High sensitivity with color duplex sonography in thrombosis screening after ankle fracture surgery.

BACKGROUND: Phlebography is regarded as the reference standard for diagnosing asymptomatic deep vein thrombosis (DVT) in studies of thromboprophylaxis. However, technical advances with noninvasive color duplex sonography (CDS) have made this procedure an interesting alternative. OBJECTIVES: The objective of the present prospective study was to compare the sensitivity and specificity of CDS with those of phlebography. PATIENTS: The first 180 consecutive patients included in a larger randomized trial for prolonged thromboprophylaxis were subject to unilateral CDS and to phlebography after ankle fracture surgery. The patients were examined 6 weeks after surgery, all examinations being evaluated blindly. After patient drop outs and exclusions, 144 patients were left for analysis. RESULTS: Phlebography and CDS examinations were inconclusive or were not completed for 19% of these patients (28/144). DVT was diagnosed by phlebography in 21% (24/116) of the remaining patients. Most of the thrombi were isolated calf DVTs (18/24). In contrast, DVT was diagnosed by CDS in 31% of these patients (36/116): only one case diagnosed by phlebography was missed by CDS. The specificity of CDS is thus 86% and its sensitivity is 96%. The positive predictive value is 64%, and the negative predictive value is 99%. CONCLUSIONS: CDS is a safe method for detecting asymptomatic distal DVT. It has a high sensitivity and high negative predictive value, which means that the method is highly reliable to rule out DVT. Our results indicate that CDS could be considered as an alternative method for DVT screening.

Mechanical load and primary guinea pig osteoarthrosis.

Hartley guinea pigs spontaneously develop knee osteoarthrosis. The reproducible course, the changes first appearing at the central medial condyle and then progressing peripherally and laterally, makes this animal a suitable model for intervention studies. We studied the effect of load, and randomized 9-month-old male animals into 4 groups: immediate killing, mid-femoral 30 degrees-valgus osteotomy, sham operation or below-knee amputation. After 3 months, the proximal tibia was step-sectioned and examined stereologically by light microscopy. Local load-redistribution from the medial to the lateral condyle (osteotomy) reduced cartilage fibrillation by 22% medially and increased it 27% laterally. Subchondral bone thickness decreased by 36% in the medial condyle. In contrast, general load-redistribution (amputation) did not affect the progress of fibrillation, despite pronounced bone atrophy. Cartilage thickness, however, did not change; calcified cartilage thickness remained remarkably constant, and it was always higher on the lateral side. Therefore tide-mark advancement does not appear to be an important mechanism in early guinea pig osteoarthrosis. Thus, when the natural course of guinea pig osteoarthrosis is interfered with surgically, in the early phase, changes in bone are more conspicuous than those in cartilage, which further indicates that mechanical load and stiffness gradients are important pathogenetic mechanisms.

Effect of an inhibitor of matrix metalloproteinases on spontaneous osteoarthritis in guinea pigs.

Recently discovered chemically modified tetracyclines have been found to be effective inhibitors of matrix metalloproteinase (MMP)-mediated connective tissue destruction in a variety of pathologic processes, including rheumatoid arthritis and osteoarthritis (OA). Since the histologic techniques used in our laboratory have been validated in Hartley guinea pigs, which have a high incidence of OA-like changes in the proximal tibia, we have used two tetracyclines which have potent inhibitory capacity against various MMPs, doxycycline (Dox) and a compound known as chemically modified tetracyclines (CMT-7). These were given by mouth to a group of guinea pigs for 4 to 8 months, and we assessed the effect of the compound on morphologic and biochemical aspects of OA. We found that prophylactic CMT-7 given orally decreases OA changes in the knee joints both in vitro and in vivo in the guinea pig OA model. Cartilage fibrillation and destruction, in addition to subchondral bone sclerosis and cyst formation, were all decreased in the central compartment of the medial condyle, which is most affected by OA compared with controls. Also collagen, hyaluronan and proteoglycancontent in cartilage was higher in the CMT-7 treated group compared with controls. In contrast, OA changes were not decreased in the Dox group. Our results confirm that various tetracyclines have reduced the severity of OA in animal models, indicating the therapeutic potential of this class of compounds in the future.

Clinical history in lumbar disc herniation. A prospective study in 160 patients.

In a prospective study of 160 consecutive patients who underwent primary surgery for lumbar disc herniation, we investigated the value of clinical history for diagnosing the degree of herniation-the main prognostic factor for the postoperative outcome. At surgery, the patients were classified into two groups: intact anulus (negative exploration or protruding disc) and ruptured anulus (subligamentary perforation or complete perforation). The strongest variables predicting the degree of herniation were duration of leg pain, progressive leg pain, educational level and whether or not the patient had previously undergone non-spinal surgery. In patients with ruptured anulus, the median durations of low back pain and sciatica were 16 and 10 weeks, respectively. The corresponding figures for the group with intact anulus were 79 and 50 weeks. 18% of those with ruptured anulus and 39% of those with intact anulus were undergoing medical or psychiatric treatment for other diagnoses; 32% and 55% had previously undergone non-spinal surgery. Thus the two groups differed not only in disc pathology but also in medical, behavioral and social factors that must be taken into account in the preoperative assessment and that may explain discrepancies between impairment and disability.

Ultrastructural immunolocalization of bone sialoprotein in guinea-pig osteoarthritis.

