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Long-term osteoarthritic changes in anterior cruciate ligament reconstructed knees.

To consolidate the indications for anterior cruciate ligament reconstruction and clarify the long-term prognosis associated with current surgical and rehabilitation techniques, the incidence of osteoarthritis in arthroscopically anterior cruciate ligament reconstructed knees requires investigation. Seventy-two patients with anterior cruciate ligament ruptures who were active in sports requiring sidestepping and pivoting, or who had recurrent episodes of giving way, underwent arthroscopic bone-patellar tendon-bone anterior cruciate ligament reconstruction. These patients were evaluated for meniscal damage and osteoarthritic changes at the time of surgery and followed up for 7 years. Fifty-three patients underwent radiographic evaluation at 7 years, which included anteroposterior, lateral, skyline, and 30 degrees posteroanterior weightbearing views. Radiographic evaluation was performed by three independent surgeons and graded as per International Knee Documentation Committee criteria. Results revealed that knees with chronic anterior cruciate ligament deficiency, even those with intact menisci before reconstruction, suffered early osteoarthritic changes. More severe changes were seen with meniscectomy. Acute anterior cruciate ligament reconstruction with meniscal preservation was shown to have the lowest incidence of degenerative change. Controversy exists regarding the timing of anterior cruciate ligament reconstruction. This study supports early reconstruction of anterior cruciate ligament deficient knees before episodes of giving way occur in individuals intent on continuing activities that involve sidestepping and pivoting.

Adult↗

Anatomy of the cruciate ligaments and their function in extension and flexion of the human knee joint.

The areas of the femoral origin of the cruciate ligaments have approximately the shape of sectors of ellipses, the one for the anterior ligament on the lateral condyle posteroproximally and the one for the posterior ligament on the medial condyle distally. By means of a new technique of dissection, combined with the use of X-rays, the change in distance between the origin and insertion and so the change of tension of single bundles of the ligaments could be analyzed. Only a rather thin bundle in each cruciate ligament is in constant tension: "guiding bundles." The maximal diminution of distance between the origin and insertion for some bundles is 65%. In the anterior cruciate ligament the majority of fibres are taut in extreme extension: "limiting bundles." The same is true in the posterior cruciate ligament in extreme flexion. There are also some fibres, especially in the posterior cruciate ligament, that are taut only in an intermediate position. The geometric analysis of the function of different groups of fibers was performed by a modification of Menschik's concept of a four-bar link.

Humans↗

Segmental variations in the elastic fiber content of the lateral costotransverse ligaments in the vervet monkey (Cercopithecus pygerythrus aethiops).

The segmental and zonal variations in the quantitative relationships between elastic and collagen fibers within the lateral costotransverse ligaments have been investigated in the vervet monkey. The lateral costotransverse ligaments of the caudal segments have a largely elastic structure in contrast to those of the cranial segments, which are characteristically collagenous. In the transitional zone extending from the 4th through to the 6th costotransverse joints, the lateral costotransverse ligaments show a zonal differentiation into a superficial collagenous portion and a deep elastic portion. It is noted that the craniocaudal structural differentiation in the lateral costotransverse ligaments corresponds with similar changes in the vertebral ligaments in that the ligamenta flava gradually extend into the interspinous spaces from the 1st thoracic vertebra (T1) so that at T5 the ligaments occupy 50% of the interspinous space and at T7 the elastic fibers almost completely replace the interspinous ligament. Functionally, however, the regional differences in the elastic fiber content of the lateral costotransverse ligament may have no collateral relationship with the morphology of the ligamenta flava, but are conditioned by movements of the ribs. Whereas movements of the upper six joints are limited by virtue of the configuration of their articular surfaces, which are reciprocally curved, on the 7th to 10th joints the articular facets are almost flat and, therefore, allow considerable movements between the ribs and the corresponding transverse processes.

Animals↗

Anatomical study of the pudendal nerve adjacent to the sacrospinous ligament.

