New developments and applications in quantitative electron spectroscopic imaging of iron in human liver biopsies

The objective of this study was to determine the effects of intra-articularly administered triamcinolone acetonide (TA) in exercised equine athletes with carpal osteochondral fragmentation. Eighteen horses were randomly assigned to each of 3 groups. An osteochondral chip fragment was created in one randomly chosen intercarpal joint of each horse. Both intercarpal joints in the placebo control group (CNT) horses were injected with intra-articular administration (IA) of polyionic fluid. Both joints in the TA control group (TA CNT) horses were treated with 12 mg of TA in the intercarpal joint without an osteochondral fragment, and the opposite intercarpal joint was injected with a similar volume of polyionic fluid. The TA treated group (TA TX) horses were treated with 12 mg of TA in the joint that contained the osteochondral fragment and the opposite intercarpal joint was injected with a similar volume of polyionic fluid. All horses were treated IA on days 13 and 27 after surgery and exercised on a high speed treadmill for 6 weeks starting on Day 14. Horses in the TA TX group were significantly less lame than horses in the CNT and TA CNT groups. Horses in either TA CNT or TA TX groups had lower total protein, and higher hyaluronan, and glycosaminoglycan concentrations in synovial fluid than did those in the CNT group. Synovial membrane collected from subjects in TA CNT and TA TX groups had significantly less inflammatory cell infiltration, subintimal hyperplasia and subintimal fibrosis compared to the CNT group. Articular cartilage histomorphological parameters were significantly better from the TA CNT and TA TX groups compared to the CNT group. In conclusions, results from this study support favourable effects of TA on degree of clinically detectable lameness, and on synovial fluid, synovial membrane, and articular cartilage morphological parameters, both with direct intra-articular administration and remote site administration as compared to placebo treatment. The clinical use of IA administered TA in horses may be therapeutically beneficial in selected cases of osteochondral fragmentation and osteoarthritis.     

Effects of intravenous administration of sodium hyaluronate on carpal joints in exercising horses after arthroscopic surgery and osteochondral fragmentation

OBJECTIVE: To evaluate the effects of arthroscopic surgery, osteochondral fragmentation, and treatment with IV administered hyaluronate on histologic, histochemical, and biochemical measurements within the carpal joints of horses. ANIMALS: 12 clinically normal horses, 2 to 7 years of age. PROCEDURE: Horses had an osteochondral fragment created at the distal aspect of the radiocarpal bone of 1 randomly chosen middle carpal joint to simulate osteochondral fragmentation. Horses were treated with 40 mg of hyaluronate or saline solution (placebo) intravenously once a week for 3 consecutive weeks (days 13, 20, and 27 after surgery). Treadmill exercise proceeded 5 days per week beginning 15 days, and ending 72 days, after surgery. Clinical evaluations were performed at the beginning and end of the study. Synovial fluid samples were obtained aseptically from both middle carpal joints on days 0, 13, 20, 27, 34, and 72 after surgery, and total protein, inflammatory cell, hyaluronate, glycosaminoglycan, and prostaglandin E2 concentrations were measured in each sample. All horses were euthanatized on day 72. Synovial membrane and articular cartilage were obtained for histologic evaluation. Articular cartilage samples were also obtained aseptically for determining glycosaminoglycan content and chondrocyte synthetic rate for glycosaminoglycans. RESULTS: Horses treated with hyaluronate intravenously had lower lameness scores (were less lame), significantly better synovial membrane histologic scores, and significantly lower concentrations of total protein and prostaglandin E2 within synovial fluid 72 days after surgery, compared with placebo-treated horses. Treatment with intravenously administered hyaluronate had no significant effects on glycosaminoglycan content, synthetic rate or morphologic scoring in articular cartilage, or other synovial fluid measurements. CONCLUSION: Intravenously administered hyaluronate appears to alleviate signs of lameness by interacting with synoviocytes, and by decreasing production and release of inflammatory mediators.     

