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Graham A R Johnston - One of the best experts on this subject based on the ideXlab platform.
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analogues of γ aminobutyric acid gaba and trans 4 aminocrotonic acid taca substituted in the 2 position as gabac receptor antagonists
British Journal of Pharmacology, 1997Co-Authors: Mary Chebib, Robert J Vandenberg, Graham A R JohnstonAbstract:1 γ-Aminobutyric acid (GABA) and trans-4-aminocrotonic acid (TACA) have been shown to activate GABAC receptors. In this study, a range of C2, C3, C4 and N-substituted GABA and TACA analogues were examined for activity at GABAC receptors. 2 The effects of these compounds were examined by use of electrophysiological recording from Xenopus oocytes expressing the human ρ1 subunit of GABAC receptors with the two-electrode voltage-clamp method. 3 trans-4-Amino-2-fluorobut-2-enoic acid was found to be a potent agonist (KD=2.43 μm). In contrast, trans-4-amino-2-methylbut-2-enoic acid was found to be a moderately potent antagonist (IC50=31.0 μm and KB=45.5 μm). These observations highlight the possibility that subtle structural substitutions may change an agonist into an antagonist. 4 4-Amino-2-methylbutanoic acid (KD=189 μm), 4-amino-2-methylenebutanoic acid (KD=182 μm) and 4-amino-2-chlorobutanoic acid (KD=285 μm) were weak partial agonists. The intrinsic activities of these compounds were 12.1%, 4.4% and 5.2% of the maximal response of GABA, respectively. These compounds more effectively blocked the effects of the agonist, GABA, giving rise to KB values of 53 μm and 101 μm, respectively. 5 The sulphinic acid analogue of GABA, homohypotaurine, was found to be a potent partial agonist (KD=4.59 μm, intrinsic activity 69%). 6 It was concluded that substitution of a methyl or a Halo Group in the C2 position of GABA or TACA is tolerated at GABAC receptors. However, there was dramatic loss of activity when these Groups were substituted at the C3, C4 and nitrogen positions of GABA and TACA. 7 Molecular modelling studies on a range of active and inactive compounds indicated that the agonist/competitive antagonist binding site of the GABAC receptor may be smaller than that of the GABAA and GABAB receptors. It is suggested that only compounds that can attain relatively flat conformations may bind to the GABAC receptor agonist/competitive antagonist binding site.
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Analogues of γ‐aminobutyric acid (GABA) and trans‐4‐aminocrotonic acid (TACA) substituted in the 2 position as GABAC receptor antagonists
British Journal of Pharmacology, 1997Co-Authors: Mary Chebib, Robert J Vandenberg, Graham A R JohnstonAbstract:1 γ-Aminobutyric acid (GABA) and trans-4-aminocrotonic acid (TACA) have been shown to activate GABAC receptors. In this study, a range of C2, C3, C4 and N-substituted GABA and TACA analogues were examined for activity at GABAC receptors. 2 The effects of these compounds were examined by use of electrophysiological recording from Xenopus oocytes expressing the human ρ1 subunit of GABAC receptors with the two-electrode voltage-clamp method. 3 trans-4-Amino-2-fluorobut-2-enoic acid was found to be a potent agonist (KD=2.43 μm). In contrast, trans-4-amino-2-methylbut-2-enoic acid was found to be a moderately potent antagonist (IC50=31.0 μm and KB=45.5 μm). These observations highlight the possibility that subtle structural substitutions may change an agonist into an antagonist. 4 4-Amino-2-methylbutanoic acid (KD=189 μm), 4-amino-2-methylenebutanoic acid (KD=182 μm) and 4-amino-2-chlorobutanoic acid (KD=285 μm) were weak partial agonists. The intrinsic activities of these compounds were 12.1%, 4.4% and 5.2% of the maximal response of GABA, respectively. These compounds more effectively blocked the effects of the agonist, GABA, giving rise to KB values of 53 μm and 101 μm, respectively. 5 The sulphinic acid analogue of GABA, homohypotaurine, was found to be a potent partial agonist (KD=4.59 μm, intrinsic activity 69%). 6 It was concluded that substitution of a methyl or a Halo Group in the C2 position of GABA or TACA is tolerated at GABAC receptors. However, there was dramatic loss of activity when these Groups were substituted at the C3, C4 and nitrogen positions of GABA and TACA. 7 Molecular modelling studies on a range of active and inactive compounds indicated that the agonist/competitive antagonist binding site of the GABAC receptor may be smaller than that of the GABAA and GABAB receptors. It is suggested that only compounds that can attain relatively flat conformations may bind to the GABAC receptor agonist/competitive antagonist binding site.