The pudendal nerve (S3-S5) is a major branch of the sacral plexus. After branching from the sacral plexus, the pudendal nerve travels through three main regions: the gluteal region, the pudendal canal, and the perineum. In the gluteal region, the pudendal nerve lies posterior to the sacrospinous ligament. The relationship of the pudendal nerve to the sacrospinous ligament has important clinical ramifications, but there is a lack of literature examining the variations in pudendal nerve anatomy in the gluteal region. This study investigates the pudendal nerve trunking in relation to the sacrospinous ligament in 37 cadavers (73 sides of pelves) of 21 males and 16 females, ranging from 18-83 years of age. Pudendal nerve trunking could be grouped into five types: Type I is defined as one-trunked (41/73; 56.2%), Type II is two-trunked (8/73; 11%), Type III is two-trunked with one trunk as an inferior rectal nerve piercing through the sacrospinous ligament (8/73; 11%), Type IV is two-trunked with one as an inferior rectal nerve not piercing through the sacrospinous ligament (7/73; 9.5%), and Type V is three-trunked (9/73; 12.3%). In summary, 56.2% of pudendal nerves adjacent to the sacrospinous ligament were one-trunked, 31.5% were two-trunked and 12.3% were three-trunked. Fifteen inferior rectal nerves originated independently from the S4 root and never joined the main pudendal nerve. Eight of fifteen inferior rectal nerves pierced through the sacrospinous ligament, perhaps making it prone for entrapment. We measured the average diameter of the main trunk of the pudendal nerve to be 4.67 +/- 1.17 mm. We also measured the average length of the pudendal nerve trunks before terminal branching to be 25.14 +/- 10.29 mm. There was no significant statistical difference in the average length, average diameter, number of trunks, and pudendal nerve variations between male and female or right or left sides of the pelves. A detailed study of pudendal nerve trunking in relationship to the sacrospinous ligament would be useful for instruction in basic anatomy courses and in relevant clinical settings as well.

Adolescent↗

The costotransverse ligaments in human: a detailed anatomical study.

This study provides a more detailed description of the costotransverse ligaments in human, aimed at investigating some controversial data and disclosing some lacking information concerning the anatomy of such ligaments. Complete spinal segments from the seventh cervical to the first lumbar vertebra were removed from 15 human cadavers (8 males, 7 females) with a mean age of 55 years. The costotransverse ligaments were exposed, bilaterally, at each vertebral level, using a posterior and an anterior approach to the spine. The lateral costotransverse, the superior costotransverse, and the costotransverse ligaments were identified and described. A rudimentary superior costotransverse ligament related to the first rib was also identified. In addition, two thick ligamentous bands were clearly observed in all dissected specimens and were referred to in the study as inferior and posterior costotransverse ligaments. Both bands were subjected to a detailed anatomical study. The importance of such ligaments in maintaining stability of the spine was also discussed.

Cadaver↗

Neutral endopeptidase from nuchal ligament of fetal calves.

The nuchal ligament of unborn calves contains a neutral endopeptidase that is biochemically and immunologically similar to the neutral endopeptidase (NEP), or enkephalinase, from human kidney. Enzymatic activity was inhibited more than 90% by phosphoramidon (1 microM). The specific activity in membrane fractions, as determined by hydrolysis of the dansylated substrate, DAPGN, was similar in tissue from fetuses of gestational ages ranging from 100 to 280 days. NEP activity in adult ligament tissue, however, was less than 10% of that in fetal tissue. Fibroblasts dissociated from ligament tissue by collagenase displayed less NEP activity than did preparations of intact ligament, and activity was even lower in cultured cells. By contrast, fibroblasts cultured from fetal calf lungs had NEP activity comparable to that in the ligament tissue. When ligament fibroblasts were cultured on subcellular matrices derived from fetal lung fibroblasts the NEP activity increased relative to those cultured on plastic alone. These studies confirm the presence of neutral endopeptidase (NEP) in the nuchal ligament of the fetal calf. The consistent activity through a range of gestational ages and the influence of the subcellular matrix suggest that this enzyme might be involved in growth of the ligament during fetal life.

Animals↗

Tendons and ligaments: a morphological and biochemical comparison.

