Simultaneous hybrid closed-wedge supramalleolar osteotomy and ankle arthrodesis for post-traumatic varus ankle arthritis with periarticular deformity: A case report.

The treatment of end-stage ankle arthritis associated with extra-articular tibial deformity, especially for ankles deformed by previous traumatic injuries and/or surgical treatment, is extremely challenging but rewarding. Only one previous report describes simultaneous tibial deformity correction and ankle arthrodesis for tibial malalignment and ipsilateral ankle arthritis. Here, we describe a unique case of post-traumatic ankle osteoarthritis concomitant with extra-articular varus deformity in a 77-year-old female. We have combined medial opening-wedge supramalleolar osteotomy (SMO) and lateral closed-wedge SMO in this case, which we termed 'hybrid' closed-wedge SMO, to overcome the limitations of traditional closed-wedge SMO. The patient was successfully treated with simultaneous hybrid closed-wedge SMO and ankle arthrodesis using a single lateral locking plate. To our knowledge, this is the first report describing the successful introduction of a hybrid closed-wedge osteotomy procedure in the distal tibia. Three years after surgery, the patient could walk without assistance and swim normally. The patient experienced no discomfort or pain in the operated ankle and was satisfied with the results. Radiographs confirmed that the pre-existing ankle joint line was parallel to the ground and almost invisible. The hind foot alignment was slightly valgus. No progression of the subtalar joint arthritis was detected. The simultaneous hybrid closed-wedge SMO and ankle arthrodesis was technically difficult but effective. This technique preserves leg length and subtalar joint motion. Additionally, a single lateral incision minimises the risk of impaired blood supply. The one-stage surgical treatment reduces the recovery time, duration of hospitalisation, and surgical costs. Rigid locking fixation with careful postoperative weight-bearing is required for uneventful bone healing.

Allergenicity of Deamidated and/or Peptide-Bond-Hydrolyzed Wheat Gliadin by Transdermal Administration.

Hydrochloric acid (HCl)-treated wheat protein (HWP) is widely used in various products, including foods, cosmetics and shampoos. Recently, immediate hypersensitivity towards facial soap containing HWP has been reported. HCl treatment of protein causes hydrolysis not only of main-chain amide bonds (peptide-bond hydrolysis) but also of side-chain ones (deamidation). We have already reported that gliadin, the main allergen in wheat, reduces allergenicity and increases digestibility by deamidation, indicating that deamidation and peptide-bond hydrolysis are effective to reduce the allergenicity of wheat protein. However, transdermally administered HWP is assumed to induce sensitization to orally administered wheat protein even in those who have been taking wheat products daily before sensitization. The present study was conducted to examine which structural change is responsible for the induction of cutaneous sensitization by comparing the allergenicity of deamidated and/or peptide-bond-hydrolyzed wheat gliadin. Because we have developed a deamidation method without causing peptide-bond hydrolysis, only deamidated wheat gliadin is available. Therefore, after deamidated-only, hydrolyzed-only, and deamidated and hydrolyzed gliadins were transdermally administered to mice for several weeks, the corresponding gliadin was intraperitoneally administered and allergenicity was evaluated. Transdermal administration of deamidated and hydrolyzed gliadin induced severe allergic reaction, while that of deamidated-only and hydrolyzed-only gliadin showed almost no allergic response. This result indicates that both deamidation and peptide-bond hydrolysis are necessary to increase the allergenic potency of transdermally administered wheat gliadin.

Calcaneocuboid Distraction Arthrodesis With Synthetic Bone Grafts: Preliminary Results of an Innovative Bone Grafting Procedure in 13 Patients.

Calcaneocuboid distraction arthrodesis (CCDA) is regarded as an effective method for reconstructing adult-acquired flatfoot deformity. In the present study, we present our experience with newly developed rigid ß-tricalcium phosphate wedges to treat CCDA to better understand the outcomes of this synthetic bone grafting procedure. A total of 13 feet in 13 patients underwent CCDA with synthetic bone grafts. One male (7.69%) and 12 females (92.31%), with a mean age of 65.07 ± 11.83 (range 36 to 77) years, were followed up for a mean duration of 32.76 ± 12.81 (range 18 to 55) months. Successful graft union was postoperatively obtained in 12 of the 13 feet (92.31%). The mean preoperative visual analog scale and American Orthopaedic Foot and Ankle Society scale score were 7.97 ± 1.52 (range 5.4 to 10) and 54.46 ± 14.72 (range 18 to 75), respectively. These scores improved to 1.52 ± 1.78 (range 0 to 6.2) and 85.46 ± 13.38 (range 50 to 97) postoperatively (p = .001 for both comparisons). On radiographic analysis, the talonavicular coverage angle, first metatarsal talar angle, calcaneal pitch, and heel alignment angle had significantly improved (p = .001, p = .028, p = .006, and p = .001, respectively). The use of bone graft substitutes in CCDA is a viable treatment option for reconstructing flexible flatfoot deformity. Although good clinical and radiographic outcomes were obtained, our method is even more challenging than conventional methods and should be used with caution. Rigid locking fixation with a long period of protected weightbearing is highly recommended to attain uneventful bone healing.

