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Biomedical subjects

Keith D K Luk

Publications and source records attributed to Keith D K Luk.

At least 19 recordsLinked to original sources

Osteoprecursor cell response to strontium-containing hydroxyapatite ceramics.

The objective of this study was to investigate the in vitro bioactivity of strontium-containing hydroxyapatite (Sr-HA), and its effect on cellular attachment, proliferation, and differentiation. The effect of Sr-HA has been compared with that of hydroxyapatite (HA), which is widely used in orthopedics and dentistry. Sr-HA ceramic containing 10 mol % was prepared. The bioactivity of Sr-HA was evaluated in vitro by immersion in simulated body fluid (SBF). After immersion in SBF, Sr-HA exhibited greater ability to induce apatite precipitation on its surface than did HA. The possible effects on cell behavior of Sr-HA were examined by culturing osteoprecursor cells (OPC1) on materials surfaces. Cell shape and cell-material interactions were analyzed by scanning electron microscope (SEM) and the MTT assay was used to determine cell proliferation on samples. When compared with HA, Sr-HA promoted better OPC1 cell attachment and proliferation, and showed no deleterious effects on extracellular matrix formation and mineralization. Confocal scanning microscopy was used to assess the expression of specific osteoblast proteins: alkaline phosphatase (ALP) and osteopontin (OPN). The results obtained indicate that the presence of Sr stimulates OPC1 cell differentiation, and enhances ALP and OPN expression.

Alkaline Phosphatase↗

Mechanical testing of a smart spinal implant locking mechanism based on nickel-titanium alloy.

STUDY DESIGN: Development and testing of a new spinal implant-locking mechanism based on the special properties of nickel-titanium alloy. OBJECTIVE: To develop a new self-tightening locking mechanism to reduce fretting corrosion at implant junctions. SUMMARY OF BACKGROUND DATA: All current implant locking involves tightening of a nut against the rod and screw head to form a coupling. Particulate debris is generated, and the coupling becomes loose because of wear between the rod and locking mechanism (fretting). To avoid this fretting, a new locking mechanism with an automatic retightening effect based on the superelastic and shape-memory properties of nickel-titanium alloy has been developed. METHOD: The new coupling made of nickel-titanium alloy will tightly lock the rod when temperature increases to 50 degrees C (shape-memory effect). If fretting occurs, the coupling will further tighten itself around the rod (superelastic effect). This new coupling is mechanically tested against 4 current implant couplings. RESULTS: In axial compression, conventional couplings failed between 570 and 740 N, while the new coupling reached 800 N without loosening. In axial rotation, conventional devices failed between 1.8 and 5.3 Nm, while the new coupling reached 6.5 Nm without failure. During testing, the retightening effect could be seen on the force versus displacement plot. CONCLUSIONS: To our knowledge, the self-tightening coupling is a new concept not previously described and is attributable to the superior superelastic effect of the new coupling. This implant coupling has the potential to be used as a very low profile system and also in nonfusion technologies in which demands on the coupling would not higher without the protection of spinal fusion.

Alloys↗

Outcome assessment of bracing in adolescent idiopathic scoliosis by the use of the SRS-22 questionnaire.

The SRS-22 questionnaire is specifically designed for the assessment of quality of life in spinal deformity patients. This study is the first to use it to assess the quality of life of adolescent idiopathic scoliosis patients under brace treatment and compares the results with an observational group matched by age and curve magnitude. Forty-six patients were enrolled into each group. Overall, it was found that patients under observation had a significantly better quality of life than braced patients. Specifically, the domains for function/activity and self-image were most affected. This effect was most apparent in those with a curve magnitude of under 20 degrees . The scores did not improve significantly with the duration of brace wear, suggesting little adaptation. This study has implications for treatment, and more attention will need to be given to those with mild but progressive curves to help improve patients' understanding of their treatment and hence their compliance and satisfaction.

Adolescent↗

Association of the Taq I allele in vitamin D receptor with degenerative disc disease and disc bulge in a Chinese population.

