Biomedical subjects

J Neidel

Publications and source records attributed to J Neidel.

At least 19 recordsLinked to original sources

PubMed2006

Proposal for a histopathological consensus classification of the periprosthetic interface membrane.

AIMS: The introduction of clearly defined histopathological criteria for a standardised evaluation of the periprosthetic membrane, which can appear in cases of total joint arthroplasty revision surgery. METHODS: Based on histomorphological criteria, four types of periprosthetic membrane were defined: wear particle induced type (detection of foreign body particles; macrophages and multinucleated giant cells occupy at least 20% of the area; type I); infectious type (granulation tissue with neutrophilic granulocytes, plasma cells and few, if any, wear particles; type II); combined type (aspects of type I and type II occur simultaneously; type III); and indeterminate type (neither criteria for type I nor type II are fulfilled; type IV). The periprosthetic membranes of 370 patients (217 women, 153 men; mean age 67.6 years, mean period until revision surgery 7.4 years) were analysed according to the defined criteria. RESULTS: Frequency of histopathological membrane types was: type I 54.3%, type II 19.7%, type III 5.4%, type IV 15.4%, and not assessable 5.1%. The mean period between primary arthroplasty and revision surgery was 10.1 years for type I, 3.2 years for type II, 4.5 years for type III and 5.4 years for type IV. The correlation between histopathological and microbiological diagnosis was high (89.7%), and the inter-observer reproducibility sufficient (85%). CONCLUSION: The classification proposed enables standardised typing of periprosthetic membranes and may serve as a tool for further research on the pathogenesis of the loosening of total joint replacement. The study highlights the importance of non-infectious, non-particle induced loosening of prosthetic devices in orthopaedic surgery (membrane type IV), which was observed in 15.4% of patients.

Adult↗

PubMed2004

[Proposal for the classification of the periprosthetic membrane from loosened hip and knee endoprostheses].

After 10 years, loosening of total joint endoprostheses occurs in about 3 to 10 percent of all patients, requiring elaborate revision surgery. A periprosthetic membrane is routinely found between bone and loosened prosthesis. Further histomorphological examination allows determination of the etiology of the loosening process. Aim of this study is the introduction of clearly defined histopathological criteria for a standardized evaluation of the periprosthetic membrane. Based on histomorphological criteria and polarized light microscopy, four types of the periprosthetic membrane were defined: periprosthetic membrane of wear particle type (type I), periprosthetic membrane of infectious type (type II), periprosthetic membrane of combined type (type III), periprosthetic membrane of indifferent type (type IV). Periprosthetic membranes of 268 patients were analyzed according to the defined criteria. The correlation between histopathological and microbiological diagnosis was high (89%, p<0,001), the inter-observer reproducibility was sufficient (95%). This classification system enables a standardized diagnostic procedure and therefore is a basis for further studies concerning the etiology of and pathogenesis of prosthesis loosening.

Arthroplasty, Replacement, Hip↗

PubMed2003

Receptor activator of nuclear factor kappaB ligand is expressed in resident and inflammatory cells in aseptic and septic prosthesis loosening.

OBJECTIVE: The pathogenesis of periprosthetic bone loss in aseptic and septic prosthesis loosening is unclear. There is considerable evidence that macrophages and osteoclasts play a key role in focal bone erosion and osteolysis around the prosthesis. RANKL (receptor activator of nuclear factor kappaB ligand) was shown to be a potent osteoclastogenic factor, and to be involved in bone destruction of myeloma and rheumatoid arthritis patients. Osteoprotegerin (OPG) is the natural RANKL inhibitor and may prevent periprosthetic bone loss. METHODS: The presence and distribution of RANKL, its receptor RANK and OPG in the periprosthetic interface of septically (n = 5) and aseptically (n = 6) loosened prostheses was examined by immunohistochemistry and immunoblotting. Additionally, the immunophenotype of the inflammatory infiltrate was determined [CD3, CD68, Ki-67, tartrate-resistant acid posphatase (TRAP)]. RESULTS: Aseptic and septic cases revealed a different histopathologic pattern. However, in all cases RANKL and RANK could be demonstrated in macrophages and giant cells. In addition, RANKL detected by immunoblot analysis proved to have the same molecular weight as a recombinant RANKL used as a control (31 kD and approximately 48 kD). OPG was detected in aseptic loosening, where macrophages showed a strong staining, but multinucleated giant cells were only weakly stained. A weak OPG staining was also observed in septic loosening. CONCLUSION: The pathogenesis of bone loss in septic loosening remains unclear, because the septic membrane bears few macrophages and giant cells, and half of them express OPG. In aseptic loosening, macrophages might not be stimulated by RANKL as a result of OPG expression. But multinucleated giant cells may be activated, as they hardly express OPG. They might be responsible for periprosthetic bone loss in aseptic loosening as a result of their RANKL and RANK expression.

