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This article describes a new technique for the arthroscopic reduction and fixation of anterior cruciate ligament (ACL) tibial avulsion fractures using bioabsorbable suture anchors. This described technique requires the use of anterolateral, anteromedial, medial mid-patellar, and lateral mid-patellar portals. A suture hook loaded with No. 2 polydioxanone (PDS) was used to pierce the ACL through the anteromedial or anterolateral portal, and bioabsorbable suture anchors were inserted through the medial and lateral mid-patellar portals. The five patients treated using this technique were evaluated at 1 year postoperatively. All patients showed bony union without anterior laxity or flexion contracture. The described technique provides firm fixation of fracture fragment and can be used in both skeletally immature and mature patients. [ABSTRACT FROM AUTHOR]

BACKGROUND: Patients with aplastic anemia are now living longer and therefore are at increased risk for the development of osteonecrosis of the hip. However, studies on the results of arthroplasty for the treatment of osteoarthritis of the hip in patients with aplastic anemia are lacking. METHODS: Twenty-six primary hip prostheses (one bipolar prosthesis fixed with cement, two bipolar prostheses fixed without cement, three hybrid total hip prostheses, and twenty total hip prostheses fixed without cement) were implanted, between March 1990 and May 1992, in nineteen patients who had been diagnosed with aplastic anemia. A specific prospective protocol was followed for the perioperative transfusion of platelets and blood. Twenty-five hips were replaced because of osteonecrosis of the femoral head, and one was replaced because of a femoral neck fracture. The patients were followed prospectively, with preoperative and serial postoperative Harris hip ratings as well as radiographs, for a minimum of six years or until death. RESULTS: No patient had excessive perioperative bleeding or a postoperative infection. After a mean duration of follow-up of seventy-nine months (range, seventy-two to ninety-five months), two patients had died with the original implant in place. No patients were lost to follow-up. The mean Harris hip score was 55 points (range, 42 to 68 points) preoperatively and 87 points (range, 56 to 95 points) at the time of the latest follow-up. At the time of this writing, no hip had been revised. One patient with a bipolar prosthesis had radiographic evidence of femoral loosening and will probably require revision. A second patient had some medial protrusion of a bipolar prosthesis, with mild symptoms. All of the acetabular components that had been fixed without cement and all of the other femoral components appeared to be stable on radiographs after a minimum of seventy-two months of follow-up. CONCLUSIONS: Total hip arthroplasty can be performed safely in patients with aplastic anemia. In the present intermediate-term study, the durability of implant fixation was maintained and the clinical results demonstrated a sustained increase in function of the hip. [ABSTRACT FROM AUTHOR]

Skeletal muscle atrophy, which is characterized by diminished muscle mass, strength, and function, is caused by malnutrition, physical inactivity, aging, and diseases. Korean mint ( Agastache rugosa Kuntze) possesses various biological functions, including anti-inflammatory, antioxidant, anticancer, and antiosteoporosis activities. Moreover, it contains tilianin, which is a glycosylated flavone that exerts antioxidant, anti-inflammatory, antidiabetic, and neuroprotective activities. However, no studies have analyzed the inhibitory activity of A. rugosa extract (ARE) and tilianin on muscle atrophy. Thus, the present study investigated the potential of ARE and tilianin on muscle atrophy and their underlying mechanisms of action in C2C12 myotubes treated with tumor necrosis factor-α (TNF-α). The results showed that ARE and tilianin promoted the phosphatidylinositol 3-kinase/protein kinase B pathway, thereby activating mammalian target of rapamycin (a protein anabolism-related factor) and its downstream factors. Moreover, ARE and tilianin inhibited the mRNA expression of muscle RING-finger protein-1 and atrogin-1 (protein catabolism-related factors) by blocking Forkhead box class O 3 translocation. ARE and tilianin also mitigated inflammatory responses by downregulating nuclear factor-kappa B expression levels, thereby diminishing the expression levels of inflammatory cytokines, including TNF-α and interleukin-6. Additionally, ARE and tilianin enhanced the expression levels of antioxidant enzymes, including catalase, superoxide dismutase, and glutathione peroxidase. Overall, these results suggest that ARE and tilianin are potential functional ingredients for preventing or improving muscle atrophy., Competing Interests: AUTHOR DISCLOSURE STATEMENT The authors declare no conflict of interest., (Copyright © 2024 by The Korean Society of Food Science and Nutrition.)

Introduction: The agreement between the radiologic and histopathologic tumor locations in T2 gallbladder cancer is critical. There is no consensus regarding the extent of curative resection by tumor locations., Methods: Between January 2010 and December 2019, a consecutive series of 118 patients with pathological T2 gallbladder cancer who underwent surgery were retrospectively analyzed in terms of the accordance between radiologic and histopathologic tumor locations, the extents of hepatic resection and the numbers of harvested lymph nodes. Radical resection was defined as liver resection with harvesting of at least four lymph nodes., Results: The accuracy of preoperative tumor localization was only 68%. After radical resection, the 5-year overall survival (OS) was 59.4%; after nonradical resection, the figure was 46.1% (p = 0.092). In subanalyses, the 5-year OS was marginally better for patients who underwent liver resection or from whom at least four lymph nodes were harvested than those who did not undergo liver resection or from whom three or fewer lymph nodes were harvested (58.2% vs. 39.4%, p = 0.072; 59.9% vs. 50.0%, p = 0.072, respectively). In patients with peritoneal side tumor, the 5-year OSs of those who did and did not undergo liver resection were 67% and 41.2%, respectively (p = 0.028). In multivariate analysis, perineural invasion and radical resection were independently prognostic of OS., Conclusion: The accuracy of preoperative tumor localization was 68%. Hepatic resection, lymph node dissection harvesting of at least four lymph nodes are required for curative resection for gallbladder cancer, regardless of tumor location., (© 2024 Published by Elsevier Ltd.)