Gradual Correction of Traumatic Hallux Varus With Metatarsal Hemicallotasis.

Traumatic hallux varus associated with osseous deformity, especially in the case of a decreased distal metatarsal articular angle, is an extremely challenging, but rewarding, deformity to treat. To the best of our knowledge, no previous reports have referred to surgical correction of traumatic hallux varus using first metatarsal hemicallotasis. We report the case of a 54-year-old male with traumatic hallux varus associated with medial subluxation of the second metatarsophalangeal joint and second metatarsocuneiform joint arthrosis. The patient was successfully treated with metatarsal hemicallotasis with medial soft tissue release, a proximal second metatarsal shortening osteotomy, and second metatarsocuneiform joint arthrodesis. After 1 year and 6 months, the correction had been maintained in a suitable position, no discomfort or pain was present, and the patient was completely satisfied with the surgical results. Metatarsal hemicallotasis can safely determine the angle of correction and minimize the risk of avascular necrosis of the metatarsal head even in deformed halluces with previous traumatic injuries and/or surgical treatment. This technique should be indicated only for hallux varus with a decreased distal metatarsal articular angle, an angular-type metatarsal head, and good metatarsophalangeal joint congruence.

Treatment of Varus Ankle Osteoarthritis and Instability With a Novel Mortise-Plasty Osteotomy Procedure.

Although joint-preserving surgery for intermediate ankle osteoarthritis has been reported to be effective, failures of supramalleolar osteotomy and plafond-plasty can occur because of persistent malalignment of the distal tibia and incongruent ankle mortise. We introduce a novel opening wedge distal tibial osteotomy procedure (mortise-plasty) with rigid plate fixation combined with synthetic bone wedges. We performed 27 mortise-plasties in 25 patients with varus ankle osteoarthritis and instability. Six males (24%) and 19 females (76%), with a mean age of 63 (range 28 to 79) years, were followed up for a mean of 27.3 (range 14 to 45) months. The mean preoperative visual analog scale score, American Orthopaedic Foot and Ankle Society score, and Takakura ankle scale score were 7.4 (range 5.4 to 10), 58.7 (range 18 to 84), and 55.9 (range 29 to 88), respectively. These scores improved significantly to 2.1 (range 0 to 6.5), 89.3 (range 67 to 100), and 84.7 (range 55 to 100) postoperatively (p < .001). The mean preoperative tibial-anterior surface angle and talar tilt angle were 84.9° (range 78° to 90°) and 8.3° (range 3° to 21°), respectively. At the most recent follow-up visit, the corresponding values were 95.0° (range 82° to 99°) and 1.8° (range 0° to 8°), respectively (p < .001). Computed tomography scans indicated that the ankle mortise narrowed by approximately 1.8 mm and the tibial plafond was lowered after osteotomy. No patients underwent lateral ligament reconstruction, ankle joint replacement, or arthrodesis. Mortise-plasty osteotomy corrects the intra-articular and extra-articular deformities simultaneously and provides good clinical and radiographic outcomes for patients with varus ankle osteoarthritis and instability.

Isolated Fifth Metatarsocuboid Coalition: A Case Report.

Isolated tarsometatarsal coalitions are extremely rare, and the previous 5 documented cases involved the first and third metatarsocuneiform joints. We report the case of a 69-year-old female with symptomatic fifth metatarsocuboid coalition associated with ipsilateral varus-type ankle osteoarthritis and instability. The patient was successfully treated by arthrodesis of the fifth metatarsocuboid joint, resection of the hypertrophied tuberosity of the fifth metatarsal, advancement of the peroneus brevis tendon, opening wedge distal tibial osteotomy, and calcaneal displacement osteotomy. After 1 year, 6 months, she was able to walk well, although she complained of minor discomfort under the fifth metatarsal base, which resolved with the use of protective padding. Radiographs at this stage confirmed consolidation of both the arthrodesis and the osteotomy sites. Although isolated fifth metatarsocuboid coalition is less likely to be encountered than other tarsal coalitions, it can sometimes be painful enough to necessitate surgery.

Accumulating microglia phagocytose injured neurons in hippocampal slice cultures: involvement of p38 MAP kinase.

