The growth rate of the humerus: long-term follow-up of treatment of solitary bone cyst of the proximal humerus using cannulated screws: a case report.

Although the growth of the proximal epiphysis of the humerus is thought to contribute 80% of the total increase in humeral length, few articles have provided evidence for this. A 9-year-old boy with a pathological fracture at the humeral neck, owing to a solitary bone cyst, was treated by the decompression method using cannulated screws for 7.5 years. During this period, we measured the longitudinal humeral bone growth. The value obtained for the longitudinal growth contribution of the proximal humerus was 88% in this particular case.

Nonviral gene transfer of human hepatocyte growth factor improves streptozotocin-induced diabetic neuropathy in rats.

Peripheral neuropathy is common and ultimately accounts for significant morbidity in diabetes. Recently, several neurotrophic factors have been used to prevent progression of diabetic neuropathy. In this study, we gave repeated intramuscular injections of the human hepatocyte growth factor (HGF) gene percutaneously, using liposomes containing the hemagglutinating virus of Japan (HVJ), to examine therapeutic efficacy of nonviral gene transfer of HGF for experimental diabetic sensorimotor neuropathy in rats. Experimental diabetes induced by intraperitoneal injection of streptozotocin resulted in a marked tactile allodynia (but not in a thermal hyperalgesia), in a reduction of both the conduction velocity and the amplitude, and in a decreased laser Doppler flux of the nerve and the muscle at 6 weeks after the induction. All these changes were significantly reversed by repeated gene transfer of HGF. Furthermore, we analyzed the density of endoneurial capillaries and morphometrical changes of the nerve. The density of endoneurial capillaries, disclosing marked reduction in diabetic rats, was also reversed significantly by repeated gene transfer of HGF; however, no considerable differences were observed morphometrically in either myelinated or unmyelinated axons. These results suggest that nonviral HVJ liposome-mediated gene transfer of human HGF has potential for the safe effective treatment of diabetic sensorimotor neuropathy.

Severe kyphoscoliosis associated with osteomalacia.

BACKGROUND CONTEXT: Kyphoscoliosis is one of the most frequent complications of osteomalacia, which only rarely results in severe deformity requiring surgery. To the best of our knowledge, there has been only one previous report of a spinal deformity as a complication of osteomalacia that was sufficiently severe so as to require surgical treatment. PURPOSE: To report here the case of a 27-year-old woman who experienced back pain of gradual onset accompanied by progressive scoliosis resulting in severe dyspnea. STUDY DESIGN: A case report. METHODS: She was diagnosed with hypophosphatemic osteomalacia and secondary hyperparathyroidism. She underwent posterior surgical correction and fusion from Th4-L1 using the ISOLA spinal system. RESULTS: At the last follow-up (3 year and 9 months postoperatively), her body balance was good and the dyspnea had disappeared. Plain radiographs demonstrated no loss of correction and also showed no evidence of instrumentation failure. CONCLUSIONS: We present a unique instance of a young woman with severe kyphoscoliosis who underwent posterior surgical correction/fusion with spinal instrumentation.

Anterior cruciate reconstruction with bioactive Leeds-Keio ligament (LKII): preliminary report.

The scaffold type Leeds-Keio artificial ligament (LK) for ligament reconstruction of the knee provides sufficient strength to require minimal sacrifice of autogenous tissue. This implant works not only as prosthesis but also as scaffold onto which natural tissue grows from the synovium. LK has been in clinical use for anterior cruciate ligament (ACL) reconstruction since 1982, although the operative procedure has been modified and has undergone significant development since that time. Recently, we developed radio frequency-generated glow discharge (RFGGD)-treated LK ligament (LKII, previously indicated as Bio-LK) to improve tissue induction and reported that cell proliferation and cell attachment to artificial fibers increased considerably with this hydrophilic treatment. In this study, we report the findings of reconstructed ACL using LKII, which has been in clinical use since 2003. At reconstruction, LKII was covered with the remnant of the original ACL as much as possible in order to preserve the nerve ending system. Thirteen cases with over 12 months' postoperative history were reviewed. Knee stability was regained after reconstruction without any complications such as joint effusion and chronic synovitis. In one case, postoperative arthroscopy showed that the reconstructed ACL was completely covered with newly formed tissue at 8 weeks postoperatively. Biopsy revealed abundant fibroblasts, collagenous fibers, and vessels around the artificial fibers without marked inflammatory findings. Transmission electron microscope study showed abundant thin collagen fibers, which demonstrated regular orientation to some extent. Fibroblasts were observed with extensive amount of rough endoplasmic reticulum. According to these results, we consider LKII to be superior to LK in tissue induction and maturation.

