Preoperative radius head dislocation affects forearm rotation after mobilization of congenital radioulnar synostosis.

BACKGROUND: The present study was carried out to answer three questions: 1) How much forearm rotation can be expected after mobilization of congenital radioulnar synostosis (CRUS)? 2) Does preoperative radius head dislocation affect forearm rotation after mobilization? 3) What factors other than radius head dislocation affect postoperative forearm rotation? METHODS: We performed mobilization of CRUS with a free vascularized fascio-fat graft and a radius osteotomy (Kanaya's procedure) on 26 forearms of 25 patients. The age at the surgery ranged from 5.3 to 13.4 years. The follow-up duration ranged 24-111 months. We classified CRUS into 3 groups according to the dislocation of the radius head: posterior dislocation (N = 13), anterior dislocation (N = 9) and no dislocation (N = 4). Since major complaints of patients and parents were poor forearm rotation and lack of supination, they were evaluated separately. RESULTS: Mean preoperative forearm ankylosis angle was 34.8° (range; neutral to 90° pronation). Preoperative pronation ankylosis angle was higher in the posterior dislocation group (mean 55.3°) than the anterior dislocation (mean 11.6°) and no dislocation groups (mean 5.0°). There was no re-ankylosis after mobilization and the mean postoperative active range of motion (ROM) was 86.5°. The mean active ROM was 75.7° in the posterior dislocation group, 96.1° in anterior dislocation group and 100.0° in no dislocation group. The mean active supination was 6.9, 33.9 and 47.5° respectively. The posterior dislocation group showed less ROM and less supination than other groups. Preoperative pronation ankylosis angle showed negative correlation with postoperative ROM (ρ = - 0.59) and postoperative supination (ρ = - 0.73). CONCLUSION: The mean postoperative active ROM of this mobilization was 86.5°. Posterior dislocation group showed higher pronation ankylosis angle preoperatively, and less postoperative ROM and less supination than anterior and no dislocation groups. Preoperative pronation ankylosis angle showed negative correlation with postoperative ROM and supination.

Imaging the interaction of αv integrin-GFP in osteosarcoma cells with RFP-expressing host stromal cells and tumor-scaffold collagen in the primary and metastatic tumor microenvironment.

Human osteosarcoma 143B cells were previously stably transfected with an αv integrin green flourescent protein (GFP) vector. 143B cells expressing αv integrin-GFP were transplanted orthotopically in the tibia of transgenic nude mice ubiquitously expressing red fluorescent protein (RFP). The primary tumors acquired RFP-expressing stroma and were passaged orthotopically in the tibia in noncolored nude mice, which maintained the RFP stroma. The interaction of αv integrin-GFP expression in 143B cells with RFP-expressing host stromal cells was observed by confocal microscopy using the Olympus FV1000. Collagen fibers were imaged simultaneously in reflectance mode. The RFP-expressing stroma included cancer-associated fibroblasts (CAFs) and tumor-associated macrophages (TAMs) which persisted even 3 weeks after passage to nontransgenic nude mice. CAFs expressing RFP were aligned between collagen fibers and cancer cells expressing αv integrin-GFP. Six weeks after transplantation, pulmonary metastases expressing αv integrin-GFP could be identified. TAMs expressing RFP accompanied metastasized osteosarcoma cells expressing αv integrin-GFP in the lung. The current study demonstrates the importance of αv integrin interaction with stromal elements in osteosarcoma.

Tumor-targeting Salmonella typhimurium A1-R arrests a doxorubicin-resistant PDGFRA-amplified patient-derived orthotopic xenograft mouse model of pleomorphic liposarcoma.

Pleomorphic liposarcoma (PLPS) is a recalcitrant soft-tissue sarcoma (STS) subtype in need of transformative therapy. We have previously established a patient-derived orthotopic xenograft (PDOX) model, of PLPS with PDGFRA amplification, using surgical orthotopic implantation. In the current study, the PLPS PDOX model was randomized into 3 groups of 7 mice each: untreated control; doxorubicin (DOX)-treated; and treated with Salmonella typhimurium A1-R (S. typhimurium A1-R) expressing green fluorescent protein (GFP). Tumor volume and body weight were monitored during the treatment period. The PLPS PDOX was resistant to DOX. In contrast, the PLPS PDOX was highly sensitive to S. typhimurium A1-R. There was no significant body-weight loss among these 3 groups. Fluorescence imaging demonstrated that S. typhimurium A1-R-GFP was very effective to target the PLPS PDOX tumor. The current study demonstrates that a PLPS PDOX, resistant to first-line therapy DOX, was highly sensitive to tumor targeting S. typhimurium A1-R.

