A clinical and ultrasonographic study of risk factors for elbow injury in young baseball players.

PURPOSE: To determine the risk factors for elbow injury and its association with glenohumeral internal rotation deficit among young baseball players. METHODS: 229 baseball players aged 9 to 14 (mean, 11) years completed a self-administered questionnaire with items related to years of playing baseball, hours of training per weekday, days of training per week, and past and present experience of elbow pain. Two orthopaedic surgeons measured the range of motion of both shoulders and elbows. Another 2 orthopaedic surgeons performed ultrasonography to detect any elbow abnormality such as fragmentation of the medial epicondylar apophysis and osteochondritis dissecans of the capitellum. Using univariate and multivariable analyses, participants with or without elbow abnormality were compared to determine the risk factors for elbow abnormality. RESULTS: Elbow abnormality was detected in 100 of the participants and comprised osteochondritis dissecans of the capitellum (n=18) and fragmentation of the medial epicondylar apophysis (n=82). Elbow abnormality was associated with being a pitcher, past and present experience of elbow pain, loss of elbow extension, and the side-to-side internal rotation difference. The 100 participants with elbow abnormality were stratified into symptomatic (n=57) or asymptomatic (n=43) of elbow pain. Those with elbow abnormality and elbow pain was associated with being a pitcher. CONCLUSION: Being a pitcher was a risk factor for both elbow abnormality and elbow pain. Nonetheless, 43% of baseball players with elbow abnormality were asymptomatic. The use of ultrasonography was effective in detecting elbow abnormality and enabling early treatment.

Bayesian modeling of virus removal efficiency in wastewater treatment processes.

Left-censored datasets of virus density in wastewater samples make it difficult to evaluate the virus removal efficiency in wastewater treatment processes. In the present study, we modeled the probabilistic distribution of virus removal efficiency in a wastewater treatment process with a Bayesian approach, and investigated how many detect samples in influent and effluent are necessary for accurate estimation. One hundred left-censored data of virus density in wastewater (influent and effluent) were artificially generated based on assumed log-normal distributions and the posterior predictive distribution of virus density, and the log-ratio distribution were estimated. The estimation accuracy of distributions was quantified by Bhattacharyya coefficient. When it is assumed that the accurate estimation of posterior predictive distributions is possible when a 100% positive rate is obtained for 12 pairs of influent and effluent, 11 out of 144, 60 out of 324, and 201 out of 576 combinations of detect samples gave an accurate estimation at the significant level of 0.01 in a Kruskal-Wallis test when the total sample number was 12, 18, and 24, respectively. The combinations with the minimum number of detect samples were (12, 9), (16, 10), and (21, 8) when the total sample number was 12, 18, and 24, respectively.

Myelopathy due to lumbar disc herniation in the presence of a tethered cord.

STUDY DESIGN: Single case report. OBJECTIVES: To present a case of lumbar disc herniation causing compression of a tethered cord that was successfully treated with lumbar decompression and fusion. BACKGROUND: A tethered cord is a rare pathology associated with a congenital spinal malformation, spinal dysraphism. Furthermore, myelopathy due to lumbar disc herniation in the presence of a tethered cord is extremely rare. METHODS: Single case report. RESULTS: A 43-year-old male with a history of spina bifida presented to our clinic for an evaluation of a progressive spastic gait disturbance and numbness in the lower limbs. A neurological examination revealed muscle weakness and pyramidal tract signs in the lower limbs. Magnetic resonance imaging of the lumbar spine showed disc herniation at L2-3 causing compression of a low-lying cord. Surgical intervention, including herniotomy via a posterolateral approach and instrumented posterolateral fusion, was performed, and a good outcome was achieved 1 year after the surgery. CONCLUSION: The potential for lumbar disc herniation in the presence of a tethered cord should be taken into account in the differential diagnosis of spinal pathologies causing spastic gait disturbances. Furthermore, posterior decompression and fusion is a useful treatment option in such cases.