The interaction of chitosan with fibroblast growth factor-2 and its protection from inactivation.

Application of ultraviolet light (UV) irradiation to a photocrosslinkable chitosan (Az-CH-LA) aqueous solution including fibroblast growth factor-2 (FGF-2) results within 30s in an insoluble, flexible hydrogel. The retained FGF-2 molecules in the chitosan hydrogel remain biologically active, and are released from the chitosan hydrogel upon the in vivo biodegradation of the hydrogel. In view of these findings, we here tested the interaction of chitosan with FGF-2, thereby modifying and stabilizing the FGF-2 activity from inactivations. The photocrosslinkable chitosan hydrogel has a low affinity for FGF-2 (Kd = 6.12 x 10(-7) M). Soluble chitosan (CH-LA; Az-CH-LA without photocrosslinkable azide group) substantially prolonged the biological half-life time of FGF-2. Furthermore, CH-LA could protect the FGF-2 activity from inactivation, such as heat, proteolysis, and acid. The effect of chitosan on the FGF-2 activity is of a protective nature, since it had no effect of modifying the FGF-2 activity directly on growth of human umbilical vein endothelial cells (data not shown). Thus, one of the ways by which the chitosan potentiated the FGF-2 activity could be through protecting it from inactivations by the interaction between FGF-2 and chitosan molecules.

Nonviral HVJ (hemagglutinating virus of Japan) liposome-mediated retrograde gene transfer of human hepatocyte growth factor into rat nervous system promotes functional and histological recovery of the crushed nerve.

Hepatocyte growth factor (HGF) is well known to be involved in many biological functions, such as organ regeneration and angiogenesis, and to exert neurotrophic effects on motor, sensory, and parasympathetic neurons. In this study, we gave repeated intramuscular injections of the human HGF gene, using nonviral HVJ (hemagglutinating virus of Japan) liposome method, to examine whether transfection of the rat nervous system with this gene is able to exert neurotrophic effects facilitating recovery of a crushed nerve. The expression of HGF protein and HGF mRNA indicated that gene transfer into the nervous system did occur via retrograde axonal transport. At 4 weeks after crush, electrophysiological examination of the crushed nerve showed a significantly shorter mean latency and a significantly greater mean maximum M-wave amplitude with repeated injections of HGF gene. Furthermore, histological findings showed that the mean diameter of the axons, the axon number and the axon population were significantly larger in the group with repeated injections of HGF gene. The above results show that repeated human HGF gene transfer into the rat nervous system is able to promote crushed-nerve recovery, both electrophysiologically and histologically, and suggest that HGF gene transfer has potential for the treatment of crushed nerve.

Evaluation of patello-femoral alignment using MRI.

In evaluating patello-femoral alignment, it is not enough to assess the conformity of the joint two-dimensionally, the direction of the extensor mechanism must be examined three-dimensionally. Using magnetic resonance imaging (MRI), we adopted an ideal extensor mechanism plane intersecting the patellar facet of the femur centrally and perpendicularly. We evaluated the alignment according to the extent to which the patella and/or the tibial tuberosity deviated from the plane. The results suggested that our method is useful for indicating proximal and distal realignment. Furthermore, two-dimensional finite element analysis in the patello-femoral joint showed that peak stress was significantly higher in the dislocation group than in the no-dislocation group. This indicates that osteoarthritic change in the future is a risk in the dislocation group.

Telomere length, telomerase activity, and expression of human telomerase reverse transcriptase mRNA in growth plate of epiphyseal articular cartilage in femoral head during normal human development and in thanatophoric dysplasia.