Effects of 0.05% chlorhexidine lavage on the tarsocrural joints of horses

In six horses, a 0.05% solution of chlorhexidine diacetate was used to lavage one tarsocrural joint; the contralateral control joint was lavaged with lactated Ringer's solution. Horses were evaluated daily for lameness. Synovial fluid samples were collected on days 1, 4, and 8 for determination of protein concentration, total and differential leukocyte counts, and mucin clot formation. After death on day 8, synovium and osteochondral samples were collected from the tarsocrural joints for examination of morphology and proteoglycan staining. Lavage with chlorhexidine solution caused lameness that was reduced but still evident at day 8. Synovial protein concentration was significantly increased by chlorhexidine lavage; the greatest increase occurred on day 1. Joint lavage increased synovial leukocyte counts on day 1, primarily by increasing polymorphonuclear (PMN) cell counts. Although total synovial leukocyte counts returned to normal by day 4, PMN cell counts remained elevated through day 8; PMN cell counts for chlorhexidine-lavaged joints were typically twice that of control joints. Chlorhexidine lavage caused synovial ulceration, inflammation, and abundant fibrin accumulation. Consistent differences in proteoglycan staining were not detected between control and chlorhexidine-lavaged joints. Joint lavage with 0.05% chlorhexidine diacetate, the lowest known bactericidal concentration, is not recommended for equine joints.     

Evaluation of sodium hyaluronate therapy in induced septic arthritis in the horse

This study was conducted to determine the efficacy of sodium hyaluronate (SH) with antibiotic therapy and joint lavage for reducing acute inflammatory and degenerative changes induced by septic arthritis. Septic arthritis was induced in six adult horses by inoculating the tarsocrural joints with 1 x 10(4) colony-forming units of Staphylococcus aureus. When clinical signs appeared, trimethoprim-sulphamethoxazole (30 mg/kg bodyweight [bwt] daily) and phenylbutazone (4.4 mg/kg bwt sid) were administered and continued until termination of the study (Treatment Day 18). Twenty-four hours post inoculation, all joints were lavaged with sterile lactated Ringer's solution. Following lavage, one joint of each horse was injected with 10 mg of SH, and the contralateral joint served as the control. Sodium hyaluronate treated joints showed significant reductions in lameness, tarsal circumference and synovial fluid protein and WBC concentrations. The synovial membrane of the SH-treated joints contained less cellular infiltrate, less granulation tissue formation and retained a more normal villous structure compared with controls. The total glycosaminoglycan loss from the articular cartilage in the SH treated joints was consistently less than that from the control joints; however, this difference was not statistically significant. Sodium hyaluronate with joint lavage appears to be more beneficial than lavage alone for treatment of septic arthritis.     

Postmortem lesions in the intercarpal ligaments of the equine midcarpal joint

OBJECTIVE: To determine the frequency of damage to the medial palmar intercarpal ligament (MPICL), and the range of sizes of the dorsomedial intercarpal ligament (DMICL) of the midcarpal joint in horses with no history of carpal joint disease. MATERIALS AND METHODS: Cadaver limbs were collected from 72 horses with no history of carpal joint disease. One hundred and forty-two midcarpal joints were dissected and the MPICL and DMICL were examined. Measurements were made with a digital micrometer. RESULTS: MPICL tearing was present in 88 of 96 joints from horses 2 years and older. Tears were predominantly of the dorsolateral bundle and complete rupture of the dorsolateral and dorsomedial bundles was not observed. Tearing was not present in foals less than 4 months of age and the severity of tearing increased significantly with age (P < 0.0001). Severity of tearing was significantly greater in racing Standardbreds than racing Thoroughbreds (P < 0.01), but there was no significant difference between racing and non-racing horses. The lateromedial thickness of the DMICL ranged from 0.4 mm to 2.6 mm in horses 2 years and older. Lateromedial thickness increased significantly with age, and was significantly greater in racing Standardbreds than racing Thoroughbreds (P < 0.01). There was no significant difference between racing and nonracing horses. CONCLUSIONS: Damage confined to the dorsolateral bundle of the MPICL is a common finding in horses over 1 year of age and is probably of little clinical significance. Complete rupture of both dorsolateral and dorsomedial bundles is uncommon in horses with no history of midcarpal joint disease. Variation in size of the DMICL is observed in horses of all ages, but is most marked in 2-year-old horses.     

