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End-organ resistance to growth hormone and IGF-I in epiphyseal chondrocytes of rats with chronic renal failure.

We tested the hypothesis that there is direct end-organ resistance to growth hormone (GH) and IGF-I in chronic renal failure (CRF) independent of circulating inhibitors. Male Sprague-Dawley rats underwent 5/6 nephrectomy and were pair-fed with weight matched (100 g) sham operated controls for two weeks. Rats with CRF had significantly higher serum creatinine and blood urea nitrogen (P < 0.01 in both cases) and gained significantly less weight and length (P < 0.01 in both cases) compared with controls. Epiphyseal chondrocytes were grown in 10% fetal calf serum (FCS). Both CRF cells and control cells maintained chondrogenic phenotypes, and showed immunohistochemical staining with antibodies to collagen II and proteoglycan (aggrecan). Distribution of the cell subpopulations according to cell size (by flow cytometry) and alkaline phosphatase activity of CRF and control chondrocyte cultures were not different. Growth responses of CRF chondrocytes were reduced (P < 0.01) compared with control chondrocytes when grown in 10% FCS and 10% normal rat serum. Under serum free conditions, growth responses of CRF chondrocytes were reduced to GH and IGF-I at concentrations of 10, 30 and 100 ng/ml, and to insulin at 100, 300 and 1,000 ng/ml compared with controls cells (P < 0.01). To show that this resistance is specific for the GH/IGF system, growth responses to fibroblast growth factor and transforming growth factor beta 1 were studied and showed no difference between CRF and control cells. Thus, the present study provides direct evidence of specific end-organ resistance to GH, IGF-I in CRF chondrocytes in the absence of circulating factors.

Animals↗

Non union of an epiphyseal fibular fracture in a pediatric patient.

There are few reports on delayed or nonunion in the pediatric ankle fracture. The authors present a case of a nonunion of a mid-epiphyseal fracture of the distal fibula, described as a type 7 pediatric fracture. Both the occurrence of this injury pattern and a nonunion has not been reported in the same patient. Operative reduction of the nonunion resulted in a satisfactory outcome.

Ankle Injuries↗

Juxta-epiphyseal fractures of the base of the proximal phalanx of the fingers in children and adolescents.

A series of 34 juxta-epiphyseal fractures of the base of the proximal phalanx of the fingers of children and adolescents are presented. The pattern of injury appeared identical in all these fractures, with a lateral angulation force separating a small triangular metaphyseal fragment from the base of the phalanx on the side of angulation and the fracture line then continuing through the metaphysis, 1-2 mm distal to the growth plate. Fractures were classified into two types according to the degree of displacement. Type 1 fractures (n=18) were mildly displaced and were all successfully treated with closed reduction and splinting. Type 2 fractures (n=16) were severely displaced and problems with obtaining an adequate reduction and long-term residual deformities were encountered. One patient with a severely displaced fracture required open reduction and Kirschner-wire fixation because of flexor tendon entrapment at the fracture site. Another five cases required Kirschner-wire fixation after closed manipulation in order to maintain the reduction. The remaining 10 patients with Type 2 fractures were treated by closed reduction and splinting, and two patients healed with malunion causing a "pseudo-claw" deformity.

Adolescent↗

[The development of epiphyses in hemophiliac arthropathy of the elbow (author's transl)].

Destructive and reparative changes in haemophiliac arthropathy can be observed particularly well in the elbow, since bleeding occurs usually in childhood during development of the epiphyses. These appear prematurely as a result of florid hemophiliac changes. They are enlarged and their structure is altered. Stress areas show typical impression deformations and in other areas the bone becomes expanded. Extensive deformities are irreversible and usually lead to severe functional impairment. It is, however, of therapeutic importance to evaluate these changes radiologically. The literature contains various special features of hemophiliac arthropathy of the elbow. As early as 1897, two years after the discovery of x-rays, Shaw described enlargement of the head of the radius. Increased depth of the groove of the trochlea, of the incisura radialis ulnae and of the olecranon fossa are regarded as typical. Deformities of the tip of the olecranon and of the coronoid process are also described (De Palma 1956, Jordan 1958, Ahlberg 1965, Weseloh 1973). At the rehabilitation centre for children and adolescents at Neckargemünd, 100 hemophiliacs have been examined systematically. Development of the arthropathy has been followed for a period of five years. Three typical hemophiliac arthropathies of the elbow are described and discussed. Classification is proposed according to a system published in 1980.

