgery with cardiopulmonary bypass and general surgery in children.

The aim of this study was to evaluate changes in concentrations of the neurospecific protein S-100 in relation to cardiac surgery with cardiopulmonary bypass (CPB) and noncardiac general surgery in children below 3 years of age. Seventeen children underwent surgery for congenital heart disease and all survived without clinical signs of neurological complications. Samples for plasma concentrations of S-100 in these patients were taken on three occasions in connection with surgery: before the start of surgery, after CPB and finally 16-20 h after CPB. In the noncardiac group of 31 children, S-100 concentrations were measured on two occasions: before surgery and during surgery. In both groups, a significant increase in S-100 concentrations was observed during surgery, although the increase in the CPB group was significantly higher than in the noncardiac group. The CPB group included four children with Down's syndrome who had higher mean S-100 concentrations on all sampling occasions compared to the remaining patients. The peak S-100 concentrations after cardiac surgery were related to the duration of CPB, the time from the termination of CPB to the first post-CPB sample, as well as mean arterial pressure and cerebral arteriovenous lactate difference during rewarming. All the children studied (Down's patients excluded) had age-dependent plasma concentrations of S-100 measured before surgery. It can be concluded that CPB initiates a marked but transient release of S-100 into the systemic circulation during open heart surgery in children who are not developing clinical signs of neurological sequelae.

Cardiac Surgical Procedures↗

Intraoperative glucose administration influences respiratory quotient during paediatric anaesthesia.

BACKGROUND: Oxidation of carbohydrates and fat yields respiratory quotients (RQ) of 1.0 and 0.7 respectively. Maintained or increased blood glucose concentrations are usually seen during paediatric anaesthesia and surgery even without glucose administration. The aim of the present study was to evaluate whether an intraoperative glucose infusion influences the RQ as an indication of a different metabolic preference in comparison to a glucose-free fluid regime. METHODS: Eighteen children between 0.5 and 24 months of age were studied during anaesthesia with controlled ventilation, oxygen in air, isoflurane, thiopentone, atracurium and fentanyl. Oxygen consumption and carbon dioxide production were measured using indirect calorimetry All children received Ringer acetate as needed; in addition, nine children were given glucose 10%, 3 ml.kg-1.h-1, corresponding to 300 mg.kg-1.h-1. Blood samples for analyses of glucose, lactate, free fatty acids and ketones were taken before and during surgery. RESULTS: RQ was significantly higher in the children given glucose 0.92 +/- 0.08, compared to 0.81 +/- 0.06 in the children without glucose (P < 0.01). Oxygen consumption tended to be higher, although not significantly so, in patients without glucose infusion. Energy expenditure was 1.70 +/- 0.29 kcal.kg-1.h-1, without significant group differences. Higher blood glucose concentrations during surgery were found in the children given glucose. CONCLUSIONS: Our results indicate a higher glucose oxidation rate in patients given glucose during surgery.

Anesthesia↗

Jugular bulb temperature compared with non-invasive temperatures and cerebral arteriovenous oxygen saturation differences during open heart surgery.

Limited information is available about the correlation between cerebral temperature and routine temperature measurements during cardiopulmonary bypass in infants. Nasopharyngeal, tympanic membrane and rectal temperatures were compared with jugular bulb temperature in ten infants operated on with moderate or deep hypothermia. The cerebral arteriovenous saturation differences were correlated with the temperatures at the four measurement sites. The jugular bulb and nasopharyngeal temperatures showed the most rapid response during cooling and rewarming. The tympanic temperature response varied in an unpredictable way. Rectal temperature, which was the target for rewarming, lagged behind during both cooling and rewarming. Overwarming at the end of cardiopulmonary bypass, seen as jugular bulb and nasopharyngeal temperatures exceeding 38 degrees C, was common after deep hypothermia. A high correlation was found between the cerebral arteriovenous oxygen saturation differences and the jugular bulb temperature (r = 0.81) and the nasopharyngeal and the tympanic temperature (r = 0.79), whereas the correlation with rectal temperature was weaker (0.66).

Body Temperature↗

Open heart surgery; pump prime effects and cerebral arteriovenous differences in glucose, lactate and ketones.

