Kashin-Beck disease: a historical overview.

In 1919, the first report on Kashin-Beck disease (KBD) made by a Japanese doctor described an endemic occurrence in the northern district of Korea. In the 1930s, Dr. Takamori and his colleagues at Manchuria Medical College produced a series of reports on its endemiology, clinical and roentgenological findings observed in the north-eastern district of China. In 1940s, a Tokyo University group led by Dr. Ogata found that the salivary glands of KBD patients were markedly degenerated. Administration of the condensed water taken from the endemic area into experimental rats produced degeneration of the salivary glands and changes in bones and joints similar to those of KBD. Thus, they proposed parotin deficiency theory as the etiology of KBD, and they recommended parotin therapy for KBD in its early stage. In the 1950s, Dr. Takizawa and his colleagues at Chiba University demonstrated that ferulic acid and p-hydroxy-cinnamic acid, found in the drinking water in the endemic area, caused degeneration of the salivary gland in rats. They recommended boiling the drinking water or using activated charcoal for the prevention of KBD. In the 1970s, the Japanese Ministry of Health and Welfare made a nationwide survey for the incidence of KBD in Japan. They concluded that there was no case of KBD in Japan with the exception of a few patients who had been brought up in the northeastern district of China and later had moved to Japan.

Structure and properties of carbocyclic 5'-nor oligodeoxynucleotides.

The hybridization properties of carbocyclic 5'-nor oligodeoxynucleotides 1, 2 (24 mer, B = A) with DNA and RNA were investigated by CD melting curves. These oligomers formed unstable duplexes with DNA, but formed stable duplexes with RNA selectively.

Acetabular augmentation using a glass-ceramic block: 3 patients followed 3-4 years.

We have developed a block of glass-ceramic to augment the dysplastic acetabulum. 3 patients with acetabular dysplasia underwent implantation of a block of glass-ceramic on the lateral surface of the ilium just above the hip joint. The patients did not require immobilization and returned to their daily lives, walking without a cane 4 weeks after the operation. The mean Harris hip score was 47 points preoperatively and 94 points 3 years postoperatively.

Synthesis and chirality analysis of carbocyclic 5'-nor nucleosides.

Achiral carbocyclic "DL-like" 5'-nor nucleosides have been synthesized and analyzed by the chiral capillary electrophoresis to elucidate the "D-like" monomers.

Cemented total hip arthroplasty with acetabular bone graft for developmental dysplasia. Long-term results and survivorship analysis.

Although the technique of autogenous acetabular bone grafting has been widely used to augment containment of the acetabulum in total hip arthroplasty (THA) for developmental dysplasia, the role of this technique in improving long-term results remains controversial. We present the long-term results of cemented THA with acetabular bone grafting in 112 patients (133 hips) in order to clarify the factors which affect the outcome. The mean follow-up was for 12.3 years (8 to 24). Kaplan-Meier survivorship analysis predicted a rate of survival of the acetabular component at 15 years of 96% (95% confidence interval (CI) 92 to 99) with revision for aseptic loosening as the endpoint, and of 75% (95% CI 65 to 85) when radiological loosening was used. Parametric survivorship analysis using the Cox proportional-hazards model indicated that trochanteric nonunion, lateral placement of the socket, and delayed trabecular reorientation of the bone graft were risk factors for loosening of the acetabular component. Our findings have shown that autologous acetabular bone grafting is of value for long-term success provided that the risk factors are reduced.

Development of bioactive bone cement and its clinical applications.

This paper is a summary of already published papers on the bioactive bone cement (BA cement) which consists of CaO-SiO2-P2O5-MgO-CaF2 (AW glass-ceramic) powder and bisphenol-a-glycidyl methacrylate (Bis-GMA) resin. Two types of BA cement, dough and injection type, were prepared by changing their chemical compositions slightly. They harden in a few minutes exhibiting much lower curing temperature than PMMA cement. They have significantly higher compressive, bending, and tensile strengths than PMMA cement and have a character of bonding directly with bone in 4-8 weeks in vivo. Intercalary prosthetic replacement of the femur and total prosthetic replacement of the hip were performed in dogs using either PMMA cement or BA cement. Mechanical tests demonstrated that fixation strengths of these prostheses with BA cement increased with time and were significantly greater than those with PMMA cement tested at any time. Results of histological examinations showed direct bonding between BA cement and bone, and that the bone trabeculae around BA cement mantle grew with time, while with PMMA cement an intervening soft tissue layer was always observed at the cement-bone interface. BA cement was used in a few aged patients to install a hip prosthesis either in cases of revision or femoral neck fracture. The longest follow-up period of the patient is 4 yrs. The patients have been doing well with no adverse effect of the cement to date.