Aged↗

PubMed2002

[Intra-articular steroid therapy for inflammatory rheumatic diseases in children and adolescents].

In addition to systemic medication,physiotherapy, and operative measures, intraarticular therapy with corticosteroids (iaST) is a well established treatment for juvenile idiopathic arthritis (JIA). IaST is indicated in children whose inflamed joints do not respond sufficiently to systemic antiarthritic drugs and is normally carried out under in-patient conditions. Triamcinolone hexacetonide (TH) is the drug of choice for iaST because of its well documented, long-lasting effects. In younger children or those who require simultaneous injections into multiple joints, a short general anesthesia is useful, while single injections in older children can be administered after topical application of a local anesthetic. Intensive physiotherapy after iaST is important for regaining mobility lost due to the arthritis, and 2 or 3 days of post-injection rest should be adhered to after iaST of joints of the lower extremities. Several studies demonstrate long-lasting remission in the majority of the injected joints in JIA patients, with good pain-relief, improved mobility, and a significant delay in further joint destruction in comparison with joints in which the synovitis could not be adequately controlled. Various sub-types of JIA have been shown to respond differently to iaST. Intraarticular steroids can also be used to treat coxitis, since recent data failed to show a subsequent increase in the rate of femoral head necrosis. Septic arthritis, the most feared complication after iaTH, seems to be extremely rare in children. Other complications, like periarticular calcifications or subcutaneous atrophy, also occur only rarely, provided the steroid is injected correctly. The present data indicate that iaST is an effective and safe treatment for JIA. The therapeutic approach to children with JIA is multidisciplinary, and these young patients should be treated in specialised centres.

Adolescent↗

PubMed2002

Grading of chronic synovitis--a histopathological grading system for molecular and diagnostic pathology.

The following is a proposition for a simple histopathological classification system to measure inflammation in synovial tissue. This synovitis-score is employed in conventionally stained routine sections, and is applicable to every kind of synovitis, irrespective of etiology and including the following relevant morphological alterations. First: hyperplasia/enlargement of synovial lining cell layer. Second: activation of resident cells/synovial stroma. Third: inflammatory infiltration. All defined histopathological qualities are graded from absent (0), slight (1) and moderate (2) to strong (3), with summaries ranging from 0 to 9. 0 to 1 corresponds to no synovitis (inflammatory grade = 0), 2 to 3 to a slight synovitis (inflammatory grade 1), 4 to 6 to a moderate synovitis (inflammatory grade 2), and 7 to 9 to a strong synovitis (inflammatory grade 3). Using this score, we analyzed 308 random specimens of synovial tissue from degenerative (osteoarthritis (OA)) and inflammatory joint diseases - reactive arthritis (ReA), psoriasis arthritis (PA) and rheumatoid arthritis (RA) - as well as synovial tissue from healthy individuals. The mean grade given to synovitis of RA turned out to be significantly higher than the mean grade of OA (p < 0.0005) and of healthy controls (p < 0.0005). On the contrary, no significant differences could be found between the mean grades of synovitis scores from patients with RA and those with PA and ReA. Another comparison between RA-synovitis types I and II according to the Stiehl classification resulted in type I (p < 0.0005), showing significantly higher values of inflammatory infiltration, and type II (p = 0.037), showing significantly higher values of stroma activation. Since in OA, synovitis is regarded as a result of degenerative cartilage destruction whereas in inflammatory joint diseases (RA, PA, ReA), synovitis is regarded to be the cause of cartilage destruction, it can be concluded that scores with considerable high values indicate the pathogenetic potential of synovitis and that the inflammatory score may be helpful in estimating the destructive potential of synovitis at the same time. Furthermore, the comparison of the score data with the Stiehl RA-synovitis types shows that the score enables us to discriminate the morphological peculiarities of the synovitis types. In experimental pathology, it could provide standardized information on molecular synovial tissue analyses where a correlation of molecular with morphological data is essential. In diagnostic pathology, this synovitis score (in combination with other typing systems) could provide basic and standardized information concerning the degree of inflammatory alterations in synovial tissue.

