Expression of leptin, leptin receptor, and connective tissue growth factor in degenerative disk lesions in the wrist.

PURPOSE: The purpose of this study was to identify whether leptin and connective tissue growth factor (CTGF) occur in the degenerative fibrocartilage disk and whether cartilage cells express leptin receptors. METHODS: The study included 23 patients diagnosed with degenerative articular disk tears of the triangular fibrocartilage (TFC) (Palmer type 2C). Patients were divided into 2 groups based on ulna length: 1 group consisted of patients with an ulna-positive variance (group A), and the other group included patients with ulna-negative or -neutral variance (group B). After arthroscopic debridement of the TFC, histologic sections of biopsy specimens were prepared. The biopsy specimens were immunohistochemically analyzed, and the quantity of leptin-, CTGF-, and leptin receptor-positive cells was assessed. RESULTS: Cells positive for leptin, leptin receptor, and CTGF were found. The number of cells positive for leptin was significantly increased in specimens of patients with an ulna-negative variance (group B). In contrast, no significant difference was found for leptin receptor and CTGF in biopsy specimens of patients with ulna-positive or ulna-negative/neutral variance. The inner, middle, and outer zones of the disk do not express significantly different quantities of marker-positive cells. CONCLUSIONS: Degenerative fibrocartilage disk tissue cells exhibit leptin receptors and are exposed to the markers leptin and CTGF, providing evidence of a local paracrine system and regenerative processes. Cells of disks from patients with an ulna-neutral/negative length express significantly higher numbers of leptin-positive cells. LEVEL OF EVIDENCE: Level II, diagnostic study.

Nerve fiber staining investigations in traumatic and degenerative disc lesions of the wrist.

PURPOSE: Traumatic and degenerative disc lesions cause ulnar-sided wrist pain. To date, anatomical investigations of cadaver triangular fibrocartilage discs examining the innervation of the triangular fibrocartilage complex have found no evidence of nerve fibers in the healthy disc. In this study, we immunohistologically investigated biopsies from patients with either central traumatic or degenerative disc lesions, to determine the existence of nerve fibers. We hypothesized that an ingrowth of nerve fibers causes ulnar-sided wrist pain associated with traumatic and degenerative disc lesions. METHODS: We included 32 patients with a traumatic Palmer 1A lesion and 17 patients with a degenerative Palmer 2C lesion in the study. We obtained a biopsy of each patient and stained the specimen with protein gene product 9.5 for nerve fiber detection. RESULTS: There were no nerve fibers in either traumatic or degenerative disc lesions. In addition, the marginal areas of the biopsies showed no evidence of nerve fibers. CONCLUSIONS: Traumatic and degenerative disc lesions show no ingrowth of nerve fibers.

Expression of TRAIL and death receptor DR4 in Palmer type 2 TFCC lesions.

INTRODUCTION: Degenerative articular disc perforations of the triangular fibrocartilage (TFC) of the wrist are characterized by fibrocartilage cell loss and are often associated with ulna-plus situations. Apoptosis has been found to play a crucial role in fibrocartilage cell loss, however, the molecular mechanism and mediators are still poorly understood. AIM: The purpose of this study was to identify receptors to apoptosis in degenerative disc lesions. PATIENTS: Included in the study were 17 patients with degenerative articular disc tears of the TFC (Palmer type 2C). Following arthroscopic debridement of the TFC, histological sections were examined to assess the presence of apoptosis. Apoptosis was determined using TRAIL and death receptor DR4 agonists for immunohistochemical analyses. The number of cells positive for apoptosis was then correlated with ulna length. RESULTS: Cells positive for TRAIL and DR4 were found in all specimens. The number of cells positive for TRAIL was significantly increased in specimens of patients with an ulna positive variance (P = 0.040). However, DR4 was not significantly increased in ulna plus (P > 0.05). Both, TRAIL and DR4 positive cells were found to be evenly distributed throughout each specimen. There was no accumulation of any type of cells in any particular zone of the biopsies. CONCLUSION: This is the first study that shows that TFCC cells express TRAIL and DR4, which suggests that apoptosis, as well as, mechanical trauma are involved in the development of disc perforation. The TRAIL/DR4 receptor system is a molecular mediator of apoptosis induction in TFC cells and therefore plays a role in cell loss in degenerative disc lesions.