The purpose of this study was to compare selected rabbit tendons and ligaments morphologically and biochemically. Five representative structures from each of six age- and sex-matched rabbits were compared. Biochemical analyses included total collagen, reducible collagen cross-links, quantitative collagen typing, DNA, and glycosaminoglycans. Histological and chemical differences were demonstrated between the tendons and the ligaments. Smaller differences were also found between the individual ligaments (collateral and cruciate) and between the two tendons (patellar and Achilles) that were examined. These findings suggest that ligaments are more metabolically active than tendons, having more plump cellular nuclei, higher DNA content, larger amounts of reducible cross-links, and the presence of more type III collagen, as compared with tendons. They also contain slightly less total collagen than tendons and more glycosaminoglycans. We conclude that the tendons and ligaments studied have unique histological and biochemical characteristics, despite their gross similarities. Relatively increased metabolic activity in ligaments, implied by our findings, may be species specific, age related (transient), or may truly represent a structural expression of functional need for more rapid adaptation. Further investigation of other similarities or differences between particular ligaments (or tendons) is indicated, and attention is directed toward the importance of such variables in development of models for tendon and ligament studies.

Animals↗

Wrist-joint ligament length changes in flexion and deviation of the hand: an experimental study.

A method to study ligament-length patterns in situ with roentgen-stereophotogrammetry, using strings of glued tantalum markers, was developed. The method was tested against a bone-to-bone marking method in five carpal ligaments in three specimens, whereby the hand was moved through dorsopalmar flexion and radioulnar deviation. The "glued-string" marking method was found to be superior to the bone-to-bone marking method. The length patterns obtained were found to be reproducible in the specimens and different from earlier expectations presented in the literature. The radiocapitate ligament seems to limit the displacements of the capitate in both radial and ulnar deviation, and dorsal flexion. The radiolunate ligament has the same effect for the lunate. Both the dorsal radiotriquetrum and the palmar triquetrocapitate ligaments seem to play a stabilizing role in the neutral position of the hand, whereas the radiotriquetrum ligament also has a function in palmar flexion and the triquetrocapitate ligament functions in dorsal flexion, ultimately resisting these excursions. These findings require confirmation in more extensive experiments, whereby the relationship between ligament length patterns and carpal motion axes is investigated.

Adult↗

Rigid immobilization alters matrix organization in the injured rat medial collateral ligament.

The effects of mobilization on matrix reorganization and density after ligament injury were studied in rat medial collateral ligaments using scanning electron microscopy (SEM). Both medial collateral ligaments of 14 Sprague-Dawley rats were sharply incised transversely at their midpoint. A 1.14-mm threaded Kirschner wire was driven through the tibia and into the femur of the right leg (through the knee) to immobilize that knee at 90 degrees of flexion. Four additional rats were used as controls. The right medial collateral ligament of the control rats was exposed in the same manner as the experimental rats and the wound closed without damaging the ligament. Rats were sacrificed on the 7th and 14th days postinjury and the ligaments evaluated by SEM. The electron micrographs from this study demonstrated that early on, the tissue at the injury site is disorganized on a gross scale with large bundles of poorly organized matrix. Large "defects" were present between bundles in the substance of the ligament and appeared as holes in the ligament around the injury site. As healing progressed, the matrix in the mobilized specimens appeared to bridge the injury site more rapidly and completely with fewer "defects" and thus higher density than the immobilized specimens.

Animals↗

Kinematics of the trapeziometacarpal joint after sectioning of ligaments.

This study was designed to examine the roles of ligaments in the maintenance of the articular kinematics of the trapeziometacarpal joint. Circumduction of the trapeziometacarpal joint was studied in 12 hands from fresh human cadavera. With use of a magnetic tracking system, changes in the motion of the base of the first metacarpal after ligament sectioning were analyzed and compared with those of the normal joint. Two sets of ligaments were sectioned: (a) the anterior oblique and ulnar collateral ligaments and (b) the first intermetacarpal ligament and the ulnar joint capsule. Sectioning of the anterior oblique and ulnar collateral ligaments resulted in a significant dorsal-ulnar shift in the path of the base of the first metacarpal. However, sectioning of the first intermetacarpal ligament did not affect the movement pattern of the center of the base. The anterior oblique and ulnar collateral ligaments provided constraint of the trapeziometacarpal joint during circumduction of the thumb.

