Adverse reaction to metal release from a modular metal-on-polyethylene hip prosthesis.

A 70-year-old man with an uncemented metal-on-polyethylene total hip prosthesis underwent revision arthroplasty 33 months later because of pain, swelling and recurrent dislocation. There appeared to be corrosion and metal release from the prosthetic head, resulting in pseudotumour formation and severe local soft-tissue destruction. The corrosion occurred at the junction between the titanium-molybdenum-zirconium-iron taper and the cobalt-chrome-molybdenum head, but the mechanism was unproven.

Estrogen and progesterone treatment: effects on muscarinic M(4) receptor subtype in the rat brain.

We investigated the effect of ovariectomy (OVX) and hormonal treatment for 10 weeks by estradiol and progesterone on muscarinic M(4) receptor subtype in different brain areas of female rats. Moreover, motor activity of OVX and hormone-treated rats was measured by automated open field exploration boxes. Receptor quantification in the hippocampus, frontal cortex, parietal cortex, amygdala and hypothalamus was done by receptor autoradiography using a selective ligand for muscarinic M(4) receptors. Ovariectomy up-regulated M(4) receptors in the dentate gyrus, CA1, CA3, frontal cortex and hypothalamus whereas the estrogen treatment restored M(4) binding to that of the sham group. Progesterone treatment had no effect on the ovariectomy-induced up-regulation of M(4) receptors. Ovariectomy significantly decreased the exploratory activity of the rats compared to the sham group. Estrogen treatment restored the exploratory behavior of the ovariectomized rats to that of the sham group whereas the progesterone-treated rats were less alert to the surrounding when compared to the sham and estrogen supplemented rats. The effect of estrogen on the hippocampal muscarinic M(4) receptor subtype is a novel finding and may have functional significance for cholinergic receptors especially in relation to postmenopausal memory problems and neurodegenerative disease like Alzheimer's disease.

Adjuvant-induced arthritis: IL-1 beta, IL-6 and TNF-alpha are up-regulated in the spinal cord.

Adjuvant-induced arthritis (AIA) is a widely used animal model of human rheumatoid arthritis (RA). We have previously shown that increased neuropeptide expression is observed in the spinal cord of AIA rats. To study the potential role of cytokines in the spinal cord of AIA, we wanted to determine whether there are changes of glial and cytokine expression (IL-1 beta, IL-6, TNF-alpha and IFN-gamma) in the spinal cord of AIA rats. Our data indicated that macroglia and MHC class II immunostaining were enhanced, astrocytes expressing GFAP were increased in number and immunostaining intensity. Using in situ hybridization and immunohistochemical methods, both mRNA and protein levels of IL-1 beta, IL-6 and TNF-alpha were significantly increased in the spinal cord of arthritic rats. Increased cytokine expression was presented in the reactive astrocytes and microglia.

Increased levels of somatostatin in rat ankles with adjuvant arthritis.

Levels of somatostatin were investigated in the ankles and spinal cords of rats suffering from acute and chronic adjuvant arthritis. As measured by radioimmunoassay, somatostatin showed significantly higher concentrations only in chronic arthritic ankles. No significant difference was observed in somatostatin levels between the spinal cords of normal and arthritic groups. Using immunohistochemical labeling and electron microscopy, we observed increased somatostatin labeling in the mature bone matrix, monocytes, and polymorphonuclear cells of bone marrow and macrophage-like synovial cells of chronically arthritic rats. Understanding the mechanism(s) which lead to increased somatostatin in chronic arthritic joints may result in more effective treatment methods.

Effects of short- and long-term rat hind limb immobilization on spinal cord insulin-like growth factor-I and its receptor.