This study included 17 young children, who were operated with cardioplumonary bypass for congenital heart defects and were cooled to 20 degrees C or 25 degrees C. No glucose, except for the pump prime solution, was administered during surgery. Samples of arterial blood, cerebral venous blood from the jugular bulb and mixed venous blood from the bypass circuit were obtained and analysed for concentrations of glucose, lactate and ketones as well as oxygen saturation. The prime content of lactate significantly contributed to the arterial lactate concentrations, which together with the cerebral arteriovenous (A-V) lactate differences remained elevated throughout the bypass period. The prime content of glucose had less influence on the arterial concentrations and these did not increase until the rewarming period, when indications of gluconeogenesis from lactate were found. Arterial ketone concentrations also increased during rewarming in parallel with significant cerebral uptake of ketones. The lowest cerebral A-V glucose, lactate and oxygen saturation differences were found at the target minimum temperature and this effect was significantly more pronounced in the patients cooled to 20 degrees C.

Analysis of Variance↗

Effects of active addition of bacterial cultures in fermented milk to patients with chronic bowel discomfort following irradiation.

Radiotherapy is a cornerstone in the treatment of malignancies in the pelvis. Consequently, there is usually exposure of the intestine and especially the lower colon and rectum, with ensuing disturbances in bowel habits at different times following radiotherapy. The main problem is diarrhoea associated with lactose intolerance, bile salt absorption and fat malabsorption. Bacterial contamination has also been described. In the present study we have evaluated the influence of the active administration of specific bacterial cultures in fermented milk, which inhibit the growth of potentially pathogenic micro-organisms, to 40 consecutive patients with chronic alteration in their bowel habits caused by previous radiotherapy of pelvic malignancies. The results suggest that intake of fermented milk products could be of value in decreasing chronic bowel discomfort following radiotherapy of pelvic malignancies. However, a more extensive study is warranted in order to very the significance of the results and to find the optimal product.

Animals↗

Early postoperative lipid administration after neonatal surgery.

The ability of neonates to eliminate and utilize lipid emulsions after surgery was investigated in 12 patients. All were subjected to major surgery within 29 h of birth. All neonates were given 10% glucose iv intraoperatively. Six patients continued with 10% glucose iv for 24 h postoperatively and 6 patients received a combination of 5% glucose and soy bean emulsion (Intralipid 20%). Both regimes provided equal amounts of fluid and energy. Blood glucose, lactate, triglycerides, free fatty acids, fractions of fatty acids in triglycerides, 3-hydroxybutyrate and arterial blood gases were measured at predetermined intervals throughout this period. Administration of a lipid emulsion early after neonatal surgery was well tolerated and utilized, with some latency. Concentrations of triglycerides, free fatty acids and 3-hydroxybutyrate were higher in the lipid group, but no accumulation of these substances was found. Palmitinic and linoleic acid were also higher in the lipid group.

Fat Emulsions, Intravenous↗

Metabolic consequences of different perioperative fluid therapies in the neonatal period.

Carbohydrate and fat metabolism during and after anaesthesia and surgery was studied in 14 neonates with major congenital non-cardiac anomalies. They were either given a glucose solution until surgery or starved for at least 4 h before surgery. Ringer-acetate alone or Ringer-acetate plus 10% glucose was used for the intraoperative fluid therapy. After anaesthesia all neonates were given a 10% glucose solution. Concentrations of glucose, free fatty acids, triglycerides, lactate, pyruvate, alanine, glycerol and 3-hydroxybutyrate were measured at predetermined intervals pre-, intra- and postoperatively. Blood glucose concentrations rose during surgery both in neonates given glucose before and during surgery (n = 6) and in neonates not given glucose before and during surgery (n = 6). Increased intraoperative levels of free fatty acids and 3-hydroxybutyrate were found in neonates not given glucose before and during surgery. The triglyceride levels were equal in both groups. In two neonates given glucose before surgery and Ringer-acetate during surgery increased levels of 3-hydroxybutyrate were found, particularly in one patient who became hypoglycaemic. In conclusion, starved neonates without intraoperative glucose supply mobilized fat and maintained blood glucose concentrations.

3-Hydroxybutyric Acid↗