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Biomedical subjects

L Carlsson

Publications and source records attributed to L Carlsson.

At least 37 records · Page 2Linked to original sources
PubMed2001

Concave versus posterior-stabilized tibial joint surface in total knee arthroplasty: randomized evaluation of 47 knees.

Forty-seven knees in 43 patients with severe deformities randomly received AMK total knee arthroplasty with concave (C, n = 25) or posterior-stabilized (PS, n = 22) polyethylene insert and with resection of the posterior cruciate ligament. Radiostereometric examinations were done postoperatively and after 3, 12, and 24 months. Two patients (1 C, 1 PS) underwent revision surgery. At the 2-year follow-up, the median absolute rotations of the tibial inserts ranged from 0.13 degrees to 0.26 degrees (C vs PS; P =.1-.7). The maximum total point motion was almost identical in the 2 groups (C, 0.38; PS, 0.39; P =.9). Maximum subsidence, lift-off, and Hospital for Special Surgery scores did not differ (P =.1-.6). Recipients of 20 of 24 knees with concave design and 14 of 19 knees with posterior-stabilized design reported that their knee could be regarded as normal or almost normal. Variations of the configuration of the polyethylene insert did not alter the outcome in the short term.

Aged↗
PubMed2001

Does metal backing improve fixation of tibial component in unicondylar knee arthroplasty? A randomized radiostereometric analysis.

In a prospective, randomized study, patients with medial gonarthrosis stage I to III according to Ahlbäck were allocated to a unicondylar knee arthroplasty (Miller-Galante, Zimmer, Inc., Warsaw, IN) with an all-polyethylene tibial component or metal-backed tibial component of the same design. The purpose of the study was to evaluate if metal backing enhanced tibial component fixation. A total of 45 knees (42 patients; 23 metal-backed components and 22 all-polyethylene components) were examined. We used radiostereometric analysis to measure micromotion of the tibial component over a period of 2 years after surgery. Hospital for Special Surgery score was used for clinical evaluation. We found no statistically significant differences in clinical results or migration of the tibial component over a 2-year follow-up period. These findings do not support better fixation of metal-backed tibial components. Because of these findings, we advocate all-polyethylene tibial components in unicondylar knee arthroplasties because of optimal biomechanical strength at a given height of tibial component, avoiding potential problems of modularity and minimizing the amount of interfaces, at a lower cost.

Aged↗
PubMed2001

Contamination of polyethylene cups with polymethyl methacrylate particles: an experimental study.

The articulating surfaces of 6 ultra-high molecular weight polyethylene cups were exposed to curing polymethyl methacrylate (PMMA) bone-cement and examined with scanning electron microscopy and laser ablation inductively coupled plasma mass spectrometry (LA-ICPMS). Three of the cups were exposed to blood and bone-cement, and the rest were exposed to bone-cement only. After removal of the bone-cement bulk, PMMA particles were found and identified in all 6 cups. The particles were verified by identifying zirconium with energy-dispersive x-ray fluorescence spectroscopy in 5 cups and with LA-ICPMS in 1 cup. The degree of surface contamination was estimated with LA-ICPMS. The number of zirconium-containing particles detected was on average 10 to 20/mm2. PMMA bone-cement left in polyethylene cups during polymerization can contaminate the articulating surface with adherent PMMA particles.

Bone Cements↗
PubMed2001

Common cancer-related symptoms among GP patients. Opportunistic screening in primary health care.

OBJECTIVE: To study the occurrence of symptoms related to the five most common forms of cancer among patients regularly visiting primary care. To estimate the proportion of symptoms needing GP examination, and the number of tumours thus diagnosed. DESIGN: Patients with some form of non-malignant chronic disease received a letter with information about cancer-related symptoms along with an invitation to regular check-up. The letter described the most common symptoms of breast, colorectal, lung, prostate and skin cancers. SETTING: 12 health centres in Kalmar County, Sweden. SUBJECTS: 5200 patients aged over 40 years. RESULTS: One patient in 13 reported cancer-related symptoms to the GP. Women reported more symptoms than men, and almost half of them had had symptoms at previous check-ups. The GP was able to explain 7 out of 10 patients' symptoms directly. When other symptoms were examined, 8 cancers were diagnosed as well as 6 pre-malignant tumours, corresponding to 3 tumour diagnoses per 1000 check-ups. CONCLUSION: While attending regular check-ups, patients may not report symptoms which cause anxiety and sometimes indicate serious diseases. It is possible to widen the perspective and link both primary and secondary prevention of certain cancers to the check-up.