Background: Acute kidney injury (AKI) is a common complication in patients undergoing liver transplantation (LT) for end-stage liver disease (ESLD), and renal replacement therapy (RRT) is required in many cases. This study was performed to identify the prognostic factors for patients undergoing RRT owing to AKI before living donor liver transplantation (LDLT)., Materials and Methods: From January 2010 to December 2018, LDLT was performed in 464 adult patients in our center. We reviewed 33 patients who underwent RRT before LDLT among 464 consecutive cases. Patients who continued to RRT after LDLT or who underwent subsequent kidney transplantation were considered to have not recovered from renal impairment., Results: Among 33 patients, there were 23 patients in the recovery group and 10 patients in the nonrecovery group. The preoperative duration of RRT was shorter in the recovery group, but it was not statistically significant. In the nonrecovery group, diabetes mellitus was found to have a higher prevalence and ischemic time was longer. Other perioperative factors were not significantly different between the 2 groups. After LDLT, the peak total bilirubin level was higher, and the intensive care unit stay was longer in the nonrecovery group. The overall survival rate was higher in the recovery group., Conclusions: Liver transplant recipients who maintain RRT after LDLT have poor outcome. It is necessary to know the risk factors and manage them well, perioperatively., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Sarcopenia, age-related muscle atrophy, weakening muscle strength, and exercise capacity, generally accompany imbalances in protein metabolism. Chrysanthemum morifolium Ramat. extract (CME) and its active compound, isochlo-rogenic acid A (IcA), have been reported to have anti-oxidative, anti-diabetic, and neuroprotective effects. However, the roles of CME and IcA in the regulation of muscle protein turnover-related signaling pathways to attenuate sarcopenia have not been explored. In this study, we investigated CME and IcA based regulation of protein turnover in synthesizing muscle in vitro and in vivo . At the molecular level, CME and IcA promoted phosphorylation of PI3K/Akt and mTOR pathways, which stimulate synthesis of muscle proteins, and suppressed FoxO3a and E3 ubiquitin ligases during protein degrada-tion. In vivo , CME and IcA increased grip strength, exercise capacity, muscle mass and volume, and cross-sectional area of myofibers in middle-aged C57BL/6J mice. These results suggest that CME and IcA may have roles as functional food supplements for delaying sarcopenia by enhancing muscle mass recovery and function., Competing Interests: AUTHOR DISCLOSURE STATEMENT The authors declare no conflict of interest., (Copyright © 2021 by The Korean Society of Food Science and Nutrition.)

A total of 116 Escherichia coli isolates from cecal contents of 81 indigenous wild birds in Korea were tested for antimicrobial susceptibility. Seventy-one isolates from sparrows (Passer montanus) and one isolate from doves (Columba livia) were resistant to three antimicrobials, including streptomycin, sulfonamide, and tetracycline (SSuT). PCR and subsequent sequence analysis revealed the SSuT gene cluster region (approximately 13 kb) harboring genes encoding resistance to streptomycin (strA and strB), sulfonamide (sul2), and tetracycline (tetB, tetC, tetD, and tetR). In particular, tetracycline resistance genes were located on the transposon Tn10-like element. The SSuT element-harboring E. coli can be an important source of the transmission of antimicrobial resistance to other pathogenic bacteria. Therefore, strict sanitary measures in human and animal environments are necessary to prevent the spread of resistant bacteria through fecal residues of wild birds.

We recently demonstrated that advanced cooling composition (ACC) has effective ingredients that exhibit anti-inflammatory effects in RAW 264.7 cells stimulated with lipopolysaccharide (LPS) and exhibit strong antimicrobial effects on Pseudomonas aeruginosa , Staphylococcus aureus , MRSA (methicillin-resistant Staphylococcus aureus ), Candida albicans , and Streptococcus mutans . To further investigate whether ACC has beneficial effects in ultraviolet B (UVB)-irradiated human keratinocytes (HaCaT cells), HaCaT cells were pretreated with ACC prior to UVB irradiation. Our data showed that ACC, which is effective at 100 µg/mL, is nontoxic and has an antioxidative effect against UVB-induced intracellular reactive oxygen species (ROS) in HaCaT cells. In addition, ACC exerts cytoprotective effects against UVB-induced cytotoxicity in HaCaT cells by inhibiting abnormal inflammation and apoptosis through the regulation of mitogen-activated protein kinase (MAPK) signals, such as jun-amino-terminal kinase (JNK), p38, and extracellular signal-regulated kinase (ERK). Therefore, these results indicate that ACC is a potentially beneficial raw material that possesses antioxidative, anti-inflammatory, and antiapoptotic effects against UVB-induced keratinocytes and may have applications in skin health.

Background: The development of natural cosmetic materials without side effects to protect skin from heat shock is necessary. We recently reported that advanced cooling composition (ACC) has anti-inflammatory effect in RAW 264.7 cells stimulated with lipopolysaccharide (LPS) and strong anti-microbial effect against Pseudomonas aeruginosa, Staphylococcus aureus, MRSA (Methicillin-resistant Staphylococcus aureus), Candida albicans, and Streptococcus mutans., Aims: To further investigate whether advanced anti-inflammation composition (AAIC), newly developed from existing ACC has beneficial effects in heat shock-induced immortalized human keratinocytes (HaCaT cells), HaCaT cells were pretreated with AAIC before heat shock treatment., Methods: Cell viability for heat shock treatment and different concentrations of AAIC in HaCaT cells were assessed by MTT assay. Anti-oxidative activity of AAIC was measured using the DPPH assay. The protein expression in heat shock-induced HaCaT cells treated with AAIC was evaluated by immunofluorescence staining and western blot analysis., Results: AAIC, which is effective at 100 µg/mL concentration, was nontoxic in HaCaT cells and had an anti-oxidative effect demonstrated by scavenging DPPH free radicals. AAIC treatment significantly attenuated the aberrant levels of pro-inflammatory and pro-apoptotic signaling molecules in heat shock-induced HaCaT cells compared with control cells., Conclusion: AAIC potentially includes effective anti-oxidative activity, anti-inflammatory, and anti-apoptotic properties against heat shock-induced keratinocytes, suggesting that it can be provided as a raw material for imparting skin health., (© 2019 Wiley Periodicals, Inc.)

Background: The purpose of this study was to investigate the effects of upper extremity immobilization and consequent walking speed on spatiotemporal gait parameters in stroke patients with hemiparesis., Methods: The following variables were assessed or measured in 29 stroke patients: age, height, weight, disease duration, Korean version of the Mini-Mental State Examination (MMSE-K), Berg balance scale (BBS-K), functional gait assessment (FGA-K), cause of the disease (type of lesion), and hemiparetic side. The measurement of gait was performed using two pressure plates of 1.5 m to create a 3 m walking distance and leaving 1.5 m of extension at both start and end, to ultimately create a 6 m walking distance that the patient could walk through. The following gait patterns were randomly selected based on card draws: self-selected walk speed (SW), self-selected walk speed with immobilized upper extremities (SWI), fast walking (FW), and fast walking with immobilized upper extremities (FWI). Each patient was assessed for four different gait patterns, with three measurements per pattern (12 gait measurements in total)., Results: While there were significant differences in the stride length, step width, velocity, and step length of the paretic side between self-selected walk speed (SW) and SWI, FWI did not show significant changes in any of the tested parameters., Conclusions: Immobilization of the upper extremities may affect walking at self-selected walk speeds. A comprehensive training program including upper extremity movement should be established for gait rehabilitation. Clinical Trial Registration . This trial is registered at http://cris.nih.go.kr/cris., Competing Interests: The authors declare that they have no competing interests., (Copyright © 2020 Seung-hyeon Hong et al.)