Telomeres are important in chromosome structure and function, protecting against their degradation. However, few studies have examined telomeres in growth plates within articular cartilage during normal development. We investigated frozen sections that were obtained from 57 reference autopsy cases (aged from 16 weeks of gestation to 91 years) and from 2 patients with thanatophoric dysplasia. In the reference cases, telomere length was significantly longer in growth plates obtained from the 10 cases that were aged from 16 weeks of gestation to 10 years than in those from 47 of the adult cases (aged 20 to 91 years). In fetal, neonatal, and child cases, telomerase activity was significantly higher in the hypertrophied zone (HZ) in growth plates than in the other 3 zones. The hTERT mRNA staining intensity (staining area) was stronger (larger) in HZ and the proliferating zone than in the calcified zone and resting zone. In thanatophoric dysplasia, telomere length and telomerase activity were short and low, respectively, compared with those of normal growth plates at an equivalent age, and expression of hTERT mRNA was negative or weakly positive in all 4 zones within growth plates. These results suggest that telomere length and telomerase activity have significant effects in the growth plates of articular cartilage, particularly at developmental ages from fetus to child. We speculate that short telomere length and low telomerase activity may be important for chondrocyte differentiation in rhizomeric shortening of the limbs in thanatophoric dysplasia.

Metal ions induce bone-resorbing cytokine production through the redox pathway in synoviocytes and bone marrow macrophages.

To evaluate the biological reactions to metal ions potentially released from prosthetic implants, we examined the ability of metal ions to produce bone-resorbing cytokines and the underlying mechanism using synoviocytes and bone marrow (BM) macrophages. The cells were incubated with NiCl(2), CoCl(2), CrCl(3) or Fe(2)(SO(4))(3) at optimal concentrations, which are detectable in joint fluid following total joint arthroplasty. The production of interleukin-1beta, interleukin-6 and tumor necrosis factor-alpha were enhanced by all metal ions tested as determined by enzyme-linked immunosorbent assay. From the results of electrophoresis mobility shift assay, all metal ions enhanced the DNA-binding activity of nuclear factor kappaB (NF-kappaB), and p50-p65 heterodimers and p50 homodimers were the major subunits. These effects of the metal ions were considerably blocked by pyrrolidine dithiocarbamate (PDTC) known as a radical scavenger. An electron spin resonance study clearly demonstrated the ability of metal ions to generate activated oxygen species (AOS), especially hydroxyl radicals (*OH), which accounts for PDTC-blockade of metal ion-induced NF-kappaB activation and subsequent cytokine production. Taken together, our data raised the possibility that small amounts of metal ions released from prosthetic implants activate synoviocytes and BM macrophages through the AOS-mediated process (i.e. the redox pathway), and contribute to the initiation of osteolysis at the bone-implant interface.

Influence of peripheral inflammation on growth-associated phosphoprotein (GAP-43) expression in dorsal root ganglia and on nerve recovery after crush injury.

An experimental study was performed to investigate the influence of the inflammation in peripheral target tissue on growth-associated phosphoprotein (GAP-43) expression in dorsal root ganglia (DRG) and on recovery of crushed nerve. Fifty-four male Wistar rats were used for this study. The sciatic nerve was operatively crushed unilaterally with an aneurysm clip. Inflammation in peripheral target tissue was induced by injection of complete Freund's adjuvant (CFA) at 1 week before crush. In crushed or crushed with arthritis rats DRGs were examined in immunohistochemistry for GAP-43 and the sciatic nerves were observed in Epon embedded sections with toluidine blue stain. In addition, electrophysiological studies of the nerves were performed to evaluate the recovery of function. Immunohistochemical studies showed the ratio of GAP-43 immunopositive cells in crushed with arthritis rats was significantly lower than that in crushed rats at 1 week after crush (P<0.01). Electrophysiological studies at 4 weeks after crush showed functional nerve recovery in crushed with arthritis rats was significantly suppressed compared with that in crushed rats (P<0.01). Histological studies showed the mean diameter of the axons in crushed with arthritis rats was significantly smaller than that in crushed rats (P<0.01). All these findings indicate that inflammation in peripheral target tissue suppresses GAP-43 expression in DRG and eventually suppresses functional and morphological recovery of the crushed nerve.

Treatment of the chronic inflammation in peripheral target tissue improves the crushed nerve recovery in the rat: histopathological assessment of the nerve recovery.