Age Factors↗

Isolation and characterization of calcifying matrix vesicles from epiphyseal cartilage.

Matrix vesicles, associated with initial calcification in cartilage, have been isolated from bovine fetal epiphyseal cartilage. Cartilage was digested with collagenase, then partitioned into seven fractions by differential centrifugation. The cellular fractions contained over 80% of the DNA in the digest. The extracellular fraction that contained matrix vesicles, in which apatite crystals were often seen on electron microscopy, also displayed the highest specific activity for alkaline phosphatase, pyrophosphatase, ATPase, and 5'-AMPase (EC 3.1.3.1., 3.6.1.1, 3.6.1.3, and 3.1.3.5, respectively). Most of the acid phosphatase (EC 3.1.3.2) activity, on the other hand, was found in the cellular fractions, indicating that matrix vesicles are quite distinct from lysosomes. This appears to be the first instance of isolation of membrane-bounded extracellular particles from any normal tissue. The matrix vesicles possess enzymes that can increase the local concentration of orthophosphate and thus could lead to the formation of hydroxyapatite. The membrane-bounded matrix vesicles may also provide a mechanism for ATP-dependent transport of calcium or phosphate into the lumen of the vesicles with resultant mineralization.

Animals↗

Identification of chondromodulin I as a novel endothelial cell growth inhibitor. Purification and its localization in the avascular zone of epiphyseal cartilage.

Cartilage is unique among tissues of mesenchymal origin in that it is resistant to vascular invasion due to an intrinsic angiogenic inhibitor. During endochondral bone formation, however, calcified cartilage formed in the center of the cartilaginous bone rudiment allows vascular invasion, which initiates the replacement of cartilage by bone. The transition of cartilage from the angioresistant to the angiogenic status thus plays a key role in bone formation. However, the molecular basis of this phenotypic transition of cartilage has been obscure. We report here purification of an endothelial cell growth inhibitor from a guanidine extract of bovine epiphyseal cartilage. The N-terminal amino acid sequence indicated that the inhibitor was identical to chondromodulin I (ChM-I), a cartilage-specific growth-modulating factor. Purified ChM-I inhibited DNA synthesis and proliferation of vascular endothelial cells as well as tube morphogenesis in vitro. Expression of ChM-I cDNA in COS7 cells indicated that mature ChM-I molecules were secreted from the cells after post-translational modifications and cleavage from the transmembrane precursor at the predicted processing signal. Recombinant ChM-I stimulated DNA synthesis and proteoglycan synthesis of cultured growth plate chondrocytes, but inhibited tube morphogenesis of endothelial cells. In situ hybridization and immunohistochemical studies indicated that ChM-I is specifically expressed in the avascular zone of cartilage in developing bone, but not present in calcifying cartilage. These results suggest a regulatory role of ChM-I in vascular invasion during endochondral bone formation.

Animals↗

Epiphyseal bone-marrow abnormalities and restitution in Legg-Calvé-Perthes disease. Evaluation by MR imaging in 86 cases.

PURPOSE: By means of MR imaging, to determine signal abnormalities in the femoral epiphysis; to determine their location, extent and restitution over time; and to correlate these findings to the Catterall radiological classification. MATERIAL AND METHODS: A total of 247 MR images in 86 patients (101 hips) with Legg-Calvé-Perthes disease were examined. The MR images were taken in the coronal plane, and the images through the center of the femoral head were used for this study. RESULTS: T1-weighted images proved as good as T2-weighted images for the MR evaluation of the extent of the necrosis. In almost every case, the central-cranial part of the epiphysis showed a low initial signal. In Catterall group I, the medial part was never involved. In Catterall III and IV, almost the entire epiphysis showed signal changes. In the period 3-6 years after diagnosis, we still found signal changes in the epiphysis in some hips but there was no correlation with the Catterall classification. After 6 years, the epiphysis showed normal signal intensity in MR imaging. In T1-weighted images, Gd-enhancement occurred in the peripheral regions in the early stages of the disease. The central part of the epiphysis became more enhanced over time and peaked in the period 1-3 years after diagnosis. CONCLUSION: MR is a valuable modality for monitoring changes in the femoral epiphysis. We propose a new classification of the extent and pattern of epiphyseal bone-marrow abnormalities based on the 4 zones most commonly observed in MR imaging.

