Measurement of rotational and coronal alignment in total knee arthroplasty using a navigation system is reproducible.

INTRODUCTION: Intraoperative kinematic analysis using a navigation system in total knee arthroplasty (TKA) has been increasing. The purpose of the present study was to assess the reproducibility of the intraoperative kinematics analysis in TKA using the image-free knee navigation system. MATERIALS AND METHODS: Fifty-one knees in 45 patients who received TKA, performed by a single surgeon (the senior consultant) with the resident, were included in this retrospective study. There were 7 men and 38 women and the mean age was 74.3 years. Cruciate retaining (CR) type and posterior stabilized (PS) type implants were inserted into 38 and 13 knees. The senior consultant and the resident analyzed initial kinematics, the axial rotation of the tibia and the coronal alignment of the lower limb, three times in each knee on manual passive knee flexion intraoperatively using the navigation system. Intra-class correlation coefficients (ICC) with 95 % confidence intervals were calculated to determine the reproducibility of this analysis. RESULTS: In regard to intra-rater reproducibility with axial rotation of the tibia, the ICC of the senior consultant was 0.965 for CR knees and 0.972 for PS knees while the ICC of the resident were 0.966 and 0.956. Inter-rater reproducibility was excellent for both knee types (ICC, 0.885 for CR knees and 0.864 for PS knees). In regard to intra-rater reproducibility with coronal alignment of the lower limb, ICC of the senior consultant was 0.990 for CR knees and 0.996 for PS knees while those of the resident were 0.990 and 0.995. Inter-rater reproducibility was also excellent for both knee types (ICC, 0.978 for CR knees and 0.994 for PS knees). CONCLUSIONS: Manual intraoperative kinematic analysis using a navigation system in TKA showed excellent reproducibility. This result may encourage further studies about intraoperative kinematic analysis using a navigation system in TKA.

Insertion of a spacer block translates the tibia anteriorly during evaluation of soft tissue balance in cruciate-retaining total knee arthroplasty.

BACKGROUND: Soft tissue balance is an important determinant of the outcome of total knee arthroplasty (TKA). However, there are differences in the joint gap and ligament balance between the osteotomized femoral and tibial surfaces and those after TKA. The aim of this study was to compare the relationship between the femur and tibia at insertion of a spacer block with that after cruciate-retaining (CR) TKA. METHODS: Thirty knees in 30 patients (26 women, 4 men) who underwent primary CR TKA with a navigation system were enrolled. Mean age at surgery was 76.3 (range, 63-87) years. After osteotomy of the femur and tibia, the flexion-extension gap and ligament balance were evaluated using a spacer block. The location of the tibial center in relation to the femoral center in the sagittal plane calculated from navigation data at insertion of an appropriately sized spacer block in knee flexion was compared with that after CR TKA using the paired t-test. RESULTS: The mean sagittal location of the tibial center relative to the femoral center in knee flexion was 5.16 (range, -2.4, 16.3) mm at insertion of the spacer block and 6.60 (range, -1.4, 15.1) mm after CR TKA, and this difference was significant (p = 0.016). CONCLUSION: Assessment of soft tissue balance using a spacer block in CR TKA during knee flexion changes the location of the tibia. Surgeons should be aware of the potential for overestimating the postoperative flexion gap in CR TKA when using a spacer block to assess the flexion gap.

Matrix extracellular phosphoglycoprotein is expressed in causative tumors of oncogenic osteomalacia.

Oncogenic osteomalacia (OOM), or tumor-induced osteomalacia, is a rare disease characterized by renal phosphate wasting and osteomalacia. It arises due to the secretion of fibroblast growth factor 23 (FGF-23) from causative tumors. Matrix extracellular phosphoglycoprotein (MEPE) is predominantly expressed in odontoblasts, osteoblasts, and osteocytes. Although the presence of MEPE mRNA has been reported in some OOM tumors, little is known about the prevalence of MEPE expression in OOM tumors. In this study, the expression of MEPE and FGF-23 in OOM tumors was investigated at the transcriptional and translational levels. Eleven causative OOM tumors were analyzed by quantitative real-time reverse transcription-polymerase chain reaction and immunohistochemistry for MEPE and FGF-23 expression. Hemangiopericytomas and giant cell tumors, pathological diagnoses that are common in cases of OOM, were obtained from non-osteomalacic patients and analyzed as controls. The gene expression level of FGF23 and MEPE in OOM tumors was 10(4)- and 10(5)-times higher, respectively, than in non-OOM tumors. Immunohistochemical staining revealed that FGF-23 protein was expressed in all OOM tumors, and MEPE was expressed in 10 out of 11 OOM tumors. Thus, MEPE expression was common in OOM tumors, similar to FGF-23. These results indicate that, in addition to the hypophosphatemic effects of FGF-23, MEPE or the MEPE-derived acidic serine aspartate-rich MEPE-associated motif peptide may contribute to decreased bone mineralization in OOM patients.