The current study compared the effects of informative and confirmatory feedback on brain activation during negative feedback processing. For confirmatory feedback trials, participants were informed that they had failed the task, whereas informative feedback trials presented task relevant information along with the notification of their failure. Fourteen male undergraduates performed a series of spatial-perceptual tasks and received feedback while their brain activity was recorded. During confirmatory feedback trials, greater activations in the amygdala, dorsal anterior cingulate cortex, and the thalamus (including the habenular) were observed in response to incorrect responses. These results suggest that confirmatory feedback induces negative emotional reactions to failure. In contrast, informative feedback trials elicited greater activity in the dorsolateral prefrontal cortex (DLPFC) when participants experienced failure. Further psychophysiological interaction (PPI) analysis revealed a negative coupling between the DLPFC and the amygdala during informative feedback relative to confirmatory feedback trials. These findings suggest that providing task-relevant information could facilitate implicit down-regulation of negative emotions following failure.

Background: This study examined the effects of ankle and knee joint immobilization on postural control in healthy young adults while standing., Methods: The 24 participants included in this study participated in postural standing tests under four different constraint conditions: free joints, ankle immobilization only, knee immobilization only, and ankle-knee immobilization. Tests were performed using a commercial balancing equipment (Biodex(TM), Inc., NY, USA) and software., Results: The overall limit-of-stability score and duration to completion of task were obtained at 75% limit-of-stability (moderate level of difficulty). The overall limit-of-stability score of free joints (34.5±9.1) were significantly different with the ankle immobilization only (26.0±11.6), and ankle-knee immobilization (26.4±7.4) conditions. The test duration increased in the following order: free joints (57.8±10.9), knee immobilization only (62.5±14.0), ankle immobilization only (68.0±14.9), and ankle-knee immobilization (69.4±17.7). The duration of the free joint condition greatly decreased than ankle immobilization only and ankle-knee immobilization conditions., Conclusions: The ankle and knee joints have sufficient range of motion to prevent falls related to decrease postural stability due to insufficient range of motion or to improve postural stability., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Background: A commercial splinting system is designed to permit quick training in opening and closing the affected hand in order to overcome the disadvantages of previous approaches., Objective: The purpose of this study was to assess the feasibility of intensive training using a spring-assisted hand orthosis on upper extremity in individuals with chronic hemiparetic stroke., Design: Five participants for the experimental group and 5 for the control group were recruited from a local rehabilitation hospital. Subjects in the experimental group participated in 4 weeks of training using a SaeboFlex orthosis for 1 hour per day, 5 times per week. Each subject in the control group wore the same orthosis for 1 hour per day without participating in upper extremity training. Outcome measures included the Fugl-Meyer Assessment, Box and Block Test, and Action Research Arm Test; kinematic parameters were collected using a 3-D motion analysis system., Results: The Fugl-Meyer assessment and the Box and Block Test score were increased significantly in the experimental group after the intervention. The resultant velocity of the wrist joint for the reach-to-grasp task decreased significantly, and the resultant velocity of the shoulder joint while performing a reach-to-grasp task at acromion height decreased significantly in the experimental group., Conclusion: A pilot clinical study of spring-assisted dynamic hand orthosis training is feasible in recovering the movement of the hemiparetic upper extremity.

Background: Total knee arthroplasty (TKA) using a cemented technique has been recommended in patients with rheumatoid arthritis owing to the initial stability of the fixation and long-term durability of the components; however, similar long-term follow-up results have been reported in patients who have undergone cementless TKA. The purpose of this study was to evaluate the radiologic and clinical outcomes of cementless TKA in patients with rheumatoid arthritis., Methods: We enrolled patients undergoing cementless TKA from March 1990 to February 2000. Clinical and radiologic evaluations were performed using the Knee Society clinical rating system and radiographic evaluation and scoring system., Results: We included the cases of 112 patients who underwent 179 cementless TKA procedures in our analysis. Their mean age was 62.3 years, and the mean follow-up period was 10.1 years. The final survival rate was 0.968 at the 15.5-year follow-up. Regarding radiologic results after surgery, the mean total valgus angle was 6.7°, the mean femoral flexion angle was 97.5° and the mean tibial angle was 89.2° on the anteroposterior radiographs. On the lateral films, the mean femoral flexion angle was 1.6° and the mean tibial angle was 89.2°. At the last follow-up, the mean total valgus angle was 6.5°, the mean femoral flexion angle was 97.4° and the mean tibial angle was 89.1°, as seen on the anteroposterior view. On the lateral views, the mean femoral flexion angle was 1.4° and the mean tibial angle was 89.0°. Regarding the clinical outcome, the mean knee score and function score on the Knee Society clinical rating system were also enhanced from 47.5 and 43.6, respectively, before the operation to 91.2 and 82.3, respectively, at the last follow-up., Conclusion: On radiologic and clinical follow-up of cementless TKA for patients with rheumatoid arthritis, there were no serious complications, and the results of the operation were satisfactory with improvement in range of motion and clinical symptoms.

Objectives: The purpose of this study was to evaluate the clinical effectiveness and radiological results of hybrid total knee arthroplasty (TKA)., Methods: This study recruited 105 patients (169 cases) who underwent hybrid TKA for osteoarthritis and rheumatoid arthritis from 1999 to 2002. Maxim (Biomet Inc., Warsaw, IN, USA) prosthesis was used, and average follow-up was 8.6 years. Radiologically, femorotibial angle was measured in a standing anteroposterior (AP) view, and a femoral flexion angle and a tibial angle were measured using the Knee Society roentgenographic evaluation and scoring system. Radiolucent lines were detected at the last follow-up. Clinically, range of joint motion and the Knee Society clinical rating system scores were evaluated., Results: The femorotibial angle was improved from varus 4.5° to 6.4° at the last follow-up. The femoral flexion in an AP view at the postoperative and last follow-up was 96.5° and 95.7°, respectively, and the tibial angle was 89.1° and 88.7°, respectively. In lateral view, the femoral flexion was 2.6° and 2.7°, respectively, and the tibial angle was 88.4° and 87.8°, respectively. Total scores of radiolucencies were 4 points or less in all cases, and the average width was 1.1 mm. Flexion contracture was improved from 10.0° to 3.5°, and further flexion was increased from 110.5° to 130.4°. Knee score and function score were also enhanced from 47.6 and 46.8 preoperatively to 89.7 and 88.4 after the operation, respectively., Conclusion: Hybrid technique for TKA can be effective clinically and radiologically on longterm follow-up.