Nerve regeneration over a 20-mm gap through a nerve conduit containing blood vessels in rats: the influence of interstump distance on nerve regeneration.

BACKGROUND: The present study was conducted in rats to investigate whether a tube with additional intrachamber vascularization could permit axons to extend over a distance greater than 10 mm, which appears to be the maximum axon regeneration distance for rat sciatic nerve axons through a normal empty tube. METHODS: A sural vessel-containing tube (VCT) was designed and interposed between transected sciatic nerve stumps in the thigh, leaving a 20-mm interneural gap. RESULTS: Twelve weeks after tubulation, six out of nine rats showed successful nerve regeneration and re-innervation of the soleus muscle using the VCT. At 24 weeks, intrachamber nerve regeneration and re-innervation of the soleus and pedal adductor muscles were electrophysiologically and histologically confirmed in all rats. However, no neural tissue was observed within any ligated sural vessel-containing tube (LVCT) or empty unmodified tube (ET) with a 20-mm interneural gap. When nerves regenerated in the VCT with a 20-mm gap were compared with those regenerated in a VCT with a 10-mm gap 12 and 24 weeks after surgery, the results produced by the VCT with a 20-mm gap were inferior to those after use of the VCT with a 10-mm gap, except for motor nerve conduction velocity at 24 weeks. CONCLUSIONS: The value recovered to almost identical levels (about 50-60% normal) in both groups.

X-ray absorption fine structure of V(2)O(5) and Li(x)V(2)O(5).

Vanadium K-edge XAFS measurements of five compounds were carried out. The compounds studied were crystalline V(2)O(5) and four types of Li(x)V(2)O(5) with different insertion levels x, which show different EMFs (2.0-3.4 V). The EXAFS data analysis shows no remarkable difference in the V-O distances in the five compounds, showing that the structure of the VO(5) square pyramids changes only slightly as lithium atoms are intercalated into the V(2)O(5). In the XANES spectra, three peaks are observed for crystalline V(2)O(5) and Li(x)V(2)O(5) (3.4 V). When the EMF is decreased, the intensity difference between the first and second peaks disappears and the third peak shifts to lower energy. The XANES data were analysed using full multiple-scattering calculations. In the calculated spectra the intensity of the first peak increases as the V(2)O(5) intercalates lithium atoms.

Prosthetic replacement of the hip in dogs using bioactive bone cement.

Total hip arthroplasties were performed in dogs using bioactive bone cement consisting of silane treated CaO-MgO-SiO2-P2O5-CaF2 glass powder as the filling particles and bisphenol-a-glycidyl methacrylate based resin as the organic matrix, and the outcomes were compared with the results of polymethylmethacrylate bone cement. The mechanical properties of the bioactive bone cement were stronger than the mechanical properties of polymethylmethacrylate bone cement. The bonding strength of the bioactive bone cement to bone in dogs' femora increased with time, reaching 4.7 MPa at 6 months, whereas that of polymethylmethacrylate bone cement did not increase, remaining at 1.0 MPa. Results of histologic examination showed direct bonding between the bioactive bone cement and bone, and the bony trabeculae around the cement mantle grew with time. However, in polymethylmethacrylate bone cement, an intervening soft tissue layer was evident at the bone cement interface. Direct bonding of the bioactive bone cement at the interface through an apatite layer of 30 microm in thickness was shown through observation with the scanning electron microscopy. Using this bioactive bone cement in clinical settings may help alleviate serious problems associated with cemented total hip arthroplasty, such as aseptic loosening of the implant and mechanical failure of the bone cement.

