Biomedical subjects

H Steen

Publications and source records attributed to H Steen.

At least 55 records · Page 3Linked to original sources

PubMed1995

Changes in Na+, K(+)-adenosinetriphosphatase, citrate synthase and K+ in sheep skeletal muscle during immobilization and remobilization.

The K+ balance and muscle activity seem to interact in a complex way with regard to regulating the muscle density of Na(+)-K+ pumps. The effect of immobilization was examined in ten sheep that had low muscle K+ content. Three additional sheep served as untreated controls. After being brought from pasture to sheep stalls one hindlimb was immobilized in a plaster splint for 9 weeks, and in five of the animals remobilization was carried out for a further 9 weeks. The weight bearing of the leg in plaster was recorded by a force plate. Open muscle biopsies from the vastus lateralis muscle were obtained before the study, after 9 weeks of immobilization, and after another 9 weeks of remobilization. The Na(+)-K+ pump density was measured as [3H]-ouabain binding to intact tissue, and citrate synthase activity was measured in tissue homogenate. The tissue content of K+ was measured in fat-free dried tissue. Muscle K+ content increased linearly by almost 70% through the 18-week period independent of intervention. Immobilization reduced thigh circumference by 8% (P < 0.05). A slight decrease in the area of type I fibres at 9 weeks and a slight increase at 18-weeks was found. The [3H]-ouabain binding was reduced by 39% and 22% in the immobilized and control legs, respectively, whereas citrate synthase activity was reduced by about 30% in both legs after 9 weeks of immobilization. During remobilization both the [3H]-ouabain binding and the citrate synthase activity increased to the same level as in the control animals. The plaster cast significantly reduced mass bearing of the immobilized leg, and a corresponding reduction in muscle activity must be assumed to have occurred in both legs as judged from citrate synthase activity. We concluded from this study that the reduction in the [3H]-ouabain binding during immobilization independent of an increase in muscle K+ content points to muscle activity as a strong stimulus for control of Na(+)-K+ pump density.

Animals↗

PubMed1995

Can a regular leg extension bench be used in testing deficits of the quadriceps muscle during rehabilitation?

Fifty-nine people, 31 healthy subjects with no previous knee injuries and 28 who had undergone an intra-articular anterior cruciate ligament reconstruction 6-12 months prior to testing took part in the study. The subjects were randomly tested bilaterally on a Cybex 6000 isokinetic testing device (ITD) and on an ordinary leg extension bench (LEB). Strength and endurance were tested with both methods. The linear relationships for paired strength and endurance differences between ITD and LEB were found to be acceptable for the operated group. The LEB alone explained 57% and 38% of the ITD outcome for strength and endurance, respectively. The agreement between observed and predicted ITD values based on the LEB measurements was found satisfactory with a positive standardized agreement index. This indicates that the LEB can be used as a helpful tool in evaluation of quadriceps muscle strength deficits.

Adolescent↗

PubMed1995

Unchanged muscle function after bilateral femoral lengthening. A prospective study of 9 patients with a 2-year follow-up.

We performed pre- and 2-3.5-year postoperative isokinetic knee-testing to assess thigh muscle function in 9 patients undergoing bilateral femoral lengthening by callotasis. The median femoral lengthening was 17 (12-18) percent. The angular testing velocities were 60 degrees/sec (strength) and 180 degrees/sec (endurance). Only small changes in muscle strength were found postoperatively. Except for peak torque at 60 degrees/sec on the last-operated side (median 2 years follow-up), there were no differences between the pre- and postoperative isokinetic measurements. There were 3 major complications, 2 fractures and 1 varus deformity. 2 patients had problems with patellar pain. All patients achieved normal range of motion. They judged the final result as very good and underlined the psychological effect and the practical advantages of being taller.

Adolescent↗

PubMed1995

Variability in Cobb angle measurements in children with congenital scoliosis.