Prognostic factors for cervical spondylotic amyotrophy: are signs of spinal cord involvement associated with the neurological prognosis?

OBJECTIVES: The purpose of this study was to clarify the prognostic factors for cervical spondylotic amyotrophy (CSA). METHODS: The authors retrospectively reviewed the medical records of 47 consecutive patients with CSA in whom the presence/absence of the pyramidal tract sign was noted. We analyzed whether the age, sex, presence of diabetes mellitus, medication (vitamin B12), type of the most atrophic and impaired muscle, the muscle strength at the presentation, the presence of the pyramidal tract sign, magnetic resonance imaging (MRI) findings, including the presence and number of T2 high signal intensity areas (T2 HIA) in the spinal cord and the conversion to surgery were associated with the recovery of muscle strength in the patients. In addition, we also investigated whether the duration of symptoms before surgery and the type of surgery were associated with the recovery of muscle strength in patients who required conversion to surgical treatment. RESULTS: The presence of T2 HIA on MRI (P=0.002), the number of T2 HIA on MRI (P=0.002) and conversion to surgery (P=0.015) were found to be significantly associated with a poorer recovery at the observational final follow-up. Further, the presence of the pyramidal tract sign (P=0.043) was significantly associated with a poor recovery at the final follow-up after surgery. CONCLUSION: The presence of a high signal intensity change on T2-weighted MRI and the pyramidal tract sign can be used as prognostic factors for patients with CSA.

Movement and afferent representations in human motor areas: a simultaneous neuroimaging and transcranial magnetic/peripheral nerve-stimulation study.

Neuroimaging combined with transcranial magnetic stimulation (TMS) to primary motor cortex (M1) is an emerging technique that can examine motor-system functionality through evoked activity. However, because sensory afferents from twitching muscles are widely represented in motor areas the amount of evoked activity directly resulting from TMS remains unclear. We delivered suprathreshold TMS to left M1 or gave electrical right median nerve stimulation (MNS) in 18 healthy volunteers while simultaneously conducting functional magnetic resonance imaging and monitoring with electromyography (EMG). We examined in detail the localization of TMS-, muscle afferent- and superficial afferent-induced activity in M1 subdivisions. Muscle afferent- and TMS-evoked activity occurred mainly in rostral M1, while superficial afferents generated a slightly different activation distribution. In 12 participants who yielded quantifiable EMG, differences in brain activity ascribed to differences in movement-size were adjusted using integrated information from the EMGs. Sensory components only explained 10-20% of the suprathreshold TMS-induced activity, indicating that locally and remotely evoked activity in motor areas mostly resulted from the recruitment of neural and synaptic activity. The present study appears to justify the use of fMRI combined with suprathreshold TMS to M1 for evoked motor network imaging.

Time course and spatial distribution of fMRI signal changes during single-pulse transcranial magnetic stimulation to the primary motor cortex.

Simultaneous transcranial magnetic stimulation (TMS) and functional magnetic resonance imaging (fMRI) may advance the understanding of neurophysiological mechanisms of TMS. However, it remains unclear if TMS induces fMRI signal changes consistent with the standard hemodynamic response function (HRF) in both local and remote regions. To address this issue, we delivered single-pulse TMS to the left M1 during simultaneous recoding of electromyography and time-resolved fMRI in 36 healthy participants. First, we examined the time-course of fMRI signals during supra- and subthreshold single-pulse TMS in comparison with those during voluntary right hand movement and electrical stimulation to the right median nerve (MNS). All conditions yielded comparable time-courses of fMRI signals, showing that HRF would generally provide reasonable estimates for TMS-evoked activity in the motor areas. However, a clear undershoot following the signal peak was observed only during subthreshold TMS in the left M1, suggesting a small but meaningful difference between the locally and remotely TMS-evoked activities. Second, we compared the spatial distribution of activity across the conditions. Suprathreshold TMS-evoked activity overlapped not only with voluntary movement-related activity but also partially with MNS-induced activity, yielding overlapped areas of activity around the stimulated M1. The present study has provided the first experimental evidence that motor area activity during suprathreshold TMS likely includes activity for processing of muscle afferents. A method should be developed to control the effects of muscle afferents for fair interpretation of TMS-induced motor area activity during suprathreshold TMS to M1.