Humans↗

Histomorphometric analysis of innervation of the anterior cruciate ligament in osteoarthritis.

The aim of this study was to determine whether there are quantitative changes in the innervation of the anterior cruciate ligament in osteoarthritis. Eleven whole anterior cruciate ligaments were obtained at autopsy from cadavera of individuals with advanced osteoarthritis: five healthy ligaments were used as controls. The ligaments were transected and stained with hematoxylin and eosin, oil red O for fat, and a modification of Gairn's gold chloride method. The latter stain permits visualization of axons, mechanoreceptors, and free nerve endings that are not apparent on routine stains. The ratio of nerve tissue to periligamentous synovial tissue was determined histomorphometrically by the point-counting method. The nerve tissue was located almost exclusively in the periligamentous synovial tissue. There was a statistically significantly greater area of nerve tissue (as a percentage of the total area) around the anterior cruciate ligaments in the osteoarthritic group than around the ligaments in the control group (p < 0.02). The nerve tissue was distributed evenly throughout the periligamentous synovial tissue in the specimens in both groups. A neurological role has been proposed for the anterior cruciate ligament in osteoarthritis. This study provides morphological evidence for neural pathology of the anterior cruciate ligament in subjects with osteoarthritis.

Adipose Tissue↗

Soft-tissue "flaws" are associated with the material properties of the healing rabbit medial collateral ligament.

This study evaluated microscopic flaws in the healing rabbit medial collateral ligament and their significance in terms of the material properties of this ligament during healing. A gap injury was created in the midsubstance of the medial collateral ligament in the right hindlimb of 15 skeletally mature (12 months old) New Zealand White rabbits. At postoperative intervals of 3, 6, or 14 weeks, histomorphometric analysis of the flaws was carried out in subgroups of animals. The medial collateral ligaments from four of the left hindlimbs (randomly selected) were used as uninjured contralateral controls. In one histologic section of each area of scar tissue and the analogous area in the controls, specified tissue flaws (blood vessels, fat cells, hypercellular areas, loose matrix, disorganized matrix, or a combination of these) were measured by four independent and blinded observers. The results showed that the mean total area of the flaws, as a percentage of the total section, and the mean area of the largest flaw decreased with healing time in each healing group but did not achieve control values by 14 weeks. Because it was not possible to test the healing medial collateral ligaments mechanically prior to measurement of the flaws (due to the destructive nature of failure testing), the data on the flaws were compared with the material strength and stiffness of a separate series of similarly injured and mechanically tested medial collateral ligaments (data published previously). A maximum likelihood statistical analysis showed a very strong functional association between the mean area of the largest flaw and the stress at failure (p < 0.004) and between the mean flaw area as a percentage of the total section area and the elastic modulus (p < 0.001). This study therefore demonstrates that it is possible to quantify material flaws in scar tissue in rabbit medial collateral ligaments, that these flaws become smaller with healing time as the scar remodels, and that flaws are functionally associated with the material properties of the ligament in this model (larger flaws with less tensile strength and more flaws with less stiffness).

Analysis of Variance↗

Primary immunolocalization of estrogen and progesterone target cells in the human anterior cruciate ligament.

To identify estrogen and progesterone target cells in the human anterior cruciate ligament immunohistochemical localization of both estrogen and progesterone receptors was performed in 17 specimens of human anterior cruciate ligament. All ligament specimens were obtained at surgery. Thirteen specimens were from women, and four were from men: the average age was 57 years (range, 18-78 years). Eleven specimens (from nine women and two men) came from total knee replacements for osteoarthritis of the knee: three (from two women and one man), from reconstructions of the anterior cruciate ligament: two (both from women), from medial meniscectomies; and one (from a man), from an amputation secondary to chondrosarcoma of the pelvis. An immunoperoxidase method using monoclonal antibodies to the estrogen and progesterone receptors was employed to identify estrogen and progesterone target cells in the anterior cruciate ligament. Staining of both receptors was demonstrable in 14 specimens and in the remaining three specimens less than 15% of the cells were stained. Both estrogen and progesterone receptors were localized to synoviocytes in the synovial lining, fibroblasts in the anterior cruciate ligament stroma and cells in the blood vessel walls of the ligament. This demonstration of receptors for estrogen and progesterone in the cells of anterior cruciate ligament suggests that female sex hormones may have an effect on its structure and composition.

