Atypical Presentation of Acute Freiberg Disease.

Freiberg disease is a chronic progressive condition that results in pain and loss of normal function of the metatarsophalangeal joint (MTPJ). We describe a case of acute Freiberg disease secondary to a short course of oral steroids. The patient presented with an acute metatarsal head fracture that was managed successfully with open reduction and internal fixation. Although a rare complication of corticosteroid use, physicians having patients start taking steroids must remember the risk of osteonecrosis.

Differential effect of molecular mass hyaluronan on lipopolysaccharide-induced damage in chondrocytes.

Hyaluronan is a biological polysaccharide that may exist in different degrees of polymerization. Several investigations reported that low molecular mass hyaluronan may have pro-inflammatory activity, while high molecular mass hyaluronan can exert beneficial effects. Starting from these data, the aim of this study was to investigate the effect of hyaluronan of different molecular mass in mouse articular chondrocyte cultures stimulated with lipopolysaccharide (LPS). Inflammation was induced in chondrocytes by acute treatment with 2.0 microg/ml LPS. High levels of tumour necrosis factor (TNF)-alpha, interleukin (IL)-1beta, IL-6, interferon (IFN)-gamma and iNOS gene expression and their related proteins were found in chondrocytes 24 h after treatment with LPS. High concentrations of NO, NF-kappaB activation, IkappaBalpha phosphorylation and apoptosis, evaluated by the increase in caspase-3 expression and its related protein amount were also produced by LPS stimulation. In contrast, LPS reduced aggrecan and collagen type II (Col2A) expression and their protein production. The treatment of chondrocytes with hyaluronan of different molecular mass produced the following effects: (i) low molecular mass hyaluronan exerted a slight inflammatory effect in untreated chondrocytes, while in LPS-treated chondrocytes it enhanced cytokine production and decreased aggrecan and Col2A compared with cells treated with LPS alone; (ii) no effect was exerted on LPS-induced apoptosis and NO production; (iii) medium molecular mass hyaluronan did not exert any inflammatory/anti-inflammatory activity in LPS-untreated/treated cells and failed to reduce apoptosis; and (iv) high molecular mass hyaluronan had no inflammatory effect in LPS-untreated cells while it was able to reduce all the detrimental effects stimulated by LPS treatment. These data confirm the multifactorial role played by hyaluronan and suggest, in particular, that hyaluronan may modulate inflammation during pathologies by its different degrees of polymerization.

The effects of ketorolac and morphine on articular cartilage and synovium in the rabbit knee joint.

Analgesics are commonly injected intra-articularly for analgesia after arthroscopic surgery, especially of knee joints. The aim of this study was to research the effects of ketorolac and morphine on articular cartilage and synovial membrane. This study used rabbit right and left hind knee joints. The treatments, saline, morphine, or ketorolac, were administered intra-articularly 24 h after injection, and 5 joints from animals in each drug group were chosen randomly to form Group I and subgroups of Group I. The same procedures were applied after 48 h and 10 days of injection to form Groups II and III, respectively, and subgroups of these groups. Knee joints were excised and a blinded observer evaluated the histopathology according to inflammation of the articular cartilage, inflammatory cell infiltration, hypertrophy, and hyperplasia of the synovial membrane. No histopathological changes were found in the control groups. In the ketorolac and morphine groups, there were varying degrees of synovial membrane inflammatory cell infiltration and minimal, mild, or moderate synovial membrane cell hyperplasia or hypertrophy. Except for the ketorolac group at 24 h, both ketorolac and morphine groups showed more histopathological changes than controls (p < 0.05). Morphine and ketorolac both cause mild histopathological changes in rabbit knee joints, morphine causing more than ketorolac, but both of the drugs can be used intra-articularly with safety.

Joint preserving surgery for osteonecrosis and osteochondral defects after chemotherapy in childhood.

BACKGROUND: As a complication of chemotherapy/corticosteroids for the treatment of acute lymphoblastic leukemia (ALL) and other malignancies during childhood, avascular osteonecrosis appears in up to 30 % of the patients. Weight-bearing joints are involved in over 90 % of the cases. Total joint replacement is often necessary to restore function. Yet, endoprostheses in young patients again bare the risk of later complications and the need for several revision surgeries. In this report, joint preserving surgical strategies will be discussed. PATIENTS: Three hips and eleven knee joints in 8 patients (4 male, 4 female) were operated on for symptomatic ON and/or osteochondral defects (OCD) after chemotherapy. Four of the patients underwent surgery in more than one joint. The average age at the time of surgery was 18 years (range 14 - 26). The procedures included retrograde drilling (core decompression), bone grafting, implantation of collagen sponges with autologous bone marrow aspirate, osteochondral autograft transplantation and transplantation of periosteal flaps. Two hip joints underwent total joint replacement. Average follow up was 25 months. RESULTS: After an average follow up of 2 years, all patients were satisfied with the functional results after the last follow up with pain free walking for a minimum of 60 minutes. No night pain was reported. One patient complained about intermittent periods of dysaesthesia around the bone harvest area at the iliac crest. CONCLUSIONS: The aim of surgery for ON and OCD after chemotherapy should be the reduction of pain and preservation of the joint to bypass the risks of joint replacement in young patients, although total joint replacement may become indicated in endstage degeneration of the involved joint.