Arthritis↗

PubMed2000

[Value of synovial analysis for prognosis of matrix synthesis of transplanted chondrocytes].

Successful transplantation of autologous chondrocytes for repair of articular cartilage defects requires an undisturbed matrix-synthesis of the transplanted cells. This, in turn, is dependent on the composition of the synovial fluid (SF) of the respective joint. We addressed the question whether analysis of a patient's SF can predict the rate of matrix-synthesis of articular cartilage exposed to this SF in vitro. SF was obtained from 115 patients with disorders of the knee, including gonarthrosis (n = 44), meniscal tears (n = 10), rheumatoid arthritis (n = 53), and reactive arthritides (n = 8). In the SF, the following parameters were determined: Interleukin-1 beta, IL-6, IL-8, IL-1-RA, TNF alpha, Insulin-like growth-factor I (IGF-I), IGF-II, IGF-binding protein-2 (IGFBP-2), IGFBP-3 as well as total proteinase activity and total collagenase activity. To assess the effect of SF on the matrix synthesis of articular chondrocytes, bovine cartilage was incubated in the presence of SF, and the rate of proteoglycan synthesis subsequently determined. In some cases, a monoclonal antibody directed against IGF-I was added. SF from patients with OA or trauma, respectively, stimulated PG-synthesis of bovine cartilage more markedly than did SF from patients with rheumatic arthritides. On the average, 60 percent of the SF-induced increase of cartilage matrix synthesis could be titrated out by an anti-IGF-I-AB. The best predictor for the SF-effects on PG-synthesis of exposed cartilage was the proportion of free IGF-I (r = 0.573, p < 0.001, Spearman rank correlation) followed by the SF-concentrations of IGF-I (with a positive sign), IGFBP-3, IL-1 beta, and TNF alpha (all with a negative sign). According to our data, IGF-I is the most important anabolic factor in human SF with respect to cartilage PG-synthesis. The proportion of free IGF-I seems to be of special importance in this regard. Low SF-levels of free IGF-I could be identified as a possible risk-factor for a sub-optimal protoeglycan synthesis of chondrocytes exposed to this synovial milieu.

Adult↗

PubMed1998

The effects of high-dose methotrexate on the development of cartilage lesions in a lapine model of osteoarthrosis.

To determine whether systemic administration of methotrexate (MTX) can prevent joint destruction in experimental osteoarthrosis (OA) in rabbits, the disorder was induced unilaterally in the knee joints of 40 rabbits by partial medial meniscectomy and sectioning of the medial collateral and both cruciate ligaments. A sham operation (arthrotomy only) was performed in another four animals. Effects on the cartilage of the femoral condyles were studied after 6 and 12 weeks. Twelve weeks after induction, femoral and tibial osteophyte formation was demonstrated on radiographs in all cases. Marked cartilage damage was found histologically (median Mankin score 10 vs 1 for non-operated controls; P < 0.05, Wilcoxon test). Cartilage proteoglycan (GAG) content (dye binding assay) was reduced in operated joints [63 +/- 8 (mean +/- SEM) vs 75 +/- 6 micrograms chondroitin sulfate/mg cartilage wet weight], and the leukocyte count in the joints was elevated (226 +/- 14 vs 7 +/- 3 leukocytes per microliter joint aspirate after injection of 0.5 ml saline solution; both P < 0.05, Wilcoxon test). The rate of GAG synthesis was unchanged (ex vivo labelling with 35S-sulfate). Treatment with MTX (30 mg x kg body weight-1 x week-1 i.m., starting 12 h postoperatively) reduced cartilage damage (median Mankin score 8 vs 10 for placebo, P < 0.05, Mann-Whitney U-test), but had no significant effect on the other parameters tested. No significant MTX effects were observed on cartilage from nonoperated joints. Our data indicate that MTX may have a limited therapeutic effect in experimental OA in the rabbit.

Animals↗

PubMed1998

Effects of methotrexate on normal articular cartilage in vitro and in vivo.