A combination of irinotecan/cisplatinum and irinotecan/temozolomide or tumor-targeting Salmonella typhimurium A1-R arrest doxorubicin- and temozolomide-resistant myxofibrosarcoma in a PDOX mouse model.

Myxofibrosarcoma (MFS) is the most common sarcomas in elderly patients and is either chemo-resistant or recurs with metastasis after chemotherapy. This recalcitrant cancer in need of improved treatment. We have established a patient-derived orthotopic xenograft (PDOX) of MFS. The MFS PDOX model was established in the biceps femoris of nude mice and randomized into 7 groups of 7 mice each: control; doxorubicin (DOX); pazopanib (PAZ); temozolomide (TEM); Irinotecan (IRN); IRN combined with TEM; IRN combined with cisplatinum (CDDP) and Salmonella typhimurium A1-R (S. typhimurium A1-R). Treatment was evaluated by relative tumor volume and relative body weight. The MFS PDOX models were DOX, PAZ, and TEM resistant. IRN combined with TEM and IRN combined with CDDP were most effective on the MFS PDOX. S. typhimurium A1-R arrested the MFS PDOX tumor. There was no significant body weight loss in any group. The present study suggests that the combination of IRN with either TEM or CDDP, and S. typhimurium have clinical potential for MFS.

Trabectedin arrests a doxorubicin-resistant PDGFRA-activated liposarcoma patient-derived orthotopic xenograft (PDOX) nude mouse model.

BACKGROUND: Pleomorphic liposarcoma (PLPS) is a rare, heterogeneous and an aggressive variant of liposarcoma. Therefore, individualized therapy is urgently needed. Our recent reports suggest that trabectedin (TRAB) is effective against several patient-derived orthotopic xenograft (PDOX) mouse models. Here, we compared the efficacy of first-line therapy, doxorubicin (DOX), and TRAB in a platelet-derived growth factor receptor-α (PDGFRA)-amplified PLPS. METHODS: We used a fresh sample of PLPS tumor derived from a 68-year-old male patient diagnosed with a recurrent PLPS. Subcutaneous implantation of tumor tissue was performed in a nude mouse. After three weeks of implantation, tumor tissues were isolated and cut into small pieces. To match the patient a PDGFRA-amplified PLPS PDOX was created in the biceps femoris of nude mice. Mice were randomized into three groups: Group 1 (G1), control (untreated); Group 2 (G2), DOX-treated; Group 3 (G3), TRAB-treated. Measurement was done twice a week for tumor width, length, and mouse body weight. RESULTS: The PLPS PDOX showed resistance towards DOX. However, TRAB could arrest the PLPS (p < 0.05 compared to control; p < 0.05 compared to DOX) without any significant changes in body-weight. CONCLUSIONS: The data presented here suggest that for the individual patient the PLPS PDOX model could specifically distinguish both effective and ineffective drugs. This is especially crucial for PLPS because effective first-line therapy is harder to establish if it is not individualized.

Use of αv Integrin Linked to GFP to Image Molecular Dynamics in Trafficking Cancer-Cell Emboli.

Human osteosarcoma cells with an αv integrin green fluorescent protein (GFP) fusion gene were previously established and imaged in vitro and in vivo. In the present study, we imaged the interaction of αv integrin-GFP in osteosarcoma cells and collagen fibers in vascular-trafficking osteosarcoma emboli in nude mice. Human 143B osteosarcoma cells, expressing αv integrin-GFP, were injected by a vascular route in an abdominal skin flap in nude mice. Osteosarcoma cells were fluorescently imaged in the epigastric cranialis vein in the abdominal skin flap by confocal microscopy. Collagen fibers were imaged in reflectance mode. At early stages of tumor embolus-formation, cancer cells adhered firmly to each other, diffusely expressing αv integrin-GFP. Two weeks after injection, collagen fiber scaffolds were visualized at the margins of tumor emboli or within them. Four weeks after injection, cancer cells invading from emboli were strongly expressing αv integrin-GFP, and were aligned along collagen fibers. The results suggest αv integrin and collagen fiber scaffolds are important for tumor embolus formation, which are potential seeds of metastasis. J. Cell. Biochem. 118: 26-30, 2017. © 2016 Wiley Periodicals, Inc.

