Minimally invasive spinal decompression for degenerative lumbar spondylolisthesis and stenosis maintains stability and may avoid the need for fusion.

Aims: The aim of this study was to investigate the clinical and radiographic outcomes of microendoscopic laminotomy in patients with lumbar stenosis and concurrent degenerative spondylolisthesis (DS), and to determine the effect of this procedure on spinal stability. Patients and Methods: A total of 304 consecutive patients with single-level lumbar DS with concomitant stenosis underwent microendoscopic laminotomy without fusion between January 2004 and December 2010. Patients were divided into two groups, those with and without advanced DS based on the degree of spondylolisthesis and dynamic instability. A total of 242 patients met the inclusion criteria. There were 101 men and 141 women. Their mean age was 68.1 years (46 to 85). Outcome was assessed using the Japanese Orthopaedic Association and Roland Morris Disability Questionnaire scores, a visual analogue score for pain and the Short Form Health-36 score. The radiographic outcome was assessed by measuring the slip and the disc height. The clinical and radiographic parameters were evaluated at a mean follow-up of 4.6 years (3 to 7.5). Results: There were no significant differences in the preoperative measurements between the group and no significant differences between the clinical parameters at the final follow-up. The mean percentage slip was 17.1% preoperatively and 17.7% at the final follow-up (p = 0.35). Progressive instability was noted in 13 patients (8.2%) with DS and 6 patients (7.0%) with advanced DS, respectively (p = 0.81). There was radiological evidence of restabilization of the spine in 30 patients (35%) with preoperative instability. The success rate of microendoscopic laminotomy was good/excellent in 166 (69%), fair in 49 (20%) and poor in 27 patients (11%) in both groups. Conclusion: Microendoscopic laminotomy is an effective form of surgical treatment for patients with DS and stenosis. Preservation of the stabilizing structures using this technique prevents postoperative instability. Cite this article: Bone Joint J 2018;100-B:499-506.

Progression, incidence, and risk factors for intervertebral disc degeneration in a longitudinal population-based cohort: the Wakayama Spine Study.

OBJECTIVE: The present study examined the progression, incidence, and risk factors for intervertebral disc degeneration (DD) throughout the lumbar spine using magnetic resonance imaging (MRI) in a large population-based cohort. METHODS: We followed up 617 subjects for more than 4 years as part of the Wakayama Spine Study. 1) "Progression of DD" in each of the entire, upper (L1/2 to L3/4) and lower (L4/5 and L5/S1) lumbar spine was defined as Pfirrmann grade progression at follow-up in at least one disc in the affected region. 2) "Incidence of DD" in each of these regions was defined if all discs were grade 3 or lower (white disc) at baseline, and at least one disc had progressed to grade 4 or higher (black disc) at follow-up. Logistic regression analyses were used to determine the risk factors for progression and incidence of DD. RESULTS: DD progression and incidence in the entire lumbar spine were 52.0% and 31.6% in men, and 60.4% and 44.7% in women, respectively. Women was associated with DD progression in the upper lumbar spine (odds ratio [OR] = 1.68, 95% confidence interval [CI] = 1.18-2.42). Aging was associated with the incidence of DD in each region (entire: OR = 1.14, CI = 1.06-1.14; upper: OR = 1.10, CI = 1.05-1.15; lower: OR = 1.11, CI = 1.05-1.19). Diabetes mellitus (DM) was associated with the incidence of DD in the upper lumbar spine (OR = 6.83, CI = 1.07-133.7). CONCLUSION: This 4-year longitudinal study is the first to demonstrate DD progression and incidence in the lumbar spine and their risk factors in a large population-based cohort.

Prevalence and distribution of intervertebral disc degeneration over the entire spine in a population-based cohort: the Wakayama Spine Study.

