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Biomedical subjects

T Moilanen

Publications and source records attributed to T Moilanen.

At least 19 recordsLinked to original sources

Spacer prostheses in two-stage revision of infected knee arthroplasty.

At present, no consensus exists on the best spacer alternative for the management of two-stage exchange arthroplasty of infected knee arthroplasties. In this retrospective study, patient records of 24 patients, who had undergone two-stage revisions in which resterilised prosthetic components were used as spacers, were reviewed. The outcome was compared to that of operations performed during the same period (1993-2003) using cement spacers (n=10). With an average follow-up of 32 months, control of infection was achieved in 26 cases (76%), with good or excellent clinical outcome in 19 cases (56%). Treatment failed and resulted in amputation at the level of the thigh before reimplantation in one case. Three patients did not undergo reimplantation. In four cases (12%) infection relapsed. The reinfection rate did not differ between the two spacer groups. Patients treated with resterilised components had a superior range of motion during the period between the two stages. Operative time was shorter and there was less blood loss in the reimplantation arthroplasty when a prosthetic spacer was used. We consider resterilised prosthetic components a safe and effective alternative to cement spacers in the management of infected knee arthroplasties.

Adult↗

TGFbeta inhibits IL-1 -induced iNOS expression and NO production in immortalized chondrocytes.

OBJECTIVE: The balance between anti-inflammatory (e.g. TGFbeta) and proinflammatory cytokines (e.g. IL-1 and TNFalpha), regulates destructive processes in OA cartilage. IL-1 and TNFalpha enhance nitric oxide (NO) production in OA cartilage through the inducible nitric oxide synthase (iNOS) pathway and NO mediates many of the destructive effects of these cytokines. The aim of the present study was to investigate the effects of TGFbeta on NO production in immortalized H4 chondrocytes exposed to IL-1. RESULTS: IL-1 induced NO production in chondrocytes through nuclear factor kappa B (NF-kappaB) sensitive and dexamethasone insensitive expression of iNOS. TGFbeta inhibited IL-1 -induced iNOS expression and NO production in chondrocytes, but it did not have any effect on iNOS mRNA levels. iNOS protein levels were similar in cells treated with IL-1 or IL-1+TGFbeta when measured after 8 h incubation, whereas when measured after 12 h and 24 h incubations, iNOS protein levels were 50% and 80% lower in cells treated with IL-1+TGFbeta than in cells treated with IL-1 alone. CONCLUSION: TGFbeta suppressed IL-1-induced iNOS expression and NO production in chondrocytes, probably by enhancing iNOS protein degradation. This finding suggests an additional mechanism for TGFbeta to counteract the destructive effects of IL-1 in OA.

Animals↗

Effects of TNFalpha-antagonists on nitric oxide production in human cartilage.

OBJECTIVE: Nitric oxide (NO) produced by cartilage and synovial membrane is implicated in the pathogenesis of osteoarthritis (OA) and rheumatoid arthritis (RA). In inflamed joints NO is synthesized in response to proinflammatory cytokines and it is involved in the joint destruction. The aim of the present study was to investigate the effects of TNFalpha-antagonists infliximab and etanercept on NO production in human cartilage. DESIGN: Cartilage specimen obtained from OA patients undergoing knee replacement surgery were studied for iNOS expression and NO production in organ culture to allow intact chondrocyte-matrix interactions. TNFalpha and soluble TNFalpha receptor release was measured by ELISA. RESULTS: Osteoarthritic cartilage produced NO spontaneously and its production was enhanced by proinflammatory cytokines TNFalpha (tumor necrosis factor alpha), IL-1beta (interleukin-1beta), IL-17 (interleukin-17) and by bacterial lipopolysaccharide (LPS). TNFalpha-antagonists infliximab and etanercept inhibited TNFalpha-induced NO production in a dose dependent manner but they had no effect on IL-1beta-, IL-17- and LPS-stimulated NO synthesis. TNFalpha and soluble TNFalpha receptors (sTNFRI and sTNFRII) were produced by human osteoarthritic cartilage. A neutralizing antibody against soluble TNFRI enhanced spontaneous NO production whereas an antibody against soluble TNFRII had no effect. CONCLUSIONS: TNFalpha-antagonists infliximab and etanercept suppressed TNFalpha-induced NO production. This effect was not seen on IL-1-, IL-17- or LPS-induced NO production suggesting that TNFalpha is not an autacoid mediator in these processes. The studies with neutralizing antibodies against soluble TNFRI suggest that endogenous cartilage-derived TNFalpha-antagonists modulate NO production in osteoarthritic cartilage.