Analysis of Stroma Labeling During Multiple Passage of a Sarcoma Imageable Patient-Derived Orthotopic Xenograft (iPDOX) in Red Fluorescent Protein Transgenic Nude Mice.

A patient-derived orthotopic xenograft (PDOX) model of undifferentiated pleomorphic sarcoma (UPS) was previously established that acquired red fluorescent protein (RFP)-expressing stroma by growth in an RFP transgenic nude mouse. In the present study, an imageable PDOX model (iPDOX) of UPS was established by orthotopic implantation in the biceps femoris of transgenic RFP nude mice. After the tumors grew to a diameter of 10 mm, they were harvested and the brightest portion of the tumors were subsequently orthotopically transplanted to both RFP and non-colored nude mice. The UPS PDOX tumor was again transplanted to RFP transgenic and non-colored nude mice, and finally a 3rd passage was made in the same manner. Five UPS tumors from each passage in both RFP and non-colored mouse models were harvested. The FV1,000 confocal microscope was used to visualize and quantitate the RFP area of the resected tumors. The average percent fluorescent area in the first passage of RFP mice was 34 ± 22%; in the second passage, 34 ± 20%; and 36 ± 11% in the third passage of RFP transgenic nude mice. The average tumor RFP area in the first passage from RFP mice to non-colored mice was 20 ± 7%; in the second passage, 28 ± 11%; in the third passage was 27 ± 13%. The present results demonstrate the extensive and stable acquisition of stroma by the UPS-tumor growing orthotopically in transgenic RFP nude mice (iPDOX). This model can be used for screening for effective drugs for individual patients and drug discovery. J. Cell. Biochem. 118: 3367-3371, 2017. © 2017 Wiley Periodicals, Inc.

Labeling the Stroma of a Patient-Derived Orthotopic Xenograft (PDOX) Mouse Model of Undifferentiated Pleomorphic Soft-Tissue Sarcoma With Red Fluorescent Protein for Rapid Non-Invasive Imaging for Drug Screening.

Our laboratory pioneered patient-derived orthotopic xenograft (PDOX) mouse models using surgical orthotopic implantation (SOI). PDOX models are patient-like, in contrast to the ectopic subcutaneous-transplant cancer models. In the present study, we demonstrate that an undifferentiated pleomorphic soft-tissue sarcoma (UPS-STS) PDOX model acquired bright RFP-expressing stroma through one passage in red fluorescent protein (RFP) transgenic mice, which upon passage to non-colored nude mice was non-invasively imageable. A PDOX nude mouse model of UPS-STS was established in the biceps femoris of nude mice. After the tumors grew to a diameter of 10 mm, the tumors were subsequently passaged to RFP transgenic mice, and after tumor growth were then passaged to non-transgenic nude mice. Tumors were divided into small fragments and transplanted in the biceps femoris at each passage. The OV100 Small Animal Fluorescence Imaging System and FV1000 laser scanning confocal microscope were used to image RFP fluorescence in the UPS-STS PDOX models. UPS-STS PDOX tumors, previously grown in RFP transgenic nude mice for only one passage, had very bright fluorescence and after passage to non-transgenic nude mice maintained the bright fluorescence and were non-invasively imageable. FV1000 confocal imaging revealed diffusely distributed bright RFP stromal cells in the PDOX tumor, both in RFP transgenic mice and after passage to non-transgenic mice. These results demonstrate a powerful method to make the PDOX UPS-STS model brightly fluorescent for non-invasive imaging, as well as for confocal microscopy of individual stromal cells associated with the tumor. The RFP-labeled UPS PDOX has the potential to rapidly screen for novel effective agents for individual patients, including stroma-targeting drugs, whereby the stromal cells are a visual target. J. Cell. Biochem. 118: 361-365, 2017. © 2016 Wiley Periodicals, Inc.

Effects of osteochondral defect size on cartilage regeneration using a double-network hydrogel.