In this study we investigated changes in the spinal cord insulin-like growth factor-I peptide (IGF-I) and its receptors (IGF-IR) after hind limb immobilization for 5 days, 2, 4, and 8 weeks. Moreover, effects on IGF-I and nicotinic cholinergic receptors (nAChRs) in two types of skeletal muscle were also investigated. IGF-I levels were measured by radioimmunoassay (RIA) whereas IGF-IR and nAChRs were measured by quantitative receptor autoradiography. Spinal cord IGF-I levels decreased significantly after 5 days, 2 and 4 weeks of immobilization, whereas IGF-IR increased significantly after 4 and 8 weeks compared to controls. In skeletal muscles, nAChRs increased significantly after 5 days and 2 weeks in the soleus (SOL) and tibialis anterior (TIB) muscles, respectively, and continued up to 8 weeks in both muscles. IGF-I concentration decrease significantly after 4 and 8 weeks in the SOL and TIB muscles, respectively. Despite the normal levels of IGF-I in both muscles at the early time points (5 days and 2 weeks), low levels of IGF-I were observed concurrently in the spinal cord ipsilateral to the immobilized limb. Our findings suggest that the early decrease in the IGF-I level and the late upregulation in the IGF-IR in the spinal cord might represent a nervous system response to disuse.

Changes in tissue levels of growth hormone, insulin-like growth factor-I, and somatostatin in the femurs of hind-limb immobilized rats.

Immobilization of an extremity causes skeletal muscle atrophy and a dramatic increase in bone resorption. Growth hormone (GH) is known to play an important role in bone remodeling mediated in part by local insulin-like growth factor-I (IGF-I). In this study, we investigated changes in the levels of GH and IGF-I peptide in bone extracts from the femur after hind-limb immobilization for 5 days, 2, 4, and 8 weeks. The levels of somatostatin, which interacts with GH, were also measured in the bone extracts. GH levels increased after 8 weeks of hind-limb immobilization whereas the IGF-I concentrations increased after 2 weeks, but returned to control levels at 4 weeks, and decreased after 8 weeks of immobilization. The somatostatin levels in the bone extracts increased only after 8 weeks of hind-limb immobilization. Our findings suggest that, after hind-limb immobilization, changes in the concentrations of GH, IGF-I, and somatostatin in bone may mediate bone resorption either directly or through interaction with other factors.

Intracerebroventricular administration of somatostatin prevents and attenuates adjuvant arthritis.

The effects of somatostatin on the development of adjuvant arthritis induced by Mycobacterium butyricum were studied. Somatostatin was injected into the lateral cerebral ventricle every day for 14 days beginning on the first day of mycobacteria inoculation in the preventive group. In the treatment group, somatostatin was injected from day 17 until day 30 post-mycobacteria inoculation. Arthritis was evaluated by measuring ankle joint circumference and diameter as well as microscopic examination of ankle joint sections. Somatostatin profoundly inhibited the development of adjuvant arthritis and an anti-inflammatory action was observed in the treatment group. These results suggest that somatostatin has a central action that can prevent or attenuate symptoms associated with arthritis.

The uncemented fully textured Lord hip prosthesis: a 10- to 15-year followup study.

One hundred fourteen total hip arthroplasties in 110 patients performed between 1979 and 1983 using the Lord femoral component were analyzed. Nine femoral revisions were performed within 13 years after surgery (two because of infection). Excluding infections there was a 94% 13-year survival according to a Kaplan-Meier analysis. Subsidence was seen in five hips (five patients), but only one needed revision surgery. Seventy-six hips (73 patients) had a radiographic followup of 10 years or more and were analyzed in detail. Changes in cortical thickness, density, and formation of spotwelds continued beyond 5 years after surgery, meaning the remodeling of periprosthetic bone continued beyond that time. Osteolysis on the femoral side was seen in seven hips, always in the proximal part of the femur, apparently as a continuation of the joint space. No remote focal osteolysis was seen. Elderly patients, women, and patients with a pedestal were overrepresented among individuals with many spotwelds. For the clinical outcome the Merle d'Aubigne and Postel score as modified by Charnley was used. Among 69 hips (66 patients) with a mean followup of 153 months 96% (66 hips) had a pain score equal to or greater than 4 and 74% (51 hips) had a score of 5 or 6. The Lord femoral component gave surprisingly good clinical long term results despite the bone remodeling (stress shielding), which in some cases was pronounced. The most obvious disadvantage with this design appears to be the difficulties associated with its removal when indicated.