Background Context: It was recently demonstrated that the postnatal transition from a notochordal to a fibrocartilaginous nucleus pulposus (NP) is accomplished exogenously by chondrocytes migrating from hyaline cartilage end plates (CEs) into the ectopic notochordal NP region. Although our previous in vivo studies showed evidences for the migration of CE chondrocyte from hyaline CEs into the notochordal NP, it is unknown whether CE chondrocytes of the intervertebral disc (IVD) really have a motile property. In addition, the effect of notochordal cells on this property has not been elucidated., Purpose: The purpose of this in vitro study was to demonstrate whether CE chondrocytes of the IVD are capable of migration, and whether there is any biological link between notochordal cells and CE chondrocytes that may regulate the CE chondrocyte migration., Study Design/setting: In vitro cell migration assays were performed using rat IVDs., Methods: Notochordal cells and chondrocytes were obtained from the NP and CE tissues, respectively, and were cultured separately. The different numbers of notochordal cells and the supernatant (conditioned medium) that contained soluble factors produced by notochordal cells were used to demonstrate their effects on the migration of CE chondrocytes. Bovine serum albumin (BSA) and lysophosphatidic acid (LPA) were used as negative and positive controls, respectively., Results: Compared with BSA, LPA, notochordal cells (N=4x, 2x, 1x, and 0.5 x 10(5)), and its conditioned media (unconcentrated and fivefold concentrated) significantly increased migration of CE chondrocytes (p<.05 in all comparisons). Particularly, notochordal cells and its conditioned media increased migration in a number- and concentration-dependent manner, respectively., Conclusions: This study demonstrates that CE chondrocytes of the IVD are capable of migration and that soluble factors produced by notochordal cells stimulate the migration. These results provide a plausible explanation to the question of why CE chondrocytes of the IVD migrate into the ectopic NP region during the natural transition from the notochordal to fibrocartilaginous NP.

With the exception of flexion gap tightness, which is common in cruciate-retaining (CR) total knee arthroplasty (TKA), the risk factors of flexion gap tightness have not been described. This retrospective study characterized factors that are associated with flexion gap tightness in CR TKA. Data on 203 consecutive knees that underwent CR TKA were reviewed. The prevalence rate of flexion gap tightness was 21.1%. By logistic regression analysis after adjusting for age, preoperative flexion contracture, and referencing method used for femoral sizing, insufficient tibial slope remained a significant independent risk factor of flexion gap tightness. Although excessive tibial slope should be avoided, the findings of the present study demonstrate that the risk of flexion gap tightness can be reduced by increasing the tibial slope in CR TKA.

The authors investigated the agreements between three different methods of estimating gap balance in cruciate-retaining (CR) total knee arthroplasty (TKA) with the use of a subvastus approach. One hundred consecutive CR TKAs were prospectively included in this study. After completing soft tissue release and bone cutting for CR TKA, flexion-extension gap balance was assessed using a distractor, spacer blocks, and trial components. Levels of agreement between the estimation techniques used were substantial. All three techniques were reliable in the assessment of gap balance. But, observations made during this study suggest that if more than one estimation technique is applied during CR TKA, the incidence of undetected gap imbalance can be reduced.

Study Design: Senescence-related markers were assessed in surgically obtained human nucleus pulposus (NP) specimens., Purpose: To demonstrate the mechanism and signaling pathway involved in the senescence of NP chondrocytes., Overview of Literature: The population of senescent disc cells has been shown to be increased in degenerated or herniated discs. However, the mechanism and signaling pathway involved in the senescence of NP chondrocytes are unknown., Methods: We examined cell senescence markers [senescence-associated beta-galactosidase (SA-beta-gal), telomere length, telomerase activity, p53, p21, pRB and p16] and the hydrogen peroxide (H(2)O(2)) content in human NP specimens., Results: The percentage of SA-beta-gal-positive NP chondrocytes increased with age, while the telomere length and telomerase activity declined. However, there was no significant correlation between age and H(2)O(2) content. The NP specimens with grade III or IV degeneration showed significantly higher percentages of SA-beta-gal-positive NP chondrocytes than those with grade II degeneration. Immunohistochemistry showed that senescent NP chondrocytes in all specimens expressed p53, p21, and pRB, while a few NP chondrocytes in only two specimens expressed p16., Conclusions: The present study demonstrates that, with increasing age and advancing disc degeneration, senescent NP chondrocytes increase or accumulate in the NP. Furthermore, the telomere-based p53, p21, pRB pathway, rather than the stress-based p16, pRB pathway, plays a more important role in the senescence of NP chondrocytes in in vivo conditions. Our results suggest that prevention or reversal of senescence of NP chondrocytes can be a novel mechanism by which to prevent human disc degeneration.

Study Design: Western blotting and flow cytometric analyses were performed using rat notochordal cells., Objective: To demonstrate the apoptotic effect of oxidative stress and the antiapoptotic effects of caspase inhibitors on rat notochordal cells., Summary of Background Data: Although oxidative stress causes apoptosis in many cell types, its effect on the apoptosis of notochordal cell and antiapoptotic effects of caspase inhibitors on the oxidative stress-induced apoptosis are unknown., Methods: Cultured rat notochordal cells were exposed to oxidative stress [500 micromol/L of hydrogen peroxide (H2O2)]. To determine the oxidative stress-induced apoptotic pathways, activations of caspases (-3, -8, and -9) as well as cleavages of Bid and poly (ADP-ribose) polymerase (PARP) were evaluated with Western blotting 6 hours after oxidative stress. To elucidate the antiapoptotic effects of caspase inhibitors on the oxidative stress induced-apoptosis, apoptotic rates of notochordal cells with or without treatment of specific caspase inhibitors (z-IETD-fmk for caspase-8, z-LEHD-fmk for caspase-9, and z-DEVD-fmk for caspase-3) were quantified by flow cytometry., Results: Oxidative stress significantly increased apoptosis of rat notochordal cells (2.1% vs. 4.75%, P = 0.008) and led to activations of initiators of intrinsic (caspases-9) and extrinsic (caspase-8) pathways as well as their common executioner (caspase-3). It also caused cleavages of Bid and PARP. Flow cytometric analysis showed that inhibition of only one of the intrinsic and extrinsic pathways by caspase-9 inhibitor (4.75% vs. 3.56%, P = 0.31) and caspase-8 inhibitor (4.75% vs. 5.24%, P = 0.84) did not significantly suppress the oxidative stress-induced apoptosis. However, inhibition of both pathways by caspase-3 inhibitor significantly reduced the oxidative stress-induced apoptosis (4.75% vs. 2.64%, P = 0.008) to the control level (2.1% vs. 2.64%, P = 0.15)., Conclusion: Oxidative stress caused apoptosis of rat notochordal cells via both intrinsic and extrinsic (Type I and Type II) pathways. Because caspase inhibitors are being used in clinical trials, inhibition of both pathways using caspase inhibitors might be of future therapeutic importance in oxidative stress-induced apoptosis of notochordal cells. Our results suggest that inhibition of inappropriate or premature oxidative stress-induced apoptosis of notochordal cells may delay the starting point of disc degeneration.