Pharmacokinetic individualization of high-dose methotrexate chemotherapy for the treatment of localized osteosarcoma.

Individualization of high-dose methotrexate (MTX) dosing is important to achieve therapeutic levels (700-1,000 microM) for osteosarcoma. Therefore we developed a pharmacokinetically (PK) individualized dosage regimen to maintain MTX concentrations of 700 microM (1 h bolus followed by 5 h maintenance infusion) and evaluated its safety and efficacy. Loading and maintenance doses were calculated by the PK parameters based on 2-compartment model analysis. Thirty-two courses of chemotherapy were performed in 9 patients with osteosarcoma. The maximum concentrations during maintenance infusion in 31 courses (97%) were above 700 microM. Only 1 patient developed severe hepatotoxicity as adverse effect. Total body clearance of MTX decreased in 4 patients when weekly MTX chemotherapy was performed for 3 consecutive weeks. Although the clearance was changed, the average MTX concentrations were maintained at about 700 microM by the PK individualization. The 5-year survival rate was 77.8% (7 of 9 patients), and all of them have survived for more than 9 years. This PK individualization is safe and useful for tailoring high-dose MTX therapy to achieve therapeutic levels.

Role of 2-deoxy-2-[F-18] fluoro-D-glucose positron emission tomography in the management of bone and soft-tissue metastases.

We retrospectively reviewed 71 histopathologically-confirmed bone and soft-tissue metastases of unknown origin at presentation. In order to identify the site of the primary tumour all 71 cases were examined with conventional procedures, including CT, serum tumour markers, a plain radiograph, ultrasound examination and endoscopic examinations, and 24 of the 71 cases underwent 2-deoxy-2-[F-18] fluoro-D-glucose positron emission tomography (FDG-PET). This detected multiple bone metastases in nine patients and the primary site in 12 of the 24 cases; conventional studies revealed 16 primary tumours. There was no significant difference in sensitivity between FDG-PET and conventional studies. The mean maximal standardised uptake value of the metastatic tumours was significantly higher than that of the primary tumours, which is likely to explain why FDG-PET did not provide better results. It was not superior to conventional procedures in the search for the primary site of bone and soft-tissue metastases; however, it seemed to be useful in the staging of malignancy.

Cytokine synthesis by chondroblastoma: relation to local inflammation.

PURPOSE: To investigate cytokine production by chondroblastoma in inducing local inflammation and adjacent-joint arthritis. METHODS: Immunohistochemical analyses of curetted tissues using anti-human interleukin (IL)-1 beta, IL- 6, IL-8, and tumour necrosis factor (TNF)-alpha were performed for 6 patients with chondroblastoma and 3 patients with giant cell tumour (GCT) of bone. In addition, prostaglandin E2, IL-1 beta, IL-2, IL-4, IL-5, IL-6, IL-8, and TNF-alpha in the cyst fluid of one of the patients with chondroblastoma and 2 with GCT of bone were measured using immunoassay kits. RESULTS: More positive staining for IL-1 beta, IL-8, IL- 6, and TNF-alpha was shown in chondroblastoma than GCT of bone samples. Osteoclast-like giant cells in chondroblastomas showed positive staining for IL- 6 only. In addition, concentrations of IL-4, IL-6, and IL-8 in the cyst fluid were higher in the one patient with chondroblastoma than the 2 patients with GCT of bone. CONCLUSION: Cytokines such as IL-1 beta, IL-8, TNF-alpha, and particularly IL-6 play an important role in local inflammation in patients with chondroblastoma.

Spontaneous osteonecrosis of the knee: histopathological differences between early and progressive cases.