Thoracic complications of illicit drug use: an organ system approach.

Illicit drug use constitutes a major health problem and may be associated with various thoracic complications. These complications vary depending on the specific drug used and the route of administration. Commonly abused drugs that may play a role in causing thoracic disease include cocaine, opiates, and methamphetamine derivatives. Intravenously abused oral medications may contain filler agents that may be responsible for disease. Thoracic complications may be categorized as pulmonary, pleural, mediastinal, cardiovascular, and chest wall complications. Pulmonary complications of drug abuse include pneumonia, cardiogenic edema, acute lung injury, pulmonary hemorrhage, and aspiration pneumonia. Filler agents such as talc may result in panacinar emphysema or high-attenuation upper-lobe conglomerate masses. The primary pleural complication of illicit drug use is pneumothorax. Mediastinal and cardiovascular complications of illicit drug use include pneumomediastinum, cardiomyopathy, myocardial infarction, aortic dissection, and injection-related pseudoaneurysms. Chest wall complications include diskitis and vertebral osteomyelitis, epidural abscess, necrotizing fasciitis, costochondritis, and septic arthritis. Categorization of thoracic complications of illicit drug use may facilitate understanding of these disorders and allow accurate diagnosis.

[Steroid-induced osteonecrosis of femoral condyles and bilateral Freyberg's disease]. / Kortisoninduzierte Osteonekrose der Femurkondylen und Morbus Freyberg beidseits.

We report on a patient with steroid-induced osteonecrosis of the femoral condyles after therapy of an acute lymphatic leukemia. Because of continuing bilateral knee pain, we performed osteochondral autografting of the right femoral condyle in two steps. During the follow-up period, the patient developed bilateral Freyberg's disease, which was also successfully treated by surgery. The MRIs which we performed as a follow-up 3 years later showed complete incorporation and vitality of the transplanted cylinders. No further clinical symptoms occurred.

Detection of collagenase-induced damage of collagen by 9A4, a monoclonal C-terminal neoepitope antibody.

To determine whether the collagen network is compromised by collagenase during acute inflammation, a monoclonal antibody (9A4) was developed with specificity for the C-terminal neoepitope sequence generated by collagenase-cleavage of type II collagen (Gly-Pro-Pro-Gly-Pro-Gln-Gly-COOH). 9A4 was shown to detect the collagen collagenase-cleavage neoepitope with a K = 1.7 x 10(-7) M (type II) and K = 2 x 10(-6) M (type I). It does not recognize uncleaved native or denatured collagen. Articular cartilage from control animals is unstained by 9A4. During acute inflammation elicited in hamsters by intra-articular LPS, positive staining for the 9A4 neoepitope indicated the collagen was damaged. Wheel running exercise was used to apply stress to control cartilage and cartilage from animals with damaged collagen. After 6 months of running, the cartilage from normal animals was unaffected. By contrast, in the group with damaged collagen, the cartilage was fibrillated in all animals and in half of those, the cartilage failed and bony eburnation resulted.

Clinical and pathological changes in the knee after accidental chlorhexidine irrigation during arthroscopy. Case reports and review of the literature.

We describe six knees in five patients, referred to us after accidental irrigation with chlorhexidine 1% in aqueous solution during arthroscopy. All six knees developed persisting pain, swelling and crepitus with loss of range of movement. Radiographs showed loss of joint space in all three compartments due to extensive chondrolysis, with many loose bodies and synovitis. Histological examination showed partial necrosis of the cartilage, with slight non-specific inflammation and fibrosis of synovial specimens. Care is needed in checking irrigation fluids, and these should have a distinctive colour.

Tolerance of growing pigs for dietary vitamin A, with special reference to bone integrity.

Weanling crossbred pigs (144) of 8 kg initial weight were fed to 90 kg on diets containing graded levels of vitamin A representing 0, 1, 5, 10, 50 and 100 times the NRC (1988) estimated requirement. No clinical signs of deficiency or toxicity were recorded although plasma and liver retinol levels were affected by treatment. Histopathological examination indicated a high incidence of lesions in the cartilage of the distal femur and ulna, but they were not related to treatment. There was some evidence that excessive vitamin A levels in the diet significantly reduced the uronic acid concentration in joint cartilage, indicating a reduced concentration of proteoglycans. However no relationship was established between dietary vitamin A level and the incidence of clinical osteochondrosis. The results suggest that the allowable range of vitamin A set out in the Canadian feeds regulations is appropriate for practical pig production.