Adult↗
PubMed2001

Effects of fatty acids and growth hormone on liver fatty acid binding protein and PPARalpha in rat liver.

The aim of this study was to investigate the interaction between long-chain fatty acids (LCFA) and growth hormone (GH) in the regulation of liver fatty acid binding protein (LFABP) and peroxisome proliferator-activated receptor-alpha (PPARalpha). Cultured rat hepatocytes were given oleic acid (OA; 500 microM) and GH (100 ng/ml) for 3 days. LFABP mRNA increased 3.6-fold by GH and 5.7-fold by OA, and combined incubation with GH and OA increased LFABP mRNA 17.6-fold. PPARalpha mRNA was decreased 50% by GH, but OA had no effect. Hypophysectomized (Hx) female rats were treated with L-thyroxine, cortisol, GH, and dietary fat for 7 days. PPARalpha mRNA levels were three- to fourfold higher in Hx than in normal female rats. GH decreased PPARalpha mRNA 50% in Hx rats. Dietary triglycerides (10% corn oil) increased LFABP mRNA and cytosolic LFABP about twofold but had no effect on PPARalpha mRNA in Hx rats. GH and dietary triglycerides had an additive effect on LFABP expression. Dietary triglycerides increased mitochondrial hydroxymethylglutaryl-CoA synthase mRNA only in the presence of GH. The diet increased serum triglycerides in Hx rats, and GH treatment prevented this increase. Addition of cholesterol to the diet did not influence LFABP levels but mitigated increased hepatic triglyceride content. In summary, these studies show that GH regulates LFABP expression independently of PPARalpha. Moreover, GH has different effects on PPARalpha-responsive genes and does not counteract the effect of LCFA on the expression of these gene products.

Animals↗
PubMed2001

Female gender does not influence the magnitude of ibutilide-induced repolarization delay and incidence of torsades de pointes in an in vivo rabbit model of the acquired long QT syndrome.

BACKGROUND: Clinical and experimental in vitro observations indicate that female gender is associated with a higher risk of developing torsades de pointes with repolarizing-delaying agents. The present study addressed the question of gender difference in the susceptibility towards developing torsades de pointes in a rabbit model of the acquired long QT syndrome in vivo. METHODS AND RESULTS: Female (F, n = 40) or male (M, n = 40) NZW rabbits, characterized as young (Y, n = 20) or adult (A, n = 20) were anesthetized with alpha-chloralose and sensitized to developing torsades de pointes by a continuous infusion of methoxamine. The class III antiarrhythmic agent ibutilide was subsequently infused at a rate of 8 nmol/kg/min for 30 minutes maximum. Before commencement of drug infusion, no gender-related differences in the QT interval were observed (121 +/- 1.9 msec and 126 +/- 3.3 msec in FA and in MA and 116 +/- 1.6 msec and 113 +/- 1.7 msec in the FY and MY, respectively). Infusion of ibutilide was associated with a rapid and marked increase in the QT interval, which did not differ significantly between the groups. Hence, the maximal QT lengthening observed was 39 +/- 3.1% in FA, 46 +/- 5.7% in MA, 38 +/- 3.9% in FY and 36 +/- 3.4% in MY, respectively (p > 0.05 between gender). In the adults, the incidence of torsades de pointes in F was 70% and in M 90% (p = 0.235), whereas in the young, the incidence in F was 45% and in M 70% (p = 0.200). The cumulative doses of ibutilide causing torsades de pointes were not statistically significantly different between the four groups of rabbits (70 +/- 15.5 nmol/kg in FA, 50 +/- 5.3 nmol/kg in MA, 59 +/- 17.2 nmol/kg in FY and 61 +/- 15.9 nmol/kg in MY, respectively). CONCLUSIONS: In this in vivo rabbit model of the acquired long QT syndrome, female gender was not associated with a longer repolarization time (QT interval), an excessive change in the baseline QT interval or a higher incidence of torsades de pointes in response to ibutilide challenge.