The effect of ovariectomy and ovarian steroid treatment on growth hormone and insulin-like growth factor-I levels in the rat femur.

Growth hormone (GH) and insulin-like growth factor-I (IGF-I) are known to play an important role in bone metabolism. The regulation of plasma levels of GH and IGF-I by ovarian steroids is well known, however, their effect on local GH and IGF-I is still unclear. In this study, we investigated the effect of ovariectomy and ovarian steroid treatment on the femur GH and IGF-I levels as well as on bone density in the rat. Nine month-old rats were ovariectomized (OVX) or sham-operated (SHAM) and 9 weeks after the surgery they were treated with daily s.c. injections of either 17beta-estradiol (OVX + E), progesterone (OVX + P), or vehicle (OVX + V) for another 10 weeks. GH and IGF-I levels in the femur extracts were measured by specific radioimmunoassay (RIA). Ovariectomy decreased GH and had no effect on IGF-I levels. Estradiol treatment increased femur GH and IGF-I levels compared to SHAM rats. Progesterone restored GH and increased IGF-I levels. Ovariectomy decreased, estrogen restored and progesterone partially restored femur bone density. Our results demonstrate that ovariectomy and ovarian steroids modulate the levels of GH and IGF-I in the bone of aged OVX rats. However, these effects appear to be limited to supraphysiological concentrations of estradiol and progesterone.

Intracerebroventricular met-enkephalin administration modulates adjuvant arthritis.

The purpose of this study was to investigate the anti-inflammatory properties of intracerebroventricular met-enkephalin (met-enk) administration in an animal model of arthritis. Adjuvant arthritis was induced in rats by intradermal inoculation of mycobacterium butyricum and the effects of intraventricular met-enk+thiorphan (enkephalinase inhibitor) were studied. Treatment was initiated either simultaneously with the bacterial inoculation (preventive group) or on post-inoculation day 17 after the appearance of inflammation (treatment group). The degree of inflammation was evaluated by measuring the diameter and the circumference of the ankle joint immediately before the sacrifice (day 31) and by histologic examination of ankle joint sections. The results of this study revealed that combined intraventricular injections of met-enk+thiorphan reduced the arthritic-like inflammation in the preventive group as well as in the treatment group. These findings suggest that centrally applied met-enk+thiorphan may suppress the development adjuvant arthritis as well as the symptoms of manifest arthritis. Thus central met-enk may be involved in both hypothalamic pituitary adrenal axis and immune forms of stress-induced modulation.

Neuromuscular effects of two types of fracture treatment.

Immobilisation causes denervation-like changes in the motor endplates, decreases the content of IGF-I, and increases the number of IGF-I receptors in the spinal cord. In the rat we investigated whether similar changes occur after a fracture of the midshaft of the femur which had been treated by intramedullary fixation with adequate or undersized pins. A more pronounced reduction in muscle wet weight was seen after fixation by undersized pins as well as decreased ash density of the ipsilateral tibia which did not completely return to normal within the 12-week experimental period. The nicotinic cholinergic receptors in the motor endplates of tibialis anterior were increased (p < 0.01) and there was a significant increase (p < 0.02) in IGF-I receptors in the lumbar spinal cord ipsilateral to the fracture after treatment by undersized nails. These changes may be associated with the impaired proprioception, co-ordination and motor activity which are sometimes seen after fractures.

Alteration of spinal cord IGF-I receptors and skeletal muscle IGF-I after hind-limb immobilization in the rat.