OBJECTIVES: The purposes of this study were to investigate the prevalence and distribution of intervertebral disc degeneration (DD) over the entire spine using magnetic resonance imaging (MRI), and to examine the factors and symptoms potentially associated with DD. DESIGN: This study included 975 participants (324 men, mean age of 67.2 years; 651 women, mean age of 66.0 years) with an age range of 21-97 years in the Wakayama Spine Study. DD on MRI was classified into Pfirrmann's system (grades 4 and 5 indicating DD). We assessed the prevalence of DD at each level in the cervical, thoracic, and lumbar regions and the entire spine, and examined DD-associated factors and symptoms. RESULTS: The prevalence of DD over the entire spine was 71% in men and 77% in women aged <50 years, and >90% in both men and women aged >50 years. The prevalence of an intervertebral space with DD was highest at C5/6 (men: 51.5%, women: 46%), T6/7 (men: 32.4%, women: 37.7%), and L4/5 (men: 69.1%, women: 75.8%). Age and obesity were associated with the presence of DD in all regions. Low back pain was associated with the presence of DD in the lumbar region. CONCLUSION: The current study established the baseline data of DD over the entire spine in a large population of elderly individuals. These data provide the foundation for elucidating the causes and mechanisms of DD.

Associations between radiographic lumbar spinal stenosis and clinical symptoms in the general population: the Wakayama Spine Study.

OBJECTIVE: Many asymptomatic individuals have radiographic lumbar spinal stenosis (LSS), but the prevalence of symptoms among individuals with radiographic LSS has not yet been established. The purpose of this study was to clarify the association between radiographic LSS and clinical symptoms in the general population. METHODS: In this cross-sectional study, data from 938 participants (308 men, 630 women; mean age, 66.3 years; range, 40-93 years) were analyzed. The severity of radiographic LSS, including central stenosis, lateral stenosis, and foraminal stenosis, was assessed by mobile magnetic resonance imaging and rated qualitatively. Assessment of clinical symptoms was based on the definition of symptomatic LSS in the North American Spine Society guideline. RESULTS: We found that 77.9% of participants had more than moderate central stenosis and 30.4% had severe central stenosis. Logistic regression analysis after adjustment for age, sex, body mass index, and severity of radiographic LSS showed that severe central stenosis was related to clinical symptoms. However, only 17.5% of the participants with severe central stenosis were symptomatic. CONCLUSION: Although radiographic LSS was common in our cohort, which resembled the general Japanese population, symptomatic persons were relatively uncommon.

Prevalence of symptomatic lumbar spinal stenosis and its association with physical performance in a population-based cohort in Japan: the Wakayama Spine Study.

OBJECTIVE: The purpose of this study was to investigate the prevalence of symptomatic lumbar spinal stenosis (LSS) and to clarify the association between symptomatic LSS and physical performance using magnetic resonance imaging (MRI) in a population-based cohort. DESIGN: This cross-sectional study was performed as a part of the research on osteoarthritis/osteoporosis against disability (ROAD) in Japan and 1,009 subjects (335 men, 674 women, mean age 66.3 years, age range 21-97 years) were analyzed. An experienced orthopedic surgeon obtained the medical history and performed the physical testing for all participants. Symptomatic LSS diagnostic criteria required the presence of both symptoms and radiographic LSS findings. A 6-m walking time, chair standing time, and one-leg standing time were obtained from all participants. RESULTS: The prevalence of symptomatic LSS was 9.3% (95% confidence interval [CI]: 7.7-11.3) overall, 10.1% (CI: 7.4-13.8) in men and 8.9% (CI: 7.0-11.3) in women. There was a difference in the prevalence with increasing age by gender. The LSS prevalence showed little difference with age greater than 70 years for men, but the LSS prevalence for women was higher with increasing age. Among physical performance measures, 6-m walking time at a maximal pace was significantly associated with symptomatic LSS (P = 0.03). CONCLUSION: The prevalence of symptomatic LSS was approximately 10% in a cohort resembling the general Japanese population. A 6-m walking time at a maximal pace was a more sensitive index than walking at a usual pace in assessing decreased physical performance associated with symptomatic LSS.

Observations in the diagnosis of cervical myelopathy in patients suffering from diabetes mellitus.