Age Factors↗
PubMed2001

The response of molecular isoforms of growth hormone to acute exercise in trained adult males.

Circulating GH consists of multiple molecular isoforms, all derived from the one gene in nonpregnant humans. To assess the effect of a potent stimulus to pituitary secretion on GH isoforms, we studied 17 aerobically trained males (age, 26.9 +/- 1.5 yr) in a randomized, repeat measures study of rest vs. exercise. Exercise consisted of continuous cycle ergometry at approximately 80% of predetermined maximal oxygen uptake for 20 min. Serum was assayed for total, pituitary, 22-kDa, recombinant, non-22-kDa, 20-kDa, and immunofunctional GH. All isoforms increased during, peaked at the end, and declined after exercise. At peak exercise, 22-kDa GH was the predominant isoform. After exercise, the ratios of non-22 kDa/total GH and 20-kDa GH/total GH increased and those of recombinant/pituitary GH decreased. The disappearance half-times for pituitary GH and 20-kDa GH were significantly longer than those for all other isoforms. We conclude that 1) all molecular isoforms of GH measured increased with and peaked at the end of acute exercise, with 22-kDa GH constituting the major isoform in serum during exercise; and 2) the proportion of non-22-kDa isoforms increased after exercise due in part to slower disappearance rates of 20-kDa and perhaps other non-22-kDa GH isoforms. It remains to be determined whether the various biological actions of different GH isoforms impact on postexercise homeostasis.

Adult↗
PubMed2001

Changes in non-22-kilodalton (kDa) isoforms of growth hormone (GH) after administration of 22-kDa recombinant human GH in trained adult males.

GH is being used by elite athletes to enhance sporting performance. To examine the hypothesis that exogenous 22-kDa recombinant human GH (rhGH) administration could be detected through suppression of non-22-kDa isoforms of GH, we studied seventeen aerobically trained males (age, 26.9 +/- 1.5 yr) randomized to rhGH or placebo treatment (0.15 IU/kg/day for 1 week). Subjects were studied at rest and in response to exercise (cycle-ergometry at 65% of maximal work capacity for 20 min). Serum was assayed for total GH (Pharmacia IRMA and pituitary GH), 22-kDa GH (2 different 2-site monoclonal immunoassays), non-22-kDa GH (22-kDa GH-exclusion assay), 20-kDa GH, and immunofunctional GH. In the study, 3 h after the last dose of rhGH, total and 22-kDa GH concentrations were elevated, reflecting exogenous 22-kDa GH. Non-22-kDa and 20-kDa GH levels were suppressed. Regression of non-22-kDa or 20-kDa GH against total or 22-kDa GH produced clear separation of treatment groups. In identical exercise studies repeated between 24 and 96 h after cessation of treatment, the magnitude of the responses of all GH isoforms was suppressed (P < 0.01), but the relative proportions were similar to those before treatment. We conclude: 1) supraphysiological doses of rhGH in trained adult males suppressed exercise-stimulated endogenous circulating isoforms of GH for up to 4 days; 2) the clearest separation of treatment groups required the simultaneous presence of high exogenous 22-kDa GH and suppressed 20-kDa or non-22-kDa GH concentrations; and 3) these methods may prove useful in detecting rhGH abuse in athletes.

Adult↗
PubMed2001

Leptin levels show diurnal variation throughout puberty in healthy children, and follow a gender-specific pattern.