In diarthrodial joints, bone and cartilage are structurally and functionally inseparable as shown in osteoarthritis (OA), where subchondral bone changes are integral in the disease process. By ultrastructural immunohistochemistry using polyclonal antibodies against guinea-pig bone sialoprotein (BSP), we investigated the distribution of this matrix protein at the osteocartilaginous interface in Hartley guinea-pig knees at different stages of primary osteoarthritis. Between 6 and 12 months they developed moderate osteoarthritic changes predominantly in the medial condyle, progressing to severe OA at 30 months. In all age groups BSP labeling was concentrated to the osteocartilaginous interface at a 1 micron narrow zone at the interface. In the medial osteoarthritic condyle, BSP was increased as compared with the lateral nonosteoarthritic condyle, but only at 30 months, when cartilage fibrillation correlated to BSP. Our observations suggest that altered BSP abundance may be a potential bone marker for late stage OA, while early events in bone cannot be monitored. BSP is expressed early in osteogenesis and may have a role in biological mineralization and growth. Since a sharp zone of intense BSP labeling remains at a remarkably constant level throughout life in guinea-pigs, BSP may have an important structural and/or regulating role at the interface. The protein may act as an anchor of calcified articular cartilage to subchondral bone or by regulating mineralization at the osteocartilaginous interface.

Focal destruction and remodeling in guinea pig arthrosis.

We investigated the proximal tibiae in adult, middle-aged and old (6,12, and 30 months) guinea pigs with spontaneous arthrosis by quantitative morphometry. Since the cartilage destruction develops predominantly in the medial tibial plateau, the lateral side may serve as an internal control, In established lesions, cartilage destructions were focal, surrounded by a brim of thickened cartilage that was grossly intact, but showed cell clustering, hypertrophy and increased metachromasia. Peripherally, there was a distinct transition to normal-appearing cartilage. Subjacent to the cartilage ulcerations, subchondral bone was thickened. Compared to the lateral plateau the height of the calcified cartilage increased and the surface density of the osteocartilaginous interface decreased. Marrow depletion and cysts developed below the cartilage ulcerations. Cysts seem to develop through fibrous tissue partially undergoing cartilage metaplasia in tiny noduli that subsequently coalesce, liquefy centrally and expand. Superficially, similar fibrocartilaginous proliferations result in incomplete resurfacing and small areas of subchondral resorption; in the periphery of the joint, they form osteophytes. In the guinea pig, arthrosis tissue destruction is thus accompanied by local tissue proliferation.

Bone sialoprotein and osteopontin distribution at the osteocartilaginous interface.

In situ hybridization and ultrastructural immunohistochemistry were used to study the synthesis and distribution of 2 bone matrix proteins, bone sialoprotein and osteopontin, in the proximal tibial epiphysis in 21-, 32-, and 84-day-old rats. Bone sialoprotein messenger ribonucleic acid expression was restricted to cells close to the osteocartilaginous interfaces, whereas osteopontin messenger ribonucleic acid was shown also in the central epiphysis. Moreover, bone sialoprotein synthesis decreased with age, while osteopontin synthesis remained unchanged. Bone sialoprotein and osteopontin immunolabeling were concentrated to a 1-micron thick zone at the border between mineralized articular cartilage and subchondral bone. Compared with the youngest animals, total bone sialoprotein immunolabeling increased in the 32-day-old group, but did not increase further in the oldest group. In contrast, osteopontin immunolabeling increased only in the oldest rats with a decelerating rate of growth. The accumulation and localization of osteopontin at osteocartilaginous interfaces differ from previous observations in metaphyseal bone where osteopontin has been found at the mineralization front of the osteoid, possibly reflecting different roles in the mineralization process in the 2 regions. The different pattern of synthesis of the 2 proteins in the epiphysis corroborates previous indications of different biological roles.

Ultrastructural changes in primary guinea pig osteoarthritis with special reference to collagen.

Collagen fibril distribution and surface and volume densities in proximal tibial articular cartilage were measured in 6- and 12-month-old Dunkin-Hartley guinea pigs developing primary osteoarthritis. At 12 months, gross fibrillation and ulceration of the articular cartilage were observed on the medial but not on the lateral condyle. Collagen volume density decreased with age in the interterritorial compartments in the superficial zone, medially by 16% and laterally by 8%. In the upper radial zone, collagen volume density decreased interterritorially by 10% on the medial condyle only. Despite gross osteoarthritic changes, only moderate and predominantly focal ultrastructural collagen changes were observed. Thus neither gross network disruption nor fibril thickening seems to be a general feature in early guinea pig osteoarthritis.

Primary osteoarthrosis in guinea pigs: a stereological study.

Volumes and surfaces of articular cartilage and subchondral bone of the proximal tibial epiphysis were measured by unbiased stereological methods on the light microscopic level in groups of 6, 12, and 30-month-old (adult, middle-aged, and old) guinea pigs with primary osteoarthrosis. At 12 months, structural changes similar to those of human osteoarthrosis had developed, predominantly on the central medial condyle, which was not covered with meniscus. The lateral condyle was virtually unaffected; this allowed separate analysis of age-related and disease-related changes. Fibrillation and destruction of cartilage was accompanied by a simultaneous increase of the volume of both cartilage (66%) and subchondral bone (50%). The epiphyseal volume increased by 27% at 12 months, predominantly on the medial (osteoarthrotic) condyle, whereas the volume of the lateral condyle increased only in the oldest age group; this indicated that the joint has a potential for growth and remodeling. Joint growth has been suggested as a pathogenic factor in osteoarthrosis. The 65% increase in thickness noted in subchondral bone was a further indication of the importance of proliferative bone changes in early osteoarthrosis. The low variability of osteoarthrosis in this animal model makes it possible to obtain stable quantitative data from relatively small groups of animals.