Local hemodynamics, permeability, and oxygen metabolism during acute inflammation of innervated or denervated isolated equine joints

OBJECTIVES: To determine oxygen metabolism, permeability, and blood flow in isolated joints in response to interleukin 1beta (IL-1beta) and contribution of innervation. SAMPLE POPULATION: One metacarpophalangeal (MCP) joint of 24 adult horses. PROCEDURE: The MCP joint was isolated for 6 hours in a pump-perfused, auto-oxygenated, innervated or denervated preparation. Isolated joints were assigned to the following 4 groups: control, control-denervated, inflamed, and inflamed-denervated, and inflammation was induced by intra-articular injection of IL-1beta. Circuit arterial and venous pressures, flows, and blood gas tensions, synovial fluid production, and intra-articular pressure were measured. Total vascular resistance; oxygen delivery, consumption, and extraction ratio (ER); and permeability surface area product were calculated. Synovial membrane blood flow was determined at 0, 60, and 330 minutes. Synovial membrane wet-to-dry ratio was obtained, and permeability to macromolecules was determined by intra-articular injection of Evans blue albumin and fluorescein isothiocyanate-conjugated dextran. RESULTS: Oxygen delivery and synovial membrane blood flow progressively increased but were not different among groups. Oxygen consumption and ER significantly increased in inflamed joints, as did intraarticular pressure and synovial fluid production. Inflamed joints had greater wet-to-dry ratio. Albumin permeability significantly increased in the villous synovial membrane of the inflamed groups, and dextran permeability was increased in the innervated groups, with a trend toward increased permeability in inflamed groups. CONCLUSION: Inflammation significantly increased oxygen demand, which was initially met by increased ER. Permeability to small molecules was increased with inflammation; innervation increased permeability to large molecules. Use of an isolated joint model enabled documentation of the physiologic responses of the joint to acute inflammation.     

Persistence of decreased T-helper cell function in industrial workers 20 years after exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin

OBJECTIVE: To evaluate the distribution of mepivacaine hydrochloride after distal interphalangeal (DIP) joint injection in horses. DESIGN: Prospective, uncontrolled study. ANIMALS: 10 adult horses. PROCEDURE: 30 minutes before euthanasia, 8 ml of 2% mepivacaine hydrochloride was injected into the dorsal pouch of a forelimb DIP joint. Synovial tissue from the DIP joint and podotrochlear (navicular) bursa and bone tissue from the medullary cavity of the distal sesamoid (navicular) bone were taken from both forelimbs immediately after death. All synovial and bone specimens were analyzed for tissue concentration of mepivacaine by high-performance liquid chromatography. Synovial tissue and bone specimen concentrations from the injected forelimb were compared with corresponding specimens from the noninjected forelimb. All synovial tissue and bone specimen concentrations were compared with an estimated effective tissue concentration of mepivacaine (0.3 microgram/mg) for local anesthesia. RESULTS: Specimen concentrations of mepivacaine from the injected forelimb were significantly greater (P < 0.05) than those in the corresponding tissues of the contralateral noninjected forelimb. All DIP joint and navicular bursa synovial tissue specimens from the injected forelimb had greater than the estimated effective tissue concentration of mepivacaine for local anesthesia. Of the 10 navicular bone specimens from the injected forelimb, 4 were higher and 2 were within 20% of the estimated effective tissue concentration of mepivacaine for local anesthesia. CONCLUSIONS: Mepivacaine hydrochloride deposited into the DIP joint should anesthetize pain arising from navicular bursa synovia and may decrease pain arising from the medullary cavity of the navicular bone. CLINICAL RELEVANCE: DIP joint injection of mepivacaine hydrochloride is not specific for DIP joint pain.     

Para-spinal regional anesthesia and prevention of thromboembolism/anticoagulation. Recommendations of the German Society of Anesthesiology and Intensive Care Medicine, October 1997

OBJECTIVE: To evaluate clinical and biomechanical consequences of desmotomy of the accessory ligament (AL) of the deep digital flexor tendon (DDFT) of equine forelimbs and determine whether this procedure is a viable treatment for chronic desmitis of the AL-DDFT. ANIMALS: 6 adult Standardbred trotters. PROCEDURE: Biomechanical recordings obtained before and 6 months after desmotomy were compared. Walk and trot joint angles, ground reaction forces, peak joint moments, and tendon forces were assessed. RESULTS: Within 10 days after surgery, all horses were sound at a trot. Swelling, increased carpal flexion in the terminal stance phase, and incidental stumbling at the beginning of exercise were observed. Flexion angle in the carpal joints was significantly increased at the end of the stance phase. Peak moments around the distal interphalangeal joint and forces in the DDFT and AL-DDFT were decreased. Metacarpophalangeal joint angles, peak metacarpophalangeal joint moments, and peak loading of the suspensory ligament and the superficial digital flexor tendon were unchanged. CONCLUSION: 6 months after desmotomy, AL-DDFT strain was reduced without causing changes in joint angles or increasing tendon loads or joint moments that could be considered hazardous for the horses. CLINICAL RELEVANCE: Changes in locomotion that remained 6 months after AL-DDFT desmotomy would be acceptable for horses with chronic desmitis if conservative treatment failed.     