Osteochondral lesions in developing rats intoxicated with thallium twenty four hours after birth.

An i.p. injection of a solution of thallium acetate in deionized water at a dose of 32 mg/kg, in 24-h-old rats, produces morphological and biochemical alterations in both cartilaginous and osseous tissues. From the beginning, there are alterations in the cartilaginous cell as well as in chrondrine, osteoblasts, osseous tissue and bone marrow. Rats were sacrificed at 24, 48, and 72 h and also at 7 days. Two animals survived for 50 days. One showed total irreversible alopecia while the other one had partial alopecia with discrete recovery. Both showed a low weight and a size of 8 cm. Microscopically, degenerative changes were produced consisting of alteration and death of many cartilaginous cells, uneven metachromasia and the chondrine and decrease of the growth cartilage, scanty bone trabeculae with few osteoblasts. The bone marrow showed few myeloblasts and megakaryocytes. Progressive cellular damage throughout the 50 days of survival represents a response of the thallium ionic accumulation and recycling in cellular mitochondria of all the body's cells. This appeared in our study as irreversible and progressive osteochondral alterations with atrophy of the skin and its adnexa, hyalinization of elastic and collagenous fibers with intense interstitial edema.

Experimental hypophosphataemia in growing pigs: effects on endochondral ossification in comparison to osteochondrosis.

Hypophosphataemia was induced in growing pigs by dietary supplementation with aluminium hydroxide. The effect on endochondral ossification was studied morphologically in comparison with normophosphataemic pigs given aluminium phosphate or left untreated. The aim of the investigation was to elucidate further the role of nutritional factors in the pathogenesis of disturbed endochondral ossification, occurring in osteochondrosis. In all pigs, focal arrestment of endochondral ossification with subsequent cartilage retention in the epiphyseal or metaphyseal growth zones was seen. In normophosphataemic pigs, focal degenerative cartilage changes were associated with impairment of vascular penetration. The lesions had morphological characteristics of early osteochondrosis. In hypophosphataemic pigs, a more generalized disturbance, endochondral ossification, was seen with impaired vascular penetration and excessive deposition of osteoid in the primary spongiosa. Focal cartilage retentions were associated with necrotic changes in the primary spongiosa and not with cartilage degeneration. The lesions were similar to rickets and it was concluded that hypophosphataemia is not an aetiological factor in the development of osteochondrosis. The differentiation between the cartilage retention seen in early stages of osteochondrosis and rickets must be based on histological examination.

Tolerance of weanling pigs for dietary vitamin A and D.

Weanling cross-bred pigs (36 or 48) were caged individually and fed diets containing a supplement of vitamin A (Expt 1) or vitamin D3 (Expt 2) at levels representing 1, 5, 10, 25, 50 and 100 times the NRC (1988) estimated requirements, for 4 weeks. Growth rate, feed intake and feed/gain ratio were not influenced significantly. In Expt 1 the plasma retinol concentrations were at 4 weeks, respectively, 31.7, 39.4, 43.2, 42.9, 44.4, and 46.3 micrograms/dl (P less than 0.05). In Expt 2, the plasma 25(OH)D3 concentrations were at 2 weeks, respectively, 22.5, 29.5, 35.7, 46.2, 79.9, 135.3 ng/ml (P less than 0.001). Histological examination of lung, stomach, kidney, liver and heart indicated no abnormalities, but focal microscopic lesions consistent with osteochondrosis were found in pigs receiving vitamin A at levels over 10 times the requirement. The incidence of osteochondrosis at 2 weeks was, respectively, 0/8, 0/8, 0/8, 0/8, 0/8, and 1/8, and at 4 weeks was, respectively, 0/8, 0/8, 0/8, 2/8, 2/8 and 2/8. The NRC (1988) estimate of the requirement for vitamin D may be somewhat low since the concentration of plasma 25(OH)D was lower with 200 or 1,000 IU vitamin D/kg diet than at the start.

Morphological investigation of osteochondrosis induced by ofloxacin in rats.