Cartilage cell proliferation in degenerative TFCC wrist lesions.

INTRODUCTION: The central zone of the triangular fibrocartilage complex (TFCC) of the wrist is thought to be avascular and is generally considered to lack any healing potential. AIM: The purpose of this study was to investigate, if cartilage cells of degenerative disc lesions possess any healing or proliferation potential and whether ulna length plays a significant role in the proliferation process. RESULTS: Cells positive for proliferating cell nuclear antigen (PCNA) were found in all specimens. Specimens of patients with ulna positive variance showed a decreased number of PCNA positive cells than specimens of patients with either negative or neutral ulna variance. CONCLUSION: We found that cartilage cells of Palmer type 2C lesions undergo mitotic cell division, thus exhibiting proliferation capability. It could not be shown that ulnar length is significantly correlated with the number of PCNA positive cells.

Ulnar shortening after TFCC suture repair of Palmer type 1B lesions.

PURPOSE: The objective of this study was to determine functional and subjective outcomes of an ulnar shortening procedure elected by patients who experienced persistent ulno-carpal symptoms following arthroscopic suture repair of a Palmer type 1B lesion. All patients had a dynamic ulna positive variance. METHODS: Five patients (3 males and 2 females) with arthroscopic repair of Palmer type 1B tears who subsequently underwent ulnar shortening were reviewed. At the time of the arthroscopic repair the patients' average age was 37 +/- 13 years (range 16-52 years). Average time to follow-up was 14 +/- 6 months (range 10-23 months). The average age was 38 +/- 14 years (range 17-53 years) when the ulnar shortening was performed. The second follow-up took place 7 +/- 2 months (range 5-9 months) after ulnar shortening. During the follow-ups, range of motion, grip strength, pain, Modified Mayo Wrist Score, DASH Score, and ulnar length were evaluated. Citing persistent ulno-carpal symptoms, the patients elected ulnar shortening an average of 17 +/- 7months (range 13-29 months) following the arthroscopic repair. Prior to ulnar shortening the average static ulnar variance was 0.2 +/- 1.3 mm (range -1 to 2 mm), the average dynamic ulnar variance was 1.4 +/- 0.5 mm (range 1 to 2 mm). RESULTS: Ulnar shortening brought about further reduction in pain after the arthroscopic repair of the triangular fibrocartilage complex (TFCC) had already reduced it. As measured by a visual analogue scale, the average value after ulnar shortening was 2.2 +/- 2.1 (range 0.7-5.0). The average static ulnar variance was -3.4 +/- 2 mm (range -5 to -1 mm). Patients were very satisfied with the results of the ulnar shortening and four out of five indicated that it had significantly improved their symptoms and they would elect ulnar shortening again. Postoperative range of motion as a percentage of the contralateral side averaged 90% for the extension/flexion arc, 80% for the radial/ulnar deviation arc, and 100% for the pronation/supination arc of motion. In addition, there was an improvement in grip strength. The Modified Mayo Wrist Score was rated excellent in three patients, and fair in two patients. The average DASH score was 22 +/- 22 (range 0-53). CONCLUSIONS: Patients who have a dynamic ulna positive variance and experience persistent ulno-carpal symptoms following arthroscopic suture repair of a Palmer type 1B lesion, benefit from an ulnar shortening procedure. Shortening the ulna can improve these patients' symptoms of pain, range of motion, and grip strength.

Apoptotic pathways in degenerative disk lesions in the wrist.