Aged↗

The femoral canal fill of two different cementless stem designs. The accuracy of radiographs compared to computed tomographic scanning.

In 19 cadaver femora we compared the fill of two types of femoral stems (plastic replica) using computed tomographic (CT) scan with a border detecting computer program and conventional radiographs. In the metaphyseal area the fill of the two types was surprisingly similar. In the diaphysis the straight stem filled significantly more than the proximally anatomic and distally over-reamed stem. Using conventional radiographs the fill measures were from 1.2 to 2.1 times higher than the values of CT scan, depending on the method of calculation. When both anteroposterior and lateral views were used, the fill as measured by radiographs correlated well with the fill as measured using CT scan. When conventional radiographs are used for evaluation of the canal fill, the calculation based on hypothetical rectangular areas at each level seemed to provide the most accurate results.

Aged↗

Regulation of the nitric oxide production resulting from the glucocorticoid-insensitive expression of iNOS in human osteoarthritic cartilage.

OBJECTIVE: Nitric oxide (NO) produced by cartilage and synovial membranes is implicated in the pathogenesis of osteoarthritis (OA) and inhibitors of NO synthesis may have indications in the treatment or prevention of joint destruction in OA. Because the signaling mechanisms as well as the NOS isoform involved in induction of NO production in human cartilage remain in many parts unclear, the present study was designed to investigate the regulation of inducible NO synthesis in human intact OA cartilage. METHODS: Cartilage specimens were collected from OA patients undergoing knee replacement surgery and studied for iNOS expression and NO production in organ culture to allow intact chondrocyte-matrix interactions. J774 macrophages were used for comparison as a well-documented source of iNOS. RESULTS: OA cartilage expressed iNOS and produced NO in the absence of exogenous cytokines. Addition of interleukin-1 beta (IL-1 beta), tumor necrosis factor alpha (TNF alpha) or lipopolysaccharide (LPS) into the culture medium enhanced NO production in a dose-and time-dependent manner. Various NOS inhibitors suppressed NO production in the following order of potency: 1400W (novel selective iNOS inhibitor)=L-NIO>L-NMMA>L-NAME. Cycloheximide (an inhibitor of protein synthesis), pyrrolidine dithiocarbamate (PDTC; an NF-kappa B inhibitor) and genistein (an inhibitor of tyrosine protein kinases) inhibited cytokine-induced NO production, while dexamethasone, diaminohydroxypyrimidine (DAHP; an inhibitor of tetrahydrobiopterin synthesis) and PD 98059 (p42/44 MAP kinase inhibitor) had no effect. CONCLUSIONS: The results suggest that NO synthesis in human osteoarthritic cartilage derives from the glucocorticoid-insensitive expression of iNOS. Very similar mechanisms appear to regulate inducible NO synthesis in human osteoarthritic cartilage and J774 macrophages with the exception that dexamethasone inhibited NO production in J774 cells but not in osteoarthritic cartilage.

Analysis of Variance↗

The effects of cementless femoral stem shape and proximal surface texture on 'fit-and-fill' characteristics and on bone remodeling.

We measured the post-operative radiological "fit and fill" of two different femoral stem designs, one with a straight proximally porous-coated (Bi-Metric, n=50) and the other with a proximally anatomic, hydroxyapatite-coated and distally over-reamed stem (ABG, n=26). A comparison was then made between the clinical and radiological 5-year follow-up data of these two series and also of the bone remodeling changes around the stems. The observed differences in "fit and fill" parameters in the metaphyseal region were minute. However, in the diaphyseal bone the straight stem had substantially more cortical contact. The clinical results were excellent for both groups. Subsidence (>2 mm) was more frequent with the anatomical ABG stems, although the ABG stems had better bone ingrowth in the lower metaphyseal area. The present results indicate that the anatomical design may improve the fit and fill of a femoral stem in the metaphysis. On the other hand, a looser fill of the diaphyseal bone made the stems of this type more susceptible to subsidence. The straight stem with tight diaphyseal fit showed excellent stability, but the good bone ingrowth and remodeling around the distal part of the stem indicates stress transfer through this region and increased stress shielding of the proximal metaphyseal femur.