The variability in measurement of angles in congenital scoliosis is not known, but it is postulated that it is larger than that in adolescent idiopathic scoliosis due to skeletal immaturity, incomplete ossification, and anomalous development of the end-vertebrae. To determine this variability, we selected 54 radiographs of adequate quality showing 67 scoliotic curves from children with congenital scoliosis. The end-vertebrae were preselected. Each curve was measured by the Cobb method on two separate occasions by six different observers, using the same goniometer and marker. The intraobserver variability was +/- 9.6 degrees and the interobserver variability +/- 11.8 degrees. If 'significant progression' is to be used as a criterion for surgical fusion in congenital scoliosis, there should be at least a 23 degrees increase, the entire range of the interobserver variability, in the curvature to ensure that the perceived increase is not due to variability in measurement.

Analysis of Variance↗

PubMed1994

Muscle function after femoral shortening osteotomies at the subtrochanteric and mid-diaphyseal level. A follow-up study.

Relative femoral shortening length at the subtrochanteric (ST) and mid-diaphyseal (MD) level was compared with isokinetic muscle strength more than 2 years postoperatively. For the ST level no upper limit for shortening length could be detected. For MD osteotomies the relative shortening length was negatively correlated to muscle strength. There was a significant difference at the MD level between those shortened more or less than 10%, indicating an upper limit of 10% of the femoral length for regaining normal muscle strength. For correction of leg length inequality and for shortening of unaccepted tallness, these results should be taken into account when choosing the level for osteotomy.

Body Height↗

PubMed1994

Effect of ethanol on hepatobiliary transport of cationic drugs. A study in the isolated perfused rat liver, rat hepatocytes and rat mitochondria.

The effect of ethanol on the hepatic uptake of various cationic drugs was studied in isolated perfused rat livers, isolated rat hepatocytes and isolated rat liver mitochondria. In isolated rat hepatocytes and in isolated perfused rat livers, the uptake of the model organic cation tri-n-butylmethylammonium was found to be markedly stimulated by ethanol in a concentration-dependent fashion. The uptake of tri-n-butylmethylammonium at 1 microM was increased to 120% and 137% at 0.5% (v/v, (= 87 mM)) and 1% (v/v. (= 174 mM)) ethanol, respectively. At 25 microM, tri-n-butylmethylammonium uptake was increased to 124% and 152% at 0.5% (v/v) and 1% (v/v) of ethanol, respectively. The uptake of the organic cations azidoprocainamide methoiodide, vecuronium, ORG 9426 and ORG 6368, the anionic compound taurocholate and the uncharged compound ouabain was not markedly increased at these ethanol concentrations. The mechanism of action of ethanol on the uptake of tri-n-butylmethylammonium was further studied. Competitive inhibitors for the type I organic cation uptake system, procainamide ethobromide and verapamil, almost completely blocked uptake of tri-n-butylmethylammonium (1 microM) in the presence of 1% (v/v) ethanol, indicating that carrier-mediated uptake is still involved and that additional passive diffusion is unlikely. Neither the plasma membrane potential nor the accumulation of the cation in mitochondria was altered after ethanol treatment, suggesting that potential driving forces for uptake and sequestration were not affected.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetaldehyde↗

PubMed1994

Muscle function after mid-shaft femoral shortening. A prospective study with a two-year follow-up.

We performed isokinetic knee testing to assess thigh muscle function in ten patients (12 legs) before and after mid-shaft femoral shortening averaging 46 mm (27 to 70). Tests were at angular velocities of 60 degrees/sec and 180 degrees/sec, and were performed preoperatively and after 3, 6, 12 and 24 months. Isokinetic tests at two years showed a significant reduction in muscle function in both quadriceps and hamstrings, but recovery of function was significantly better for the hamstrings. There was a linear relationship with correlation of r2 = 0.31 to 0.86 between loss of muscle force at two years and the magnitude of shortening. Long-term loss of muscle force should be expected after a mid-shaft shortening of the femur of more than 10%.

Adolescent↗

PubMed1993

Differential effects of metabolic inhibitors on cellular and mitochondrial uptake of organic cations in rat liver.