Oral doses of 300 or 900 mg/kg/day of ofloxacin, a quinolone antibacterial agent, for 8 weeks induced a high incidence osteochondrotic lesions in rats. The predilection site of the lesions was the caudal area of the medial femoral condyle. Early changes included thickening of the middle zone of the articular cartilage with a markedly thinned deep zone. As the course of administration progressed, the columns of chondrocytes in the thickened middle zone became more and more numerous, many degenerated cells were seen, and the staining intensity of the matrix of the cartilage with with safranin-O decreased slightly. After the completion of dosing, the articular cartilage was markedly thickened and was made up mainly of middle zone cartilage. In advanced cases, a cleft was formed along the tidemark which occasionally extended to the articular surface. This resulted in erosion of the articular cartilage. Beneath the cleft there were focal necrosis of the subchondral bone and fibrotic lesions in the marrow space. Nalidixic acid also produced similar lesions in rats. The two drugs induced osteochondrosis in rats when treatment began at 4 weeks of age, but not at 8 weeks of age. This lesion was different in developmental process from the spontaneous osteochondrosis of rats, which is characterized by retention of the inherently thick deep zone.

Critical risk/benefit analysis of pefloxacine use in children under 15 years--the problem of arthralgias.

Pefloxacine belongs to a group of new quinolone antibiotics with more general indications than the urinary quinolones marketed about twenty years ago. The contraindication of the quinolones in children under 15 years of age limits their usage exclusively to adults. In this paper, the adverse arthralgic effects of these quinolones, which have largely motivated the contraindication, have been analyzed from an experimental, clinical and pathophysiological point of view. It is concluded that the pediatric benefits associated with the marked antibacterial activity of pefloxacine, particularly in pseudomonas and enterobacteriae infections, should be balanced against the risks associated with arthralgia whenever the condition of the patient is grave and decisions vital to a favorable prognosis for the sick child are necessary.

The effects of natural exposure to high levels of zinc and cadmium in the immature pony as a function of age.

To study the effects of environmental exposure to zinc and cadmium in immature foals, five pregnant ponies were raised within 2.9 km of the New Jersey Zinc Smelter in Palmerton, Pennsylvania. The mares and their foals were kept outdoors on timothy hay and orchard grass. The foals were examined daily for signs of illness and blood samples were taken monthly for estimation of serum zinc, copper, and ceruloplasmin levels. The foals were sacrificed at 2.5, 4.5, 8.5, 13.5, and 18.5 months of age. Necropsy revealed generalized osteochondrosis in joints of the limbs and cervical vertebrae, lymphoid hyperplasia, and eosinophilia. Two of the foals had developed mild lameness. The concentrations of zinc, cadmium, copper, lead, magnesium, and calcium were determined in liver, kidney cortex, and pancreas. The concentration of cadmium and zinc were the only elements that were greatly elevated in all three tissues as compared to control animals. The concentration of cadmium was directly correlated with age in the three tissues (e.g., 23.9 to 212.7 micrograms/g wet wt in kidney cortex), whereas zinc was significantly increased (range 132 to 954 micrograms/g wet wt in liver) but there was no correlation with age. It was concluded that the development of osteochondrosis is associated with increased exposure to zinc and possibly cadmium. The classical signs of cadmium toxicosis, such as renal damage and osteomalacia, were not observed.

Exercise increases osteophyte formation and diminishes fibrillation following chemically induced articular cartilage injury.

The present study shows that a treadmill exercise regimen imposed on guinea-pigs whose articular cartilage has been damaged by intra-articular injection of IA reduces chondrocyte depletion, results in an increase in pericellular Safranin-O staining around surviving chondrocytes, and prevents fibrillation of the articular surface. The data suggest that exercise protected, or facilitated recovery of, chondrocytes subjected to chemical injury, and that the surviving cells then synthesised a matrix which was sufficiently normal to withstand impulsive joint loading. On the other hand, the exercise regimen accelerated osteophyte formation, and led to formation of osteophytes in sites at which they did not develop in animals which received intra-articular IA but which were not exercised.

Environmental zinc and cadmium pollution associated with generalized osteochondrosis, osteoporosis, and nephrocalcinosis in horses.

Several suspect causes of chronic zinc/cadmium toxicosis in horses near a zinc smelter were investigated following observations of lameness, swollen joints, and unthriftiness, particularly in foals. Two foals born and raised near the smelter were lame and had joint swellings that were attributable to severe generalized osteochondrosis. Zinc and cadmium concentrations were markedly increased in the pancreas, liver, and kidney. The serum of 1 foal, zinc and potassium concentrations were high, whereas calcium and magnesium concentrations were low. Marked nephrocalcinosis and osteoporosis were observed in this foal. Nephrocalcinosis also was observed in his dam, who died of a punctured lung following rib fractures, though there was no history of trauma. The joint cartilage lesions were similar to those induced experimentally in animals fed high-zinc diets and may have been the result of zin-induced abnormality of copper metabolism. The osteoporosis and nephrocalcinosis were consistent with chronic cadmium toxicosis.