Mary Chebib - One of the best experts on this subject based on the ideXlab platform.
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analogues of γ aminobutyric acid gaba and trans 4 aminocrotonic acid taca substituted in the 2 position as gabac receptor antagonists
British Journal of Pharmacology, 1997Co-Authors: Mary Chebib, Robert J Vandenberg, Graham A R JohnstonAbstract:1 γ-Aminobutyric acid (GABA) and trans-4-aminocrotonic acid (TACA) have been shown to activate GABAC receptors. In this study, a range of C2, C3, C4 and N-substituted GABA and TACA analogues were examined for activity at GABAC receptors. 2 The effects of these compounds were examined by use of electrophysiological recording from Xenopus oocytes expressing the human ρ1 subunit of GABAC receptors with the two-electrode voltage-clamp method. 3 trans-4-Amino-2-fluorobut-2-enoic acid was found to be a potent agonist (KD=2.43 μm). In contrast, trans-4-amino-2-methylbut-2-enoic acid was found to be a moderately potent antagonist (IC50=31.0 μm and KB=45.5 μm). These observations highlight the possibility that subtle structural substitutions may change an agonist into an antagonist. 4 4-Amino-2-methylbutanoic acid (KD=189 μm), 4-amino-2-methylenebutanoic acid (KD=182 μm) and 4-amino-2-chlorobutanoic acid (KD=285 μm) were weak partial agonists. The intrinsic activities of these compounds were 12.1%, 4.4% and 5.2% of the maximal response of GABA, respectively. These compounds more effectively blocked the effects of the agonist, GABA, giving rise to KB values of 53 μm and 101 μm, respectively. 5 The sulphinic acid analogue of GABA, homohypotaurine, was found to be a potent partial agonist (KD=4.59 μm, intrinsic activity 69%). 6 It was concluded that substitution of a methyl or a Halo Group in the C2 position of GABA or TACA is tolerated at GABAC receptors. However, there was dramatic loss of activity when these Groups were substituted at the C3, C4 and nitrogen positions of GABA and TACA. 7 Molecular modelling studies on a range of active and inactive compounds indicated that the agonist/competitive antagonist binding site of the GABAC receptor may be smaller than that of the GABAA and GABAB receptors. It is suggested that only compounds that can attain relatively flat conformations may bind to the GABAC receptor agonist/competitive antagonist binding site.
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Analogues of γ‐aminobutyric acid (GABA) and trans‐4‐aminocrotonic acid (TACA) substituted in the 2 position as GABAC receptor antagonists
British Journal of Pharmacology, 1997Co-Authors: Mary Chebib, Robert J Vandenberg, Graham A R JohnstonAbstract:1 γ-Aminobutyric acid (GABA) and trans-4-aminocrotonic acid (TACA) have been shown to activate GABAC receptors. In this study, a range of C2, C3, C4 and N-substituted GABA and TACA analogues were examined for activity at GABAC receptors. 2 The effects of these compounds were examined by use of electrophysiological recording from Xenopus oocytes expressing the human ρ1 subunit of GABAC receptors with the two-electrode voltage-clamp method. 3 trans-4-Amino-2-fluorobut-2-enoic acid was found to be a potent agonist (KD=2.43 μm). In contrast, trans-4-amino-2-methylbut-2-enoic acid was found to be a moderately potent antagonist (IC50=31.0 μm and KB=45.5 μm). These observations highlight the possibility that subtle structural substitutions may change an agonist into an antagonist. 4 4-Amino-2-methylbutanoic acid (KD=189 μm), 4-amino-2-methylenebutanoic acid (KD=182 μm) and 4-amino-2-chlorobutanoic acid (KD=285 μm) were weak partial agonists. The intrinsic activities of these compounds were 12.1%, 4.4% and 5.2% of the maximal response of GABA, respectively. These compounds more effectively blocked the effects of the agonist, GABA, giving rise to KB values of 53 μm and 101 μm, respectively. 5 The sulphinic acid analogue of GABA, homohypotaurine, was found to be a potent partial agonist (KD=4.59 μm, intrinsic activity 69%). 6 It was concluded that substitution of a methyl or a Halo Group in the C2 position of GABA or TACA is tolerated at GABAC receptors. However, there was dramatic loss of activity when these Groups were substituted at the C3, C4 and nitrogen positions of GABA and TACA. 7 Molecular modelling studies on a range of active and inactive compounds indicated that the agonist/competitive antagonist binding site of the GABAC receptor may be smaller than that of the GABAA and GABAB receptors. It is suggested that only compounds that can attain relatively flat conformations may bind to the GABAC receptor agonist/competitive antagonist binding site.