PURPOSE: Degenerative articular disk perforations of the triangular fibrocartilage (TFC) of the wrist could result from chronic loading of the ulnocarpal joint. Apoptosis played a crucial role in fibrocartilage cell loss, and the purpose of this study was to clarify which apoptotic pathway was involved in the development of degenerative disk lesions. We also investigated whether ulna length played an etiologic role in the occurrence of fibrocartilage cell loss. METHODS: Included in the study were 17 patients with degenerative articular disk tears of the TFC (Palmer type 2C). After arthroscopic debridement of the TFC, histologic sections were examined to assess the presence of apoptosis. Apoptosis was determined by use of caspase 3, caspase 8, and caspase 9 immunohistochemistry. Furthermore, Fas ligand and BID (BH3 interacting domain death) agonist were applied for immunohistochemical analysis. RESULTS: Cells positive for caspase 3, caspase 8, caspase 9, Fas ligand, and BID were found in all specimens. The number of cells positive for caspase 3 and BID was significantly increased in specimens from patients with an ulna-positive variance. In contrast, for cells positive for caspase 8, caspase 9, and Fas ligand, no significant difference was found between specimens from patients with an ulna-positive variance and those from patients with an ulna-neutral/ulna-negative variance. CONCLUSIONS: The extrinsic and intrinsic apoptotic pathways are involved in the development of degenerative disk lesions. Fibrocartilage cell loss occurs mainly through the intrinsic apoptotic pathway. The accumulation of apoptotic cells is not significantly different between the 3 zones of the TFC. It could be verified that ulna length is correlated with fibrocartilage cell loss. CLINICAL RELEVANCE: Ulnar shortening is a valuable treatment option for degenerative TFC lesions. Knowledge of the specific apoptotic pathway that is causing degenerative disk lesions is critical in selecting the appropriate and most beneficial therapeutic treatment to halt further cell loss and the degeneration of the TFC.

Incidence and distribution of blood vessels in punch biopsies of Palmer 1A disc lesions in the wrist.

INTRODUCTION: Although the partial excision of triangular fibrocartilage complex (TFCC) tears appears to be a clinically effective technique, little is known about the ability of the central disc tears to heal. Unlike peripheral tears, central tears do not have immediate access to blood supply. The purpose of this study was to examine the incidence and distribution of blood vessels in punch biopsies of symptomatic central TFCC tissue. In addition, the study investigated if arthroscopic debridement can reach vascularized tissue to enable a reparative response of the tear. MATERIALS AND METHODS: Thirty-two patients with symptomatic central traumatic tears in the TFCC (Palmer 1A) were included in this study. The cartilage was debrided arthroscopically using a biopsy punch. The debrided tissue was then examined histologically. To visualize blood vessels, the histological sections were stained with CD 31 antibodies. The presence/absence of blood vessels was recorded on a qualitative level. RESULTS: In six patients, five or more blood vessels (CD31 positive endothelial cells) could be detected. In eight patients, fewer than five vessels could be found in the periphery of the slides. In 18 patients no vessels could be identified. The incidence of vessels in the outer region was higher than in the inner region of the peripheral area. There was no correlation found between the time of trauma and incidence of blood vessels (P > 0.05). CONCLUSION: Only in 43% of arthroscopic debridements of Palmer 1A tears vascularized tissue could be reached.

Changes in gene expression and protein distribution at different stages of mechanically induced disc degeneration--an in vivo study on the New Zealand white rabbit.

The objective of the study was to improve the biological understanding of degenerative disc disease using a rabbit model in which different stages of disc degeneration are induced by variation of the duration of loading with an external compression-device applying 2.4 MPa. Gene expression and protein distribution were analyzed in controls and after 1, 28, and 56 days of hyperphysiologic loading. To evaluate extracellular matrix genes, quantitative real-time reverse-transcriptase polymerase chain reaction was applied for collagen I, collagen II, biglycan, decorin, fibromodulin, fibronectin, aggrecan, and osteonectin. As representatives of catabolic, anticatabolic, and anabolic factors, matrix metalloproteinase-13 (MMP-13), tissue inhibitor of matrix metalloproteinase-1 (TIMP-1), and bone morphogenetic protein-2 (BMP-2) were chosen. To evaluate protein distribution, immunohistochemistry was performed for collagen I, collagen II, and BMP-2/4. Matrix gene expression was characterized by two major developments: collagen I and II, biglycan, and decorin showed early elevation followed by later downregulation to control levels, whereas fibromodulin, fibronectin, aggrecan, and osteonectin showed continuous upregulation or remained at similar levels. Induction of MMP-13 gene expression was found in degenerated discs. TIMP-1 and BMP-2 were elevated immediately after hyperphysiologic loading and presented highest levels in the 56-day group. Immunohistochemistry showed less collagen II and BMP-2/4 positive cells after compression. In conclusion, elevated matrix gene expression represents an early cellular response to hyperphysiologic loading. As degeneration progresses, some matrix genes increase upregulation, whereas others start downregulation. Continuous upregulation of catabolic, anticatabolic, and anabolic factors indicates their important role in the degeneration process.