Nerve regeneration over a 25 mm gap in rat sciatic nerves using tubes containing blood vessels: the possibility of clinical application.

This study was undertaken to investigate the effect of including vessels in a tube used to promote nerve regeneration across a gap. A tube containing sural vessels was designed in a rat model and interposed between the proximal and distal stumps of a divided sciatic nerve, leaving a 25 mm gap. At 12 weeks, a few myelinated axons were seen at the most distal parts of regenerated nerves in 6 out of 10 rats, none of which evoked action potentials in the tibialis anterior muscle, but by 24 weeks all the rats had developed neural tissue in the tubes, which evoked action potentials in the muscle. The vessels within the tube enhanced nerve regeneration and its distance up 25 mm. This type of vessel-containing tube would be useful for the repair of divided human peripheral nerves with long gaps, almost equivalent to or slightly longer than the maximum length over which nerve fibres can regenerate through a unvascularised unmodified tube.

Intercalary replacement of canine femora using a new bioactive bone cement.

We have developed a bioactive bone cement (BA cement) consisting of Bis-GMA resin and bioactive glass powder. It has high compressive and tensile strengths, a low curing temperature and its bioactivity allows it to bond directly with bone. We operated on the 18 femora of nine mongrel dogs for intercalary replacement of part of the bone by a metal prosthesis using either PMMA cement or BA cement for fixation. Three dogs were killed at each of 4, 12 and 26 weeks after surgery for the evaluation of fixation strength by a push-out test and for histological examination by Giemsa surface staining and SEM. Fixation strengths with PMMA cement at 4, 12 and 26 weeks after surgery were 46.8 +/- 18.9, 50.0 +/- 24.7, and 58.2 +/- 28.9 kgf (mean +/-sD), respectively. Those with BA cement were 56.8 +/- 26.1, 67.2 +/- 19.2, and 72.8 +/- 22.2 kgf, respectively. Fibrous tissue intervened between bone and PMMA cement but BA cement had bonded directly to bone at 12 and 26 weeks. This suggests that BA cement will be useful in providing long-lasting fixation of implants to bone under weight-bearing conditions.

Transmission electron microscopy observations at the interface of bone and four types of calcium phosphate ceramics with different calcium/phosphorus molar ratios.

Four kinds of calcium phosphate ceramics, beta-calcium pyrophosphate (Ca2P2O7), beta-tricalcium phosphate (Ca3(PO4)2), hydroxyapatite (Ca10(PO4)6(OH)2) and tetracalcium phosphate (Ca4(PO4)2O), were prepared. The calcium/phosphorus molar ratios were 1, 1.5, 1.66 and 2, respectively. Particles (150-300 microns) of these ceramics were packed into holes (diameter 2.5 mm) made in the tibial metaphysis of mature male rats. At 2 weeks, 4 weeks, 8 weeks and 6 months after the operation, undecalcified specimens were prepared. Transmission electron microscopy showed that the bone-bonding behaviour of calcium phosphate ceramics at the interface with bone did not vary with the calcium/phosphate molar ratio. Amorphous substances or needle-like microcrystals were observed on the surface of the ceramics at 2 weeks after implantation. The ceramics showed direct continuity with small crystallites of bone tissue at 4 weeks, 8 weeks and 6 months after implantation. The ceramics appeared to be getting smaller with time. Collagen fibres were not observed at the bone/ceramic interface. Neither chemical bonding nor mechanical bonding by interlocking between bone and ceramics was described by morphological observation using transmission electron microscopy.

Bone-bonding behavior under load-bearing conditions of an alumina ceramic implant incorporating beads coated with glass-ceramic containing apatite and wollastonite.