Adult↗

Diversity of proximal femoral medullary canal.

To analyze the endosteal dimensions of the proximal femoral medullary canal, we studied 50 cadaver femora using computed tomography and a border detection method from 20 mm above the lesser trochanter, the osteotomy level, down to the isthmus. We documented the presence of a dense calcar septum in 96% of femora studied. In addition to mediolateral, anteroposterior, and neck-oriented dimensions, we calculated canal flare indices (CFIs) between the osteotomy level and the isthmus and metaphyseal canal flare indices (MCFIs) between the osteotomy level and the level 20 mm below the lesser trochanter midpoint to describe the shape of the endosteal cavity. With respect to the canal opening, the anteroposterior and mediolateral planes parallelled each other over the entire region as indicated by the high correlation (r = .7, P < .001) between the CFIs in these directions. The prediction of one dimension from another was unreliable in the metaphyseal region, where bone ingrowth is supposed to occur in a femoral prosthesis. The MCFI seemed to be the best parameter to distinguish the various types of proximal femoral canal shapes. We have described the variability of the proximal femoral endosteal dimensions in detail and find that the wide variation in the shape and size of the proximal femoral medullary canal means that it is almost impossible to achieve 100% cortical contact with the stem, especially in the metaphysis.

Aged↗

Anteroposterior and rotational movement of femur during knee flexion.

This study was designed to analyze anteroposterior and rotational movement of femoral condyles during knee flexion from 15 degrees to 90 degrees using magnetic resonance imaging. After a pilot study, scans were made in 10 healthy male Japanese volunteers. When centers of the circular profiles of posterior femoral condyles were used as reference points, the medial and lateral femoral condyles displaced posteriorly 1.9 +/- 0.8 mm and 2.3 +/- 0.5 mm, respectively (mean +/- standard error). Duplicate examinations on two separate occasions revealed the accuracy of this procedure was in the range of 1 to 2 mm. These results have confirmed that femoral rollback occurs in the unloaded normal knee during flexion from 15 degrees to 90 degrees, but its magnitude is small (2 mm). The results obtained in this in vivo measurement of anteroposterior movement of the femoral condyles have relevance for total knee replacement design.

Adult↗

Bone scintigraphic appearance of asymptomatic hydroxyapatite-coated hip arthroplasties.

To obtain information about the bone scintigraphic appearance of a hydroxyapatite (HA)-coated proximal femoral implant, this examination was performed on 24 patients with a clinically and radiologically successful femoral implant in hip arthroplasty. The prosthesis had a proximal HA coating for supplementary fixation. The patients' mean age was 50.3 years (range, 28-65 years) at operation. The interval from the operation to the scintigraphy ranged from 6 months to 5.5 years (mean, 2.2 years). Scintigraphy was performed using 99mTc-medronic acid. Quantitative counts were recorded in 4 zones: 3 along the length of the implant (trochanteric region with HA coating, midprosthesis, and distal tip) and 1 below the prosthesis. The results were expressed as ratios using the nonoperated femur as a control value. The results demonstrated that the mean activities in all 4 zones were increased relative to the untreated side. The highest activity was observed in the region around the prosthetic tip, with an elevation of 46% above the control value. This activity showed a significant decline over time. The counts recorded in the trochanteric region, where the implant was coated with HA, were 20% above the control value and similar to those seen in its adjacent noncoated midprosthetic region. In the trochanteric region, however, the activity did not show a decline over the follow-up period.

Adult↗

Associations between diet and the hyperapobetalipoproteinemia phenotype expression in children and young adults: the Cardiovascular Risk in Young Finns Study.