The purpose of this study was to explore the early treatment potential of anterior cruciate ligament (ACL) injuries using artificial juxtacrine stimulation by photo-immobilization of a growth factor. A photo-reactive epidermal growth factor complex (EGF-Az) was synthesized by conjugating EGF with N-(4-azidobenzoyloxy) succinimide followed by immobilization onto polystyrene culture plates using UV irradiation. ACL cells from human tissues (1 x 10(5)cells, 100 microl/well) were cultured as follows: control, no EGF; 50 microl native EGF; 50 microl EGF-Az immobilized; and 100 microl EGF-Az immobilized. The ACL cells were cultured long-term and evaluated for possible differences in their responses to EGF. An in vitro wound closure assay was developed to enable examination of cellular proliferation and migration. ACL cell proliferation was most evident in the photo-immobilized EGF culture group and was seen to increase in proportion to the amount of added EGF. In the in vitro wound closure assay, the lesioned area at 72 h after culture initiation was indistinguishable in the photo-immobilized cultures, but remained clearly visible in the controls. We conclude that photo-immobilized EGF induced rapid proliferation of ACL fibroblast cells by artificial juxtacrine stimulation and speculate that similar EGF immobilization onto bioabsorbable material (e.g., polyglycolic acid or polylactic acid) might contribute to a new therapy for the treatment of ACL injuries., ((c) 2006 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.)

Symptoms of fowl cholera including orofacial edema, swollen and edematous wattles and combs, and severe respiratory disorders were detected in domestic poultry in two broiler breeder farms: one located in Gyeong-gi Province (October, 2000) and the other in Chung-cheong-nam Province (March, 2001). Gram-negative, bipolar staining bacillus was easily found in a direct smear. The biochemical properties of isolates were examined using a standard diagnosis method, proving that they were 99.7% similar to the Pasteurella multocida (P. multocida: PM), a pathogenic and causative agent of fowl cholera (FC). As a result, an FC outbreak in domestic fowls was confirmed for the first time in Korea since 1942. Because FC was detected in broiler breeder farms for the first time in 59 years at the same time as an FC outbreak was confirmed in wild birds (October, 2000), our concern was focused on whether the PM strains that originated in wild birds were transmitted into poultry farms. The possibility was tracked down by comparing phenotypic and genetic properties between the two types of PM strains. PM strains of chicken origin showed prominent differences from the PM strains of wild bird origin in both phenotypic and genetic properties. An examination of the origin of the wild bird bacteria was conducted, but no evidence has been identified that PM strains from the wild bird were introduced into domestic poultry farms.

In this study, the genetic diversities of multi-resistant Salmonella typhimurium (ST) isolates were analyzed via the application of both pulsed field gel electrophoresis (PFGE) and Polymerase chain reaction (PCR) analysis methods, using 6 kinds of primers (REP, ERIC, SERE, BOX, P-1254 and OPB-17). And their discriminative abilities (DA) were also compared in order to determine the most effective and reliable analysis method. 118 S. typhimurium isolates, cultured from diverse animals and human patients in Korea beginning in 1993, were analyzed and subjected to a comparison of Simpson's index of diversity (SID), using both PFGE and PCR methods. PFGE by XbaI enzyme digestion allowed for discrimination into 9 pulsotypes, with high SID values (0.991) on the genomic DNA level. This shows that PFGE is a very discriminative genotypic tool, and also that multiple clones of S. typhimurium isolates had existed in domestic animals and humans in Korea since 1993. However, we could ultimately not to trace the definitive sources or animal reservoirs of specific S. typhimurium isolates examined in this study. Depending on the SID values, the combined method (7 kinds of method) was found to be the most discriminative method, followed by (in order) SERE-PCR, REP-PCR, ERIC-PCR, PFGE & OPB-17 (RAPD), P-1254 (RAPD), and BOX-PCR at the 80% clone cut-off value. This finding suggests that the REP-PCR method (which utilizes 4 primer types) may be an alternative tool to PFGE for the genotyping of S. typhimurium isolates, with comparable cost, time, and labor requirement. The establishment of a highly reliable and discriminatory method for epidemiologic analysis is considered necessary in order for researchers to trace the sources of specific pathogens and, consequently, to control and prevent the spread of epidemic S. typhimurium isolates to humans.

In previous studies, it has been reported that both S. enteritidis, the most common serotype, and S. enteritidis Phage Type 4 (SEPT 4) isolates were identified as the most prevalent PT in domestic poultry and also in humans in Korea until 2002. The aim of this study was to analyze the genetic diversity and epidemiological properties of both PT isolates, and also to trace the source of SEPT 4 isolates from domestic poultry and humans by Pulsed-field gel electrophoresis (PFGE). In order to understand the molecular epidemiologic properties of SEPT 4 isolates, which have very similar phenotypic properties to our preliminary investigations (serotyping, phage typing, large plasmids and antibiograms), PFGE analysis with XbaI enzyme was performed on the representative SEPT 4 isolates. Thirty-six SEPT 4 isolates were analyzed and differentiated with 10 pulsed-field profiles (PFP) expressing very high discriminative ability (SID: 0.921). In PFP, SEPT 4 isolates from human patients showed a perfect genetic match with those from broiler chickens and meats. Therefore, this study was able to successfully trace the major source of SEPT 4 isolates and also to determine the usefulness of the PFGE method for genetic analysis of epidemic strains.