OBJECTIVES: To identify any observations that could aid in the diagnosis of cervical myelopathy in patients suffering from diabetes mellitus (DM). We compared the preoperative neurological findings in patients with cervical myelopathy among non-diabetics, mild diabetics and severe diabetics. STUDY DESIGN: A retrospective comparative study. SETTING: Department of Orthopaedic Surgery, Wakayama Medical University, Japan. METHODS: We retrospectively reviewed 111 patients who had undergone laminoplasty for cervical compressive myelopathy: 56 without DM and 29 with severe diabetes more than 10 years of medication; more than 7.0% HbA1c; diabetic retinopathy; and delayed conduction velocity of peripheral nerves. For preoperative neurological assessment we compared the following among the three groups: the 10 s test whereby the myelopathy in the hand was quantified; sensory disturbance; deep tendon reflexes; Hoffmann's, Trömner's and Babinski's reflexes; and bladder dysfunction. RESULTS: There was no significant difference preoperatively in the 10 s test between the groups. Deep tendon reflexes were significantly decreased in group S. There were no significant differences in sensory disturbance and bladder dysfunction. Although Hoffmann's and Trömner's reflexes significantly disappeared in group S, there was no significant difference in positivity of Babinski's reflex between the groups. CONCLUSIONS: The 10 s test and Babinski's reflex are helpful for the diagnosis of cervical myelopathy in patients suffering from DM.

Posterior endoscopic surgery for lumbar disc herniation with contralateral symptoms - a report of two cases.

We report two cases of lumbar disc herniation with contralateral nerve root involvement, surgically treated with a microendoscopic disectomy system (METRx-MED system). The nerve root of the symptomatic side (contralateral to the side of the disc herniation) had been compressed to the superior facet by herniated disc from the opposite side. Endoscopic observation revealed inflammatory findings of the nerve root on the symptomatic side, such as fibrosis, adhesion, redness and swelling. In contrast, on the non-symptomatic side (ipsilateral side of the disc herniation), the nerve root had been merely compressed by the herniated disc but did not demonstrate any inflammatory findings. Excision of the herniated disc and decompression of the non-symptomatic nerve root should be done first, approaching from the disc herniation side. After that, through the same approach, the nerve root of the opposite (symptomatic) side should be decompressed.

The use of sintered bone in spinal surgery.

The sintered bovine bone True Bone Ceramics (TBC) is one of the biomaterials based on calcium phosphate, an organized crystal of bone mineral and a biomaterial possessing a natural trabecular structure. We examined whether the sintered bovine bone can integrate with recipient bone and adjust to the strength of recipient bone for anterior spinal fusion in an animal model. Based on radiographic evaluation, manual palpation, biomechanical testing, and histological examination, spinal fusion with TBC resulted in a composition and structure similar to that of autograft (and to no implantation). TBC, with its moderate strength, tended to adjust to the bone stiffness of the host bone in the respective specimens as new bone growth developed. Our observations warrant further clinical investigation of the use of sintered bone as an effective spinal arthrodesis, especially in patients who have fragile vertebrae, as in osteoporosis.

Evaluation of carriers of bone morphogenetic protein for spinal fusion.