Anteversion of the acetabular component aligned with the transverse acetabular ligament in total hip arthroplasty.

In total hip arthroplasty (THA), accurately positioning the cup is crucial for achieving an adequate postoperative range of motion and stability. For 47 THA cases in which the inferomedial rim of the cup had been positioned parallel to the transverse acetabular ligament, we retrospectively performed the measurements of the radiographic cup anteversion angle relative to the anterior pelvic plane using 3-dimensional reconstruction computed tomography. The mean anteversion angle was 21.2°, with no significant difference detected in mean cup anteversion between the dysplastic hip group (15 hips) and the control group (15 hips). We suggest that the transverse acetabular ligament is a practical anatomical landmark for determining cup anteversion in THA for both dysplastic and nondysplastic hip cases.

Preoperative Planning Using Three-dimensional Printing for Full-endoscopic Spine Surgery: A Technical Note.

Transforaminal full-endoscopic spine surgery (TF-FESS) is a novel minimally invasive spine surgery that requires only an 8-mm skin incision and causes minimal damage to the paravertebral muscles. To perform TF-FESS safely and efficiently, preoperative planning is quite important as the intervention requires anatomical understanding and high technical skills. Recently, three-dimensional (3D) printing has become a useful tool in various surgeries, and several studies have addressed its efficacy; however, there are no reports on the application of 3D printing to FESS. In this study, we present two cases of severe lumbar deformities for which preoperative 3D printing was useful. The 3D printing enabled the surgeons to visualize and plan the drilling of the superior articular process for a successful foraminoplasty at a low cost. The manufacturing equipment cost about USD 900 and is able to produce an actual-size model at a cost of less than USD 10 per patient. In conclusion, preoperative planning using 3D printing should be adopted to safely perform FESS.

The levels of somatostatin receptors in causative tumors of oncogenic osteomalacia are insufficient for their agonist to normalize serum phosphate levels.

Oncogenic osteomalacia (OOM) is a rare disease characterized by renal phosphate wasting and osteomalacia and is caused by the secretion of fibroblast growth factor 23 (FGF-23) from causative tumors. Scintigraphy with octreotide, which binds to somatostatin receptors (SSTRs), is a useful way to locate causative tumors in OOM patients. However, the therapeutic effects of octreotide acetate are still controversial. Two OOM patients were administered octreotide acetate intramuscularly. Ten causative OOM tumors, including two resected from the patients participating in the octreotide administration study, were examined for expression of genes encoding SSTRs by quantitative real-time RT-PCR and immunohistochemistry. Octreotide therapy did not improve hypophosphatemia in either case, despite temporal decreases in FGF-23 levels in one patient. The mean expression levels of SSTR1, SSTR3, and SSTR5 were similar in the OOM and non-OOM tumors. Expression of SSTR2 was significantly higher in the OOM tumors than in the non-OOM tumors. Immunohistochemical examinations revealed the presence of SSTR2A, SSTR2B, and SSTR5 in both the OOM and non-OOM tumors. The expression of SSTR genes in OOM tumors contributes to positive imaging using octreotide scintigraphy. However, the levels of SSTRs seem to be insufficient for the octreotide therapy to improve hypophosphatemia. Further studies are needed to clarify the mechanisms by which FGF-23 secretion from OOM tumors is suppressed by octreotide acetate.

Fibroblast growth factor 23 in oncogenic osteomalacia and X-linked hypophosphatemia.