Comparison of biopersistence of experimental glass fibres in the lung and peritoneal cavity

An epitope of keratan sulphate (KS) and total glycosaminoglycans (GAG) were measured in synovial fluid samples from joints of 53 horses immediately following humane destruction. Internal examination of the joints post mortem ensured that there was no gross evidence of osteoarthritis or other joint disease. Joints sampled were distal interphalangeal (DIP), proximal interphalangeal (PIP), metacarpophalangeal (MCP), metatarsophalangeal (MTP), tarsometatarsal (TMT), tarsocrural (TC), femoropatellar (FP) and antebrachiocarpal (ABC) joints. The age of each horse was assessed by examination of the teeth. Samples were analysed for the KS epitope using a monoclonal antibody 5D4 and an inhibition ELISA and for total GAG level by a direct dye binding technique. There was no significant correlation between KS or GAG concentration and age. However, there were significant differences in the concentrations of KS and GAG in different joints. The median level (+semi interquartile range) of KS:GAG ratio in the MCP was significantly lower than the PIP (0.25 [0.05] vs. 0.35 [0.08]; P < 0.007) and also the DIP joints (0.25 [0.05] vs. 0.47 [0.09] P < 0.001). This study provides information which is both valuable in the investigation of normal joint metabolism and essential in the interpretation of synovial fluid KS and GAG values in their potential role as aids in the evaluation of joint disease.     

The intercarpal ligaments of the equine midcarpal joint, Part 1: The anatomy of the palmar and dorsomedial intercarpal ligaments of the midcarpal joint

OBJECTIVE: To describe in detail the structure of the medial palmar intercarpal ligament (MPICL), the lateral palmar intercarpal ligament (LPICL), and a dorsomedial intercarpal ligament (DMICL) of the equine midcarpal joint. STUDY DESIGN: Dissections of equine midcarpal joints. ANIMALS AND SAMPLE POPULATION: Ten carpal joints from eight thoroughbred horses. METHODS: Detailed dissections of the midcarpal joint were performed, with particular attention paid to the MPICL, the LPICL, and the DMICL. The attachments and dimensions of these structures were recorded, as well as their behavior during joint movement. RESULTS: The DMICL arose from the dorsomedial surface of the radial carpal bone (CR) and coursed palmarodistally to insert on the dorsomedial aspect of the second carpal bone (C2). The LPICL attached proximally predominantly on the distal part of the palmaromedial surface of the ulnar carpal bone (CU). From here the ligament coursed distomedially and slightly palmarly to the proximal palmarolateral surface of the third carpal bone (C3). The structure of the MPICL was complex. It attached proximally to the distolateral surface of the CR and distally to the proximal palmaromedial surface of C3, and the proximal palmarolateral aspect of the C2. It could be divided into four fiber bundles in all carpi. The predominant direction of fibers was dorsoproximal to palmarodistal, whereas the palmaromedial bundle coursed palmaroproximal to dorsodistal. CONCLUSIONS: The orientation of their fibers indicate that the MPICL and DMICL primarily resist dorsomedial displacement of CR, whereas the LPICL resists dorsolateral displacement of the CU and intermediate carpal bone. CLINICAL RELEVANCE: An understanding of the structure of the intercarpal ligaments of the midcarpal joint is important in interpreting their function and the reasons for damage to their structure.     

A clinical perspective on lameness originating in the carpus

Clinical experience continues to expand our understanding of the pathophysiology of pain and injury within the carpal joints. The anatomical and physiological capacity of the equine carpus to neutralise loading stress plays a significant role in the prevention of carpal injury. The ability of joint surfaces to dissipate axial force by transfer to the interosseous ligaments is the principal means by which carpal injury is avoided. In the medial aspect of the intercarpal joint and the dorsal aspect of the radial carpal joint, however, the effects of chronic maximal stress and isolated acute supraphysiological loads cannot be neutralised. Progressive osseous remodelling and stress induced changes within the bone, which outstrip its ability to accommodate increasing loads, lead to the loss of structural integrity and fracture in horses in training.     