Robert J Vandenberg - One of the best experts on this subject based on the ideXlab platform.
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analogues of γ aminobutyric acid gaba and trans 4 aminocrotonic acid taca substituted in the 2 position as gabac receptor antagonists
British Journal of Pharmacology, 1997Co-Authors: Mary Chebib, Robert J Vandenberg, Graham A R JohnstonAbstract:1 γ-Aminobutyric acid (GABA) and trans-4-aminocrotonic acid (TACA) have been shown to activate GABAC receptors. In this study, a range of C2, C3, C4 and N-substituted GABA and TACA analogues were examined for activity at GABAC receptors. 2 The effects of these compounds were examined by use of electrophysiological recording from Xenopus oocytes expressing the human ρ1 subunit of GABAC receptors with the two-electrode voltage-clamp method. 3 trans-4-Amino-2-fluorobut-2-enoic acid was found to be a potent agonist (KD=2.43 μm). In contrast, trans-4-amino-2-methylbut-2-enoic acid was found to be a moderately potent antagonist (IC50=31.0 μm and KB=45.5 μm). These observations highlight the possibility that subtle structural substitutions may change an agonist into an antagonist. 4 4-Amino-2-methylbutanoic acid (KD=189 μm), 4-amino-2-methylenebutanoic acid (KD=182 μm) and 4-amino-2-chlorobutanoic acid (KD=285 μm) were weak partial agonists. The intrinsic activities of these compounds were 12.1%, 4.4% and 5.2% of the maximal response of GABA, respectively. These compounds more effectively blocked the effects of the agonist, GABA, giving rise to KB values of 53 μm and 101 μm, respectively. 5 The sulphinic acid analogue of GABA, homohypotaurine, was found to be a potent partial agonist (KD=4.59 μm, intrinsic activity 69%). 6 It was concluded that substitution of a methyl or a Halo Group in the C2 position of GABA or TACA is tolerated at GABAC receptors. However, there was dramatic loss of activity when these Groups were substituted at the C3, C4 and nitrogen positions of GABA and TACA. 7 Molecular modelling studies on a range of active and inactive compounds indicated that the agonist/competitive antagonist binding site of the GABAC receptor may be smaller than that of the GABAA and GABAB receptors. It is suggested that only compounds that can attain relatively flat conformations may bind to the GABAC receptor agonist/competitive antagonist binding site.
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Analogues of γ‐aminobutyric acid (GABA) and trans‐4‐aminocrotonic acid (TACA) substituted in the 2 position as GABAC receptor antagonists
British Journal of Pharmacology, 1997Co-Authors: Mary Chebib, Robert J Vandenberg, Graham A R JohnstonAbstract:1 γ-Aminobutyric acid (GABA) and trans-4-aminocrotonic acid (TACA) have been shown to activate GABAC receptors. In this study, a range of C2, C3, C4 and N-substituted GABA and TACA analogues were examined for activity at GABAC receptors. 2 The effects of these compounds were examined by use of electrophysiological recording from Xenopus oocytes expressing the human ρ1 subunit of GABAC receptors with the two-electrode voltage-clamp method. 3 trans-4-Amino-2-fluorobut-2-enoic acid was found to be a potent agonist (KD=2.43 μm). In contrast, trans-4-amino-2-methylbut-2-enoic acid was found to be a moderately potent antagonist (IC50=31.0 μm and KB=45.5 μm). These observations highlight the possibility that subtle structural substitutions may change an agonist into an antagonist. 4 4-Amino-2-methylbutanoic acid (KD=189 μm), 4-amino-2-methylenebutanoic acid (KD=182 μm) and 4-amino-2-chlorobutanoic acid (KD=285 μm) were weak partial agonists. The intrinsic activities of these compounds were 12.1%, 4.4% and 5.2% of the maximal response of GABA, respectively. These compounds more effectively blocked the effects of the agonist, GABA, giving rise to KB values of 53 μm and 101 μm, respectively. 5 The sulphinic acid analogue of GABA, homohypotaurine, was found to be a potent partial agonist (KD=4.59 μm, intrinsic activity 69%). 6 It was concluded that substitution of a methyl or a Halo Group in the C2 position of GABA or TACA is tolerated at GABAC receptors. However, there was dramatic loss of activity when these Groups were substituted at the C3, C4 and nitrogen positions of GABA and TACA. 7 Molecular modelling studies on a range of active and inactive compounds indicated that the agonist/competitive antagonist binding site of the GABAC receptor may be smaller than that of the GABAA and GABAB receptors. It is suggested that only compounds that can attain relatively flat conformations may bind to the GABAC receptor agonist/competitive antagonist binding site.