The effects of several metabolic inhibitors on the uptake of tri-n-butylmethylammonium (TBuMA) were studied in isolated rat liver mitochondria, isolated rat hepatocytes and isolated perfused rat livers, in order to characterize further the mechanisms for carrier-mediated uptake and cellular accumulation of organic cations in the liver. Treatment of isolated hepatocytes with valinomycin, carbonylcyanide-m-chlorophenyl-hydrazone (CCCP), dinitrophenol, oligomycin or antimycin resulted in a rapid decrease in cellular ATP within 3 min of addition. The initial uptake rate of TBuMA was generally largely affected by these treatments. However, fructose at 10 mM had no effect at all on the uptake rate of the cation whereas cellular ATP was decreased to an extent comparable to that after treatment with the metabolic inhibitors. Consequently it was hypothesized that the metabolic inhibitors affected the initial cellular uptake rate of organic cations due to either altered intracellular sequestration (e.g. mitochondria) or alternatively to direct effects on the plasma membrane rather than by decreasing cellular ATP. Isolated rat mitochondria were shown to take up organic cations very efficiently. Accumulation in this organelle is probably driven by the negative membrane potential as measured by the uptake of the lipophilic cation [3H]tetraphenylphosphonium. Treatment of the isolated mitochondria with various metabolic inhibitors decreased the membrane potential in parallel to the effects on the uptake of TBuMA. Since mitochondria constitute a considerable intracellular volume, they may contribute largely to the storage of the organic cation in the hepatocyte. In isolated perfused livers, preloaded with either TBuMA or tetraphenylphosphonium (TPP+), the addition of valinomycin or CCCP leads to a marked backflux of the cations from the liver into the perfusion medium. This suggests strongly that a large part of the intracellular storage capacity is lost after metabolic inhibitor treatment, probably as the consequence of dissipation of the mitochondrial membrane potential. Since the metabolic inhibitors in contrast to TBuMA uptake did not decrease the initial uptake rate of TPP+ into isolated hepatocytes, it was concluded that mitochondrial uptake (mitochondria are the major storage sites for TPP+) is not an essential determinant of the initial uptake rate in intact hepatocytes.(ABSTRACT TRUNCATED AT 400 WORDS)

Adenosine Triphosphate↗

PubMed1993

Modulators of the protein kinase C system influence biliary excretion of cationic drugs.

To investigate whether hepatobiliary transport of organic cations is under regulatory control, we studied transport of tri-n-butylmethylammonium in the isolated perfused rat liver and in isolated rat hepatocytes. Transport was investigated in the presence of modulators of the protein kinase C and the cyclic AMP second-messenger system. In the isolated perfused rat liver, it was observed that compounds modulating protein kinase C activity clearly affected the biliary excretion process of the cation tri-n-butylmethylammonium. Phorbol 12-myristate 13-acetate, a compound that directly stimulates protein kinase C, elevated the biliary excretion rate of tri-n-butylmethylammonium in a concentration-dependent manner, reaching a twofold increase at 60 nmol/L of the phorbol ester. The inactive derivative 4 alpha-phorbol 12, 13-didecanoate (60 nmol/L) did not show any effect. Vasopressin (48 nmol/L), a receptor-mediated activator of protein kinase C, stimulated the excretion rate of the cation by about 50%. Staurosporin (1 mumol/L), an inhibitor of protein kinase C, clearly decreased the biliary excretion rate of the cation and also blocked its stimulation by phorbol 12-myristate 13-acetate. Neither phorbol 12-myristate 13-acetate nor vasopressin (at concentrations ranging from 10(-9) to 10(-6) mol/L) affected the initial uptake velocity of tri-n-butylmethylammonium in isolated hepatocytes and isolated perfused livers, whereas staurosporin (1 mumol/L) showed only a modest inhibition of the uptake of the cation. It is inferred that the effect of protein kinase C modulators on hepatobiliary transport of organic cations occurs at the level of carrier-mediated transport in the canalicular membrane.(ABSTRACT TRUNCATED AT 250 WORDS)

Alkaloids↗

PubMed1992

A multispecific uptake system for taurocholate, cardiac glycosides and cationic drugs in the liver.