Biomechanical testing of bioabsorbable cannulated screws for slipped capital femoral epiphysis fixation.

This study compared cannulated 4.5-mm bioabsorbable screws made of self-reinforced poly-levolactic acid to cannulated 4.5-mm steel and titanium screws for resistance to shear stress and ability to generate compression in a polyurethane foam model of slipped capital femoral epiphysis fixation. The maximum shear stress resisted by the three screw types was similar (self-reinforced poly-levolactic acid 371 +/- 146 MPa, steel 442 +/- 43 MPa, and titanium 470 +/- 91 MPa). The maximum compression generated by both the self-reinforced poly-levolactic acid screw (68.5 +/- 3.3 N) and the steel screw (63.3 +/- 5.9 N) was greater than that for the titanium screw (3 +/- 1.4 N, P <.05). These data suggest cannulated self-reinforced poly-levolactic acid screws can be used in the treatment of slipped capital femoral epiphysis because of their sufficient biomechanical strength.

Subjective and functional outcome after revision surgery in carpal tunnel syndrome.

INTRODUCTION: In spite of carpal tunnel release's prevalent good postoperative results, the number of revision surgeries needed should not be underestimated. In this study, subjective and functional results after carpal tunnel revision surgery were determined. MATERIALS AND METHODS: Thirty-eight patients were examined approximately 2 years after their revision surgery of the carpal tunnel release. The subjective outcome of the patients was assessed using two different questionnaires (Amadio and DASH). A clinical examination was undertaken on selected patients who had persistent complaints. The clinical assessment analyzed grip strength, thumb opposition, pulp-to-pulp-pinch, key-pinch, hook-grip, Moberg-Pickup-test, two-point-discrimination, Phalen-test, and the Hoffmann-Tinel-sign. RESULTS: The subjective assessment showed that after the revision surgery, patients experienced load induced pain that occurred during daytime. However, the revision was able to improve the impaired sensibility. The functional outcome showed a persistent lack of strength when performing daily activities. The clinical assessment of the patients with relevant complaints confirmed the subjective outcome. CONCLUSION: The revision surgery can improve the impaired sensibility, particularly, paresthesia nocturna. The persistent weakness of the hand can only partly be improved. In spite of remaining complaints, revision surgery can yield satisfactory results for the patients.

Intradiscal pressure measurements in normal discs, compressed discs and compressed discs treated with axial posterior disc distraction: an experimental study on the rabbit lumbar spine model.

Intervertebral disc (IVD) pressure measurement is an appropriate method for characterizing spinal loading conditions. However, there is no human or animal model that provides sufficient IVD pressure data. The aim of our study was to establish physiological pressure values in the rabbit lumbar spine and to determine whether temporary external disc compression and distraction were associated with pressure changes. Measurements were done using a microstructure-based fibreoptic sensor. Data were collected in five control rabbits (N, measurement lying prone at segment L3/4 at day 28), five rabbits with 28 days of axial compression (C, measurement at day 28) and three rabbits with 28 days of axial compression and following 28 days of axial distraction (D, measurement at day 56). Disc compression and distraction was verified by disc height in lateral radiographs. The controls (N) showed a level-related range between 0.25 MPa-0.45 MPa. The IVD pressure was highest at level L3/4 (0.42 MPa; range 0.38-0.45) with a decrease in both cranial and caudal adjacent segments. The result for C was a significant decrease in IVD pressure (0.31 MPa) when compared with controls (P=0.009). D showed slightly higher median IVD pressure (0.32 MPa) compared to C, but significantly lower levels when compared with N (P=0.037). Our results indicate a high range of physiological IVD pressure at different levels of the lumbar rabbit spine. Temporary disc compression reduces pressure when compared with controls. These data support the hypothesis that temporary external compression leads to moderate disc degeneration as a result of degradation of water-binding disc matrix or affected active pumping mechanisms of nutrients into the disc. A stabilization of IVD pressure in discs treated with temporary distraction was observed.