BACKGROUND: There has been increased interest in one-step cell-free procedures to avoid the problems related to cell manipulation and its inherent disadvantages. We have studied the chondrogenic induction ability of a PAMPS/PDMAAm double-network (DN) gel and found it to induce chondrogenesis in animal osteochondral defect models. The purpose of this study was to investigate whether the healing process and the degree of cartilage regeneration induced by the cell-free method using DN gel are influenced by the size of osteochondral defects. METHODS: A total of 63 mature female Japanese white rabbits were used in this study, randomly divided into 3 groups of 21 rabbits each. A 2.5-mm diameter osteochondral defect was created in the femoral trochlea of the patellofemoral joint of bilateral knees in Group I, a 4.3-mm osteochondral defect in Group II, and a 5.8-mm osteochondral defect in Group III. In the right knee of each animal, a DN gel plug was implanted so that a vacant space of 2-mm depth was left above the plug. In the left knee, we did not conduct any treatment to obtain control data. Animals were sacrificed at 2, 4, and 12 weeks after surgery, and gross and histological evaluations were made. RESULTS: The present study demonstrated that all sizes of the DN gel implanted defects as well as the 2.5mm untreated defects showed cartilage regeneration at 4 and 12 weeks. The 4.3-mm and 5.8-mm untreated defects did not show cartilage regeneration during the 12-week period. The quantitative score reported by O'Driscoll et al. was significantly higher in the 4.3-mm and 5.8-mm DN gel-implanted defects than the untreated defects at 4 and 12 weeks (p < 0.05). The 2.5-mm and 4.3-mm DN gel implanted defects maintained relatively high macroscopic and histological scores for the 12-week implantation period, while the histological score of the 5.8-mm DN gel implanted defect had decreased somewhat but statistically significantly at 12 weeks (p = 0.0057). CONCLUSIONS: The DN gel induced cartilage regeneration in defects between 2.5 and 5.8 mm, offering a promising device to establish a cell-free cartilage regeneration therapy and applicable to various sizes of osteochondral defects.

3-dimensional tissue is formed from cancer cells in vitro on Gelfoam®, but not on Matrigel™.

Cell and tissue culture can be performed on different substrates such as on plastic, in Matrigel™, and on Gelfoam(®), a sponge matrix. Each of these substrates consists of a very different surface, ranging from hard and inflexible, a gel, and a sponge-matrix, respectively. Folkman and Moscona found that cell shape was tightly coupled to DNA synthesis and cell growth. Therefore, the flexibility of a substrate is important for cells to maintain their optimal shape. Human osteosarcoma cells, stably expressing a fusion protein of α(v) integrin and green fluorescent protein (GFP), grew as a simple monolayer without any structure formation on the surface of a plastic dish. When the osteosarcoma cells were cultured within Matrigel™, the cancer cells formed colonies but no other structures. When the cancer cells were seeded on Gelfoam(®), the cells formed three-dimensional tissue-like structures. The behavior of 143B osteosarcoma cells on Gelfoam(®) in culture is remarkably different from those of these cells in monolayer culture or in Matrigel™. Tissue-like structures were observed only in Gelfoam(®) culture. The data in this report suggest a flexible structural substrate such as Gelfoam(®) provides a more in vivo-like culture condition than monolayer culture or Matrigel(TM) and that Matrigel(TM) does not result in actual three-dimensional culture.

Comparison of UVB and UVC effects on the DNA damage-response protein 53BP1 in human pancreatic cancer.

We have previously demonstrated that ultraviolet (UV) light is effective against a variety of cancer cells expressing fluorescent proteins in vivo as well as in vitro. In the present report, we compared the DNA damage repair (DDR) response of pancreatic cancer cells after UVB or UVC irradiation. The UV-induced DNA damage repair was imaged with green fluorescent protein (GFP) fused to the DDR-related chromatin-binding protein 53BP1 in MiaPaCa-2 human pancreatic cancer cells growing in 3D Gelfoam® histoculture and in superficial tumors grown in nude mice. 53BP1-GFP forms foci during DNA damage repair. A clonogenic assay in 2D monolayer culture initially showed that UVC and UVB inhibited MiaPaCa-2 cell proliferation in a dose-dependent manner, with UVC having more efficacy. Three-dimensional Gelfoam® histocultures and confocal imaging enabled 53BP1-GFP foci to be observed within 1 h after UV irradiation, indicating the onset of DDR response. UVB-induced 53BP1-GFP focus formation was observed up to a depth of 120 µm in MiaPaCa-2 cells on Gelfoam® compared to 80 µm for UVC. UVB-induced 53BP1-GFP focus formation was observed up to a depth of 80 µm in MiaPaCa-2 cells, implanted within skin flaps in mice, at a significantly greater extent than UVC. MiaPaCa-2 cells irradiated by UVB or UVC in the skin-flap mouse model had a significant decrease in tumor growth compared to untreated controls with UVB having more efficacy than UVC. Our results demonstrate that UVB has greater tissue penetration than UVC because of its longer wavelength and has clinical potential for eradicating superficial cancer.