STUDY DESIGN: Large scale, case-control study. OBJECTIVE: To assess the effect of the Taq I alleles in vitamin D receptor on the risk of developing degenerative disc disease in a Southern Chinese population. SUMMARY OF BACKGROUND DATA: Previous studies in Finns and Japanese suggest that the Taq I polymorphism of vitamin D receptor is associated with the development of degenerative disc disease in the lumbar spine. However, sample sizes were small, and the results need to be confirmed in other populations. METHOD: Lumbar degenerative disc disease was defined by magnetic resonance imaging (MRI) on 804 Southern Chinese volunteers between 18 and 55 years of age. Restriction enzyme digestion of polymerase chain reaction products was used to analyze the Taq I alleles. The resulting genotypes were correlated with the presence of lumbar disc degeneration and bulge on MRI. RESULTS: Using logistic regression analysis and adjusting for age and sex, the t allele of Taq I in vitamin D receptor gene was significantly associated with degenerative disc disease, with an odds ratio (OR) of 2.61 (95% confidence interval [CI] 1.15-5.90, P = 0.041). Further subgroup analysis showed that in individuals younger than 40 years, the OR was even higher, at 5.97 (95% CI 1.69-21.15, P = 0.002). Similarly, disc bulge was significantly associated with t allele (OR = 7.17, 95% CI 1.43-36.01, P = 0.001) in individuals younger than 40 years. Anular tears and the Schmorl nodes were not associated with the t allele of Taq I polymorphism. CONCLUSION: To our knowledge, this is the largest scale genetics study to date using MRI to define precisely degenerative disc disease in the Southern Chinese population. We showed that the t allele of vitamin D receptor Taq I is associated with a high risk of degenerative disc disease and disc bulge developing, especially in individuals younger than 40 years.

Adolescent↗

Continuous dynamic spinal motion analysis.

STUDY DESIGN: Continuous dynamic lumbar intervertebral flexion-extension is assessed by a videofluoroscopy with a new auto-tracking system. OBJECTIVES: To develop and validate a new method for the continuous assessment of lumbar kinematics. SUMMARY OF BACKGROUND DATA: Instability of the lumbar spine is thought to be associated with low back pain, but the diagnosis remains difficult. Functional radiographs have been used for diagnosis of spinal instability but error and limitation exist, whereas videofluoroscopy provides a cost-effective way for such analysis. However, common approaches of image analysis of videofluoroscopic video are tedious and time-consuming because of the low quality of the images. Physicians have to extract the vertebrae manually in most cases; thus, continuous motion analysis is hardly achieved. METHODS: A new system that can perform automatic vertebrae segmentation and tracking is developed. In vitro and in vivo validity were evaluated. Intervertebral flexion and extension was assessed in 30 healthy volunteers. RESULTS: In vitro and in vivo validity tests have been conducted with good results. A linear-liked pattern of the intervertebral flexion-extension (IVFE) curves in different levels was found, and the IVFE decreased in descending order from L1-L5 at different points of range of motion in flexion. Conversely, extension is evenly contributed at different levels, and the concavity of lumbar lordosis increases steadily in backward movement. CONCLUSIONS: The newly developed technique in assessing the dynamic lumbar motion is reliable and able to analyze the lumbar intervertebral movement from videofluoroscopic images automatically and accurately. The proposed system requires less human intervention than common approaches. It may have a potential value in the evaluation of spinal "instability" in clinical practice.

Adult↗

Assessment of linkage and association of 13 genetic loci with bone mineral density.

Bone mineral density (BMD), an important risk factor for osteoporosis, is a complex trait likely affected by multiple genes. The linkage and/or association of 13 polymorphic loci of seven candidate genes (estrogen receptor alpha [ERalpha] and beta [ERbeta], calcium-sensing receptor, vitamin D receptor, collagen type 1alpha1, low-density lipoprotein [LDL] receptor-related protein 5 [LRPS], and transforming growth factor beta1) were evaluated in 177 southern Chinese pedigrees of 674 subjects, with each pedigree identified through a proband having a BMD Z score of -1.28 or less at the hip or spine. A suggestive linkage was detected between the IVS1-351A/G polymorphism of ERalpha and spine BMD, and between the 1082G/A, 1730G/A, and D14S1026 polymorphisms of ERbeta and BMD at both spine and hip. The quantitative transmission disequilibrium test (QTDT) detected total family association between 1730G/A of ERbeta and BMD at spine and hip; between D14S1026 of ERbeta and hip BMD; and between the 266A/G and 2220C/T polymorphisms of LRP5 and hip BMD. Similar total family associations were detected when only the females were analyzed. In addition, the IVS1-397T/C polymorphism of ERalpha was associated with spine BMD, and the 266A/G and 2220C/T polymorphisms of LRP5 were associated with femoral neck BMD in the females. A within-family association was detected with the IVS1-397T/C polymorphism of ERalpha, and the 266A/G and 2220C/T polymorphisms of LRP5 in the females. The effect of each polymorphism on BMD variance ranged from 1% to 4%. In conclusion, ERalpha, ERbeta and LRP5 are important candidate genes determining BMD variation, especially in females.