BACKGROUND: Mutations in fibroblast growth factor 23 (FGF-23) cause autosomal dominant hypophosphatemic rickets. Clinical and laboratory findings in this disorder are similar to those in oncogenic osteomalacia, in which tumors abundantly express FGF-23 messenger RNA, and to those in X-linked hypophosphatemia, which is caused by inactivating mutations in a phosphate-regulating endopeptidase called PHEX. Recombinant FGF-23 induces phosphaturia and hypophosphatemia in vivo, suggesting that it has a role in phosphate regulation. To determine whether FGF-23 circulates in healthy persons and whether it is elevated in those with oncogenic osteomalacia or X-linked hypophosphatemia, an immunometric assay was developed to measure it. METHODS: Using affinity-purified, polyclonal antibodies against [Tyr223]FGF-23(206-222)amide and [Tyr224]FGF-23(225-244)amide, we developed a two-site enzyme-linked immunosorbent assay that detects equivalently recombinant human FGF-23, the mutant form in which glutamine is substituted for arginine at position 179 (R179Q), and synthetic human FGF-23(207-244)amide. Plasma or serum samples from 147 healthy adults (mean [+/-SD] age, 48.4+/-19.6 years) and 26 healthy children (mean age, 10.9+/-5.5 years) and from 17 patients with oncogenic osteomalacia (mean age, 43.0+/-13.3 years) and 21 patients with X-linked hypophosphatemia (mean age, 34.9+/-17.2 years) were studied. RESULTS: Mean FGF-23 concentrations in the healthy adults and children were 55+/-50 and 69+/-36 reference units (RU) per milliliter, respectively. Four patients with oncogenic osteomalacia had concentrations ranging from 426 to 7970 RU per milliliter, which normalized after tumor resection. FGF-23 concentrations were 481+/-528 RU per milliliter in those with suspected oncogenic osteomalacia and 353+/-510 RU per milliliter (range, 31 to 2335) in those with X-linked hypophosphatemia. CONCLUSIONS: FGF-23 is readily detectable in the plasma or serum of healthy persons and can be markedly elevated in those with oncogenic osteomalacia or X-linked hypophosphatemia, suggesting that this growth factor has a role in phosphate homeostasis. FGF-23 measurements might improve the management of phosphate-wasting disorders.

Lumbar radiculopathy caused by extradural rheumatoid nodules. Case report.

The authors report on a 51-year-old woman with a 9-year history of rheumatoid arthritis (RA) who presented with symptomatic rheumatoid nodules in the lumbar extradural region with compression on the L-5 nerve roots bilaterally. She had also suffered from dysesthesia in the right lower leg and intermittent claudication. Magnetic resonance imaging revealed masses compressing the dural sac, and on lumbar myelography and computed tomography myelography a filling defect at L4-5 was revealed, which was compressing the dural sac posterolaterally on both sides. The masses were surgically removed. On histological examination the typical characteristics of rheumatoid nodules were found. Soon after the operation all of the patient's symptoms disappeared. There have been few reports on extradural rheumatoid nodules. Patients with RA usually complain of articular symptoms, and in fact the patient in the present study had been referred to the authors' institution for total hip arthroplasty. However, various symptoms other than those arising from articular lesions were found clinically. The authors believe that if patients with RA are also examined for extraarticular lesions, it is likely that these will be more frequently detected.

Cementless calcar-replacement stem with integrated greater trochanter plate for unstable intertrochanteric fracture in very elderly patients.

PURPOSE: To evaluate the clinical results of rigid fixation of the greater trochanter fragment through a consecutive hemiarthroplasty series using a cementless and modular calcar-replacement prosthesis with an integrated plate (MOD-Centaur stem) with 1-year follow-up in very elderly patients with unstable intertrochanteric fractures. METHODS: We assessed 44 consecutive very elderly patients (age >85 years; 2 men, 42 women; mean age at surgery: 89.6 years) with an unstable intertrochanteric fracture who underwent bipolar hemiarthroplasty using the MOD-Centaur stem by the same surgeon. Operative time and blood loss were evaluated, and postoperative complications and mortality rate within 1 year were assessed. Bony union of the greater trochanter was evaluated using plain X-ray images at least 6 months postoperatively. Walking ability was evaluated at the time of discharge and at 1 year postoperatively. RESULTS: The mean operative time was 95.8 min, and the mean intraoperative blood loss was 358.0 mL. Postoperative peripheral infection occurred in one patient. Four patients died within 1 year postoperatively (mortality rate: 9.1%). Bony union of the greater trochanter was achieved in all the patients who had a plain X-ray taken at least 6 months postoperatively. At 1-year follow-up, 20 patients could walk independently. CONCLUSION: Hemiarthroplasty using the MOD-Centaur stem for unstable intertrochanteric fracture in very elderly patients offers favorable outcomes. These findings encourage early walking without any loading limitations, despite severe osteoporosis, and emphasize the importance of greater trochanteric fixation, which reconstructs the mechanism of the gluteus medius muscle.