Adolescent↗

Patellar tendon and anterior cruciate ligament have different mitogenic responses to platelet-derived growth factor and transforming growth factor beta.

The healing responses of the anterior cruciate ligament and the patellar tendon differ markedly. The anterior cruciate ligament fails to heal, whereas the patellar tendon heals slowly. The basis of these differences is unknown. Since cellular proliferation is a critical element of healing, we investigated the response to explants of anterior cruciate ligament and patellar tendon from sheep knees to platelet-derived growth factor-AB and transforming growth factor beta 1 as a function of time and dose. Explants cultured for 48, 72, and 96 hours with transforming growth factor beta 1 (0-100 ng/ml) or platelet-derived growth factor-AB (0-200 ng/ml) were radiolabeled for the final 24 hours with [3H]thymidine, and DNA synthesis was quantified as trichloroacetic acid-precipitable radioactivity normalized to dry tissue weight. Statistical analyses (analysis of variance) showed that transforming growth factor beta 1 induced a significant proliferative response in the anterior cruciate ligament at 96 hours with equivalent responses at 10, 50, and 100 ng/ml, whereas the patellar tendon only responded to one condition, 10 ng/ml at 96 hours. Conversely, the patellar tendon had a significant dose-dependent response to platelet-derived growth factor-AB at 72 and 96 hours, whereas the anterior cruciate ligament showed no proliferative response to platelet-derived growth factor-AB. The minimal response of anterior cruciate ligament to platelet-derived growth factor-AB could explain, at least in part, the poor repair capacity of this tissue. The response of the anterior cruciate ligament to transforming growth factor beta suggests that exogenous transforming growth factor beta may promote initial healing. Although growth factors have the potential to modulate soft-tissue repair, tissue responses in tendons and ligaments may vary at different anatomic sites.

Animals↗

Coloured microsphere assessment of blood flow to knee ligaments in adult rabbits: effects of injury.

Coloured microspheres were used to determine standardized blood flow in an established model of medial collateral ligament injury in the adult rabbit knee. Resting blood flow in the ligament was ascertained to be on the order of 0.68 +/- 0.08 ml/min/100 g (mean +/- SEM) in normal rabbit knees, although errors in flow estimates of this magnitude may be quite high. In healing medial collateral ligament, however, flow had increased markedly 3 weeks after injury (21.45 +/- 5.48 ml/min/100 g). Flows in sham-operated control medial collateral ligaments were not significantly increased compared with those in control normal ligaments. Six weeks after injury, blood flow in the ligament remained elevated (16.90 +/- 3.20 ml/min/100 g) and was similarly elevated in other neighbouring joint tissues (i.e., ipsilateral synovial fat pad). The increase in flow to ipsilateral noninjured articular tissues did not persist beyond 6 weeks, but flow in the healing medial collateral ligament scar tended to remain elevated after 17 weeks (4.20 +/- 1.79 ml/min/100 g), although this did not achieve statistical significance. We conclude from these data that it is possible to measure the increase in blood flow in injured and healing articular tissues using the coloured microspheres technique and that ligament injury is a potent stimulus for increasing blood flow. Coloured microsphere measurements of blood flow to joint connective tissues may offer a valuable approach to future investigations of joint injury and arthritis.

Animals↗

Evaluation of the effect of joint constraints on the in situ force distribution in the anterior cruciate ligament.