The effect of diet on blood lipids has been under intensive study during recent decades. However, diet in the context of the hyperapobetalipoproteinemia (hyperapoB) phenotype has received less attention. The hyperapoB phenotype is commonly encountered in patients with premature coronary heart disease. It is defined as a combination of an increased concentration of apolipoprotein B (apo B), a normal concentration of LDL cholesterol (LDL-C), and as a result, a low LDL-C/apo B ratio. We studied the associations between diet and blood lipids in a cohort of 534 children and young adults 9 to 24 years old. The ratio of polyunsaturated to saturated fats (P/S ratio) correlated (r=-0.19, P<.001) with the LDL-C/apo B ratio. This association was also found when the model was adjusted with triglycerides (r=-0.24, P<.001). A change in the P/S ratio from 0.10 to 0.60 corresponded to a decrease of 0.12 in the LDL-C/apo B ratio, and in the highest apo B decile, the P/S value was higher in hyperapoB individuals (0.33) than in others (0.28, P=.019). Our results imply that the fatty acid composition of the diet may be one of the environmental factors that influence the hyperapoB phenotype expression.

Adolescent↗

Nitric oxide synthase is expressed in human macrophages during foreign body inflammation.

Although nitric oxide (NO) is a well documented effector molecule in rodent macrophages, its significance in human mononuclear phagocytic cells has been controversial. The foreign body inflammatory reaction around loosened joint replacement implants leads to formation of an osteolytic granulomatous pseudo-synovial membrane rich in activated macrophages. We studied 13 specimens of interface membrane tissue collected from revision surgery of aseptically loosened hip and knee prostheses for the presence of inducible NO synthase (iNOS). The presence of iNOS was demonstrated immunohistochemically in 10 of these specimens. Within the tissue this enzyme was confined to macrophages and vascular endothelial cells. iNOS activity was demonstrated biochemically by measuring the calcium-independent generation of citrulline from L-arginine, and the presence of iNOS mRNA was demonstrated using reverse transcriptase polymerase chain reaction. NO synthesis in the interface tissue may be an important factor in the maintenance of the inflammatory and osteolytic processes.

Adult↗

Endogenous nitric oxide and prostaglandin E2 do not regulate the synthesis of each other in interleukin-1 beta-stimulated rat articular cartilage.

Increased levels of nitric oxide (NO) and prostaglandins (PG) are present in the synovial fluid from patients with rheumatoid arthritis and osteoarthritis. Interleukin-1 beta (IL-1) has been shown to induce the synthesis of both of these mediators. The present work was designed to study the interactions of NO and PGE2 synthesis induced by IL-1 in rat articular cartilage. Incubation of intact cartilage with IL-1 resulted in different dose response curves for NO and PGE2 synthesis. Two inhibitors of nitric oxide synthase N-monomethyl-L-arginine (L-NMMA) and L-N-iminoethylornithine, (L-NIO), abolished the IL-1-induced nitrite production but failed to have any influence on the PGE2 synthesis. Exogenous NO, produced by two chemically different NO-releasing compounds (SIN-1 and GEA 3175) had no effect on PGE2 synthesis in articular cartilage. Dexamethasone and ketoprofen inhibited IL-1 induced PGE2 production, while nitrite synthesis remained unaltered. Acetylsalicylic acid (ASA) reduced PGE2 synthesis and had a slight inhibitory action also on NO production. In conclusion, our results show, that IL-1 induces the synthesis of both PGE2 and NO in articular cartilage but these two inflammatory mediators are not mediating the synthesis of one another.

Animals↗

Hydroxyapatite coating of an acetabular prosthesis. Effect on stability.