Alumina ceramic with a porous surface coated with glass-ceramic containing apatite and wollastonite (AW-GC) was implanted in a state of press-fit under load-bearing conditions in the femoral condylus of the mongrel dog and compared with a non-glass-ceramic-coated alumina ceramic. A trapezoid alumina ceramic implant (7 x 10 x 5 mm) with a lateral recess (0.9 mm deep) coated with alumina ceramic beads (mean diameter, 750 microns) in a single layer was prepared. The alumina ceramic beads were bonded to the alumina ceramic substratum using an identical alumina binder. The thickness of coating was 10-50 microns (mean, 30 microns). The surface of the beads and the substratum of the alumina implant were coated with AW-GC. A pull-out test and histologic examination were performed at 4, 8, and 24 weeks after implantation. The interfacial shear load was significantly increased from 8 to 24 weeks in both groups. The shear load of the glass-ceramic-coated implant was significantly greater than that of the noncoated implant at every stage. The interface shear load of the noncoated implant was 12.13 +/- 2.76 kg at 4 weeks, 13.92 +/- 4.18 kg at 8 weeks, and 24.17 +/- 5.17 kg at 24 weeks after implantation. The interface shear load of the glass-ceramic-coated implant was 17.96 +/- 2.81 kg at 4 weeks, 24.92 +/- 9.87 kg at 8 weeks, and 34.83 +/- 4.12 kg at 24 weeks after implantation. Histologic examination showed more ingrown bone tissue in the glass-ceramic-coated implants. It is suggested that AW-GC stimulated the bone ingrowth.(ABSTRACT TRUNCATED AT 250 WORDS)

Tissue reaction of bioabsorbable ultra high strength poly (L-lactide) rod. A long-term study in rabbits.

Bioabsorbable ultra high strength poly (L-lactide) rods, which were developed for internal fixation of fractures, were fabricated using a drawing technique. These rods were implanted in the subcutaneous tissue and in the medullary cavity of rabbits to investigate tissue reactions to poly (L-lactide) and to study their degradation process. After 18 months, histiocytes were found, and their phagocytic activity continued for as long as 42 months, with maximum activity observed between 24 and 36 months after implantation. At 62 months after intramedullary implantation, the materials had been absorbed almost completely and were replaced by bone marrow cells, with only a small amount of residual tissue reaction. At 69 months after subcutaneous implantation, the materials had been absorbed completely without any scar formation. During degradation, no foreign body giant cells were found and osteolytic expansion caused by liquid degradable materials was not seen.

Relationship between axonal regeneration and vascularity in tubulation--an experimental study in rats.

This study investigated the effect of vascularity in a nerve conduit on peripheral nerve regeneration. The effect of three different types of tube (empty, blood vessel-containing and ligated vessel-containing) was compared using a rat sciatic nerve preparation with a 10-mm gap. Nerve regeneration through the vessel-containing tube was more efficient than in the other tubes 6 and 12 weeks after tubulation surgery, but there were no statistically significant differences among the three types of tube after 24 weeks. Electrophysiological, histological and microangiographic studies showed that vessels which were preinserted in the nerve conduit accelerated axonal regeneration through rapid capillary formation in the tube.

Anterior decompression and fusion for ossification of posterior longitudinal ligament in the thoracic spine.

Twelve cases are reviewed of ossification of posterior longitudinal ligament (OPLL) in the thoracic spine for which anterior decompression and fusion were performed. A transthoracic approach was used in 10 patients, and median sternotomy and a transsternal approach were used in one each. The clinical symptoms and the Japanese Orthopaedic Association (JOA) score improved in 10 patients, whereas they were unchanged in two patients who underwent a revision operation for a previous laminectomy. An anterior procedure that results in adequate decompression of the spinal cord and good spinal stability is recommended for anterior lesions, such as OPLL, which compress the anterior spinal cord at each level of the thoracic spine.

m-calpain in rat growth plate chondrocyte cultures: its involvement in the matrix mineralization process.

m-Calpain, a Ca(2+)-dependent neutral cysteine proteinase (EC 3.4.22.17), has been demonstrated to be present in the lower hypertrophic zone of the rat growth plate. Using the pelleted culture system as an in vitro model of rat epiphyseal chondrocyte differentiation, we studied m-calpain contents and activities in pelleted cultures during chondrocyte differentiation and the role of m-calpain in the mineralization process. m-Calpain was demonstrated immunohistochemically in epiphyseal chondrocytes, and immunoreactive m-calpain content in cells increased with terminal differentiation into hypertrophic cells. Immunoblotting also showed the association of the increase in m-calpain in cell pellets and in cell culture medium with development of the culture. Ca(2+)-dependent caseinolytic activities of m-calpain extracted from cell pellets and from the medium increased with chondrocyte differentiation, coincident with the increase in enzyme content. The inhibition of m-calpain by the addition of calpastatin, a specific inhibitor of calpain, caused suppression of matrix mineralization in pelleted cultures; the addition of E-64c, a specific inhibitor of cysteine proteinases, during the mineralization stage also caused a significant inhibition of the matrix mineralization. The addition of E-64c resulted in altered composition of proteoglycan monomers and aggregates in cell pellets and in suppression of mineral growth. These findings support an important role of cysteine proteinases, especially m-calpain, in the regulation of the cartilage mineralization process through proteoglycan degradation.