In this study, microglial migration and phagocytosis were examined in mouse organotypic hippocampal slice cultures, which were treated with N-methyl-D-aspartate (NMDA) to selectively injure neuronal cells. Microglial cells were visualized by the expression of enhanced green fluorescent protein. Daily observation revealed microglial accumulation in the pyramidal cell layer, which peaked 5 to 6 days after NMDA treatment. Time-lapse imaging showed that microglia migrated to the pyramidal cell layer from adjacent and/or remote areas. There was no difference in the number of proliferating microglia between control and NMDA-treated slices in both the pyramidal cell layer and stratum radiatum, suggesting that microglial accumulation in the injured areas is mainly due to microglial migration, not to proliferation. Time-lapse imaging also showed that the injured neurons, which were visualized by propidium iodide (PI), disappeared just after being surrounded by microglia. Daily observation revealed that the intensity of PI fluorescence gradually attenuated, and this attenuation was suppressed by pretreatment with clodronate, a microglia toxin. These findings suggest that accumulating microglia phagocytosed injured neurons, and that PI fluorescence could be a useful indicator for microglial phagocytosis. Using this advantage to examine microglial phagocytosis in living slice cultures, we investigated the involvements of mitogen-activated protein (MAP) kinases in microglial accumulation and phagocytosis. p38 MAP kinase inhibitor SB203580, but not MAP kinase/extracellular signal-regulated kinase inhibitor PD98059 or c-Jun N-terminal kinase inhibitor SP600125, suppressed the attenuation of PI fluorescence. On the other hand, microglial accumulation in the injured areas was not inhibited by any of these inhibitors. These data suggest that p38 MAP kinase plays an important role in microglial phagocytosis of injured neurons.

Neuronal injury induces microglial production of macrophage inflammatory protein-1α in rat corticostriatal slice cultures.

Chemokines are potent chemoattractants for immune and hematopoietic cells. In the central nervous system, chemokines play an important role in inflammatory responses through activation of infiltrating leukocytes and/or resident glial cells. We previously demonstrated that N-methyl-D-aspartate (NMDA)-evoked neuronal injury induced astrocytic production of monocyte chemoattractant protein-1 (MCP-1, CCL2) via sustained activation of extracellular signal-regulated kinase (ERK) in rat organotypic slice cultures. In the present study, we examined mRNA expression and protein production of macrophage inflammatory protein-1α (MIP-1α, CCL3) induced by NMDA-evoked neuronal injury in the slice cultures. MIP-1α mRNA expression was transiently increased by NMDA treatment in a concentration-dependent manner. Double-fluorescence immunohistochemistry revealed that MIP-1α was produced predominantly in microglia. Depletion of microglial cells from the slice cultures by pretreatment with liposome-encapsulated clodronate abrogated the increase in MIP-1α mRNA expression after NMDA treatment. NMDA-induced MIP-1α mRNA expression was partially but significantly inhibited by the c-Jun N-terminal kinase inhibitor SP600125; conversely, the p38 mitogen-activated protein (MAP) kinase inhibitor SB203580 enhanced it. U0126, a MAP kinase/ERK kinase inhibitor, did not affect mRNA expression. These results, combined with our previous findings, demonstrate that NMDA-evoked neuronal injury differentially induces MIP-1α and MCP-1 production in microglia and astrocytes, respectively, through activation of different intracellular signaling pathways.

Etanercept treatment reduces the serum levels of interleukin-15 and interferon-gamma inducible protein-10 in patients with rheumatoid arthritis.

Tumor necrosis factor-alpha (TNF-alpha) has an essential role in the pathogenesis of rheumatoid arthritis (RA) and has been known to induce the production of several inflammatory molecules in vivo. To analyze in vivo the active mechanism of the TNF-alpha blocking agent, etanercept, the serum levels of the cytokine interleukin-15 (IL-15) and the chemokines growth-regulated protein-alpha (Gro-alpha), and interferon-gamma inducible protein-10 (IP-10) in RA patients were measured. Twenty-two patients with RA were administered etanercept once or twice a week for more than 6 months. The clinical and laboratory parameters were measured and serum levels of IL-15, Gro-alpha, and IP-10 were determined using enzyme-linked immunosorbent assay (ELISA) kits at the baseline and at 3 and 6 months after the initial treatment. Additionally, the production of IL-15 and IP-10 by cultured synovial cells stimulated with TNF-alpha from RA patients was determined by ELISA. A significant decrease in serum levels of IL-15 and IP-10 was observed at 3 and 6 months after initial treatment with etanercept, but not in those of Gro-alpha. TNF-alpha induced production of IP-10, but not IL-15 in cultured synovial cells from RA patients. This study demonstrated for the first time the reduction of IP-10 and IL-15 production in RA patients as active mechanisms of etanercept.