STUDY DESIGN: Posterolateral lumbar transverse process fusion in a rabbit model was performed using two different carriers for recombinant human morphogenetic protein-2, one having a porous structure and the other being a Type I collagen sheet. OBJECTIVES: To compare the effectiveness of two different carriers for recombinant human morphogenetic protein-2 in achieving lumbar intertransverse process arthrodesis. SUMMARY OF BACKGROUND DATA: The application of osteoinductive growth factors at various anatomic sites, such as in long bones and spinal segments, has been performed experimentally by many researchers. Although many carriers of osteoinductive factors have been reported, the most effective carrier has not been established. We have reported the efficacy of sintered bovine bone, True Bone Ceramics, which is coated with Type I collagen as a carrier of recombinant human bone morphogenetic protein-2 in achieving lumbar intertransverse process arthrodesis. True Bone Ceramics is a crystallized form of bone minerals made from sintering bovine bone at high temperatures and possesses natural trabecular structure. The crystalline character of True Bone Ceramics is similar to that of artificial hydroxyapatite. In this study we focused on the structure of two different carriers to facilitate osteosynthesis in lumbar arthrodesis. METHODS: Fifty-four adult rabbits underwent bilateral lumbar intertransverse process arthrodesis at L4-L5. The animals were divided into five groups and had implants placed as follows: Group 1, autograft group, harvested autologous corticocancellous bone from the posterior iliac crest; Group 2, TBC group, True Bone Ceramics alone; Group 3, TBC-TBMP group, True Bone Ceramics coated with Type I collagen infiltrated with 100 microg of recombinant human bone morphogenetic protein-2; Group 4, collagen group, Type I collagen sheet; and Group 5, collagen-BMP group, implanted collagen sheet containing 100 microg of recombinant human bone morphogenetic protein-2. Spinal fusion was evaluated by radiographic analysis, manual palpation, biomechanical testing, and histologic examination at both 3 and 6 weeks after surgery. RESULTS: Radiographs in the TBC-TBMP group showed a continuous trabecular pattern within the intertransverse area at 3 weeks after surgery. The fusion mass in the intertransverse area was more prominent than in the other groups. At 3 weeks after surgery the TBC-TBMP group had higher fusion rates based on manual palpation, and the fusions showed significantly higher tensile strength and stiffness. The histologic findings in the TBC-TBMP group at 3 weeks after surgery showed a cortical bone rim around the edge of the fusion mass, and contiguous new bone appearing between the recipient bone and the matrix of TBC without evidence of foreign body formation. In the collagen-BMP group, less mature bone formation was present within the grafted area and the new bone was not contiguous, even at 6 weeks after surgery. CONCLUSIONS: As a carrier for recombinant human bone morphogenetic protein-2, True Bone Ceramics, possessing a bony or porous structure, was more effective than a Type I collagen sheet in achieving a faster and stronger lumbar spinal fusion in a rabbit model.

Mechanical compression of the lumbar nerve root alters pain-related behaviors induced by the nucleus pulposus in the rat.

The purpose of this study was to refine a method of nerve-root injury in the rat to produce hyperalgesia, a pain-related behavior, and to determine if there were any relationships between the histological extent of nerve-root injury and the magnitude of hyperalgesia. Three methods were used to produce hyperalgesia: irritation of a nerve root by ectopic nucleus pulposus, silk loop alone, or both silk loop and ectopic nucleus pulposus. Autologous nucleus pulposus obtained from coccygeal intervertebral discs was relocated on the lumbar nerve roots after laminectomy. Two loops of 4-0 silk were placed around the exposed nerve roots. Hyperalgesia was measured preoperatively and postoperatively. The distribution of myelinated axons in the dorsal nerve roots was evaluated histologically. Mechanical hyperalgesia was detected in rats in which autologous nucleus pulposus was applied to the nerve root but not in those in which silk loops were used. Silk loops around the nerve root resulted in thermal hyperalgesia only in rats in which autologous nucleus pulposus was applied to the nerve root. Fewer large myelinated fibers were seen in the rats in which silk loops were used. Although a silk loop around the nerve root was not sufficient to produce hyperalgesia, supplemental application of autologous nucleus pulposus to the nerve root produced thermal hyperalgesia. It is possible that mechanical constriction of the nerve root alters the pain-related behavior elicited by chemical factors from the nucleus pulposus.

An experimental approach to spinal fusion using sintered bovine bone in a pig model.

Sintered bovine bone is a biomaterial based on calcium phosphate, an organized crystal of bone mineral that possesses a natural trabecular structure. The authors considered whether sintered bovine bone can integrate with recipient bone and adjust to the strength of recipient bone for anterior spinal fusion in an animal model. Either autologous iliac bone or sintered bovine bone was implanted for a spinal body fusion. Some pigs underwent exposure of the spinal bodies without implantation. Based on radiographic evaluation, manual palpation, biomechanical testing, and histologic examination, spinal fusion with sintered bovine bone resulted in a composition and structure similar to that of the autograft (or of no implantation). The sintered bovine bone with its moderate strength tended to adjust to the bone stiffness of the host bone in the specimens as new bone grew.