To test the hypothesis of multiplicity in carrier-mediated uptake mechanisms for organic cations in the liver and to study the possible relation with bile acid and cardiac glycoside uptake mechanisms, mutual interaction during uptake of various radiolabeled quaternary amines has been studied in isolated rat hepatocytes. Inhibition patterns at low concentrations (1 microM) of the presumed type I monovalent organic cation tri-n-butylmethylammonium were markedly different from those at relatively high concentrations (25 microM). Both the cardiac glycoside K-strophantoside and the bile acid taurocholate clearly reduced the uptake rate of tri-n-butylmethylammonium at 25 microM whereas these agents completely failed to reduce the uptake at low concentrations of the cation. Subsequently, inhibition of uptake of some multivalent amphipathic organic cations (muscle relaxants) for the type II uptake system was investigated. It was found that the uptake of these muscle relaxants both at tracer concentrations (< 1 microM) and at relatively high concentrations (25 microM) was decreased in the presence of low concentrations of the cardiac glycoside K-strophantoside, while taurocholate only inhibited the uptake at the concentration range > 25 microM of the muscle relaxants. Procainamide ethobromide, a typical type I organic cation, did not affect the uptake either at the low or high concentration range of the muscle relaxants. It is concluded that for each of the type I-like compounds and type II-like compounds tested at least two systems are involved in uptake into hepatocytes: tri-n-butylmethylammonium in a concentration range < or = 1 microM is mainly taken up by the type I uptake system and at concentrations > or = 25 microM also by system(s) that can be inhibited by taurocholate and K-strophantoside. Bulky amphipathic organic (type II) cations at concentrations < 1 microM are also transported by an uptake system that is inhibitable by cardiac glycosides but not by bile salts. At concentrations > 25 microM these compounds are predominantly accommodated by an uptake system that possibly mediates uptake of both cardiac glycosides and bile acids. This concept was supported by the observation that both type II organic cations and bile salts can inhibit ouabain uptake, while type II organic cations as well as the cardiac glycosides reduce taurocholate uptake rate. The present data support the idea that the liver seems to be equipped with a "multispecific" uptake system that transports hydrophobic compounds irrespective of charge, including some type I and type II organic cations at relatively high substrate concentrations.

Androstanols↗

PubMed1992

Bilateral femoral shortening for unaccepted tallness.

We performed bilateral femoral shortening operations on 15 skeletally mature patients (11 women and four men). Their mean height pre-operatively was 193.5 cm and they were shortened by 5 to 9 cm. We used a subtrochanteric Z-osteotomy with an AO condylar plate in 11 patients, and mid-diaphyseal osteotomy with an intramedullary locking nail in four. After an average follow-up of 8.1 years, isokinetic muscle testing showed that muscle strength was reduced bilaterally in five patients. The strength ratio between hamstrings and quadriceps muscles was normal in all those treated by subtrochanteric shortening; in those shortened at the mid-shaft the quadriceps was relatively weaker. The result was rated as excellent by 11 patients, very good by three, and good by one.

Adolescent↗

PubMed1991

Mechanisms for the uptake of cationic drugs by the liver: a study with tributylmethylammonium (TBuMA).

The mechanisms of hepatic organic cation transport were examined in isolated rat hepatocytes, using the model compound [methyl-3H]tributylmethylammonium (TBuMA). [3H]TBuMA is shown to be taken up into rat hepatocytes by two carrier-mediated systems in addition to a nonsaturable process. The transport mechanisms for TBuMA share common features with both the type I and type II carrier systems reported for exogenous organic cations such as procainamide ethobromide and vecuronium, respectively. Only slight effects were seen in the presence of relatively high concentrations of endogenous organic cations such as thiamine, choline and N1-methyl nicotinamide. The total uptake of [3H]TBuMA was neither influenced by an electronegative membrane potential and variations in external and internal pH, nor by the absence of Na+, K+ or Cl- in the incubation medium. The presence of the inorganic anion I- stimulated the uptake of [3H]TBuMA. An improved presentation or binding to the carrier may be involved because symport with the anion could not be demonstrated. Lowering of the temperature produced a significant reduction in the uptake velocity of [3H] TBuMA, whereas metabolic inhibitors such as valinomycin and carbonylcyanide-m-chlorphenylhydrazone reduced the uptake rate by 80 and 90%, respectively, which was correlated with the extent of ATP depletion. It is concluded that the monovalent cationic drug TBuMA can be considered as a mixed type I/type II compound that exhibits an electroneutral and anion-sensitive uptake mechanism, depending on metabolic energy. The uptake mechanism is dissimilar from Na(+)-dependent and H(+)-dependent transport systems that have been described for endogenous cations, such as thiamine, choline and N1-methylnicotinamide.