Osteosarcoma cells enhance angiogenesis visualized by color-coded imaging in the in vivo Gelfoam® assay.

We previously described a color-coded imaging model that can quantify the length of nascent blood vessels using Gelfoam® implanted in nestin-driven green fluorescent protein (ND-GFP) nude mice. In ND-GFP mice, nascent blood vessels are labeled with GFP. We report here that osteosarcoma cells promote angiogenesis in the Gelfoam® angiogenesis assay in ND-GFP mice. Gelfoam® was initially transplanted subcutaneously in the flank of transgenic ND-GFP nude mice. Seven days after transplantation of Gelfoam®, skin flaps were made and human 143B osteosarcoma cells expressing green fluorescent protein (GFP) in the nucleus and red fluorescent protein (RFP) in cytoplasm were injected into the transplanted Gelfoam®. The control-group mice had only implanted Gelfoam®. Skin flaps were made at days 14, 21, and 28 after transplantation of the Gelfoam® to allow imaging of vascularization in the Gelfoam® using a variable-magnification small animal imaging system and confocal fluorescence microscopy. ND-GFP expressing nascent blood vessels penetrated and spread into the Gelfoam® in a time-dependent manner in both control and osteosarcoma-implanted mice. ND-GFP expressing blood vessels in the Gelfoam® of the osteosarcoma-implanted mice were associated with the cancer cells and larger and longer than in the Gelfoam®-only implanted mice (P < 0.01). The results presented in this report demonstrate strong angiogenesis induction by osteosarcoma cells and suggest this process is a potential therapeutic target for this disease.

Influence of the gel thickness on in vivo hyaline cartilage regeneration induced by double-network gel implanted at the bottom of a large osteochondral defect: short-term results.

BACKGROUND: A double-network (DN) gel, which is composed of poly(2-acrylamido-2-methylpropanesulfonic acid) and poly(N,N'-dimethyl acrylamide), can induce hyaline cartilage regeneration in vivo in a large osteochondral defect. The purpose of this study was to clarify the influence of the thickness of the implanted DN gel on the induction ability of hyaline cartilage regeneration. METHODS: Thirty-eight mature rabbits were used in this study. We created an osteochondral defect having a diameter of 4.3-mm in the patellofemoral joint. The knees were randomly divided into 4 groups (Group I: 0.5-mm thick gel, Group II: 1.0-mm thick gel, Group III: 5.0-mm thick gel, and Group IV: untreated control). Animals in each group were further divided into 3 sub-groups depending on the gel implant position (2.0-, 3.0-, or 4.0-mm depth from the articular surface) in the defect. The regenerated tissues were evaluated with the Wayne's gross and histological grading scales and real time PCR analysis of the cartilage marker genes at 4 weeks. RESULTS: According to the total Wayne's score, when the depth of the final vacant space was set at 2.0 mm, the scores in Groups I, II, and III were significantly greater than that Group IV (p<0.05), although there were no significant differences between Groups I and IV at a 3.0-mm deep vacant space. The expression levels of type-2 collagen in Groups II and III were significantly higher (p<0.05) than that in Group IV. CONCLUSIONS: The 1.0-mm thick DN gel sheet had the same ability to induce hyaline cartilage regeneration as the 5.0-mm thick DN gel plug. However, the induction ability of the 0.5-mm thick sheet was significantly lower when compared with the 1.0-mm thick gel sheet. The 1.0-mm DN gel sheet is a promising device to establish a cell-free cartilage regeneration strategy that minimizes bone loss from the gel implantation.

Vascularized fibular graft for bone defects after wide resection of musculoskeletal tumors.