Akio Fujimura - One of the best experts on this subject based on the ideXlab platform.
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Involvement of Wee1 in the Circadian Rhythm–Dependent Intestinal Damage Induced by Docetaxel
Journal of Pharmacology and Experimental Therapeutics, 2013Co-Authors: Yuri Obi-ioka, Kentaro Ushijima, Mikio Kusama, Eiko Ishikawa-kobayashi, Akio FujimuraAbstract:Docetaxel, a semisynthetic taxane, is effective for the treatment of some solid cancers; however, docetaxel-induced intestinal damage leads to poor prognosis in some patients. Although such adverse effects have been reported to depend on the dosing-time of docetaxel, the mechanisms involved remain unclear. Wee1 expression is controlled by the clock gene complex, clock/bmal1 , and contributes to cell-cycle progression. The present study was undertaken to evaluate the potential role of Wee1 in the circadian rhythm–dependent profile of docetaxel. Male mice were maintained under a 12-hour light/dark cycle. Intestinal damage after repeated dosing of docetaxel (20 mg/kg) for 3 weeks was more severe at 14 hours after light on (Halo) than at 2 Halo. The intestinal protein expressions of Wee1, phosphorylated CDK1, and cleaved Caspase-3 were higher in the 14-Halo Group than in the 2-Halo Group, whereas that of survivin was lower in the 14-Halo Group. Thus, it is speculated that elevated Wee1 expression inhibited CDK1 activity more by phosphorylation, which in turn caused the lower expression of survivin and consequently more activated Caspase-3 in the 14-Halo Group. There were no significant differences in plasma docetaxel concentrations between the 2- and 14-Halo Groups. Bindings of CLOCK and BMAL1 to the E-box regions at the wee1 gene promoter were not altered by docetaxel treatment at 2 and 14 Halo. These findings suggest that Wee1 is directly or indirectly involved in the mechanism of the circadian rhythm–dependent changes in docetaxel-induced intestinal damage. However, the mechanism for a circadian rhythm–dependent change in intestinal Wee1 expression by docetaxel remains to be determined.
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Influence of Dosing Time on the Efficacy and Safety of Finasteride in Rats
Journal of Pharmacology and Experimental Therapeutics, 2011Co-Authors: Masafumi Kumazaki, Hitoshi Ando, Kentarou Ushijima, Tomohiro Maekawa, Yuya Motosugi, Makoto Takada, Masato Tateishi, Akio FujimuraAbstract:Finasteride (FIN), a widely used medication for the treatment of androgen-dependent diseases, blocks the conversion of testosterone to a more potent androgen, dihydrotestosterone (DHT). In this study, we investigated a dosing time-dependent effect and safety of FIN in rats. Androgen receptor (AR) mRNA and nuclear protein levels exhibited clear daily rhythms with the peak during the dark period in the prostate and during the light period in the liver. Repeated oral administration of FIN (5 or 100 mg/kg) at 3 h after lights on (Halo) for 2 weeks decreased serum DHT concentration throughout a 24-h period, whereas the dosing of the agent at 15 Halo decreased its level only transiently even in the higher dose Group. FIN caused laboratory abnormalities in the 3 Halo Group but not in the 15 Halo Group. However, the effect of FIN on the prostate weight was not influenced by the dosing time. These results suggest that the safety, but not effect, of FIN depends on its dosing time in rats. The dosing of FIN in the active period might be a rational dosage regimen, which is needed to be confirmed in human subjects.