Matrix metalloproteinase activity in equine synovial fluid: influence of age, osteoarthritis, and osteochondrosis

OBJECTIVE: To investigate the influence of age, osteoarthritis (OA), and osteochondrosis (OC) on the matrix metalloproteinase (MMP) activity in the synovial fluid (SF) of equine joints. METHODS: SF was collected from normal and osteoarthritic metacarpophalangeal joints (normal: 14 adult, 28 juvenile; OA: 22 adult). And from normal and osteochondrotic tarsocrural joints (5 months: 11 normal, 8 OC; 11 months: 7 normal, 6 OC). Subsequently, overall MMP activity was measured. RESULTS: The level of active MMPs was almost twofold higher in SF from juvenile horses (age up to 11 months) than in SF from mature animals (4-30 years; p < 0.001). In juvenile horses MMP activity was higher in 5 month old foals than in 11 month old foals (p < 0.01). In adult horses MMP activity was independent of age. In OA joints the activity was nearly twice as high as in normal joints (p < 0.001). In OC joints MMP activity was not significantly different from normal, age matched, control joints. CONCLUSIONS: MMP activity in SF from normal adult joints is not related to age. In juvenile joints MMP activity is significantly higher than activity in joints from adult animals. It is hypothesised that the gradual decrease in MMP activity with increasing age reflects the declining metabolic activity resulting from ceasing growth and the accompanying decrease in cartilage remodelling. The increased MMP activity in osteoarthritis joints most likely reflects matrix destruction. In osteochondrosis MMP mediated matrix degradation appears not to be different from normal joints.     

Accessory ossification centres associated with osteochondral fragments in the extremities of horses

Fifty-six tarsocrural joints and 94 metatarsophalangeal joints were examined, at necropsy, from horses aged < or = 2 years. Osteochondral fragments at the cranial aspect of the intermediate ridge of the distal part of the tibia were seen in six horses, and at the proximoplantar aspect of the proximal phalanx in seven horses. Defects in the proximoplantar aspect of the proximal phalanx without osteochondral fragments were seen in a further two horses. Inflammatory and degenerative changes were not observed in any of the joints examined. From the incidence and natural course of these fragments, and from the radiological and microscopical findings, accessory ossification centres would seem the most probable cause of the osteochondral fragments at the cranial aspect of the intermediate ridge of the distal part of the tibia and at the proximoplantar aspect of the proximal phalanx.     

Direct determination of dopamine D4 receptors in normal and schizophrenic postmortem brain tissue: a [3H]NGD-94-1 study

Normal speed videography was used to determine the angular parameters of 28 Spanish Thoroughbreds at trot. Horses were divided into 3 groups: Group UT, comprising 9 animals (provided by the VII National Stud, Cordoba, Spain) which had undergone no specific training programme and which were hand led at the trot; Group T, formed by 19 horses considered to be highly bred and trained, and which were also hand led; and Group RT, comprising the same horses as the latter group but this time trotted by a rider. Each animal was filmed 6 times from the right-hand side, using a Hi8 (25 Hz) video camera. Angular parameters for fore- and hindlimb joints were measured in each stride from computer-grabbed frames and entered into a spreadsheet for calculation; parameters included maximum and minimum angles, range of motion, and angles at landing, lift off and maximum hoof height; the times at which maximum angle, minimum angle, lift off and maximum hoof height occurred were calculated as percentages of total stride duration. Stride velocity (mean [s.d.]) was 4.01 (0.62), 3.60 (0.34) and 3.07 (0.36) m/s for Groups UT, T and RT, respectively. Data were then compared between Groups UT-T and Groups T-RT. Compared with Group UT, horses from Group T featured a shorter stance percentage (P<0.001) in both fore- and hindlimbs. The range of motion in forelimbs was smaller (P<0.05), due to lower retraction (P<0.001); moreover, maximum retraction appeared earlier (P<0.05). Greater scapular inclination was in evidence (P<0.05) and the shoulder joint extended further (P<0.05). Fore- and hind fetlock joints revealed a relatively shorter hyperextension period during the stance phase (P<0.01). Compared with Group T, horses from Group RT had a longer stance percentage, with belated maximum retraction of the fore- and hindlimbs. The range of movement in scapular inclination was greater (P<0.05), due to a smaller minimum angle (P<0.01), and the shoulder joint flexed more (P<0.05). The elbow joint extended more and for longer during the stance phase. Initial extension of the hip joint (P<0.05) and tarsus (P<0.001) lasted longer. The carpal and fore and hind fetlock joints recorded relatively longer hyperextension times, in addition to greater hyperextension during the stance phase. The results from the present study suggest that rider-effect must be taken in consideration when well gaited horses are selected for dressage purposes.     