OBJECTIVE: Methotrexate (MTX) has become the disease modifying drug of choice for the treatment of rheumatoid arthritis (RA). Direct effects of MTX on articular cartilage in vivo and in vitro were studied to determine possible adverse effects of the drug. METHODS: For in vitro experiments, adult bovine articular cartilage explants were cultured in the presence of MTX (0 to 100 microM), and effects on DNA and matrix metabolism were studied. For in vivo studies, 48 adult female rabbits were treated with MTX (30 mg/kg/week intramuscularly) or placebo, respectively, for up to 12 weeks, and effects on the cartilage of the femoral condyles were assessed. RESULTS: In vitro, MTX dose dependently increased the uptake of [3H]-thymidine, and decreased incorporation of [3H]-d-uridine into chondrocytes with a half maximal effect at 0.03 microM, suggesting inhibition of thymidylate-synthetase activity by the drug. MTX also dose dependently reduced the proportion of chondrocytes in S-phase, as determined by flow cytometry. MTX did not affect LDH release from chondrocytes or the proportion of viable cells, nor did it change the rate of protein synthesis, proteoglycan synthesis, proteoglycan breakdown, or the hydrodynamic size of newly synthesised proteoglycans. In vivo, MTX did not appreciably affect proteoglycan synthesis of the chondrocytes, proteoglycan content of the cartilage matrix, density of the chondrocyte population, or histological integrity of the cartilage. CONCLUSIONS: The data suggest the absence of major adverse effects by MTX on articular cartilage proteoglycan metabolism. Chondrocyte DNA metabolism seems to be changed by MTX only in concentrations and exposition periods clearly exceeding those found in synovial fluid of RA patients receiving the commonly prescribed doses of the drug.

Animals↗

PubMed1998

The treatment of severe hyponatremia.

Severe hyponatremia may be chronic (days) or acute (hours), symptomatic or asymptomatic. Severe chronic symptomatic hyponatremia (serum sodium concentration < 110 to 115 mM/liter) occurs most commonly in the syndrome of inappropriate antidiuretic hormone secretion (SIADH). The treatment of this hyponatremia is a challenge to practicing physicians, in part because an overly rapid correction of hyponatremia may cause brain damage. The latter sometimes takes the form of central pontine myelinolysis (CPM). On the basis of available clinical and experimental literature, the rate of correction of this symptomatic hyponatremia should be no more than 0.5 mM per liter per hour, and the initial treatment should be halted once a mildly hyponatremic range of the serum sodium concentration has been reached (approximately 125 to 130 mM/liter). In contrast, severe chronic asymptomatic hyponatremia may be treated sufficiently by a fluid restriction. On the other hand, severe symptomatic acute hyponatremia should be treated promptly and rapidly, using hypertonic saline, to initially reach a mildly hyponatremic level.

Adolescent↗

PubMed1997

Elevated levels of insulin-like growth factor (IGF) binding protein-3 in rheumatoid arthritis synovial fluid inhibit stimulation by IGF-I of articular chondrocyte proteoglycan synthesis.

The objective of this study was to quantify insulin-like growth factor (IGF) binding proteins (IGFBPs) in the synovial fluid (SF) and plasma of patients with rheumatic diseases and to study the role of these proteins in the regulation of cartilage proteoglycan (PG) synthesis. Immunological determination of IGFBP-2, IGFBP-3, IGF-I, IGF-II, interleukin-1 beta (IL-1 beta) and tumour necrosis factor alpha (TNF alpha) was undertaken in the SF and plasma of 115 patients with rheumatoid arthritis (RA; n = 53), osteoarthritis (OA; n = 44) and other rheumatic disorders. We also determined the effects of SF on bovine cartilage PG synthesis in culture. IGFBP-2 and IGFBP-3 were elevated in the plasma (by 38% and 28%, respectively) and SF (by 56% and 59%, respectively) of patients with RA compared to age- and sex-matched OA controls (determined by RIA and confirmed by Western ligand blot). IGF-I and IGF-II did not differ significantly between the two groups. OA SF, and, to a lesser extent, RA SF stimulated cartilage PG synthesis in culture, and more than 60% of this activity was neutralised by a specific monoclonal anti-IGF-I antibody. Human IGFBP-3 dose-dependently inhibited the stimulation of cartilage PG synthesis effected by SF or human IGF-I. In RA patients, the SF concentration of IGFBP-3 was positively correlated with SF levels of IL-1 beta and TNF alpha, with the serum levels of C-reactive protein and with the erythrocyte sedimentation rate. We concluded that IGF-I is, under the conditions studied, the most important anabolic factor in human SF with respect to articular cartilage PG synthesis. The bioactivity of IGF-I in joints is modulated by IGFBP-3, which is elevated in RA SF compared to OA SF. Elevated IGFBP-3 in RA SF may reduce the availability of IGF-I to articular chondrocytes, thus interfering with cartilage PG synthesis in RA.