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Dosing‐Time–Dependent Differences in Lipopolysaccharide‐Induced Liver Injury in Rats
Chronobiology International, 2005Co-Authors: Yasuhiko Kitoh, Eiji Kobayashi, Masami Ohmori, Nobutaka Araki, Fujiko Miyashita, Hitoshi Ando, Norio Sogawa, Akio FujimuraAbstract:Dosing‐time–dependent differences in lipopolysaccharide (LPS)‐induced liver injury were examined in rats housed under a 12 h light∶dark (LD) cycle. LPS (5 mg/kg) was intravenously injected into different Groups of rats at 2, 14, or 20 h after light on (Halo). Elevations in serum liver enzymes after 14 Halo were significantly greater than those after 2 Halo. These parameters were lower in rats given LPS at 20 Halo, compared to 14 Halo. The number of polymorphonuclear cells (PMN) in the liver and the amount of hepatic myeloperoxidase activity, which reflects the number of PMN in liver tissues, was significantly greater in the 14 than in the 2 Halo Group. In addition, hepatic interleukin‐6 (IL‐6) production in the 14 Halo Group was enhanced compared to that in the 2 Halo trial. These results suggest that LPS‐induced liver injury is greater during the early active than during the early resting period. Dosing‐time–dependent variation in the accumulation of PMN in the liver and, potentially, subsequent IL‐6 pro...
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Dosing time dependency of doxorubicin-induced cardiotoxicity and bone marrow toxicity in rats.
Journal of Pharmacy and Pharmacology, 2003Co-Authors: Shigehiro Ohdo, Akio Fujimura, Mikiko Shin, Hiroki Uchimaru, Eiji Yukawa, Shun Higuchi, Eiji KobayashiAbstract:Cardiac toxicity caused by doxorubicin (adriamycin) is a serious dose-limiting factor in the clinical situation. However, the influence of doxorubicin dosing time has not been clarified from the viewpoints of cardiotoxic development and its mechanism. In this study, we have investigated the dosing time dependency of doxorubicin-induced cardiotoxicity and bone marrow toxicity after repeated administration of doxorubicin in rats. When doxorubicin (5 mg kg(-1), i.p.) was administered every seven days (total of 30 mg kg(-1)) at 3, 9, 15 or 21 h after the light was turned on (Halo), toxic death was significantly higher in the 9 Halo treated Group than the other Groups. When doxorubicin was injected every seven days for 28 days at 9 or 21 Halo, we measured the levels of creatine kinase, malondialdehyde (MDA; an index of lipid peroxide), and glutathione peroxidase (GPx) as markers of cardiotoxicity. On days 14 and 28, creatine kinase levels were significantly higher in the 9-Halo Group compared with the 21-Halo Group (P< 0.01, respectively). On day 14, MDA levels increased significantly in the 9 Halo Group compared with the 21 Halo Group (P< 0.01). A single dose of doxorubicin was administered at 9-h or 21-h after the light was turned on to investigate the dosing-time-dependent difference of the pharmacokinetics. The area under the plasma time-concentration curve showed a significant increase at 9 Halo compared with 21 Halo (P< 0.05). These results suggested that the dosing-time-dependent difference of cardiotoxicity induced by doxorubicin was closely related to the daily variation of doxorubicin pharmacokinetics. In conclusion, the choice of optimal dosing time based on the chronopharmacokinetics of doxorubicin may decrease the cardiotoxicity and enable the practice of effective and safe chemotherapy of doxorubicin.
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Chronotherapy with active vitamin D3 in aged stroke-prone spontaneously hypertensive rats, a model of osteoporosis.
European Journal of Pharmacology, 2001Co-Authors: Shuichi Tsuruoka, Kenta Nishiki, Koh-ichi Sugimoto, Akio FujimuraAbstract:The chronotherapeutic effects of 1-α-(OH) vitamin D3, a pro-drug of 1,25(OH)2 vitamin D3 (1,25(OH)2D3), were evaluated by repeated dosing of the drug in aged stroke-prone spontaneously hypertensive male rats, a model of osteoporosis. Animals (7 months old) were kept in rooms with a 12-h light/dark cycle. Drug (0.5 μg/kg) or vehicle was given once daily at 2 or 14 h after lights on for 3 months. The severity of adverse effects such as body weight loss, hypercalcemia and hyperphosphatemia was significantly less when the drug was given at 14 h after lights on (14 Halo). Serum 1,25(OH)2 vitamin D3 concentrations of 2 h after lights on (2 Halo) Group and 14 Halo Group did not differ significantly after dosing. The decrease in parathyroid hormone (PTH) level 12 weeks after the start of the study was greater in the 14 Halo Group than in the 2 Halo Group. Urinary excretion of inorganic Ca and P in the 2 Halo Group was greater than that in the 14 Halo Group. Urinary excretion of deoxypyridiniline, an index of the bone resorption capacity of osteoclasts, was much suppressed in the 14 Halo Group, suggesting that the efficacy of vitamin D3 for suppressing bone resorption might vary with the dosing time. The increase in bone density of both femurs, determined by dual-energy X-ray absorption at the end of the study, was greater in the 14 Halo Group than in the 2 Halo Group. This is the first study to show the dosing time-dependent efficacy and toxicity of active vitamin D3 in an animal model of osteoporosis. These results indicate that a chronopharmacological approach is beneficial for establishing a more effective and/or safer regimen of active vitamin D3 for the treatment of osteoporosis.