The effects of 4 weeks' hind-limb immobilization on the spinal cord insulin-like growth factor-I (IGF-I) receptors and skeletal muscle IGF-I level was investigated in rats. Quantitative receptor autoradiography using [125I]IGF-I as a ligand was performed to measure IGF-I receptors in cryosections from the lumbar region of the spinal cord. IGF-I receptor levels were significantly higher in all spinal cord laminae on the side ipsilateral to the immobilized limb than in the same spinal level of the controls. Using radioimmunoassay (RIA), IGF-I levels were significantly low in the soleus (SOL), but not the tibialis anterior (TIB) muscles, compared to the controls. The enhancement of the spinal cord IGF-I receptors after hind-limb immobilization may constitute part of the nervous system response to disuse.

Neurokinin-A in bone and joint tissues: changes in adjuvant arthritis.

The localization of neurokinin A (NK-A) in the normal ankle joint of rats was investigated by an immunoelectron microscopic technique with specific antisera to NK-A. Immunoreactivity was detected in bone matrix, myelinated nerve fiber in the periosteum, and bone marrow and synovial cells. No immunoreactivity was observed in osteoblasts, osteocytes, and osteoclasts. Using radioimmunoassay (RIA), a detectable concentration of NK-A was observed in the bone marrow, periosteum, cortical bone, and ankle of normal rats. In rats with chronic adjuvant arthritis, induced by intradermal injection of mycobacterium butyricum in paraffin oil into the base of the tail, the concentrations of NK-A using RIA in ankles and spinal cords were found to be significantly increased compared with acute or control rats. There were no significant differences between the latter two. Similarly, increased NK-A labeling was observed using immunoelectron microscopy in bone matrix and bone marrow monocyte cells of the chronic arthritic rats. These findings indicate the existence of as well as a biological role of NK-A in bone and joint tissues.

Prolactin, growth hormone, and IGF-1 in ankles and plasma of adjuvant arthritic rats.

In this study we have investigated the levels of prolactin, growth hormone, and insulin-like growth factor-1 in plasma and in tissue extracts of ankle joints of rats with acute or chronic adjuvant arthritis using enzyme immunoassay (EIA) and radioimmunoassay (RIA). We found a stable content of prolactin in plasma of the different groups but a significantly increased concentration of growth hormone was observed in the plasma of the group with chronic arthritis. Moreover, an increased concentration of insulin-like growth factor-1 was noted in the plasma of the acute group. This evidently had returned to normal levels in the chronic group. In contrast, decreased concentrations of prolactin, growth hormone, and insulin-like growth factor-1 were found in tissue extracts of ankle joints of the group with chronic arthritis. The changes in the levels of these hormones in adjuvant arthritis might suggest that they play a role in the pathogenesis of the disease. Understanding the mechanism(s) of hormonal participation in adjuvant arthritis may open new treatment strategies for rheumatoid arthritis and other inflammatory disorders.

Local plate infections in a rabbit model.

We used 30 New Zealand white rabbits to compare the susceptibility to bacterial challenge of two different orthopaedic implants: a standard-design stainless steel plate, or a PC-FIX titanium plate applied on the right tibia were compared with sham operated animals. Directly after surgery Staphylococcus aureus (10(8)-10(9) colony forming units) were inoculated close to the plate. The infection rate in the group of plated animals was 11/20 (stainless steel plates 6/10, PC-FIX titanium plates 5/10) and in sham operated animals only 1/10. Thus, a foreign body increased the risk for infection (p = 0.02). However, the implant type did not appear to be of major importance when the bacteria were inoculated locally. In experimental haematogenous infections, by contrast, implant design and material are considered to be important. This may either indicate different pathogenic mechanisms in locally and haematogenously induced infections, or simply that the large number of microorganisms in local inoculation 'overload' the normal defence systems.

Material and design in haematogenous implant-associated infections in a rabbit model.