Complement and immunoglobulins in synovial fluid from synovectomized patients with rheumatoid arthritis

In order to see if the complement (C) consumption and conversion, which are typical of rheumatoid joints, continue after synovectomy, 23 knee joints in which synovectomy had been performed from 4-5 to 6-5 years previously, were studied. The mean ratio of the concentration of C3, C4, and C5 in synovial fluid to that in palsma of the same patient was significantly lower than the corresponding ratio for the total protein content. This was found both in joints with active arthritis and in joints without clinical signs of arthritis, and in both seropositive and seronegative patients. Conversion products of C3 were found in 7 of the synovial fluids. The study thus indicated that the complement alterations in synovectomized joints are very similar to those in nonsynovectomized rheumatoid joints. In one synovial fluid agarose electrophoresis showed multiple sharp bands in the gamma region. By crossed immunoelectrophoresis some bands seemed to contain IgG with one type of light chains only. In plasma of the same patients the bands were much weaker, indicating local production of oligoclonal IgG in the joint.     

Plasma nitrogen oxides and blood lactate concentrations in Ghanaian children with malaria

OBJECTIVES: To titrate a clinically effective eltenac dosage (0.1, 0.5, and 1.0 mg/kg of body weight), compared with vehicle only, and to compare efficacy of the most effective eltenac dosage with that of 1.1 mg of flunixin meglumine/kg. ANIMALS: 40 healthy horses, ranked after model induction on the basis of lameness severity, were randomly assigned to 5 treatment groups, with 4 replicates of 10 horses each. PROCEDURE: On day -5, after surgical preparation of the left carpal region, 0.7 ml of Freund's complete adjuvant was injected into the intercarpal space. Horses were observed daily, from the day of carpitis induction to day 0, when stride length was used as the method of ranking horses for randomization to treatment assignment. Treatments were administered i.v. once daily for 3 consecutive days, starting on day 0. Prior to carpitis induction on day -5, and at time 0 (pretreatment), 2, 4, 12, 24, 36, 48, 60, 72, and 96 hours after treatment initiation, resting respiratory rate and pulse, rectal temperature, carpal circumference, carpal flexion angle, stride length, carpal hyperthermia, and signs of carpal pain were recorded. RESULTS: Compared with the vehicle and 0.1 mg of eltenac/kg, 0.5 and 1.0 mg/kg caused statistically significant improvements (ie, reduction of carpal circumference, increase in carpal flexion angle, and increase in stride length of the affected limb), but values did not differ significantly between the 2 dosages. Thus, a dose-response plateau for eltenac was reached at 0.5 mg/kg. Comparison with flunixin meglumine at a dosage of 1.1 mg/kg did not indicate significant differences between the 2 treatment groups at the pivotal time of 96 hours for carpal circumference, carpal flexion angle, stride length, carpal hyperthermia, and signs of carpal pain. Adverse reactions were not observed. CLINICAL RELEVANCE: Under conditions of this study, a dosage plateau for eltenac was determined (0.5 mg/kg) that was statistically equivalent to eltenac (1.0 mg/kg) and flunixin meglumine (1.1 mg/kg) in a 3-day i.v. dosing regimen.     

Listeria monocytogenes arthritis of several joints

A patient with rheumatoid arthritis (RA) developed an infection caused by Listeria monocytogenes in her left knee and both shoulder joints. The clinical presentation of the disease was rather indolent with relatively moderate joint symptoms. Moreover, the synovial fluid sample was only slightly turbid with a white blood cell count of 23.5 x 10(9)/1. As compared to the earlier reported cases of L. monocytogenes septic arthritis, our patient is unique because she had infection in several joints. The polyarticular joint involvement combined with the clinical symptoms resembling the activation of RA posed us diagnostic difficulties.     