Expression of involucrin by ocular surface epithelia of patients with benign and malignant disorders.

PURPOSE: Keratinization of the ocular surface epithelium is associated with various disorders impairing vision. We immunohistochemically determined whether the ocular surface epithelia express involucrin, and whether its expression pattern may differ in benign vs. malignant disorders. Expression of cytokeratins was also examined to provide further information relative to the epithelial differentiation. METHODS: We evaluated 17 specimens; 6 specimens of the normal ocular surface epithelia, 3 specimens from cases of conjunctival intraepithelial neoplasia (CIN), 6 of conjunctival squamous cell carcinoma (SCC) and 2 of conjunctivae from cases of superior limbic keratoconjunctivitis (SLK). RESULTS: Corneal epithelium exhibited intracellular immunoreactivity for involucrin. Four of the 6 specimens of bulbar conjunctival epithelium showed involucrin immunoreactivity in the perimembranous region, whereas the fornical conjunctiva was negative. Cornified envelope in SLK specimens was positive for involucrin. The CIN showed its immunoreactivity in the perimembranous region in all levels of the hyperproliferative epithelium without keratinization, i.e., similar to the bulbar conjunctiva. The neoplastic cells of well-differentiated SCC showed involucrin in the perimembranous region, and those of moderately- to poorly-differentiated SCC have involucrin in their cytoplasm. The expression pattern of cytokeratins was unrelated to grade of malignancy in ocular SCC. CONCLUSION: The epithelia of normal subjects and of CIN expresses involucrin without keratinization. In contrary, the keratinized SLK epithelium markedly expresses involucrin in the cornified envelope. The subcellular immunolocalization of involucrin in the ocular SCC may help in evaluating the differentiation, i.e., malignancy, of neoplastic cells.

Experimental spinal fusion using sintered bovine bone coated with type I collagen and recombinant human bone morphogenetic protein-2.

STUDY DESIGN: Posterolateral lumbar transverse process fusion using recombinant human bone morphogenetic protein (rhBMP)-2 carried by sintered bovine bone and Type I collagen complex was compared with fusion achieved using autogeneous bone graft or sintered bovine bone alone. OBJECTIVES: This study examined the efficacy of sintered bovine bone coated with Type I collagen as a carrier of rhBMP-2 for lumbar intertransverse process arthrodesis. SUMMARY OF BACKGROUND DATA: Posterolateral intertransverse process arthrodesis using osteoinductive growth factors is performed experimentally in the lumbar spine. The previous studies revealed the efficacy of osteoinductive factors applied to carriers having no bony structures, such as collagen sheet or polylactic acid polymer, for the spinal fusion. However, in their studies, a large amount of osteoinductive proteins have been applied for the spinal fusion. We used the sintered bovine bone "True Bone Ceramics" (TBC; Koken Co., Tokyo, Japan) coated with type I collagen as the carrier. True Bone Ceramics is the only biomaterial possessing a natural trabecular structure and an organized crystal of bone minerals. METHODS: Twenty-two adult rabbits underwent bilateral lumbar intertransverse process arthrodesis at L4-L5. The animals were divided into four groups and had materials implanted as follows: autologous bone group, grafted autologous corticocancellous bone harvested from the posterior iliac crest; implanted TBC group; TBC collagen group, implanted TBC coated with Type I collagen infiltrating into the porous space; and BMP group, implanted sintered bovine bone coated with Type I collagen infiltrated with 100 micrograms of rhBMP-2. Spinal fusion was evaluated by radiographic analysis, manual palpation, biomechanical testing, and histologic examination 6 weeks after surgery. RESULTS: Two rabbits were killed because of infection and lumbar plexus palsy. Radiographs of the BMP group showed a homogeneous fusion mass at the intertransverse area, and stability was confirmed by dynamic radiographs at 3 and 6 weeks after surgery. In the BMP group, a bony mass in the intertransverse area was more prominent than in the other groups. The BMP group had a higher fusion rate based on manual palpation than the-other groups, and BMP fusions showed significantly higher tensile strength and stiffer fusion. The histologic findings in the BMP group demonstrated membranous bone and endochondral bone formations between the transverse process and the fusion mass. In the other groups, continuous trabecular bone formation was observed in the area surrounding the transverse process, but gaps between grafted fragments and less mature bone formation were present in the intertransverse area. CONCLUSIONS: Sintered bovine bone coated with Type I collagen and rhBMP-2 resulted in a higher fusion rate than the autograft and can be used as a carrier for rhBMP-2 in spinal fusion.