We prospectively examined the physical and imaging findings, including MRI, of 23 patients with spontaneous osteonecrosis of the knee after obtaining informed consent to acquire tissue specimens at surgery. There were four men and 19 women, with a mean age of 67.5 years (58 to 77). Plain radiographs were designated as stages 1, 2, 3 or 4 according to the classification of Koshino. Five knees were classified as stage 1, five as stage 2, seven as stage 3 and six as stage 4. The histological specimens were stained with haematoxylin and eosin and tetrachrome. In the early stages of the condition, a subchondral fracture was noted in the absence of any features of osteonecrosis, whereas in advanced stages, osteonecrotic lesions were confined to the area distal to the site of the fracture which showed impaired healing. In such cases, formation of cartilage and fibrous tissue, occurred indicating delayed or nonunion. These findings strongly suggest that the histopathology at each stage of spontaneous osteonecrosis is characterised by different types of repair reaction for subchondral fractures.

Transplantation of autologous rabbit BM-derived mesenchymal stromal cells embedded in hyaluronic acid gel sponge into osteochondral defects of the knee.

BACKGROUND: Mesenchymal stromal cells (MSC) have the potential to differentiate into distinct mesenchymal tissues including cartilage, suggesting that these cells are an attractive cell source for cartilage tissue engineering approaches. Various methods, such as using hyaluronan-based materials, have been employed to improve transplantation for repair. Our objective was to study the effects of autologous transplantation of rabbit MSC with hyaluronic acid gel sponges into full-thickness osteochondral defects of the knee. METHODS: Rabbit BM-derived MSC were cultured and expanded with fibroblast growth factor (FGF). Specimens were harvested at 4 and 12 weeks after implantation, examined histologically for morphologic features, and stained immunohistochemically for type II collagen and CD44. RESULTS: The regenerated area after autologous transplantation of hyaluronic acid gel sponge loaded with MSC into the osteochondral defect at 12 weeks after surgery showed well-repaired cartilage tissue, resembling the articular cartilage of the surrounding structure, of which the histologic score was significantly better than that of the untreated osteochondral defect. In the regenerated cartilage, type II collagen was found in the pericellular matrix of regenerative chondrocytes, while CD44 expression in the regenerative tissue could not be revealed. DISCUSSION: These data suggest that the autologous transplantation of MSC embedded in hyaluronan-based material may support chondrogenic differentiation and be useful for osteochondral defect repair.

Changes in biochemical parameters after anterior cruciate ligament injury.

We studied the biochemical characteristics of human knees with deficient anterior cruciate ligaments (ACL) and analysed their relationship to the time after ligamentous injury. Thirty-two patients with isolated ACL-injured knees and six healthy volunteers were enrolled. Synovial fluid samples were centrifuged after aspiration during arthroscopic examination, and aliquots of supernatant were frozen and stored at -80 degrees C. The samples were analysed for interleukin (IL)-1beta, tumour necrosis factor (TNF)-alpha, IL-6, matrix metalloproteinase (MMP)-3, and tissue inhibitor of metalloproteinase (TIMP)-1 using commercially available sandwich enzyme-linked immunosorbent assay. In fluid from ACL-injured knees, the average concentrations of IL-6, MMP-3 and TIMP-1 were highly elevated in comparison with normal controls. There was a statistically significant correlation between the concentrations of MMP-3 and IL-6. The IL-6 and TIMP-1 concentrations were interrelated. The concentration of MMP-3 remained high, independent of the duration since the injury, whereas the TIMP-1 and IL-6 levels decreased. The results suggest that the timing of the treatment of an ACL-injured knee might be of importance.

Osteoid osteoma treated with computed tomography-guided percutaneous radiofrequency ablation: a case series.