Adolescent↗

PubMed1995

Association between degree of bone-erosion and synovial fluid-levels of tumor necrosis factor alpha in the knee-joints of patients with rheumatoid arthritis.

OBJECTIVE: To determine whether concentrations of cytokines and matrix-degrading enzymes in synovial fluid of patients with rheumatoid arthritis or osteoarthritis are associated with the degree of bone-destruction in the same joint. METHODS: Determination of Interleukin-1 alpha, IL-1 beta, IL-1-receptor-antagonist, IL-6, IL-8, tumor necrosis factor alpha (by ELISA), collagenase-activity and caseinase-activity (by substrate-assays) in the SF (knee) of patients with RA (n42) or OA (n35). The degree of bone-destruction was assessed radiographically. RESULTS: SF cytokine- and enzyme-levels were higher in patients with RA than in those with OA. In the RA group, SF-levels of TNF alpha were positively correlated with the degree of bone destruction of the respective joint. No correlation was found between radiographically assessed joint changes and SF-concentrations of other cytokines, enzyme activities, serum CRP, or duration of disease. In the OA-group, none of the examined parameters was associated with the degree of joint destruction. CONCLUSIONS: Our data may support the assumption of TNF alpha playing an important role in joint destruction in RA. Possible alternative conclusions are discussed.

Adult↗

PubMed1994

Insulin-like growth factor I accelerates recovery of articular cartilage proteoglycan synthesis in culture after inhibition by interleukin 1.

Interleukin 1 (IL-1) is a cytokine which induces cartilage proteoglycan (PG) depletion by inhibiting PG synthesis and increasing PG breakdown. Insulin-like growth factor I (IGF-I), in contrast, is known to promote matrix formation. We examined the effects of both mediators in a bovine tissue culture model. IL-1 dose-dependently inhibited PG formation of articular cartilage [half-maximal effect (EC50) at 4 ng/ml], while PG synthesis was increased by IGF-I (EC50 = 15 ng/ml). After inhibition of PG formation with IL-1 for 2 days and subsequent removal of free IL-1, addition of IGF-I dose-dependently accelerated restoration of the original rate of synthesis with a half-maximal effect at 20 ng/ml and a maximal effect at 50 ng/ml. The IGF-I concentration required to elicit a half-maximal effect on cartilage PG synthesis remained constant in the absence or presence of IL-1. We therefore conclude that inhibition of cartilage PG synthesis by IL-1 is not effected by damage to the IGF receptor. Synovial fluid (SF) of 40 patients with rheumatoid arthritis (RA) was found to contain 64 +/- 6 ng IGF-I/ml (mean +/- SEM). The reported effects of IGF-I in vitro therefore occurred at concentrations comparable to those present in joints in vivo. IL-1 beta was detectable (> 0.5 pg/ml) in 38 of 40 RA-SF samples (mean 28 +/- 6 pg/ml).(ABSTRACT TRUNCATED AT 250 WORDS)

Arthritis, Rheumatoid↗

PubMed1993

Independent effects of interleukin 1 on proteoglycan synthesis and proteoglycan breakdown of bovine articular cartilage in vitro.

We studied the effects of human recombinant interleukin-1 beta on proteoglycan metabolism of bovine articular cartilage in organ culture. IL-1 was more potent in inhibiting synthesis (IC50 4 ng/mL) than in stimulating breakdown of proteoglycans (EC50 200 ng/mL). Inhibition of proteoglycan synthesis began to plateau earlier (2 days) than stimulation of proteoglycan release (4 days). Both effects could be neutralized with a polyclonal anti-IL-1 beta antibody; however, higher antibody titers were required to block IL-1 effects on proteoglycan synthesis than to neutralize those on proteoglycan release. Chloroquine, but not hydrocortisone, blocked IL-1-mediated proteoglycan breakdown. Both drugs, however, augmented IL-1-induced inhibition of proteoglycan synthesis. Our data suggest that the effects of IL-1 on articular cartilage proteoglycan synthesis and proteoglycan breakdown can be regulated independently.

Animals↗

PubMed1993

Normal plasma levels of IGF binding protein in Perthes' disease. Follow-up of previous report.