Ligamentum flavum hematoma in the lumbar spine.

A patient who presented with symptoms suggestive of nerve root compression secondary to an extradural mass was found to have a hematoma in the ligamentum flavum. Pathological examination of surgical specimens revealed an old hemorrhage, and hemosiderin deposits around organized granulation tissue within the ligamentum flavum. Vessels within the ligamentum flavum had, presumably, ruptured during minor trauma when the patient stood up.

Effects of sintered bovine bone on cell proliferation, collagen synthesis, and osteoblastic expression in MC3T3-E1 osteoblast-like cells.

To determine the function of biomaterials on osteoblasts, we studied the effects of two different biomaterials, sintered bovine bone (true bone ceramic) and hydroxyapatite-related material, on DNA and collagen synthesis and osteoblastic expression in osteoblast-like cells in vitro. Osteoblasts cultured with true bone ceramic exhibited greater increases in DNA and collagenous protein synthesis and alkaline phosphatase activity than those cultured with hydroxyapatite. Furthermore, expression of mRNA for type-I collagen and osteocalcin, as assessed by reverse transcription-polymerase chain reaction, was higher in cultures grown on true bone ceramic or hydroxyapatite than in those grown with glass fragments, and levels of gene expression in true bone ceramic and hydroxyapatite cultures were at almost the same level. These findings indicate that osteoblasts cultured with true bone ceramic increase their activity, suggesting that true bone ceramic may be a more favorable substrate than hydroxyapatite for growth and differentiation of osteoblast-like cells.

Effects of basic fibroblast growth factor on spontaneous resorption of herniated intervertebral discs. An experimental study in the rabbit.

STUDY DESIGN: Histologic examination was performed on the autologous intervertebral disc material that was removed from the intervertebral space at L1-L2 and then relocated to the L4 posterior epidural space after the addition of basic fibroblast growth factor (bFGF) in a rabbit. OBJECTIVES: To evaluate whether basic fibroblast growth factor influences the resorption process of the herniated intervertebral disc through the promotion of angiogenesis and chemotaxis. SUMMARY OF BACKGROUND DATA: It has been reported that newly formed vessels, inflammatory cells, and their products may play an important role in the spontaneous resorption process of herniated intervertebral discs. In a rabbit model that mimics the sequestration type of intervertebral disc herniation, it has been reported that the autologous intervertebral disc material that relocated into the epidural space was penetrated by newly formed vessels originating from the epidural fat tissue. Therefore, it is possible that promotion of angiogenesis may influence the resorption of herniated intervertebral discs. Basic fibroblast growth factor is well known as an angiogenesis stimulation factor in vivo. METHODS: Thirty-six adult rabbits were divided into three groups. The L1-L2 intervertebral disc was partially incised through a retroperitoneal approach in each rabbit. The harvested disc material, which contained nucleus pulposus and anulus fibrosus, was immersed in one of three kinds of solution before relocation into the posterior epidural space at L4. In the control group, the harvested intervertebral disc was immersed in physiologic saline for 2 hours before relocation. In the group receiving 5 micrograms bFGF, the disc was immersed in 5 micrograms/mL bFGF for 2 hours before the relocation. In the group receiving 20 micrograms bFGF, the disc was immersed in 20 micrograms/mL bFGF for 2 hours before the relocation. Rabbits of each group were killed for histologic examination 1, 2, 4, and 8 weeks after surgery. RESULTS: In the bFGF-treated groups, newly formed vessels were observed to be in more numerous than those in the control group, 1 and 2 weeks after surgery. The number of inflammatory cells, including macrophages, lymphocytes, and fibroblasts, also increased in the bFGF-treated groups. The period from the surgery to the degradation of the intervertebral disc in the bFGF-treated groups was shorter than that in the control group, although the resorption process of the relocated discs was also observed in the control group. The size of relocated intervertebral discs in the bFGF-treated groups decreased at a higher rate than in the control group as time progressed. The rate of decrease in the size of discs in the group treated with 20 micrograms bFGF was more than that in the group treated with 5 micrograms. CONCLUSIONS: Epidural injection of bFGF facilitated the resorption of the intervertebral disc relocated to the epidural space.