Animals↗

PubMed1990

Biomechanical factors in the metaphyseal- and diaphyseal-lengthening osteotomy. An experimental and theoretic analysis in the ovine tibia.

A post hoc comparison of the mechanical factors that affected the outcome of experimental metaphyseal- and diaphyseal-lengthening osteotomies in sheep tibiae was performed. The resulting motions between bone segments at the metaphyseal and diaphyseal levels were estimated using measured fixator stiffnesses, postural muscle activity, ground reaction forces, and calculated internal and external loads. Relative displacements of bone segments of up to 2.8 degrees were estimated in postural activities; displacements were up to 4.9 times larger at the metaphyseal than at the diaphyseal osteotomy level. The results suggest that due to these increased motions, mechanically inferior conditions for healing at the metaphyseal-lengthening osteotomy level may counteract any supposedly superior biologic healing potential that the metaphyseal region of the bone may have compared with the diaphyseal region. These results correlate well with the clinical findings of the earlier animal study.

Animals↗

PubMed1989

Limb lengthening by epiphyseal distraction in chondrodystrophic bone: an experimental study in the canine femur.

Epiphyseal distraction of the left distal femur was accomplished in 18 chondrodystrophic dogs (age 19-22 weeks). A distraction rate of 0.5 mm/day was applied by means of a unilateral device. Epiphysiolysis occurred after 4 to 9 days. Lengthening was continued for 3 weeks. The animals were killed at 3 (Group 1; n = 5), 19 (Group 2; n = 10), and 71 (Group 3; n = 3) weeks after the end of distraction to verify the magnitude of elongation at removal of the device (Group 1) and at the time of growth cessation (Groups 2 and 3), and to register possible permanent secondary joint changes (Group 3). The average lengthening of 1.2 cm (12.3%) at removal of the device was reduced to 0.7 cm (6.4%) at cessation of growth. The middiaphyseal diameter of the elongated femur was enlarged after the lengthening procedure in all animals. The average torsional strength of the elongated femur compared with the contralateral control was 83% in Group 1, 98% in Group 2, and 107% in Group 3. Degenerative changes were observed in the knee joints of three animals in each group. A two-way analysis of variance was applied for all data sets to test differences between control and elongated bones and between time periods. The reduction in gained length by retardation of residual growth in the distal femur was significant (p less than 0.05). The difference in external diameter between lengthened and control bones was significant in Groups 1 and 3 (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Achondroplasia↗

PubMed1989

Lengthening osteotomy in the metaphysis and diaphysis. An experimental study in the ovine tibia.

In 20 sheep, aged seven to eight months, a tibial lengthening osteotomy was performed to compare the process of repair of the metaphyseal and diaphyseal regions of the bone. Analogous to clinical lengthening, two frame configurations of a bilateral external fixation device were used to obtain adequate fixation of the bone segments in the metaphyseal and diaphyseal lengthening osteotomies. A daily distraction rate of 1 mm for 4.5 weeks yielded an average length increase of 2.6 cm (12.5%). After death at 4.5 weeks postdistraction, the elongated bones were tested mechanically with the contralateral tibiae as controls. No significant difference in relative torsional strength of the elongated tibiae was found between the two groups. Inferior mechanical stability of the bone segments in metaphyseal compared with diaphyseal lengthening (due to differences in frame rigidity and distribution of muscular moments) influenced healing to such an extent that any superior biologic, osteogenic potential in the metaphyseal bone region was nullified. With the clinical use of two configurations of a given external device necessary for fixation of the bone segments in a metaphyseal or diaphyseal lengthening osteotomy, the empirically accepted idea that metaphyseal healing is superior may not be correct.

Animals↗

PubMed1988

Limb lengthening by low rate epiphyseal distraction. An experimental study in the caprine tibia.