We report the radiological and clinical outcome of a press-fit (SLF) acetabular component at two to three years in two groups of patients having primary total hip replacement. In 69 the implant was coated with hydroxyapatite (HA) and in 40 it was uncoated. The stability of the cup was assessed by measurement of proximal migration and change in the angle of inclination. The clinical results in the two groups did not differ significantly, and the mean proximal linear wear was similar in both. Fewer radiolucent lines (RLLs) were seen on the radiographs of cups coated with HA. The mean proximal migration was studied by calculating regression lines for each patient using migration measurements: for the SLF+HA group the mean slope was 0.06 mm/year and for the SLF-HA group 0.20 mm/year (p = 0.22). The change in the angle of inclination during follow-up was also consistently smaller in HA-coated cups. Using regression methods the SLF+HA group had a mean slope of 0.08 degrees/year and the SLF-HA group 0.44 degrees/year and the SLF-HA group 0.44 degrees/year (p = 0.023). Partial HA coating appeared to have no effect on the clinical outcome or on the rate of wear of polyethylene, but there was a trend towards a reduced rate of proximal migration, and a significant reduction in rotational migration and the number of radiolucent lines. This suggests that HA coating enhances the stability of this acetabular component.

Acetabulum↗

Association between serum lipids and apolipoprotein E phenotype is influenced by diet in a population-based sample of free-living children and young adults: the Cardiovascular Risk in Young Finns Study.

Apolipoprotein E (apoE) is a genetic determinant of coronary heart disease and lipid levels in several populations. We studied whether the association of apoE alleles with serum lipids varies with diet in a population of free-living young Finns. One thousand twelve subjects, aged 9-24 years, were studied as a part of the Cardiovascular Risk in Young Finns Study in 1986. Serum lipid concentrations and apoE phenotypes were determined, and the composition of the diet was assessed by the 48-h recall method. The subjects were divided into three groups according to the intake of dietary saturated fatty acids (SAFA, g/1000 kcal) and cholesterol (mg/1000 kcal). Group one (high SAFA-cholesterol group) was formed from subjects belonging to the highest tertiles of both cholesterol and SAFA intakes (n = 175); group two (middle SAFA-cholesterol group) consisted of subjects belonging to the middle respective tertiles (n = 119); and group three (low SAFA-cholesterol group) consisted of subjects belonging to the lowest respective tertiles (n = 192). The statistical significance of the association of serum total cholesterol and low density lipoprotein (LDL) concentration with apoE phenotype increased from the low SAFA-cholesterol group (P = 0.024 for total cholesterol and P = 0.015 for LDL-cholesterol, respectively) to the high SAFA-cholesterol group (P = 0.0022 and P = 0.00073, respectively). The middle SAFA-cholesterol group fell between these two groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Nutritional and genetic contributions to serum cholesterol concentration in a children's follow-up study.

In the Finnish multicentre study of cardiovascular risk in young Finns in 1980, 1983 and 1986, 2429, 2052 and 1841 9 to 18-year-old children and adolescents participated. In 1980, subjects of eastern origin living in the west had, despite their western diet, higher serum cholesterol concentrations than subjects both residing in and originating from the west. In males, eastern origin increased the east/west difference in serum cholesterol concentrations. Between 1980 and 1986 the mean serum total cholesterol of the study cohorts decreased by 5.5% and simultaneously the east/west differences in serum cholesterol concentrations disappeared in boys. The study suggests that genetic background is a separate factor determining serum total cholesterol level, but with declining serum cholesterol concentrations the effect of the genetic factor does not become manifest.

Adolescent↗

Tracking of serum fatty acid composition: a 6-year follow-up study in Finnish youths.

The composition of fatty acids in serum cholesteryl esters was analyzed with gas chromatography in 759 Finnish boys and girls aged 3-18 years in 1980 and again in the same subjects in 1983 and in 1986. The mean percentage of linoleate (18:2 n-6) increased from 50.85% in 1980 to 52.60% in 1986, while there was a decrease in myristate (14:0), palmitate (16:0), and eicosapentaenoate (20:5 n-3). The percentage of oleate (18:1) did not change. The stability (tracking) of cholesteryl ester fatty acid composition was examined by calculating linear correlation coefficients among the percentages of each fatty acid at the three study points. For linoleate, 3- and 6-year tracking correlations were 0.59-0.61 and 0.50, respectively; they were of about the same magnitude for arachidonate (20:4 n-6) and lower for the other fatty acids. Results indicate that the serum cholesteryl ester fatty acid composition has somewhat lower tracking than the total cholesterol concentration. The changes in the mean fatty acid composition of the study population obviously reflect a shift from saturated to unsaturated dietary fats.

Adolescent↗