Sintered bone implantation for the treatment of benign bone tumours in the hand.

We report the results of treatment of benign bone tumours in the hand with curettage and sintered bone implantation using bovine sintered bone (True Bone Ceramics). There were 22 patients who underwent sintered bone implantation in our department in 1984 or later. The follow-up survey period varied from 9 months to 11 years and 2 months (mean, 5.8 years). Recurrence of tumours and complications such as infection or fracture were not observed, and there were no clinical symptoms. X-rays revealed new bone formation connecting the implanted blocks to bone. Sintered bone was not absorbed, and lucent zones around the implants or other abnormal findings were not observed. Bone union was achieved in all patients who had pathological fractures before surgery.

Changes in the extracellular matrix on the surface of sintered bovine bone implanted in the femur of a rabbit: an immunohistochemical study.

The interface of implanted True Bone Ceramics (TBC; sintered bovine bone; Koken, Tokyo, Japan) was examined. In the primary experiment, TBC was implanted into the bone marrow of a rabbit's femur. The extracellular matrices (types I, II, and III collagens and fibronectin) of decalcified specimens collected 1-48 weeks postoperatively were immunohistochemically examined. Undecalcified sections collected 6 weeks postoperatively were used for line analyses of calcium and phosphorus, by a scanning electron microscope-electron probe microanalysis (SEM-EPMA) method. In a secondary experiment, TBC was implanted into an osteochondral defect of a femoral condyle, harvested 1-12 weeks postoperatively, and decalcified to examine the extracellular matrices at the interface. In the bone marrow in the early phase, TBC had absorbed quantities of fibronectin. Immature bone (containing both types I and III collagens) in direct apposition to the ceramic surface had matured (containing type I collagen alone) in the TBC pores. SEM-EPMA revealed the continuity of high levels of calcium and phosphorus at the TBC-bone interface. In the secondary experiment, enchondral ossification or fibrous tissue formation was observed near the articular surface. However, in the subchondral layer, direct bone formation was observed in the TBC pores. It was concluded that TBC has excellent bioactivity for inducing maturation of new bone matrix on porous surfaces.

Immunolocalization of prolyl 4-hydroxylase subunits, alpha-smooth muscle actin, and extracellular matrix components in human lens capsules with lens implants.