Effects of unisegmental disc compression on adjacent segments: an in vivo animal model.

It is controversial whether fusion of discs in the spine leads to increased degeneration on the remaining discs or whether the degenerative changes are merely a part of the inevitable natural history process. To determine the effects of unisegmental compression and subsequent recovery on adjacent segments, we studied histology, radiology and intradiscal pressure using an in vivo rabbit model. Fifteen New Zealand rabbits were divided in to three groups of five. In the first group, the intervertebral disc L4-L5 of the lumbar spine was axially loaded for 28 days with an external loading device. In the second group, the intervertebral disc was compressed for 28 days and allowed to recover for an equal amount of time, with the loading device removed. Five animals underwent a sham operation, in which the external loading device was situated, but their discs remained unloaded for 28 days. The intradiscal pressure was determined in the loaded discs as well as in the cranial and caudal adjacent discs. Lateral radiographs were taken from each subjected intervertebral disc with adjacent vertebral bodies and the cranial and caudal adjacent segments. The compressed discs showed lower intradiscal pressure in comparison with the control group, which remained unloaded. In the cranial and caudal discs adjacent to the loaded discs the average intradiscal pressure was similar to the unloaded controls. The loaded discs demonstrated a significant decrease in disc space. No discs adjacent to the loaded discs changed in height. The lamellar architecture of the inner, middle, and outer annulus became more disorganized in the loaded discs. The nucleus pulposus showed increase of mucoid degeneration and increased cell death. Intervertebral discs from the control group and the adjacent discs to the compressed discs maintained their normal morphology. This study shows that mechanical loading of discs in the spine can cause rapid degeneration. Adjacent discs, however, did not change in terms of radiology, intradiscal pressure, or histology.

New in vivo animal model to create intervertebral disc degeneration and to investigate the effects of therapeutic strategies to stimulate disc regeneration.

STUDY DESIGN: A new rabbit model was developed that produces disc degeneration through the application of controlled and quantified axial mechanical load. OBJECTIVES: To characterize the changes associated with disc degeneration, and to evaluate the feasibility of local transfer of agents to the compressed discs to stimulate disc regeneration. SUMMARY OF BACKGROUND DATA: Studies have shown that accelerated degeneration of the intervertebral disc results from altered mechanical loading conditions. The development of methods for the prevention of disc degeneration and the restoration of disc tissue that has already degenerated is needed. METHODS: New Zealand white rabbits (n = 33) were used for this study. The discs in five animals remained unloaded and served as controls, whereas in 28 animals the discs were axially compressed using a custom-made external loading device. After 1 (n = 7), 14 (n = 7), and 28 (n = 7) days of dynamic loading, or 28 (n = 7) days of loading followed by 28 days of unloaded recovery time, the animals were killed and the lumbar spine was harvested for tissue preparation. Disc height, disc morphology, cell viability, disc stiffness, and load to failure were measured. Recombinant adenovirus encoding for two different marker genes (Ad-Luciferase and Ad-LacZ) was injected into the discs in loaded specimens and the gene expression was measured. RESULTS: The unloaded intervertebral discs of the rabbits consisted of a layered anulus fibrosus, a cartilaginous endplate, and a nucleus pulposus comparable with those of humans. After 14 and 28 days of loading, the discs demonstrated a significant decrease in disc space. Histologically, disorganization of the architecture of the anulus occurred. The number of dead cells increased significantly in the anulus and cartilage endplate. These changes were not reversible after 28 days of unloading. The stiffness and the load to failure did not change significantly in the discs after 28 days of loading, as compared with the unloaded control discs. Adenovirus-mediated gene transfer to discs was tolerated by all the animals. LacZ gene expression was found 2 weeks after injection of AdLacZ in loaded disc cells. CONCLUSIONS: The results of this study suggest that disc degeneration can be induced by axial dynamic loading in the rabbit intervertebral disc. The compressed rabbit intervertebral discs were large enough for the application of local transmitters through a percutaneous approach. We anticipate that this animal model could be used as a basic model to study intervertebral disc degeneration and to investigate new local therapeutic strategies for maintaining disc health or initiating tissue repair.