OBJECTIVE: To investigate the levels and diurnal rhythm of serum leptin in healthy children, and to investigate the association between leptin levels and sex steroids. METHODS: Four girls and four boys, all healthy volunteers, were followed longitudinally throughout puberty. Their chronological ages ranged from 8.7 to 19.5 years, and body composition, expressed as weight-for-height standard deviation scores (SDS), ranged between -1.7 and +2.4. Serum leptin, oestradiol and testosterone concentrations were measured by radioimmunoassay at 1000, 1400, 1800, 2200, 0200 and 0600 h. RESULTS: In all girls and boys, both prepubertally and during pubertal development, serum leptin levels increased during the night, with no difference in relative peak amplitude. In boys, the leptin concentrations increased until the initiation of puberty and then declined, whereas in girls, the concentrations increased throughout puberty. The inter-individual variation in mean leptin levels among girls decreased to 11% at the time of menarche. A positive correlation was found for both oestradiol and testosterone versus leptin in girls throughout puberty (r=0.64 and r=0.71 respectively, P<0.001). A negative correlation was found between leptin and testosterone in boys in mid- and late puberty (r=-0.66, P<0.01). No correlation was found between oestradiol and leptin in boys or between testosterone and leptin in pre- and early pubertal boys. CONCLUSION: Serum leptin concentrations show diurnal variation throughout pubertal development in both girls and boys. The changes in leptin levels during puberty follow a gender-specific pattern, probably due to an influence of sex steroids on leptin production.

Adolescent↗
PubMed2001

Autoantibodies to prostasomes as new markers for prostate cancer.

Prostate cancer is one of the leading causes of cancer-related death among men. Given the varying clinical course and the long natural history of the disease, it is important to have good diagnostic and prognostic markers. Prostate specific antigen (PSA) is currently the best marker for the detection of prostate cancer, but in many cases it does not reveal whether metastases have appeared. Since metastases of prostate cancer release prostasomes, which are immunogenic secretory granules of both normal and neoplastic prostate cells, we checked whether anti-prostasome antibodies will appear when the cancer is metastasing. In a pilot study, all 13 patients with serum PSA between 50-500 microg/L had anti-prostasome antibodies, while 39 healthy controls with low PSA values showed background values. There was no overlapping, i.e. the upper range value of controls did not reach the lower range value of patients.

Autoantibodies↗
PubMed2000

Antibacterial activity of human prostasomes.

BACKGROUND: Prostasomes are prostate-derived organelles in semen exhibiting pluripotent properties. The present study deals with their possible antibacterial effects. METHODS: Antibacterial activity was assessed by growth inhibition of bacteria in an incubation medium containing prostasomes, after which the incubate was inoculated on cystine lactose electrolyte deficient agar (CLED) plates. In cases involving Bacillus megaterium, the effects were also documented ultrastructurally with scanning electron microscopy and atomic force microscopy. RESULTS: A dose-dependent growth inhibition was apparent, and a complete inhibition of growth was seen at a prostasome protein concentration of 30 microg/ml with Bacillus megaterium. Ultrastructurally, increasingly irregular contours and a loosening of the smooth surface were observed, combined with a fragmentation of the bacteria. Among 9 other bacterial strains tested, a complete growth inhibition by prostasomes was attained in 3 strains, while the other 6 were unaffected. CONCLUSIONS: Our data suggest that prostasomes, or prostasome-derived proteins, are responsible for the antibacterial effects on Bacillus megaterium and some other bacterial strains. The results may serve as a basis of development of a new class of antibacterial drugs.

Bacillus megaterium↗
PubMed2000

In vivo kinematics of total knee arthroplasty: flat compared with concave tibial joint surface.