Study Design: Immunohistochemistry was performed in organ-cultured intact and cartilage endplate (CE)-fractured rat intervertebral discs (IVDs)., Objectives: To demonstrate biologic events associated with migration of chondrocytes from hyaline CE into nucleus pulposus (NP)., Summary of Background Data: It was recently revealed that the transition from a notochordal NP to a fibrocartilaginous NP in the rabbit IVD is accomplished exogenously by chondrocytes migrating from CEs into the NP. This observation has not been studied in other animal models, and the biologic events associated with chondrocyte migration have not been elucidated in the literature., Methods: IVDs including cranial and caudal CEs were obtained from 4-week, 6-month, 12-month, and 18-month old Wistar rats. To accelerate chondrocyte migration, CEs of IVDs were fractured and cultured for 48 hours. IVDs without CE-fracture were used as a control for each age group. Expressions of membrane-type I matrix metalloproteinase (MT1-MMP, as a marker for cell migration and extracellular matrix digestion) and Ki-67 protein (as a proliferation marker) and pericellular deposition of type II collagen (as a marker for fibrocartilaginous matrix) by the chondrocytes migrating from CE into NP were examined immunohistochemically., Results: In the control groups, chondrocyte migration limited only along the periphery of the notochordal NP and no chondrocytes were inside the NP proper. However, all the IVDs in the CE-fracture groups showed direct and more extensive migration of chondrocytes from CEs into the NP proper. The migrating chondrocytes in both control and CE-fracture groups expressed MT1-MMP and Ki-67 protein and deposited type II collagen in the NP., Conclusions: This report demonstrates the chondrocyte migration from CE into NP in the organ-cultured rat IVDs. This phenomenon is accelerated in the presence of CE fracture. The chondrocytes migrating from CEs into the NP expressed MT1-MMP and Ki-67 protein and deposited type II collagen. These biologic strategies probably enable chondrocytes of the hyaline CE to migrate into the ectopic NP region, replace notochordal cells, and change the notochordal tissue into fibrocartilage. These results suggest that similar biologic mechanisms may be involved in the natural transition from the notochordal NP to the fibrocartilaginous NP in other animal models, including human.

Study Design: Immunohistochemistry and in situ nick end-labeling (TUNEL) were performed in rat lumbar intervertebral discs., Objectives: To demonstrate the mechanism of notochordal cell death in the nucleus pulposus (NP)., Summary of Background Data: With age, notochordal cells gradually disappear in the NP. We hypothesized that this phenomenon might be related to Fas-mediated apoptosis., Materials and Methods: Expressions of Fas; Fas ligand (FasL); caspase 3, 8, 9, 10; Ki-67 protein; and TUNEL were examined in 4-week-, 6-month- and 12-month-old rat NPs. Apoptosis (TUNEL-positive) and proliferation potential (Ki-67-positive) indexes of notochordal cells were calculated and compared among age groups., Results: Notochordal cells constitutively expressed both Fas and FasL. Among their downstream initiator (caspase 8, 9, and 10) and executioner (caspase 3) caspases tested, caspase 9 and 3 were expressed. Proliferation potential of the notochordal cells was the highest at 4 weeks (1.96 +/- 1.3%) and decreased to a significantly lower level at 6 (0.81 +/- 0.68%) and 12 months (0.8 +/- 0.37%; P = 0.03 and 0.01, respectively). In contrast, apoptosis of the notochordal cells was the lowest at 4 weeks (3.52 +/- 1.07%) and increased to a significantly higher level at 6 (19.38 +/- 10.99%) and 12 months (21.51 +/- 16.99%; P < 0.001 in both comparisons)., Conclusions: Fas-mediated mitochondrial caspase 9 pathway is constitutively present in the rat notochordal cells. The constitutive expression of Fas, FasL and its downstream caspases, as well as the homogeneity ofnotochordal cell population suggests an autocrine or paracrine Fas-mediated counterattack to be a potential mechanism for apoptosis of rat notochordal cells. A regulated negative balance of notochordal cell proliferation against apoptosis is likely to involve the disappearance of notochordal cells in the rat NP. This information on the mechanism for apoptosis of notochordal cells could be important in the investigation of intervertebral disc development as well as aging and perhaps degeneration.

Background: Non-erosive reflux disorder, which represents more than 60% of gastro-esophageal reflux disorders, lacks objective parameters for diagnosis. The purpose of this study was to evaluate the correlation between non-erosive minimal lesions at the lower esophagus and gastro-esophageal reflux disorder., Methods: Patients were asked to answer a symptom questionnaire. The endoscopic findings were either graded by LA classification or recorded as non-erosive minimal lesions. Patients with minimal lesions were treated with rabeprazole or a placebo and responses were evaluated at weeks 1 and 4., Results: In 8 centers, 3454 patients were screened. In patients with heartburn or acid regurgitation as the most bothersome symptom, 23.7% had endoscopy negative reflux disorder, 40.1% showed minimal lesions, and 36.20% had mucosal break esophagitis. Thirty-four percent of patients with minimal lesions and 39.1% of patients with LA 'grade A' mild esophagitis reported typical reflux symptoms as their main symptom. In patients with minimal lesions, medication with rabeprazole reduced symptoms significantly at weeks 1 and 4, but not with the placebo., Conclusion: Patients with non-erosive minimal esophageal lesions had similar reflux symptoms comparable to those with mild erosive reflux esophagitis, and reflux symptoms were improved with a short-term proton pump inhibitor. Thus, non-erosive minimal esophageal lesion constitutes a great part of gastro-esophageal reflux disorder.

Oncogenic osteomalacia is a rarely described clinical entity characterized by hypophosphatemia, phosphaturia, and a low concentration of 1,25-dihydroxyvitamin D(3). It is most often associated with benign mesenchymal tumor and can be cured with surgical removal of the tumor. In this paper, we present a case of oncogenic osteomalacia caused by chondromyxoid fibroma in the soft tissue of the sole of the foot in a 56-year-old woman.