Infliximab treatment reduces the serum levels of interleukin-23 in patients with rheumatoid arthritis.

In this study, we investigated the effect of the antitumor necrosis factor alpha (anti-TNF-alpha) antibody, infliximab, combined with methotrexate (MTX) and MTX alone on the serum levels of interleukin (IL)-23 and IL-17 in rheumatoid arthritis (RA) patients. Infliximab combined with MTX was administered to 26 patients with RA (infliximab group), and MTX alone was given to 20 patients with RA (MTX group). We evaluated clinical and laboratory parameters, including the Disease Activity Scores of 28 joints (DAS28) and serum levels of IL-23 and IL-17 at baseline and at 14 and 30 weeks after the initial treatment with these drugs. Single regression analysis was performed between the levels of serum IL-23 and other clinical and laboratory parameters at baseline before the initial treatment with infliximab or MTX. A significant reduction of DAS28 scores was observed in both the infliximab and the MTX group at 14 and 30 weeks after the initial treatment. A significant decrease in serum levels of IL-23 was observed in the infliximab group but not in the MTX group at 14 and 30 weeks after the initial treatment. Serum IL-17 levels did not show a significant change during the follow-up period. At baseline, before the initial treatment with infliximab or MTX, serum IL-23 levels showed a significant correlation with DAS28 and the number of swollen joints. This study indicated that the reduction of serum IL-23 levels in RA patients was a novel action of infliximab.

Etanercept reduces the serum levels of macrophage chemotactic protein-1 in patients with rheumatoid arthritis.

This study was performed to analyze the effect of etanercept, the soluble tumor necrosis factor-alpha (TNF-alpha) receptor, on the serum levels of several chemokines including monocyte chemotactic protein-1 (MCP-1), regulated upon activation normal T expressed and presumably secreted (RANTES), and granzyme B in rheumatoid arthritis (RA) patients. Twenty-eight patients with RA were administered etanercept once or twice a week for more than 6 months. Clinical and laboratory parameters were measured and serum levels of MCP-1, RANTES, and granzyme B were determined using enzyme-linked immunosorbent assay (ELISA) kits at baseline and at 3 and 6 months after the initial treatment. In addition, the levels of MCP-1, RANTES, and granzyme B produced by cultured synovial cells stimulated with TNF-alpha were measured. A significant decrease in serum MCP-1 levels was observed at 3 and 6 months after initial treatment with etanercept. Serum RANTES and granzyme B levels did not show significant changes. TNF-alpha induced MCP-1, RANTES, and granzyme B production in cultured synovial cells from RA patients. Serum MCP-1 levels were significantly correlated with the disease activity scores of 28 joints combined with CRP (DAS28-CRP), indicating the role of MCP-1 in the pathogenesis of rheumatoid inflammation. This study demonstrated that a reduction of MCP-1 production in RA patients was a newly determined effect of etanercept. Another cascade not associated with TNF-alpha may induce granzyme B and RANTES production in RA patients.

Successful introduction of modified dorsolumbar epidural anesthesia in a bovine referral center.

This study describes the successful use of modified dorsolumbar epidural anesthesia with a fixed volume of anesthetic in a bovine referral center. Among the 130 Holstein cattle scheduled for flank surgery, 90 cattle received a mixed anesthetic consisting of 1 ml of xylazine hydrochloride and 3 ml of lidocaine hydrochloride by modified dorsolumbar epidural anesthesia. Eighteen cattle with dehydration and/or lameness received a mixed anesthetic containing 0.5 ml of xylazine and 3 ml of lidocaine. Infiltration anesthesia was performed in 22 cattle whose epidural space could not be reached in order to perform the flank surgery. The surgeries began about 12 min after the administration of the anesthetic and lasted for about 36 min. The modified method using a fixed volume of anesthetic was successfully introduced and effectively used in a bovine referral center. This modified method will allow veterinarians to save time and effort, thus lowering the cost of each surgery.

Osteoma arising from the lumbar articular process.

A 57-year-old man presented with an extremely rare osteoma originating from the left L-5 inferior articular process and causing lumbo-crural sciatica. Postmyelography computed tomography and magnetic resonance imaging showed an osteoma compressing the spinal nerve root at the lateral recess. Decompression facetectomy and excision of the lesion followed by transforaminal lumbar interbody fusion between L-5 and S-1 provided complete relief from the symptoms. Histological examination confirmed the diagnosis of benign osteoma. The previous seven cases of spinal osteoma involved the vertebral body, pedicle and posterior elements. Spinal osteomas should be considered in the differential diagnosis of benign lesion originating from the articular process.