The nidi of osteoid osteoma are small and difficult to identify precisely; this can necessitate substantial resection of the surrounding normal bone. We applied percutaneous, image-guided radiofrequency ablation to treat 5 patients with osteoid osteoma. The precise location of each nidus was determined using a 3-mm-thick spiral computed tomographic scan. The most appropriate needle pathway was selected to avoid major neural and vascular structures. A 14-gauge core needle was introduced into the nidus and then exchanged for a 17-gauge straight rigid electrode with a 1-cm exposed tip to heat the lesion to 90 degrees centigrade for 5 minutes. Four of the 5 patients were discharged on the day after surgery without any external supports, and were pain-free after a few days. The remaining patient had a pes equinus contracture induced by the penetration of the calf muscles through a posterior approach but was fully recovered 6 days later. The mean follow-up period was 20.6 months. No recurrences or late complications were observed in this series. This case series shows that the computed tomography-guided percutaneous radiofrequency ablation is a simple, minimally invasive, and highly effective technique for the treatment of osteoid osteoma.

Discovery of the short gamma-ray burst GRB 050709.

Gamma-ray bursts (GRBs) fall into two classes: short-hard and long-soft bursts. The latter are now known to have X-ray and optical afterglows, to occur at cosmological distances in star-forming galaxies, and to be associated with the explosion of massive stars. In contrast, the distance scale, the energy scale and the progenitors of the short bursts have remained a mystery. Here we report the discovery of a short-hard burst whose accurate localization has led to follow-up observations that have identified the X-ray afterglow and (for the first time) the optical afterglow of a short-hard burst; this in turn led to the identification of the host galaxy of the burst as a late-type galaxy at z = 0.16 (ref. 10). These results show that at least some short-hard bursts occur at cosmological distances in the outskirts of galaxies, and are likely to be caused by the merging of compact binaries.

Motility and growth of human bone-marrow mesenchymal stem cells during ex vivo expansion in autologous serum.

Human bone-marrow mesenchymal stem cells have an important role in the repair of musculoskeletal tissues by migrating from the bone marrow into the injured site and undergoing differentiation. We investigated the use of autologous human serum as a substitute for fetal bovine serum in the ex vivo expansion medium to avoid the transmission of dangerous transfectants during clinical reconstruction procedures. Autologous human serum was as effective in stimulating growth of bone-marrow stem cells as fetal bovine serum. Furthermore, medium supplemented with autologous human serum was more effective in promoting motility than medium with fetal bovine serum in all cases. Addition of B-fibroblast growth factor to medium with human serum stimulated growth, but not motility. Our results suggest that autologous human serum may provide sufficient ex vivo expansion of human bone-marrow mesenchymal stem cells possessing multidifferentiation potential and may be better than fetal bovine serum in preserving high motility.

Quantitative evaluation of anterior tibial translation during isokinetic motion in knees with anterior cruciate ligament reconstruction using either patellar or hamstring tendon grafts.

We studied 79 patients with unilateral injury to the anterior cruciate ligament (ACL). The patients were randomly allocated to reconstruction with autologous patellar bone-tendon-bone (BTB) grafts (49 knees) or hamstring tendon (ST) grafts (30 knees). We measured anterior tibial translation (ATT) during isokinetic concentric contraction exercise 18-20 months after surgery using a computerized electrogoniometer. In both groups the highest ATT during exercise was observed at a knee flexion of about 20 degrees and was 13.5+/-3.0 mm in the BTB group and 13.9+/-3.4 mm in the ST group. There was no difference in the ATT between the reconstructed and healthy knees. For a range of knee flexion between 30 and 50 degrees the ATT in the ST group was significantly higher on the reconstructed side than on the healthy side. In the BTB group, the mean ATT in the reconstructed group was similar to that on the healthy side at a knee flexion angle between 0 and 90 degrees .

Effects of YM529, a novel minodronic acid, on adjuvant arthritis in rats.

OBJECTIVE: The effects of a new third-generation bisphosphonate, YM529, on both the development and treatment of adjuvant arthritis were investigated in rats. METHODS: Five-week-old Lewis rats with adjuvant arthritis were prophylactically and therapeutically treated with 0.001, 0.01 and 0.05 mg/kg/day of YM529 and the arthritis scores were measured. Soft X-ray and histological finding were compared to those of the control group. Body weights were also measured. RESULTS: YM529 suppressed the severity of adjuvant arthritis in a dose-dependent manner when used as either a prophylactic or therapeutic drug. Administration of the drug had little effect on body weight. CONCLUSION: YM529 may act on arthritic joints locally to prevent inflammation. However, further experiments are necessary to elucidate the underlying mechanisms.