Protein kinase A potentiates adrenal 4 binding protein/steroidogenic factor 1 transactivation by reintegrating the subcellular dynamic interactions of the nuclear receptor with its cofactors, general control nonderepressed-5/transformation/transcription domain-associated protein, and suppressor, dosage-sensitive sex reversal-1: a laser confocal imaging study in living KGN cells.

The mechanism through which protein kinase A (PKA) potentiates the transactivation ability of adrenal 4 binding protein/steroidogenic factor 1 (Ad4BP/SF-1) is currently unclear. In the present study, we investigated the mechanism by applying laser confocal microscopy and fluorescence recovery after photobleaching technique. In KGN cells, forskolin (a PKA stimulator) could reorganize wild-type Ad4BP/SF-1, but not mutant Ad4BP/SF-1 (G35E), from a diffuse distribution pattern to foci formation in the nucleus. The subcellular distributions of GCN5 (general control nonderepressed) and TRRAP (transformation/transcription domain-associated protein), both of which were recently proved to be working in the same complex as the third class of nuclear receptor coactivators, were unexpectedly diffuse inside and outside the nucleus, respectively, when they were separately transfected. However TRRAP was translocated into the nucleus in the presence of GCN5, and together with GCN5 colocalized with Ad4BP/SF-1 in the same foci when PKA was activated. A luciferase assay also indicated that these two cofactors enhanced Ad4BP/SF-1 transactivation.Dosage-sensitive sex reversal (DAX-1) interacts with and thus inhibits Ad4BP/SF-1 transactivation. The coexistence of the two proteins dramatically altered their respective subnuclear distributions. They colocalized extensively, suggestive of binding, and Ad4BP/SF-1 was sharply immobilized when DAX-1 was coexpressed, whereas PKA could maintain mobility, as evidenced by Fluorescence Recovery After Photobleaching showing that Ad4BP/SF-1 mobility recovered after forskolin treatment.Therefore, the PKA signal pathway may modify the interaction between Ad4BP/SF-1 and its activators and repressor (GCN5 and TRRAP are integrated, whereas DAX-1 is disassociated), and thus stimulate the Ad4BP/SF-1 transactivation.

Treatment of dysplastic osteoarthritis with labral tear by Chiari pelvic osteotomy: outcomes after more than 10 years follow-up.

INTRODUCTION: The presence of a damaged labrum is one of many factors influencing the outcomes of Chiari pelvic osteotomy. However, there are few previous papers describing the long-term outcomes of Chiari pelvic osteotomy with labrectomy. The purpose of this study was to evaluate the long-term clinical and radiological outcomes of Chiari pelvic osteotomy for dysplastic hips with labral tears. We compared outcomes between labrectomy (+) and labrectomy (-) groups. PATIENTS AND METHODS: Chiari pelvic osteotomies were performed by one surgeon on 34 dysplastic hips with labral tears between 1983 and 1996, in which labrectomy was performed on 23 hips but not on 11 hips. Three patients undergoing labrectomy were lost to follow-up evaluation within 5 years after surgery. The average age of the remaining 31 patients was 35.5 years (range, 16-54 years). The clinical and radiographic surveillance averaged 16.0 years (range, 10-23.3 years). RESULTS: In all patients, pain disappeared after the operation. At the end of the study, 8 of the 31 patients displayed clinical deterioration. Progression of osteoarthritis (OA) was observed in 11 hips. Patients with poor results have not opted for revision surgery except for one patient. In the labrectomy (+) group, 10 of the 20 hips showed progression of OA and the clinical outcomes of 6 patients deteriorated. In the labrectomy (-) group, 1 of the 11 hips showed progression of OA and 2 patients deteriorated clinically. Radiological outcomes differed significantly between the two groups. CONCLUSION: Labrectomy accompanying Chiari pelvic osteotomy is an acceptable procedure for relieving pain caused by the damaged labrum, but the outcomes have a tendency to deteriorate after 10 or more years postoperatively.