BACKGROUND: In reconstruction by vascularized fibular graft (VFG) after wide resection of musculoskeletal tumors, there are problems such as the method of fixing the fibular graft, the period of achieving bone union, and the avoidance of postoperative fractures. We have performed VFG on 19 cases over a 30-year period. We have investigated these problems and now report the results. METHODS: From 1980 to 2009, we performed VFG on 19 cases to reconstruct the bone defect after resection of a musculoskeletal tumor. The mean age was 19.5 years. Reconstructed bone defects were located in the femur in 10 cases (1 of inlay graft, 1 of individual intercalary graft, 7 of intercalary graft into treated bone, 1 of curettaged bone marrow), the tibia in 3 cases (1 of individual intercalary graft, 2 of intercalary graft into treated bone), the humerus in 3 cases (2 of sling procedure, 1 of individual intercalary graft), the foot in 2 cases individual intercalary graft, and the sacroiliac joint in 1 case of individual intercalary graft. The mean follow-up period after surgery was 7.25 years. We evaluated the success of primary bone union, the period required to achieve bone union, complications, clinical outcome, and the Musculoskeletal Tumor Society (MSTS) score. RESULTS: Successful bone union was achieved for 79% of cases (15/19 patients). The average period required to achieve bone union was 7.8 months. There were 4 cases of non-union and 2 other complications. Clinical outcome status was continuous disease-free in 12 cases and died of disease in 7. The mean MSTS score was 98% (93-100%). CONCLUSION: Vascularized fibular graft is a useful reconstructive procedure for long-bone defects after wide excision of musculoskeletal tumors. The method of fixation can be selected according to the situation; although times required for bone union are long, it is possible to prevent postoperative fractures by a combined approach with treated bone and/or double barrel fibular grafts.

Responsiveness of the Japanese version of the patient-rated wrist evaluation (PRWE-J) and physical impairment measurements in evaluating recovery after treatment of ulnocarpal abutment syndrome.

BACKGROUND: We evaluated the responsiveness of patient-derived questionnaires and physical findings in evaluating recovery after treatment of ulnocarpal abutment syndrome. METHODS: Patients were assessed at their initial visit to our clinic and again 3 months after the treatment. At each visit, patients completed a Short Form-36, the Japanese Society for Surgery of the Hand version of Disability of the Arm, Shoulder, and Hand questionnaire (DASH-JSSH), and the Japanese version of patient-rated wrist evaluation (PRWE-J). Grip strength, range of motion, and visual analogue scale for wrist pain were also examined at each visit. Satisfaction with treatment was questioned after 3 months using a Likert scale. Standardized response means (SRM) and effect sizes were calculated to evaluate the responsiveness. RESULTS: The PRWE-J (SRM, 1.35) was the most responsive questionnaire, followed by the DASH-JSSH (SRM, 0.81) and the Short Form-36 (SRM, -0.38 to -1.19). Of the physical tests, grip strength (SRM, 0.81) was more responsive than range of motion (SRM, 0.01 to -0.29). The visual analogue pain scale (SRM, 1.56) was highly responsive. Changes in the PRWE score were correlated with the satisfaction rating for the treatment. CONCLUSIONS: Responsive patient-derived scales can assist in the outcome evaluation of patients with ulnocarpal abutment syndrome.

Epidemiology of hip fractures in Okinawa, Japan.

This study investigated the current incidence of hip fractures in Okinawa prefecture and compared the data with those obtained in our previous study, which was conducted using similar methods in 1987/1988. All patients, aged 50 years or older and residing in Okinawa, admitted to Okinawa hospitals in 2004 for a fresh hip fracture were identified from hospital registries. Details were obtained from the medical records and radiographs of all patients and classified according to fracture type (cervical or trochanteric), age, sex, and fracture location. Subtrochanteric fractures and pathological fractures were excluded. A total of 1,349 patients (242 men and 1,107 women) were admitted for a fresh hip fracture in 2004. Their average age was 76.9 years for men and 82.4 years for women. There were 671 cervical fractures, 654 trochanteric fractures, and 24 unclassified proximal femoral fractures. Comparing the data from 1987/1988 to those from 2004, the total number of hip fractures increased by 188%, from 469 to 1,349. The age-adjusted incidence rates per 100,000, standardized to the 2000 US population, were 75.7 and 296.1 in 1987/1988 and 123.6 and 420 in 2004 for men and women, respectively. The incidence rates in all age groups (at 5-year intervals) were higher in 2004 than in 1987/1988, indicating that people 50 years of age or older became more susceptible to hip fractures. Accordingly, the accretion of the hip fracture incidence rate was greater than that which could be explained purely by changes in population size and structure.

Joint immobilization inhibits spontaneous hyaline cartilage regeneration induced by a novel double-network gel implantation.