The function of the anterior cruciate ligament was investigated for different conditions of kinematic constraint placed on the intact knee using a six-degree-of-freedom robotic manipulator combined with a universal force-moment sensor. To do this, the in situ forces and force distribution within the porcine anterior cruciate ligament during anterior tibial loading up to 100 N were compared at 30, 60, and 90 degrees of flexion under: (a) unconstrained, five-degree-of-freedom knee motion, and (b) constrained, one-degree-of-freedom motion (i.e., anterior translations only). The robotic/universal force-moment sensor testing system was used to both apply the specified external loading to the intact joint and measure the resulting kinematics. After tests of the intact knee were completed, all soft tissues except the anterior cruciate ligament were removed, and these motions were reproduced such that the in situ force and force distribution could be determined. No significant differences in the magnitude of in situ forces in the anterior cruciate ligament were found between the unconstrained and constrained testing conditions. In contrast, the direction of in situ force changed significantly; the force vector in the unconstrained case was more parallel with the direction of the applied tibial load. In addition, the distribution of in situ force between the anteromedial and posterolateral bundles of the ligament was nearly equal for all flexion angles for the unconstrained case, whereas the anteromedial bundle carried higher forces than the posterolateral bundle at both 60 and 90 degrees of flexion for the constrained case. This demonstrates that the constraint conditions placed on the joint have a significant effect on the apparent role of the anterior cruciate ligament. Specifically, constraining joint motion to one degree of freedom significantly alters both the direction and distribution of the in situ force in the ligament from that observed for unconstrained joint motion (five degrees of freedom). Furthermore, the changes observed in the distribution of force between the anteromedial and posterolateral bundles for different constraint conditions may help elucidate mechanisms of injury by providing new insight into the response of the anterior cruciate ligament to different types of external knee loading.

Animals↗

Viability of fibroblast-seeded ligament analogs after autogenous implantation.

Fibroblast-seeded collagen scaffolds or ligament analogs are potentially useful for reconstruction of the anterior cruciate ligament of the knee. To provide lasting benefits, the seeded cells must survive implantation within the harsh synovial environment of the knee joint. Our objective was to determine the in vivo fate of autogenous fibroblast-seeded ligament analogs as a function of fibroblast source (anterior cruciate ligament or skin), implantation site (knee joint or subcutaneous space), and time after implantation (1, 2, 4, 6, or 8 weeks). Before implantation, fibroblasts were labeled with PKH26-GL, a fluorescent membrane dye. Immediately after retrieval of the implant, the viability of the labeled seeded cells was assessed under a fluorescent microscope. Viable seeded fibroblasts remained attached to the collagen fibers within the ligament analogs for at least 4 weeks (skin fibroblasts) or 6 weeks (anterior cruciate ligament fibroblasts) after implantation. A larger number of viable seeded cells were consistently observed in the subcutaneous space than in the knee joint. Scaffold resorption prevented observation at the 8-week time period. Fibroblast-seeded ligament analogs remained viable for prolonged periods in the knee joint and therefore have the potential to influence the formation and remodeling of neoligament tissue after reconstruction of the anterior cruciate ligament.

Animals↗

Identification of sex hormone receptors in human and rabbit ligaments of the knee by reverse transcription-polymerase chain reaction: evidence that receptors are present in tissue from both male and female subjects.

Gender-related factors have been attributed to observed differences in the rate of injury to ligaments (e.g., anterior cruciate ligament) between male and female subjects. These differences may be a result of unique regulatory mechanisms within the tissue in response to the sex hormones estrogen and progesterone. These hormones, when bound to specific intracellular receptors (estrogen receptor and progesterone receptor, respectively), modulate gene expression within hormone-responsive tissue. The purpose of this study was to evaluate the expression of the estrogen and progesterone receptors in ligament tissue from male and female rabbits and humans by the sensitive molecular technique of reverse transcription-polymerase chain reaction. Total RNA was extracted from human anterior cruciate ligament tissue and from medial cruciate ligament, anterior cruciate ligament, patellar tendon, and synovium tissue of the New Zealand White rabbit by the newly developed TRIspin method. The total RNA was reverse transcribed and analyzed by polymerase chain reaction to assess the expression of estrogen and progesterone receptors. Our results demonstrate that estrogen and progesterone receptor transcripts are expressed in ligament tissue of male and female rabbits and humans and that alterations in receptor expression occur in ligaments during pregnancy. In the human samples, only a small percentage of the estrogen receptor appeared to be a nonfunctional mRNA splice variant, and the predominant form contained the estrogen-binding domain.

Alternative Splicing↗