This study evaluated the influence of the geometric configuration of the tibial joint area on the kinematics of the knee. Twenty-two patients with noninflammatory arthritis and minor preoperative deformity were studied. They each received an AMK total knee replacement with retention of the posterior cruciate ligament. Eleven patients without any knee abnormalities were used as controls. The patients were stratified to either the flat (terminology of the manufacturer: standard) or concave (terminology of the manufacturer: constrained) polyethylene insert (n = 11 in each group). Knee kinematics were assessed 1 year after the operation by having the patient ascend a platform corresponding to an extension of the knee from 50 to 70 degrees of flexion. During this motion, two film-exchangers simultaneously exposed six to 13 pairs of serial stereoradiographs. The concave geometric configuration of the tibial insert resulted paradoxically in increased anterior-posterior translations compared with the flat insert but no significant change of rotations and translations in the other directions. Compared with normal knees, the most obvious abnormality was increased anterior-posterior translations (p < 0.004). At 50 degrees of flexion, the implants with the flat tibial polyethylene insert had displaced 2 times and the concave ones had displaced 2.5 times more posteriorly than the normal knees (p < or = 0.001). Less internal tibial rotation was also recorded in the flexed positions for both types of inserts compared with the normal knees (p < 0.02). Four knees in four patients, who reported symptoms of instability and abnormal knee function, showed significantly increased proximal displacement of the center of the tibial plateau in the flexed position. The findings suggest that current prosthetic designs and surgical technique do not restore normal knee kinematics and indicate that design improvements should rely on in vivo kinematic studies.

Aged↗
PubMed2000

Differences in the distribution of synemin, paranemin, and plectin in skeletal muscles of wild-type and desmin knock-out mice.

Mice lacking the gene encoding for the intermediate filament protein desmin have a surprisingly normal myofibrillar organization in skeletal muscle fibers, although myopathy develops in highly used muscles. In the present study we examined how synemin, paranemin, and plectin, three key cytoskeletal proteins related to desmin, are organized in normal and desmin knock-out (K/O) mice. We show that in wild-type mice, synemin, paranemin, and plectin were colocalized with desmin in Z-disc-associated striations and at the sarcolemma. All three proteins were also present at the myotendinous junctions and in the postsynaptic area of motor endplates. In the desmin K/O mice the distribution of plectin was unaffected, whereas synemin and paranemin were partly affected. The Z-disc-associated striations were in general no longer present in between the myofibrils. In contrast, at the myotendinous and neuromuscular junctions synemin and paranemin were still present. Our study shows that plectin differs from synemin and paranemin in its binding properties to the myofibrillar Z-discs and that the cytoskeleton in junctional areas is particularly complex in its organization.

Aging↗
PubMed2000

Growth hormone induces CCAAT/enhancer binding protein alpha (C/EBPalpha) in cultured rat hepatocytes.

BACKGROUND/AIMS: The transcription factor CCAAT/enhancer binding protein alpha (C/EBPalpha) is a transactivator of several genes in the liver, which are regulated by growth hormone. METHODS: Growth hormone (100 ng/ml) was added to primary rat hepatocytes cultured on a laminin-rich matrix. C/EBP mRNA and protein levels were measured by RNase protection assay and Western blotting, respectively. DNA binding activity was measured by electrophoretic mobility shift assay (EMSA). RESULTS: Growth hormone treatment for 6 h to 3 days increased C/EBPalpha mRNA levels. Addition of growth hormone for 24 h and 4 days also enhanced the levels of the 42 and 30 kDa isoforms of immunoreactive C/EBPalpha. EMSA showed that addition of growth hormone for 24 h enhanced the abundance of a protein complex binding to a consensus C/EBP binding DNA oligonucleotide. This protein complex was supershifted by antibodies directed against C/EBPalpha but not against C/EBPbeta. There were no consistent effects on C/EBPbeta mRNA or protein at any timepoint. The growth hormone effect on C/EBPalpha expression was not affected by simultaneous incubation with insulin or glucocorticoids, two hormones that previously have been reported to affect C/EBPs. CONCLUSIONS: Growth hormone enhances the levels of C/EBPalpha mRNA and protein as well as the DNA binding activity of C/EBPalpha in cultured rat hepatocytes.

Animals↗
PubMed2000

Tibial component fixation in porous- and hydroxyapatite-coated total knee arthroplasty: a radiostereo metric evaluation of migration and inducible displacement after 5 years.