Differentiation and regeneration of adrenal tissues: An initial step toward regeneration therapy for steroid insufficiency.

In animal experiments, adrenal cortical tissue has been successfully regenerated through xenotransplantation of cloned adrenocortical cells, suggesting that the intraadrenal stem cells required for such tissue formation may be present in the adrenal cortex. Stable expression of Ad4BP/SF-1, a key factor for adrenal and gonadal development and steroidogenesis, has been shown to direct embryonic stem cells toward the steroidogenic lineage. However, this steroidogenic capacity was very limited since progesterone was only produced in the presence of an exogenous substrate. Bone marrow mesenchymal cells are thought to contain pluripotent progenitor cells, which differentiate into multiple lineages. We have demonstrated that adenovirus-mediated forced expression of SF-1 in long-term cultured bone marrow cells can produce steroidogenic cells with the capacity for de novo synthesis of various steroid hormones in response to ACTH. This discovery may represent the first step in autologous cell transplantation therapy for patients with steroid hormone deficiency.

Functional characterization of a new human Ad4BP/SF-1 variation, G146A.

Ad4BP/SF-1 plays key roles at all levels of the hypothalamic-pituitary-steroidogenic organ axis and its functional disruption causes endocrine disorders of these organs. However, only three human subjects with Ad4BP/SF-1 mutations have been reported to date, suggesting limited clinical significance as a cause of inborn adrenal or sexual abnormalities. We report the first functional characterization of a new variation found in the hinge region of human Ad4BP/SF-1, G146A. Resulting from a single nucleotide shift (GGG-->GCG), G146A bears slightly diminished transactivation activity evidenced by both adrenal specific cyp11A promoter and ovary specific cyp19 promoter II. The variation does not affect protein expression or stability, exhibiting no dominant negative effect. G146A has a normal interaction pattern with standard co-regulators and subnuclear distribution pattern, and can be considered as a nonsynonymous single nucleotide polymorphism, since it occurs in normals and patients with adrenal diseases. In normal Japanese the allele C frequency is 8%, while in a preliminary population of patients with adrenal diseases it is elevated to 30%; suggesting the G146A variation might be of clinical importance.

Human pituitary tumor transforming gene (hPTTG) inhibits human lung cancer A549 cell growth through activation of p21(WAF1/CIP1 ).

Pituitary tumor transforming gene (PTTG) is a proto-oncogene cloned from rat GH4 cells. This gene was able to induce cell transformation in vitro and is also associated with p53-dependent and -independent apoptosis. In this study, we cloned human PTTG (hPTTG) from a pituitary tumor and then stably transfected the hPTTG into HeLa and A549 cells. An overexpression of hPTTG significantly inhibited cell growth, which was determined by the adherent cell growth properties, colony formation in soft agar and [3H] thymidine incorporation, respectively, in HeLa and A549 cells. The inhibitory effect on cell growth was associated with the activation of p21WAF1/CIP1 in A549 cells, but not in HeLa cells. The hPTTG overexpression increased both the p21WAF1/CIP1 mRNA and protein expression levels as determined by both Northern and Western blot analysis, respectively, in A549 cells. The increased expression of p21WAF1/CIP1 mRNA was regulated at the transcription level and was independent on p53 expression because the luciferase activity increased after the co-transfection of hPTTG and p21WAF1/CIP1 promoter fragments with and without a p53 binding sequence. The subcellular distribution of hPTTG was dependent on cell type, and was predominantly in the nucleus in HeLa, Cos-7 and DU145 cells, but showed a diffuse distribution in both the nucleus and cytoplasm in A549, DLD-1 and NIH3T3 cells. These results indicate that an overexpression of hPTTG inhibits the cell growth due to different mechanisms, which are p21WAF1/CIP1 -dependent and -independent.