We have recently discovered that spontaneous hyaline cartilage regeneration can be induced in an osteochondral defect in the rabbit, when we implant a novel double-network (DN) gel plug at the bottom of the defect. To clarify whether joint immobilization inhibits the spontaneous hyaline cartilage regeneration, we conducted this study with 20 rabbits. At 4 or 12 weeks after surgery, the defect in the mobile knees was filled with a sufficient volume of the hyaline cartilage tissue rich in proteoglycan and type-2 collagen, while no cartilage tissues were observed in the defect in the immobilized knees. Type-2 collagen, Aggrecan, and SOX9 mRNAs were expressed only in the mobile knees at each period. This study demonstrated that joint immobilization significantly inhibits the spontaneous hyaline cartilage regeneration induced by the DN gel implantation. This fact suggested that the mechanical environment is one of the significant factors to induce this phenomenon.

Open repair for massive rotator cuff tear with a modified transosseous-equivalent procedure: preliminary results at short-term follow-up.

BACKGROUND: Many surgical procedures have been reported for rotator cuff tears. We adopted the modified transosseous-equivalent procedure, also termed "surface-holding repair with transosseous sutures," and demonstrated that this procedure has a biomechanical advantage regarding the concentration of stress on the tendon stump. This study aimed to evaluate the clinical and structural outcomes of this technique, which has been demonstrated by postoperative magnetic resonance imaging (MRI) to produce high intact rates. METHODS: Twenty-nine massive rotator cuff tears involving at least two tendons were treated by open repair using this procedure. Twenty-four patients were evaluated at an average of 43.2 months (range 24-71) postoperatively (the follow-up rate was 83.8%). The pre- and postoperative clinical outcomes were examined using the scoring system of the Japanese Orthopedic Association (JOA score). In an A-P radiograph, the presence of osteoarthritis (OA) of the glenohumeral joint and upward migration of the humeral head were compared pre- and postoperatively. The repair integrity of the cuff tendon was evaluated by applying Sugaya's classification to the postoperative MRIs. RESULTS: The JOA score improved from 42.8 points preoperatively to 89.3 points at final follow-up. Radiographic examination showed that OA progressed in 16.7% and upward migration of the humeral head progressed in 20.8%. Postoperative MRI scans revealed 14 shoulders with type 1 repair based on Sugaya's classification, 4 shoulders with type 2, 4 shoulders with type 3, 2 shoulders with type 4, and no shoulders with a type 5 repair. CONCLUSIONS: Although osteoarthritis of the glenohumeral joint and upward migration of the humeral head had both progressed postoperatively in some cases, postoperative MRI scans revealed that 91.7% of the repairs resulted in a continuous rotator cuff. Therefore, this technique produces a high healing rate.

Effects of Different Core Suture Lengths on Tensile Strength of Multiple-Strand Sutures for Flexor Tendon Repair.

Purpose: To compare 2 types of newly devised 8-strand quadruple-looped suture (QLS) techniques with a 6-strand triple-looped suture (TLS) technique; and to assess the effects of different core suture lengths (CSLs) (the length between 2 locking sites of a suture strand) within each suture row on tensile strength. Methods: We repaired 24 flexor tendons from 12 rabbits using the TLS and QLS techniques, with equal CSL (QLS) or unequal CSL (unequal QLS) among each suture row. The QLS was composed of 4 looped sutures on the anterolateral and posterolateral aspects of the tendon. The cross-sectional area of the locking portion of each thread in the QLS was equal to that in the TLS. In the QLS technique, the CSL on each aspect of the tendon was 13 mm. In the unequal QLS technique, the CSL on each aspect of the tendon was 13 and 17 mm. The load at 1- and 2-mm gaps, the maximum load until the 3-mm gap, and the ultimate load were compared among the 3 techniques. Results: The QLS was significantly stronger than the unequal QLS and the TLS for loads at 1-mm and 2-mm gaps, maximum load until 3-mm gap, and ultimate load. There was no significant difference between the unequal QLS and TLS techniques. The QLS technique showed an approximately 30% increase in gap resistance and ultimate strength compared with the TLS technique. Conclusions: The QLS technique showed an estimated increase in tensile strength proportional to the number of suture strands compared with the TLS technique. Our study suggests that a consistent CSL in each suture row provides the highest strength in multistrand sutures consisting of the same configuration of suture rows. Clinical relevance: The QLS technique may reduce the risk for tendon rupture associated with early active mobilization after flexor tendon repair.