Transforming growth factor-beta 1 stimulates articular chondrocyte proteoglycan synthesis and induces osteophyte formation in the murine knee joint

BACKGROUND: High concentrations of active transforming growth factor-beta (TGF-beta) have been found in synovial fluids from arthritic joints. TGF-beta stimulates articular cartilage proteoglycan synthesis and suppresses proteoglycan degradation in vitro. In an earlier study, we found no effect on cartilage proteoglycan metabolism shortly after a single intra-articular injection of TGF-beta 1. In the present study, we used multiple intra-articular injections and a longer time-scale. EXPERIMENTAL DESIGN: TGF-beta 1 was injected into the murine knee joint to gain insight in the consequences of its overproduction in joint diseases. This was evaluated using histologic sections of the whole knee joint and measurements of articular cartilage proteoglycan synthesis and content. RESULTS: At 6 hours after a single TGF-beta 1 injection, recruitment of polymorphonuclear leukocytes (PMNs) was observed. After 24 hours, the amount of inflammatory cells had already decreased. Multiple TGF-beta 1 injections induced synovial hyperplasia and synovitis predominantly consisting of cells of the macrophage/monocyte lineage. Both single and multiple TGF-beta 1 injections induced strong and long-lasting stimulation of articular cartilage proteoglycan synthesis. This in vivo stimulation of proteoglycan synthesis was similar in cartilage of young (3 months) and old mice (18 months). Multiple TGF-beta 1 injections resulted in an increased GAG content in patellar cartilage. After triple TGF-beta 1 injections, impressive osteophyte formation was noted at specific sites. The size and the localization of osteophytes was identical in young and old mice. Interestingly, the localization of TGF-beta 1-induced osteophytes was very similar to that of osteophytes observed in experimental arthritis and osteoarthritis models, suggesting a role for endogenous TGF-beta in osteophyte formation during joint pathology. CONCLUSIONS: Our data indicate that TGF-beta 1 injection into a normal joint induces inflammation, synovial hyperplasia, osteophyte formation, and prolonged elevation of proteoglycan synthesis and content in articular cartilage.     

Calcified cartilage morphometry and its relation to subchondral bone remodeling in equine arthrosis

The calcified layer of articular cartilage is known to be affected by age and mechanical factors that may play a role in the development of arthrosis. Because these factors are also related to subchondral remodeling and sclerosis, a morphometric study was carried out in fluorochrome-labeled animals to determine whether the level of subchondral remodeling affected the thickness of the calcified cartilage layer and its irregularity and vascularity at the interface with subchondral bone. These parameters were also studied at a site of increased mechanical stress. The area and thickness of the calcified cartilage layer was determined in basic fuchsin-stained ground sections (120 microm). The irregularity of the chondro-osseous interface was expressed as the ratio of its length to that of the relatively straight tidemark (Int/Tid) and the number of abutting vessels with and without fluochrome labels were counted (N.Ves/Tid,%L.Ves/Tid). These were compared with single-labeled surface (sLS/BS, %) in subchondral bone, which was used as an index of remodeling. In a group of 12 horses, in which one carpus had an osteochondral fragment surgically created 10 weeks earlier, there was activation of subchondral remodeling in the third carpal bone opposite the fragment. An increase in %L.Ves/Tid (p < 0.01) at the interface was correlated with the increase in %sLS/BS in subchondral bone (r=0.431, p=0.035). The number of abutting vessels and the interface irregularity were not significantly changed on the fragmented side. In the metacarpal condyles from the fetlock joints of the same horses there were no differences associated with the surgically created fragment in the carpus and no correlation of %L.Ves/Tid with subchondral %sLS/BS. At a site where mechanical overload and traumatic osteochondrosis is known to occur on the palmar surface, the calcified cartilage was thinner, and the interface irregularity tended to be greater. These findings indicate that activated subchondral remodeling extends to involve the calcified layer, but the thickness and irregularity of the calcified cartilage are not consistently related to current subchondral remodeling. At sites of mechanical overload the calcified cartilage was thinner and the interface tended to be more irregular, suggesting previous increased remodeling.