An experimental study was performed to investigate the influence of subsidence of chronic inflammation in peripheral target tissue on the recovery of crushed nerve. Seventy-eight male Wistar rats weighing 300-370 g were used. The sciatic nerve was operatively crushed unilaterally with an aneurysm clip (250 gf) applied for 5 min. Chronic inflammation, localized to the ankle, was induced by intra-articular injection of complete Freund's adjuvant 1 week preoperatively. Prednisolone farnesylate (PNF-21) 1.4% gel was applied on the ankle as an anti-inflammatory agent for consecutive days after the operation. The animals were divided into five groups as follows: crush injury with ipsilateral arthritis (CIA); crush injury with ipsilateral arthritis and PNF-21 gel applied on the ipsilateral ankle (CIA + IPNF); crush injury with ipsilateral arthritis and PNF-21 gel applied on the contralateral ankle (CIA + CPNF); crush injury with contralateral arthritis (CCA); crush injury without arthritis (C). Specimens for histopathological examination were taken from the nerve at a site 5 mm distal to the crush lesion at 4 weeks postoperatively. The average axon diameter was significantly larger in the CIA + IPNF group than in the CIA group (p < 0.01). No significant difference was observed between the CIA + CPNF group and the CIA group. In conclusion, chronic inflammation in peripheral target tissue suppresses recovery of the crushed nerve, and subsidence of this chronic inflammation improves this suppression histopathologically.

An atelocollagen honeycomb-shaped scaffold with a membrane seal (ACHMS-scaffold) for the culture of annulus fibrosus cells from an intervertebral disc.

The aim of this study was to investigate the possibility of using the atelocollagen honeycomb-shaped scaffold with a membrane seal (ACHMS-scaffold) for the culture of annulus fibrosus (AF) cells in tissue engineering procedures of intervertebral disc repair. AF cells from the intervertebral discs of Japanese white rabbits were cultured for up to 3 weeks in the ACHMS-scaffold to allow a high density, three-dimensional culture. Although the DNA content in the scaffold increased at a lower rate than in the monolayer culture, scanning electron microscopy data showed that the scaffold was filled with the grown AF cells and produced extracellular matrix on day 21. The amount of type II collagen and its mRNA expression by the scaffold cultured cells were determined using Western blotting and Northern blotting analyses, respectively, and remained at a higher level than in the monolayer cultured cells. Furthermore, glycosaminoglycan (GAG) accumulation in the scaffold culture was at a higher level than in the monolayer culture. Western blot analysis for extracted proteoglycans from the scaffold culture also exhibited a much higher proteoglycan accumulation than the monolayer culture. These results indicate that the AF cells are able to grow and remain phenotypically stable in the scaffold.

The effect of hyperbaric oxygen therapy on the bout of treatment for soft tissue infections.

OBJECTIVES: Hyperbaric oxygen (HBO) therapy is often combined with antibiotic therapy for infections such as gas gangrene and osteomyelitis. Although numerous investigations have been undertaken to assess the effect of adjunctive HBO therapy on the treatment of infections, the bout of treatment has not been referred in the previous investigations. The purpose of this retrospective study was to evaluate the efficacy of HBO therapy on the bout of treatment for soft tissue infections. PATIENTS AND METHODS: In the period between 1994 and 2001, we treated 23 patients with soft tissue infections. Nine patients were treated with antibiotic chemotherapy alone, and 14 patients were treated with a combination of antibiotic chemotherapy and HBO therapy. The mean bout of treatment was compared between these two groups. RESULTS: The mean bout treated with a combination of antibiotic and HBO was significantly shorter than that with antibiotic alone. CONCLUSION: Our result indicates that HBO therapy combined with antibiotic therapy is able to shorten the bout of treatment for soft tissue infections. Therefore, we recommend HBO therapy combined with antibiotic therapy for soft tissue infections.

Surgical fixation of massive osteochondritis dissecans lesion using cylindrical osteochondral plugs.

Abstract The prognosis of osteochondritis dissecans (OCD) depends on the age of manifestation and the size of the lesion. Before epiphyseal closure, OCD usually responds well to the restriction of the patient's sporting activities. Surgical intervention is not always necessary. However, if the disease manifests after epiphyseal closure, it often needs surgical treatment because the lesion is usually found at an advanced stage (International Cartilage Repair Society [ICR] OCD II or more). Furthermore, if a massive lesion develops to separation (ICR OCD II or III) or displaced loose bodies (ICR OCD IV), despite restriction of sporting activities, the prognosis is poor. This report discusses 2 cases of OCD. One patient had a massive stage ICR I lesion, although the disease was found before epiphyseal closure. In the other patient, a 22-year-old man, a large separated fragment (ICR OCD IV) was found after epiphyseal closure. The separated surfaces of the fragment and the mother bed had become sclerotic. Cylindrical osteochondral grafts using jigs for Mosaicplasty (Smith & Nephew, Andover, MA) were performed on the 2 patients, both of whom made successful recoveries. These cases suggest that cylindrical osteochondral grafting is a useful procedure for difficult cases of large lesion size or late manifestation.