Bone Marrow↗

Cartilage resorption in the tibial epiphyseal plate of growing rats.

An electron microscopic study of the tibial epiphyseal plates of growing rats reveals that the resorption of unmineralized and mineralized cartilage occurs by two different mechanisms. During resorption the unmineralized transverse cartilaginous walls between chondrocytes are invaded by capillary sprouts. At the resorption zone, numerous cytoplasmic processes derived primarily from the perivascular cells and, to a lesser extent, from the endothelial cells of the sprouts penetrate and appear to lyse the unmineralized transverse cartilaginous walls. Hydrolases released from the degenerating chondrocytes and/or capillary sprouts may also participate in this process. The second resorption mechanism involves the mineralized longitudinal cartilaginous septa. Resorption of these septa is mediated by chondroclasts whose fine structure is identical with that of osteoclasts. The active surface of the chondroclasts has a ruffled border. The surface membrane of the chondroclasts is relatively smooth on either side of the ruffled border and lies in direct apposition with the underlying mineralized cartilage. This observation suggests that the microenvironment in the zone of resorption may be maintained by the neighboring unruffled surfaces of the chondroclasts, which thus seal off and segregate the active portions of these cells.

Animals↗

Lysozyme in epiphyseal cartilage. II. The effect of egg white lysozyme on mouse embryonic femurs in organ cultures.

Embryonic mouse femoral cartilage, like the epiphyseal cartilage of the calf scapula, contains large amounts of lysozyme. The addition of egg white lysozyme to organ cultures of embryonic mouse femurs induces unique alterations in the gross and microscopic morphology of the femurs. The sites of these alterations are precisely related to the natural distribution of lysozyme in calf scapula. If the exogenous lysozyme is withdrawn from the culture, the morphological changes disappear, accompanied by a resumption or derepression of growth. The effect on growth is evident only in 17-day embryos. These observations support the idea that lysozyme has a physiological role in cartilage, perhaps related to a regulatory mechanism in bone formation.

Animals↗

Sulfate incorporation from ascorbate 2-sulfate into chondroitin sulfate by embryonic chick cartilage epiphyses.

Radioactivity was significantly incorporated from ascorbate 2-[35S]sulfate into chondroitin sulfate by embryonic chick cartilage epiphyses. The extent of incorporation was comparable with that from inorganic [35S]sulfate. The radioactive chondroitin sulfate formed from ascorbate 2-[35S]sulfate gave two radioactive disaccharides on chondroitinase-ABC [EC 4.2.2.4] digestion. The incorporation was markedly decreased by inorganic sulfate. The time course of incorporation from ascorbate 2-[35S]sulfate and inorganic [35S]sulfate into chondroitin sulfate and the constituent disaccharides suggest that the incorporation rates from the two radioactive substances are different.

Animals↗

A single stage osteotomy and epiphysiodesis for treatment of moderately displaced femoral capital epiphyses.

Epiphysiodesis and subtrochanteric osteotomy have long been recognized as valuable procedures in the treatment of the patient with a moderately or markedly displaced femoral capital epiphysis. Typically these have been performed individually or sequentially. The operation herein described combines the two in one single-stage procedure. Using a stainless steel Lorenzo Screw, the epiphyseal plate is transfixed and further capital displacement prevented. The subtrochanteric compensatory osteotomy is performed using simple visual clinical guidelines and is held rigidly immobilized with a variable angle sideplate affixed to the Lorenzo Screw. The firm fixation enables one to dispense with plaster immobilization and begin the patient on an early exercise program. Restoration of a more normal range of motion, especially regarding rotation internally, abduction, and flexion is easily obtained. Radiographic correction of varus and posterior tilting are thereby secured.