Synovectomy reduces stromal-cell-derived factor-1 (SDF-1) which is involved in the destruction of cartilage in osteoarthritis and rheumatoid arthritis.

We have compared the concentrations of stromal-cell-derived factor-1 (SDF-1), matrix metalloproteinase-1 (MMP-1), MMP-9 and MMP-13 in serum before and after synovectomy or total knee replacement (TKR). We confirmed the presence of SDF-1 and its receptor CXCR4 in the synovium and articular cartilage by immunohistochemistry. We established chondrocytes by using mutant CXCR4 to block the release of MMPs. The level of SDF-1 was decreased 5.1- and 6.7-fold in the serum of patients with OA and RA respectively, after synovectomy compared with that before surgery. MMP-9 and MMP-13 were decreased in patients with OA and RA after synovectomy. We detected SDF-1 in the synovium and the bone marrow but not in cartilage. CXCR4 was detected in articular cartilage. SDF-1 increased the release of MMP-9 and MMP-13 from chondrocytes in a dose-dependent manner. The mutant CXCR4 blocked the release of MMP-9 and MMP-13 from chondrocytes by retrovirus vector. Synovectomy is effective in patients with OA or RA because SDF-1, which can regulate the release of MMP-9 and MMP-13 from articular chondrocytes for breakdown of cartilage, is removed by the operation.

Muscle performance after anterior cruciate ligament reconstruction.

We measured muscle strength in 36 patients after anterior cruciate ligament (ACL) reconstruction with autogenous bone-patellar tendon-bone graft. Quadriceps and hamstring isokinetic strength was assessed during concentric contraction at 60 and 180 degrees /s and was measured at 1, 6, 12 and 24 months postoperatively. At 24 months quadriceps muscle strength had recovered to approximately 90% of the level of the uninvolved side, both at 60 and 180 degrees /s. In contrast, hamstring muscle strength had already recovered to approximately 90% at 6 months. Age, gender, activity level, and anterior tibial laxity did not affect the muscle performance. However, the recovery of muscle strength was delayed in patients with anterior knee pain.

FDG-PET for preoperative differential diagnosis between benign and malignant soft tissue masses.

OBJECTIVE: To evaluate the standardized uptake value (SUV) of [(18)F]2-deoxy-2-fluoro- d-glucose at positron emission tomography (FDG-PET) for preoperative differential diagnosis between benign and malignant soft tissue masses. DESIGN: One hundred and fourteen soft tissue masses (80 benign, 34 malignant) were examined by FDG-PET prior to tissue diagnosis. The SUVs were calculated and compared between benign and malignant lesions and among different histologic subgroups which included three or more cases. RESULTS: There was a statistically significant difference in SUV between benign (1.80+/-1.42 [SD]) and malignant (4.20+/-3.16) soft tissue masses in total (P<0.0001). However, a considerable overlap in SUV was observed between many benign and malignant lesions. Liposarcomas (2.16+/-1.72) and synovial sarcomas (1.60+/-0.43) did not show significantly higher SUV than any benign lesions. Metastases (4.23+/-2.35) showed no statistically significant difference in SUV as compared with schwannomas (1.75+/-0.84), desmoids (2.77+/-1.32), sarcoidosis (3.62+/-1.53), or giant cell tumors of tendon sheath (GCT of TS; 5.06+/-1.63). Even malignant fibrous histiocytomas (5.37+/-1.40) could not be differentiated from sarcoidosis or GCT of TS, based on the SUV. CONCLUSIONS: A large accumulation of FDG can be observed in both benign and malignant histiocytic, fibroblastic, or neurogenic lesions. SUV at conventional FDG-PET is limited to differentiating benign from malignant soft tissue masses, when all kinds of histologic subtypes are included.