We used 111 rabbits to study the susceptibility to intravenously injected bacteria of conventional stainless steel plates, and titanium plates of either traditional design or of the PC-FIX concept, that is less traumatic to bone. After plating, the animals were given between 1 x 10(8) and 2 x 10(9) colony forming units of Staphylococcus aureus Wood 46 intravenously. Significant differences in infection rates (positive cultures) were found between conventional stainless steel plates (36-67% infected, depending on inoculum size) and titanium PC-FIX plates (6-7% infected). In fact, the infection rate at the PC-FIX plate did not differ from sham operated animals. Since conventionally designed titanium plates had an intermediate infection rate, it appears that design and material both are important for the risk of infection.

met-Enkephalin decreases in adjuvant arthritic ankles.

OBJECTIVE: To study whether met-enkephalin (met-enk) concentration changes in adjuvant arthritic ankles and spinal cords. METHODS: Adjuvant arthritis was induced by intradermal injection of Mycobacterium butyricum in paraffin oil, into the base of rat tail. The levels of met-enk were measured using radioimmunoassay and high performance liquid chromatography electrochemical detection in arthritic ankle and spinal cord of arthritic and control rats. Protein concentration was measured according to Lowry method. RESULTS: We observed a significant decrease of concentration of met-enk in ankle joints of chronic arthritic rats. However, increased concentration of met-enk was obtained in the spinal cord of chronic arthritic rats. CONCLUSION: The significant reduction of met-enk concentration in the arthritic ankle joints indicates a possible role for the endogenous opioid peptide in arthritis.

Somatostatin immunoreactivity in bone and joint tissues.

Using immunoelectron microscopy we have investigated the presence of somatostatin in normal bone and joint tissues. We observed somatostatin labeling in the myelinated nerve fibers of the periosteum, the bone marrow cells and in the mature bone matrix but only slightly in the synovial cells. Quantification of somatostatin in bone tissue by radioimmunoassay showed highest levels in bone marrow followed by periosteum and cortical bone. These findings suggest a role for somatostatin in bone and joint physiology.

Methionine-enkephalin in bone and joint tissues.

Methionine-enkephalin (met-enk), an endogenous opiate, mimics many of the effects of morphine by binding to opiate receptors, thereby eliciting similar cellular and behavioral effects. Using biochemical and immunohistochemical techniques, several peptides have been identified in bone and joint tissues. Here we report, for the first time, the presence as well as concentration of met-enk in bone and joint tissues. Immunohistochemistry using electron and immunofluorescence microscopy showed cellular and neuronal distribution of met-enk in bone and joint tissues. The concentration of met-enk analyzed by high performance liquid chromatography electrochemical detection or radioimmunoassay was high in bone marrow, periosteum, ankle joint tissue, and cortical bone. Analysis by fast atom bombardment mass spectrometry suggested that the recovered fragment was met-enk Administration of met-enk inhibits osteoblast cell growth in culture, which is reversible by naltrexone. In arthritic rats, the concentration of met-enk was significantly decreased in ankle joints compared with controls, suggesting a role for met-enk in the pathophysiology of adjuvant arthritis.

Effect of immobilization on skeletal muscle nicotinic cholinergic receptors in the rat.

The effect of 4 weeks of hind limb immobilization on nicotinic acetylcholinergic receptors (nAChRs) in the neuromuscular junction of the soleus (SOL) and tibialis anterior (TIB) muscles was studied in rats. Quantitative measurements of the receptors was performed using [3H]alpha-bungarotoxin ([3H]alpha-BTx) receptor autoradiography. Junctional and extrajunctional nAChRs were significantly increased in the SOL and TIB after 4 weeks immobilization. However, a significant decrease in fiber cross-sectional area was observed only in the SOL muscle. Remobilization for 4 weeks reversed the changes in cholinergic receptors and muscle fibers but not in bone. Our findings suggested that lack of nerve impulses are of importance for the events that take place after immobilization leading to muscle atrophy and osteoporosis.