Adolescent↗

An irreducible juxta-epiphyseal fracture of the proximal phalanx. Report of a case.

The causes of irreducibility of juxta-epiphyseal fractures of the proximal phalanx are illustrated in a patient with button hole rent in the periosteum and extensor hood mechanism causing trapping of the distal fragment. The entrapment, in the manner of a Chinese finger trap, was aggravted by traction on the digit. Open reduction was necessary to reduce the fracture.

Adolescent↗

Fixation of slipped capital femoral epiphyses with unthreaded 2-mm wires.

Twenty chronic and three acute-on-chronic slipped capital femoral epiphyses (SCFEs) were fixed with unthreaded 2-mm wires. Nineteen hips were fixed with three wires, and four with four wires. Postoperatively, patients bore full weight after 6 weeks. There were no pin penetrations or cases of chondrolysis. No femoral heads grew off the wires. Fifteen hips showed no change in the head-shaft angle postoperatively. Of the remaining eight, two improved their head-shaft angles in the anteroposterior (AP) view (6,7 degrees), and five improved in the lateral view (6-13 degrees, average, 11 degrees). Two hips worsened in the AP view (9,10 degrees), and none in the lateral view.

Adolescent↗

Treatment of nonunion of fractures in the epiphyseal-metaphyseal region of long bones.

Twenty-four consecutive patients with fracture nonunion in the metaphyseal-epiphyseal areas of long bones were surgically treated. Average time from injury to treatment of the nonunion was 10 months, and average follow-up time after surgical treatment was 29 months. Eight patients with infected nonunions had initial debridement procedures; three of these patients then had placement of external fixators and bone grafting. The remaining five patients and 13 others were then treated by open reduction and internal fixation alone or with the addition of autogenous cancellous bone grafting. Single or double plates and screws were used. Arthrolysis, joint manipulation, and intensive postsurgical exercises were considered necessary to regain joint function. One patient underwent a hemiarthroplasty, and two others underwent arthrodesis as the initial nonunion treatment. Twenty of the 21 patients not treated by arthrodesis or arthroplasty healed their fractures in an average time of 7 months. Fifty-two percent of the patients achieved good or excellent range of motion (ROM) of the contiguous joint, with 70% of the patients reporting no pain in this joint. These fractures have excellent intrinsic healing capability because they occur in anatomical regions with a normally abundant circulation. We recommend stable fixation, with the need for bone grafting only in defect nonunions, together with intra- and postoperative joint mobilization to obtain a satisfactory functional end result.

Adult↗

Obscure distal femoral epiphyseal injury.

Undisplaced type I epiphyseal fracture of the distal femur in the adolescent athlete may mimic injury to a ligament. Roentgenographic examination with the knee under stress will reveal the diagnosis, thereby avoiding unnecessary arthrotomy and dictating appropriate treatment and follow-up.

Adolescent↗

Outcome of physeal and epiphyseal injuries of the distal tibia with intra-articular involvement.

The authors reviewed 83 physeal and epiphyseal injuries of the distal tibia with intra-articular involvement. The children, aged 11 to 14 years, were treated in the authors' department during 1987 to 1999. Treatment was nonoperative for 72.25% (60/83) and surgical for 27.75% (23/83) according to specific indications. This gives the basis for a classification of these injuries. The main purpose of the study was to investigate the long-term results of these injuries according to a radiologic classification. The parameters considered were the patient's age, the mechanism of injury, and the possibility of growth deformities or functional disorders. They were studied relative to the long-term results, with a follow-up of 2 to 13 years. Regardless of treatment, varus deformity, ranging from 10 to 15 degrees in relation to the normal opposite leg, occurred in four cases. In only one case was there painful limitation of ankle joint movement; in two other children an overgrowth of the medial malleolus was detected, with no functional impairment.

Adolescent↗