Plasma levels of insulin-like growth factor binding protein-3 (IGFBP-3) were measured in 55 children with Perthes' disease and 55 age- and sex-matched controls. IGFBP-3 values did not differ between the 2 groups and corresponded well to normal values found by others. The IGF I/IGFBP-3 ratio was reduced during the first 2 years of Perthes' disease. Our findings indicate that low levels of circulating IGF I in Perthes' disease, as we have reported previously, are caused neither by altered concentrations of the principal IGF-binding protein, IGFBP-3, nor by an underlying growth hormone deficiency.

Adolescent↗

PubMed1993

[Importance of newly defined epiphyseal version in diagnosis and therapy of epiphysiolysis capitis femoris (additional data to epiphyseal dislocation and epiphyseal torsion)].

The displacement of the femoral epiphysis in epiphyseolysis capitis femoris is usually determined by measuring both the epiphysis-diaphysis angle (ED angle) in the plane of the dislocation and the epiphysis-torsion angle (ET angle) in the torsional plane. In this paper we define an epiphyseal version angle (EV angle) in the sagittal plane of the femur, calculate it trigonometrically and show it in diagrams and tables. The clinical application of the EV angle indicates that in cases of displacement with an ED angle of less than 135 degrees, absolute displacement is better shown than with the ET angle. Additionally, the EV angle improves our comprehension of the 3-D displacement due to the fact that, in the "Lauenstein" x-ray, the femur is increasingly projected more in a sagittal plane with increasing abduction. The essential correction using the Imhäuser-osteotomy is also done in the sagittal plane. The ability of the orthopaedic surgeon to visualize the situation in three dimensions is also improved by this additional standard plane.

Biomechanical Phenomena↗

PubMed1992

No physiologic age-related increase of circulating somatomedin-C during early stage of Perthes' disease: a longitudinal study in 21 boys.

Perthes' disease was originally viewed as a local ischaemic necrosis of the femoral head. Several authors, however, have presented data suggesting that children with this disease also suffer from a general disorder of skeletal maturation. Hormonal changes in the hypothalamus-pituitary-growth plate axis have been discussed as a possible underlying cause and contradictory results reported on the role of the somatomedins in this process. In this report for the first time sequential data are presented on plasma somatomedin-C (Sm-C/insulin-like growth factor I) levels in 21 boys with Perthes' disease. Values were compared with data from 105 control subjects. The physiologic increase with age of plasma Sm-C levels in the control group was either absent or diminished in children with early-stage Perthes' disease (P less than 10(-6), signs test). The Sm-C values in affected children were low. Our data correlate well with reports from others of retarded skeletal maturation in children with Perthes' disease and support the hypothesis of an accompanying disorder of the synthesis or release of Sm-C/IGF-I or its binding proteins.

Aging↗

PubMed1992

Intra-articular injections and articular cartilage metabolism. An experimental study in rabbits.

We studied the effects of repeated intra-articular injections of sterile 140 mM NaCl solution on articular cartilage in adult rabbits. After 20 injections into the knee joints over a period of 4 weeks, chondrocyte glucosaminoglycan synthesis was evenly reduced in all cartilage layers, accompanied by a significant proteoglycan depletion of the matrix which was most marked in the superficial half of the cartilage. These and other changes only partially reversed during a further 4-week period after the injections had been stopped. Our data underline the need for a clear-cut indication for intra-articular injections. The microtrauma caused by injection, in conjunction with the introduction of a carrier solution into the joint, may, at least when repeated at short intervals, lead to measurable damage to the articular cartilage.

Animals↗

PubMed1992

Low plasma levels of insulin-like growth factor I in Perthes' disease. A controlled study of 59 consecutive children.

We studied Insulin-like Growth Factor I (IGF I) plasma levels, standing height, and weight in 59 consecutive children with Perthes' disease and 59 matched controls. The plasma-IGF I levels, measured by radioimmunoassay after acid ethanol extraction, were reduced in affected children during the first 2 years after the diagnosis of Perthes' disease. Partially paralleling the alterations in IGF I plasma levels, there was a tendency towards growth arrest and impaired weight-gain during early-stage disease, followed by catch-up growth and increased weight-gain. No relation was found between degree of femoral head involvement, according to Catterall (1971), and IGF I plasma-levels or body mass. Our data may reflect an impaired synthesis or release of IGF I relative to age in Perthes' disease, or changes in the affinity or metabolism of IGF binding proteins. The observed changes seem to be of a temporary nature.

Adolescent↗