Lens capsules become fibrotic after the extraction of a cataract. To understand this phenomenon, we evaluated the immunolocalization of prolyl 4-hydroxylase (an enzyme involved in procollagen hydroxylation), and extracellular matrix components and cytoskeletal components in a normal human lens capsule and in others with intraocular lenses. Lens capsules containing intraocular lenses were removed from a patient with proliferative vitreoretinopathy and three with proliferative diabetic retinopathy during vitreous surgery. Two circular sections of the anterior capsules with lens epithelial cells were obtained by anterior capsulotomy during cataract surgery. In addition, a lens capsular bag was obtained immediately after phacoemulsification. The lens capsules were processed for light microscopic immunohistochemical detection of the alpha and beta subunits of prolyl 4-hydroxylase, extracellular matrix components (including collagen types, laminin and cellular fibronectin) or cytoskeletal components (such as cytokeratin, vimentin and alpha-smooth muscle actin). Monolayer lens epithelial cells were seen on the inner surface of the normal anterior capsules. Each intraocular lens was found to be fixed in the capsular bag. Light microscopic immunohistochemistry showed that these proliferating cells expressed vimentin and alpha-smooth muscle actin; in contrast, quiescent lens epithelial cells did not stain for alpha-smooth muscle actin. Marked immunostaining for subunits of prolyl 4-hydroxylase was detected in lens epithelial cells proliferating on the capsules, while no or only faint prolyl 4-hydroxylase immunoreactivity was detected in quiescent lens epithelial cells immediately after phacoemulsification. Collagen types I, III and VI and cellular fibronectin were observed diffusely in accumulated connective tissue on a capsule with an intraocular lens. Type IV collagen immunoreactivity was seen both in the capsules and in the connective tissue accumulation on the capsules. Collagen V and laminin were detected in association with cellular proliferation. Collagen VII and VIII and laminin 5 were not seen. We concluded that during wound healing of the lens capsule after cataract extraction, the lens epithelial cells that proliferate on the inner surface of the capsule transform it into a myofibroblastic phenotype, expressing prolyl 4-hydroxylase and alpha-smooth muscle actin. These proliferating cells are involved in the production of collagen on the lens capsule. This results in a postoperative fibrotic process and contraction of the lens capsule.

Effects of steroid and lipopolysaccharide on spontaneous resorption of herniated intervertebral discs. An experimental study in the rabbit.

STUDY DESIGN: Histologic examination was performed on autografted intervertebral disc materials of rabbit models, which were partially incised through a retroperitoneal approach at L1-L2 and grafted within the posterior epidural space at L4. OBJECTIVE: To evaluate whether the resorption process of the herniated intervertebral disc is influenced and controlled by treatments with medications. SUMMARY OF BACKGROUND DATA: Regarding resorption of herniated intervertebral discs, recent studies of magnetic resonance images and histologic investigations of surgically resected specimens in lumber disc herniation patients have been reported. It has been shown that inflammatory factors may play an important role in the mechanism of resorption of the herniated intervertebral disc. However, little is known about the origin of newly formed vessels and inflammatory cells detected in herniated disc specimens from patients. In this study, The resorption process of disc material grafted into the epidural space was observed in a rabbit model. METHODS: Thirty-six adult rabbits were used. The L1-L2 intervertebral disc was partially incised through a retroperitoneal approach. The harvested disc material, which contains the nucleus pulposus and the anulus fibrosus were placed into the posterior epidural space at L4 of the same rabbit. The animals were divided into control, and steroid groups. The control group received no treatment after surgery. In the lipopolysaccharide group, rabbits were injected 1 mg/kg into the peritoneum immediately and at 7 days after surgery. In the steroid group, rabbits were injected with 1 mg/kg betamethasone into the epidural space daily from 1 to 7 days after surgery. Rabbits of each group were killed for histologic examination at 1, 2, 4, and 8 weeks after surgery. RESULTS: At 1 and 2 weeks after surgery, inflammatory cells and newly formed vessels were more frequently observed in the lipopolysaccharide group than in the control and steroid groups. At 4 weeks after surgery, derangement and loosening of collagen fibers were also observed in the lipopolysaccharide group. At 8 weeks after surgery, fragmentation and partial disappearance of matrix were observed in the control and lipopolysaccharide groups. Most of the intervertebral discs were replaced by fibrous tissues in the lipopolysaccharide group. However, the matrix of the intervertebral disc almost remained. CONCLUSIONS: Autologous intervertebral disc material grafted into the epidural space was penetrated by newly formed vessels produced from the epidural fat tissue and resolved as the result of inflammatory reaction. Lipopolysaccharide accelerated the replacement of grafted intervertebral disc by fibrous tissue, which suggests the resorption of the disc in the epidural space of the rabbit, whereas high-dose steroid suppressed the replacement.