To evaluate the degree of competitive exclusion against Salmonella gallinarum(S. gallinarum) of Salmonella enteritidis(S. enteritidis) infected chickens, fifty-six, 4-week old Hyline layer suspected of S. enteritidis infection were challenged with S. gallinarum. All chickens were tested for S. enteritidis isolation using cloacal swabs and serum plate agglutination test using S. enteritidis Ag. before challenge and classified into four groups(SE isolated, SE nonisolated, SE seropositive and SE seronegative). None of the SE isolated and the SE seropositive groups died after challenge and the average weight gains were 245.5g and 254.6g, respectively. But in the SE nonisolated and the SE seronegative groups, mortality was 18.2% and 20.6% and the average weight gains were 150.1g and 111.2g. The incidence of reisolation of S. gallinarum of the SE isolated and the SE seropositive groups were 41.7% and 47.6% from liver, 33.3% and 47.6% from spleen and 8.3% and 14.3% from cecum, respectively, and the SE nonisolated and the SE seronegative group were 63.6% and 64.7% from liver, 84.1% and 88.2% from spleen and 47.7% and 52.9% from cecum. The serological response of the SE isolated and the SE seropositive groups hardly changed from 75.0 and 81.8% before challenge to 75.0 and 85.7% after. But, the other two groups were found to be significantly higher after challenge and increased from 0 and 18.2% to 100%. Consequently, S. enteritidis preinfected chickens were found to be significant different in terms of mortality, weight gain, reisolation of S. gallinarum and serological response compared to noninfected chickens. Moreover, our study shows that S. enteritidis infected chickens appear strong competitive exclusion against the colonization of S. gallinarum.

A success or failure of an intertransverse process fusion has been determined by the fusion status of the intertransverse fusion mass alone, and little consideration has been given to the fusion status of the facet joint. The purpose of this study was to assess the fusion status of the facet joints at the fusion level and its impact on the overall fusion outcome. Sixteen patients (19 levels) treated with decompression and intertransverse process fusion using pedicle screw fixation without facet arthrodesis were entered into a cross sectional study in which the fusion status of the intertransverse fusion masses and facet joints at each fusion level were evaluated and combined at an average duration of followup of 35 months (range, 22-61 months). Union rate of the intertransverse process fusion (58%, 22 of 38) was lower than the spontaneous fusion rate of the facet joint (68%, 26 of 38). However, the combination of the two fusion statuses at each fusion level generated 89% of the overall fusion rate (17 of 19 levels). With surgery, all patients had a good or excellent clinical outcome, but the outcome had no relation to the overall fusion status. The results suggest that the fusion status of the facet joint should be considered in determining overall fusion status after combined decompression with instrumented intertransverse process fusion.

Study Design: Patients in whom good intertransverse fusion had been achieved were selected for the volumetric study of the fusion mass using sequential computed tomography scans., Objectives: To assess the natural volumetric change of intertransverse fusion mass and the effect of the disease entity and spinal instrumentation on the fusion mass volume., Summary of Background Data: The magnitude of volumetric change of the graft bone after intertransverse fusion is still inconclusive., Methods: Fifteen adult patients who underwent decompression surgery with single-level lumbar and lumbosacral intertransverse fusion were selected for this study. Preoperative diagnoses were degenerative spondylolisthesis in nine patients and isthmic spondylolisthesis in six. Seven of the 15 patients received pedicle screw fixation. They were categorized into two major groups: 1) instrumented and noninstrumented groups and 2) isthmic and degenerative groups. To assess the volumetric change of the graft bone, sequential computed tomography scans were obtained 2 weeks after surgery and again 18 months after surgery., Results: The overall initial mean graft volume was 6251 mm3, which decreased to 2842 mm3 by 18 months after surgery (P < 0.001). The overall mean volume loss between the two periods was 54.8% of the initial graft volume. Although there was no significant difference in the mean graft volume between the groups at either 2 weeks or 18 months after surgery (P > 0.05 in all comparisons), the mean graft volume in each group decreased significantly during the observation period (P < 0.01 in all comparisons). There was no significant difference in the mean volume loss or in the ratio of residual volume to the initial graft volume between the groups during the study period (P > 0.05 in all comparisons). The initial graft volume correlated positively with the graft volume at 18 months after surgery (r = 0.612, P < 0.01) and volume loss (r = 0.949, P < 0.01), but negatively with the residual volume ratio (r = -0.507, P < 0.01)., Conclusions: These results showed that more than one half of the initial graft bone volume was being absorbed during the consolidation processes of the graft bone, and that the volume loss during the period was not significantly affected by the spinal instrumentation or by the disease entity. It was also found that the greater the amount of the initial graft bone, the larger the fusion mass at 18 months after surgery. The volume loss, however, increased proportionally to an increase in the initial graft bone volume. The efficiency (ratio of residual volume to the initial graft volume) of the intertransverse fusion also tended to decline as the initial graft volume increased.

Hydroxyapatite (HA) particle impregnated polymethylmethacrylate (PMMA) bone cement was fabricated in order to induce bony tissue ingrowth into the pores left behind by resorption of the HA. The amount of HA was 0%, 10%, and 30% by weight. After mixing the HA with bone cement it was cast in a 4 mm inside diameter glass tube (10 mm long). Each specimen was cut into half and used for in vitro and in vivo experiment. Diametral tensile and flexural bend tests were made to evaluate its mechanical properties. SEM (scanning electron microscope) and ESCA (electron spectroscopy for chemical analysis) were used to evaluate the surface characteristics of the specimen. Push-out test and histology studies were made after implanting the specimens for six weeks in the distal portion of rabbit femur. The mechanical test results showed significant decrease of the flexural and diametral tensile strength linear with the increased amount of HA (p < 0.05). The SEM and ESCA analyses showed no definite exposure of HA particles on the surface of the specimens due to the covering by PMMA. The interfacial shear strength of the implanted specimens showed significant increases in the 30% HA specimens compared with the 0% ones but the 10% specimens did not show any difference. Histological observation showed little HA particle apposition to new bone in 10% specimens but more in the 30% ones. In conclusion, this study showed the decreased mechanical properties both by increasing the amount of HA particles and with the bone particles impregnated bone cement. In vivo study showed much lower interfacial shear strength due to implant site compared to other studies but the 30% HA specimens showed statistically significant increase in the push-out strength after implanting into the distal end of rabbit femora.