Yasser Assaghir - One of the best experts on this subject based on the ideXlab platform.
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Burst C2 Fractures Combined with Traumatic Spondylolisthesis: Can Atlantoaxial Motion Be Preserved? Including Some Technical Tips for Reduction and Fixation
Global Spine Journal, 2016Co-Authors: Yasser AssaghirAbstract:Study Design Retrospective comparative clinical case series. Objective Burst C2 fractures are very rare. Treatment options include conservative treatment or fusion (anterior, posterior, or anterior and posterior). Anterior fusion addresses mainly hangman component. The bursting body usually needs posterior or combined anterior-posterior fusion, but both permanently sacrifice atlantoaxial motion. Can anterior-“first” approach preserve C1–C2 motion and restore function? Methods We report nine cases of burst C2 combined with C2–C3 spondylolisthesis and an odontoid fracture. The surgical Group included six patients treated initially with an anterior approach, moving to a posterior one when necessary. All were treated with anterior diskectomy fusion using one session and one incision. The Halo Group included three patients treated conservatively using Halo traction followed by rigid collar. Assessments included self-reported, physiologic, and functional measures. Reduction was assessed using Roy-Camille's criteria and improvement of canal compression ratio. Clinical outcome was graded excellent, very good, good, or poor according to pain, range of motion, and work status. Results Mean follow-up was 44.5 ± 8.3 (range 36.0 to 62.0) weeks. Results in the surgical Group were judged to be excellent in four and good in two. One patient developed atlantoaxial osteoarthritis. Results were good in one patient and poor in two patients in the Halo Group. Two patients developed atlantoaxial osteoarthritis. All three cases had work limitations. Conclusion A single anterior approach achieved union and preserved C1–C2 motion and function in some cases. Conservative treatment achieved union but failed to achieve good reduction or good clinical outcome in grossly instable fractures. However, we believe that the ideal management is yet to evolve.
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Burst C2 Fractures Combined with Traumatic Spondylolisthesis: Can Atlantoaxial Motion Be Preserved? Including Some Technical Tips for Reduction and Fixation.
Global spine journal, 2015Co-Authors: Yasser AssaghirAbstract:Retrospective comparative clinical case series. Burst C2 fractures are very rare. Treatment options include conservative treatment or fusion (anterior, posterior, or anterior and posterior). Anterior fusion addresses mainly hangman component. The bursting body usually needs posterior or combined anterior-posterior fusion, but both permanently sacrifice atlantoaxial motion. Can anterior-"first" approach preserve C1-C2 motion and restore function? We report nine cases of burst C2 combined with C2-C3 spondylolisthesis and an odontoid fracture. The surgical Group included six patients treated initially with an anterior approach, moving to a posterior one when necessary. All were treated with anterior diskectomy fusion using one session and one incision. The Halo Group included three patients treated conservatively using Halo traction followed by rigid collar. Assessments included self-reported, physiologic, and functional measures. Reduction was assessed using Roy-Camille's criteria and improvement of canal compression ratio. Clinical outcome was graded excellent, very good, good, or poor according to pain, range of motion, and work status. Mean follow-up was 44.5 ± 8.3 (range 36.0 to 62.0) weeks. Results in the surgical Group were judged to be excellent in four and good in two. One patient developed atlantoaxial osteoarthritis. Results were good in one patient and poor in two patients in the Halo Group. Two patients developed atlantoaxial osteoarthritis. All three cases had work limitations. A single anterior approach achieved union and preserved C1-C2 motion and function in some cases. Conservative treatment achieved union but failed to achieve good reduction or good clinical outcome in grossly instable fractures. However, we believe that the ideal management is yet to evolve.