Theoretical use of 3D CT to predict method of patella realignment.

Procedures for the treatment of patello-femoral malalignment are grouped into two categories, proximal realignment and distal realignment. However, no clear indications in respect of these realignments have been reported. We have tried to evaluate patello-femoral alignment three-dimensionally using CT. The results lead us to group patients with recurrent patella dislocation into three types. Type 1 comprises patients with normal patello-femoral alignment. Type 2 comprises patients whose patella only deviates laterally and who need proximal realignment. Type 3 comprises patients whose patella and tibial tuberosity both deviate laterally and who need both proximal and distal realignment.

Osteochondromatosis with high concentration of procollagen II C peptide in joint fluid.

Procollagen II C peptide is used as a joint fluid marker of collagen synthesis by chondrocytes in patients with osteoarthritis. Since osteochondromatosis activates ectopic chondrogenesis in the synovial membrane, procollagen II C peptide is expected to be a good marker of the disease. Procollagen II C peptide can be used to evaluate the condition of the disease metabolically by simply aspirating the joint fluid. We have experienced a case of osteochondromatosis (Miligram's stage 2) with a high concentration of procollagen II C peptide. This case suggests that the concentration of procollagen II C peptide is a good marker of chondrogenesis by osteochondromatosis.

Comparative study of the covered area of Leeds-Keio (LK) artificial ligament and radio frequency generated glow discharge treated Leeds-Keio (Bio-LK) ligament with synovial cells.

The Leeds-Keio artificial ligament (LK), which was developed not only as a ligament substitute but also as a scaffold for tissue induction in knee ligament reconstruction, has been in clinical use since 1982 in Europe and Japan. Recently, we have developed radio frequency generated glow discharge (RFGD)-treated LK ligament (Bio-LK) to expedite the process of tissue induction and its maturation. In this study of cell adhesion to the scaffold, we report the difference in the covered area with synovial cells when using scaffolds made from treated and untreated materials. Plasma clot methods were used in this study. The covered area on LK and Bio-LK by cells was stained by 0.1% toluidine blue and analyzed using NIH image. The covered area of Bio-LK was about three times higher than that of LK (untreated) at 3 weeks. In scanning electron microscopy, more cells were observed on fibers of Bio-LK, and these filled the space among the fibers more extensively. The spreading of covered area means that cell attachment, cell proliferation, and cell migration on the fibers are likely to be improved. Our experimental study indicates that Bio-LK will possibly speed up the process of induction of autogenous tissue from synovium.

Multiple neurilemmomas of the median and ulnar nerves with a communicating branch in the same upper extremity.

A 30-year-old woman presented with multiple neurilemmomas in the same upper extremity. One originated from the main trunk of the ulnar nerve and two others from the sensory branch of the median nerve. A communicating branch in the palm from the ulnar nerve to the median nerve was confirmed. All the tumours were successfully enucleated and she made a satisfactory recovery.

Primary repair of the collateral ligament of the proximal interphalangeal joint using a suture anchor.

Ten out of 12 complete ruptures of the collateral ligament of the proximal interphalangeal joint were repaired primarily using a suture anchor. Active finger exercise was started gently by taping the injured finger to adjacent one one week postoperatively. All patients returned to their original occupation or sports activities within seven weeks of operation. No patients complained of pain on the involved finger at rest or during movement. There was no instability of the proximal interphalangeal joint on manual lateral stress test postoperatively.

Ruptures of flexor tendons at the wrist as a complication of fracture of the distal radius.

We report two cases of rupture of flexor tendons after fracture of the distal radius. The first case was a rupture of the flexor digitorum profundus and superficialis tendon to the index finger that happened 20 years after the fracture. The second was a rupture of the flexor pollicis longus tendon that occurred two years after, and the flexor profundus tendon to the index finger that occurred four years after the fracture. In the first case, the ruptures were caused by the bony protuberance of the radius after long interval without interference of the ulnar head.