Biodegradable plate fixation of rabbit femoral shaft osteotomies. A comparative study.

Femoral shaft transverse osteotomies in 58 rabbits were fixed with ultrahigh strength poly-L-lactic acid plates made by a drawing technique. Similar osteotomies in another 35 rabbits were fixed using stainless steel plates. The union rate, the mechanical strength of the united bones, bone mineral content and density in the area beneath the plate using dual energy x-ray absorptiometry, and the cortical thickness beneath and opposite the plate using a digitizer was compared between the poly-L-lactic acid and stainless steel groups after postoperative periods of 8, 25, and 40 weeks. The poly-L-lactic acid and stainless steel groups showed union rates of 67% (39 of 58) and 80% (28 of 35) without displacement, respectively. In the poly-L-lactic acid group, plate failure occurred in 14% (8 of 58). The mechanical strength of the specimen was restored to a level equal to that on the untreated side by 25 weeks, and cortical thickness and bone mineral content and density were maintained almost normal for 40 weeks in the poly-L-lactic acid group. The stainless steel group showed significantly lower mechanical strength and led to osteopenia because of stress shielding after 25 weeks.

Appearance of calpain correlates with arthritis and cartilage destruction in collagen induced arthritic knee joints of mice.

OBJECTIVES: To determine the relevance of calpain in murine collagen induced arthritis (CIA) and to correlate the presence of m-calpain with the appearance of arthritis and cartilage destruction. METHODS: The immunohistochemical appearance and localisation of m-calpain at different stages of arthritis were analysed and compared with the histological changes occurring during type II CIA. The arthritic knee joint lavage was also examined for m-calpain by immunoelectrophoretic blotting. RESULTS: Immunohistochemical staining demonstrated a clear positive correlation between the appearance of m-calpain and both a histological grade of arthritis and an acute phase of cartilage destruction. Further development of the disease showed continual presence of m-calpain but with reduced intensity. Intra-articular inflammatory cells (mainly polymorphonuclear leucocytes, synovial lining cells, and sublining fibroblasts) were found to be the most positively stained, but extracellular localisation of m-calpain on the surface of cartilage and synovium, and in the articular cartilage matrix and chondrocyte lacunae, was also observed. In the knee joint lavage obtained at the most intensive stage of acute arthritis, m-calpain was detectable by immunoelectrophoretic blotting. CONCLUSIONS: The findings suggest that m-calpain may act at an early phase of CIA as a matrix proteinase and take part in the destruction of articular cartilage or activate other destructive enzymes.

Bioactive bone cement: the effect of amounts of glass powder and histologic changes with time.

A study was conducted to examine the influence of the amount of glass powder added to a bioactive bone cement of our formula on its mechanical and biologic properties. Serial changes in the cement with time were also examined. The bioactive bone cement consisted of CaO-SiO2-P2O5-CaF2 glass powder and bisphenol-a-glycidyl methacrylate resin. Glass powder was added to the cement in 30, 50, 70, and 80% weight ratios. The compressive strengths of the resulting cements (171-239 MPa) were more than double that of polymethylmethacrylate cement (68 MPa). Histologic examination of rat tibiae bearing artificial defects packed with each bioactive cement showed direct bone contact 4 weeks after surgery. The cement with a higher percentage of glass powder showed better direct formation of bone around its periphery with a thicker reactive layer. Under scanning electron microscopic observation, the reactive layer showed increased levels of calcium and phosphorus. Examination of histologic changes up to 26 weeks showed progressive bone formation around the cement and no sign of biodegradation.