Low-rate epiphyseal distraction of the left proximal tibia using a modified bilateral Hoffmann external fixation device, was accomplished in 14 goats (age 6-7 months). Daily distraction at a rate of 0.5 mm was continued for 5.5 weeks. Epiphysiolysis occurred after 5-9 days. After distraction had been discontinued, the external device was left in situ for fixation for 4 weeks. The animals in group 1 (n = 6), group 2 (n = 3), and group 3 (n = 5) were killed at 4, 16, and 32 weeks, respectively, from the end of the distraction period. The proximal growth plate of the elongated tibia appeared radiolucent at the conclusion of the study but was less distinct and reduced in height as compared with the control leg. The gained length at the end of the distraction period was on the average 2.2 cm (11.9%). This gain in length was reduced with further growth. In group 3, the final gain in length was reduced to half. A reduced cortical thickness of the bone within the area subjected to distractional force was observed. This finding is attributable to stress protection. An interesting observation comparing control and operated tibia was an increase of the cross-sectional diameter of the elongated bone. Both tibiae of all animals were tested mechanically. The torsional strength of the elongated tibiae as compared with controls was on the average 29% in group 1, 79% in group 2, and 95% in group 3. We conclude that leg lengthening by low-rate epiphyseal distraction in the proximal tibia is a justifiable alternative to other lengthening procedures in individuals approaching adolescence. In juveniles, lengthening by epiphyseal distraction may result in reduction in the longitudinal growth.

Animals↗

PubMed1988

Limb lengthening by diaphyseal corticotomy, callus distraction, and dynamic axial fixation. An experimental study in the ovine femur.

Limb lengthening of the left femur was performed in 12 sheep, 7-8 months of age. After weakening of the cortex by drill holes, a controlled fracture was created in the diaphysis. The bone segments were fixed in reduced position using a unilateral external fixation device. The fixator was left in neutral position for 10 days postoperatively when lengthening started. By means of daily distraction at a rate of 1.0 mm once a day for 3 weeks, an average lengthening of 1.9 cm (11.9%) was obtained. Two weeks after distraction had been discontinued, distinct callus bridging of the lengthening zone was confirmed radiographically in all animals. At this time the rigid state of fixation was converted to a system allowing axial compression by loading in half the animals. The other half of the animals served as controls with the fixator remaining unchanged. The external device was left on until 5 weeks after the end of distraction. At this time the animals were killed. Both femora of all animals were tested mechanically in torsion. The average ultimate torsional strength of the elongated femur compared with control was 71% in the group with dynamic axial fixation and 65% in the control group. No significant difference in relative strength of the tested bones in the two groups was found. We conclude that intermittent axial compression by loading during consolidation had no significant effect on the bone-healing process evaluated by radiography and mechanical testing.

Animals↗

PubMed1987

Limb lengthening by epiphyseal distraction. An experimental study in the caprine femur.

Epiphyseal distraction of the left distal femur was accomplished in 10 goats (aged 3-4.5 months). A modified Hoffmann external fixation device was used as a unilateral distraction frame. A distraction rate of 1.5 mm/day was applied for 5.5 weeks. Epiphysiolysis occurred after 3-7 days of distraction. After the lengthening procedure, the growth plate had reduced in height in eight animals on radiographic examination. In two animals the growth plate was fused. Three animals were killed at 4 (Group 1) and 8 (Group 2) weeks and four animals at 16 (Group 3) weeks after the end of the distraction period. The gain in leg length obtained by distraction was reduced owing to growth retardation in the distal femur of the operated limb. The average final lengthening was 24.9, 19.4, and 13.4% in Groups 1, 2, and 3, respectively. Femur and tibia from both sides were tested mechanically in torsion. Only one femur fractured in the elongation area. All but one elongated femur fractured in the area of the diaphysis subjected to distractional force. The torsional strength of the elongated femur compared with control was reduced to approximately 50% in all groups. The corresponding torsional strength of the tibia on the elongated extremity compared with control was reduced to approximately 75% in all groups. The difference in relative strength of femur compared with that of tibia was statistically significant. This finding can be explained by a stress-protective effect on the femur in the distraction area caused by the external device.

Animals↗