A total of 51 knees (45 patients) with osteoarthrosis were stratified in a randomized study to receive a hydroxyapatite-coated Freeman-Samuelson (FS HA) or a porous-coated Miller-Galante II (MG II) uncemented total knee arthroplasty. Repeated clinical, radiographic, and radiostereometric analysis (RSA) evaluations of the tibial components were done for 5 years. The clinical outcome was equal at the 5-year follow-up (mean Hospital for Special Surgery score, 93). Standard radiographs displayed more zones around the tibial stem in the MG II group. RSA revealed that the FS HA components migrated less (smaller maximum total point motion and maximum subsidence) after 5 years and showed less inducible displacements at the 1-year follow-up. The stability of the implants obtained is equal to or better than cemented implants after 5 years. Key words: knee prosthesis, cementless, hydroxyapatite, radiostereometry, inducible displacement.

Aged↗
PubMed2000

Lentivirus vector gene expression during ES cell-derived hematopoietic development in vitro.

The murine embryonal stem (ES) cell virus (MESV) can express transgenes from the long terminal repeat (LTR) promoter/enhancer in undifferentiated ES cells, but expression is turned off upon differentiation to embryoid bodies (EBs) and hematopoietic cells in vitro. We examined whether a human immunodeficiency virus type 1-based lentivirus vector pseudotyped with the vesicular stomatitis virus G protein (VSV-G) could transduce ES cells efficiently and express the green fluorescent protein (GFP) transgene from an internal phosphoglycerate kinase (PGK) promoter throughout development to hematopoietic cells in vitro. An oncoretrovirus vector containing the MESV LTR and the GFP gene was used for comparison. Fluorescence-activated cell sorting analysis of transduced CCE ES cells showed 99.8 and 86.7% GPF-expressing ES cells in the VSV-G-pseudotyped lentivirus (multiplicity of infection [MOI] = 59)- and oncoretrovirus (MOI = 590)-transduced cells, respectively. Therefore, VSV-G pseudotyping of lentiviral and oncoretrovirus vectors leads to efficient transduction of ES cells. Lentivirus vector integration was verified in the ES cell colonies by Southern blot analysis. When the transduced ES cells were differentiated in vitro, expression from the oncoretrovirus LTR was severely reduced or extinct in day 6 EBs and ES cell-derived hematopoietic colonies. In contrast, many lentivirus-transduced colonies, expressing the GFP gene in the undifferentiated state, continued to express the transgene throughout in vitro development to EBs at day 6, and many continued to express in cells derived from hematopoietic colonies. This experimental system can be used to analyze lentivirus vector design for optimal expression in hematopoietic cells and for gain-of-function experiments during ES cell development in vitro.

Animals↗
PubMed2000

Direct effects of growth hormone on production and secretion of apolipoprotein B from rat hepatocytes.

The aim of this study was to investigate the direct effects of growth hormone (GH) on production and secretion of apolipoprotein B (apoB)-containing lipoproteins from hepatocytes. Bovine GH (5-500 ng/ml) was given for 1 or 3 days to rat hepatocytes cultured on laminin-rich matrigel in serum-free medium. The effects of GH were compared with those of 3 nM insulin and 500 microM oleic acid. GH increased the editing of apoB mRNA, and the proportion of newly synthesized apoB-48 (of total apoB) in the cells and secreted into the medium changed in parallel. GH increased total secretion of apoB-48 (+30%) and apoB-48 in very low density lipoproteins (VLDL) more than twofold. Total apoB-100 secretion decreased 63%, but apoB-100-VLDL secretion was unaffected by GH. Pulse-chase studies indicated that GH increased intracellular early degradation of apoB-100 but not apoB-48. GH had no effect on apoB mRNA or LDL receptor mRNA levels. The triglyceride synthesis, the mass of triglycerides in the cells, and the VLDL fraction of the medium increased after GH incubation. Three days of insulin incubation had effects similar to those of GH. Combined incubation with oleic acid and GH had additive effects on apoB mRNA editing and apoB-48-VLDL secretion. In summary, GH has direct effects on production and secretion of apoB-containing lipoproteins, which may add to the effects of hyperinsulinemia and increased flux of fatty acids to the liver during GH treatment in vivo.

Animals↗