Study Design: Thirty-nine adults and five children with active spinal tuberculosis and resulting kyphosis of the dorsal and lumbar spine who had combined posterior instrumentation and anterior interbody fusion were observed to determine whether the corrected spinal deformity could be maintained until solid fusion., Objective: To evaluate the effectiveness of the combined two-stage procedure for treating kyphosis due to active spinal tuberculosis., Summary of Background Data: Until 1970, with all methods of treatment, kyphosis due to active spinal tuberculosis tended to increase during therapy. Most of the patients treated with these methods were not happy with this residual kyphosis, even though their disease was arrested or cured. Kyphosis became their main concern regarding further treatment., Methods: A combined two-stage procedure, under the cover of 18 months of triple chemotherapy, was used for all patients. For posterior stabilization, the Harrington distraction system, Rush nails or Steinmann pins and wires, and Texas Scottish Rite Hospital instrumentation were used. The diagnosis of successful interbody fusion was made if there was no loss of correction, no graft resorption or graft bed resorption, and if there was visible graft remodeling, such as trabeculation between the graft beds and graft and the graft hypertrophy., Results: In the 39 adults, average preoperative, immediate postoperative, and last follow-up kyphosis angles were 37 degrees, 16 degrees, and 18 degrees, respectively. In four children, the average preoperative, immediate postoperative, and last follow-up kyphosis angles were 55 degrees, 28 degrees, and 31 degrees, respectively. The loss of correction did not exceed 3 degrees. For one-segment spondylodesis, the average fusion times were 4 months in adults and 3.5 months in children. For a two-segment fusion, the average fusion times were 6 months in adults and 6.3 months in children., Conclusion: Posterior instrumental stabilization and anterior interbody fusion were found helpful in arresting the disease early, providing early fusion, preventing progression of kyphosis, and correcting the kyphosis.

The primary goal of this investigation is to study whether soft tissue homeostatic responses secondary to decrease or increase in physiological stress levels and range of motion are a change of mechanical properties or a change of mass, or both. Two experimental animal studies are presented. One is a stress and motion deprivation study by immobilization of a rabbit knee, and the other is an increase in stress and motion study by running exercise of the miniature swine. The findings are that changes in stress and motion significantly altered the tissue properties as well as mass in the case of ligaments and digital extensor tendons. Whereas, no significant changes in properties and mass were detected for the digital flexor tendons. Possible mechanisms of the difference in tissue responses to stress and motion are discussed, and nonlinear relationships between stress and tissue remodeling are suggested.

The incidence and size of meniscal regeneration after medial meniscectomy on the right knee and lateral meniscectomy on the left knee of 44 rabbits was observed and correlated with development of degenerative arthritis. Complete meniscal regeneration was found in 23% of medial meniscectomy knees, partial regeneration in 68%, and no regeneration in 9%. Among 44 lateral meniscectomies, only 5% had complete meniscal regeneration, and 68% had no meniscal regeneration. The remaining 27% of knees had partial regeneration. Degenerative changes of articular cartilage in the tibiofemoral joints of all knees were inversely correlated with the size of the regenerated meniscus. These observations suggest that poor results following lateral meniscectomy may be due to a lower level of meniscal regeneration and relatively poor morphological regeneration of the lateral meniscus compared to the medial meniscus.

Twenty-five cases of unstable fractures and fracture-dislocations of the spine are reviewed. They were treated at the Catholic Medical College and Centre in a 3-year period, 1975 to 1978. 1. Eleven of the 25 patients were treated by anterior interbody fusion performed at 6 to 8 weeks from injury or initial surgery. 2. Eleven patients had neurological deficits, 3 with incomplete lesions and 8 with complete lesions. Open reduction and decompression laminectomies were performed on patients having neurological deficits prior to anterior interbody fusion. Two patients with incomplete paraplegia showed marked neurological recovery whilst one with complete paraplegia regained some sensation. 3. Solid clinical fusion was obtained in all but one patient within four months of interbody fusion. 4. Amongst the 18 patients with kyphosis at the time of admission 10 had a final improvement of their kyphosis ranging from 3 to 10 degrees (average 6 degrees). Three had no change and 5 demonstrated a mild increase of kyphosis (average 4 degrees). 5. Pain was relieved in 21 patients out of 25. The advantages of this technique include effective stabilization, prevention of late deformity and relatively early mobilization without internal fixation.

We have treated 75 cases of spinal tuberculosis with chemotherapy as outpatients. The drugs used were INH, rifampicin and ethambutol for the 48 adults, and INH, rifampicin and PAS for the 27 children. No operations, apart from the evacuation of large abscesses, were carried out. Every patient was followed up for at least three years and the outcome was judged to be favourable in 95%. This is better than in some series in which radical surgery has been used. Although we recognize the advantages of operation in certain circumstances, we believe that our conservative regimen can be confidently recommended for use in less privileged countries, where adequate facilities for hospital treatment may not be available.

A screening process to determine the most appropriate model for the study of cartilage growth from perichondrium obtained from the rabbit's left tenth costal cartilage has resulted in the following observations: (1) best growth is achieved when fixation of the graft is secure and conformity to the recipient bed is complete; (2) immobilization enhances fixation, but permits fibrous tissue growth onto the graft, and (3) diminishing periods of immobilization enhance perichondrial growth, but have a deleterious effect on fixation.

In the application of "rigid" plates for diaphyseal fractures, lack of callus healing and overprotection of the underlying bone are viewed by many investigators as undesirable consequences. Potential solutions offered to overcome these deficiencies include modification of the timing of plate removal, use of biologically degradable materials for plates so that stress-shielding can be minimized, and use of less rigid plate fixation systems. This study emphasizes the selection of appropriate design criteria for less rigid plate-fixation systems. To accomplish this goal, the axial, bending, and torsional stiffness parameters are considered in place of the oversimplified terms such as "flexible plate" or "elastic fixation." With the aid of finite element modeling and simplified bench experiments, we performed parametric studies and singled out the plate axial stiffness as the dominant factor in altering the bone stresses. As a result, we designed two experimental plates, one a thin Ti-6Al-4V (titanium with 6% aluminum and 4% vanadium) alloy plate with low stiffness in axial and bending directions, and the other a tubular stainless steel plate with low stiffness in the axial direction but moderate stiffness in bending and torsional directions. The low-stiffness Ti-6Al-4V alloy plate was first tested in a demanding bilateral canine midshaft osteotomy, and proved to be inadequate. Both experimental plates were successful in the unilateral osteotomies, with the tubular plate yielding the best results. After 6 months of plating, the bones beneath the tubular plate had superior mechanical and structural properties as compared to those of the control "rigid" stainless steel and the Ti-6Al-4V alloy plates. Application of this plate prolonged for 9 months did not cause reduction in bone properties and strength. The success of the tubular plate is due to its moderate bending and torsional stiffnesses, which provide adequate fixation to achieve callus union, while its low axial stiffness permits the underlying bone to share the physiological stresses needed for bone remodeling. These drastic changes in mechanical demands on the internal fixation plate during the early healing phase and the postunion remodeling phase are discussed.