Adult↗

Consequence of paraspinal muscle after spinal fusion: an experimental study.

Posterior lumbar spinal fusion is a common surgery of spine. The parapsinal muscular dysfunction was postulated to be due to injured paraspinal muscle inflicted by the surgery. To better understand the muscle dysfunction after spinal fusion, this descriptive study evaluated electrophysiology and histology changes in paraspinal muscle of rabbits with and without fusion. Three New Zealand white rabbits underwent 2-level posterior spinal fusion with instrumentation. Anothor 3 rabbits underwent surgical exposure alone and served as sham control. Pre-operative and follow-up electromyography (EMG) and histological assessment were performed in a 6-month interval. All fusion achieved solid union judged by post-mortem examination. Root mean square (RMS) of EMG showed decrease in both fusion and control group immediately after surgery, but the control group recovered to pre-operative value at 6 months follow-up. At 6 months after operation, the fusion group showed lower RMS in fused region than adjacent region. In term of median frequency (MF) changes, the control group did not show obvious difference between pre- and post-operative period. However, fusion group showed obvious decrease of MF in fusion region, but increase in lower adjacent region. Histology reviewed fatty infiltration in fusion region at 6 months after spinal fusion. In addition, the muscle fiber size presented smaller in fusion region than that of pre-operative status. These results would demonstrate the lower activities and muscle disuse atrophy of paraspinal muscles in the fusion region. While, higher muscular activities were found in the lower adjacent region, which may indicate muscle hypertrophy.

Animals↗

In-vivo demonstration of the effectiveness of thoracoscopic anterior release using the fulcrum-bending radiograph: a report of five cases.

Thoracoscopic anterior release of stiff scoliotic curves is favored because of its minimally invasive nature. Animal and human cadaveric studies have shown that it can effectively improve spinal flexibility in non-scoliotic spines; however it has not been demonstrated to be effective in actual patients with scoliosis. The fulcrum-bending radiograph has been shown to accurately reflect the post-operative correction. To demonstrate that the flexibility was increased after the anterior release; five patients with idiopathic thoracic scoliosis who underwent staged anterior thoracoscopic release and posterior spinal fusion were assessed using the fulcrum-bending radiograph. The average number of discs excised was four. Spinal flexibility as revealed by the fulcrum-bending technique, was compared before and after the anterior release. The patients were followed for an average of 4 years (range 2.2-4.9 years). Fulcrum-bending flexibility was increased from 39% before the thoracoscopic anterior spinal release to 54% after the release (P<0.05). The average Cobb angle before the anterior release was 71 degrees on the standing radiograph and 43 degrees with the fulcrum-bending radiograph. This reduced to 33 degrees on the fulcrum-bending radiograph after the release, and highly corresponded to the 30 degrees measured at the post-operative standing radiograph and at the latest follow-up. Previous animal and cadaveric studies demonstrating the effectiveness of thoracoscopic anterior release did not have scoliosis. We are able to demonstrate in patients with adolescent idiopathic scoliosis, that thoracoscopic anterior spinal release effectively improves the spinal flexibility.

Adolescent↗

The TRP2 allele of COL9A2 is an age-dependent risk factor for the development and severity of intervertebral disc degeneration.

STUDY DESIGN: Low back pain (LBP) and sciatica are usually caused by degenerative disc disease (DDD). Although they are common, the etiology of these conditions is poorly understood. A large population case-control study in the Southern Chinese was performed to study genetic risk factors to DDD. OBJECTIVES: To gain a better understanding of the etiology of DDD in relation to structural defects of the intervertebral disc. SUMMARY OF BACKGROUND DATA: A Finnish study found an association between LBP and sciatica with two variants of the alpha-chains of collagen IX, encoded by the Trp2 and Trp3 alleles, representing Gln326Trp and Arg103Trp amino acid substitutions in the COL9A2 and COL9A3 genes, respectively. Trp2 was found only in affected individuals (4%), whereas Trp3 was present in both affected (24%) and unaffected (9%) individuals. Because of the low frequency of the Trp2 allele in whites, the significance and contribution of this allele to DDD are not known. Using more objective criteria to define the disease by magnetic resonance imaging (MRI), we tested these alleles for association with DDD in a large population study. METHODS: Lumbar DDD, the presence of anular tears, and disc and endplate herniations were defined by MRI in 804 Southern Chinese volunteers 18 to 55 years of age. These were correlated with the frequencies of the Trp2 and Trp3 alleles. RESULTS: The Trp2 allele was present in 20% of the population and was associated with a fourfold increase in the risk of developing anular tears at 30 to 39 years and a 2.4-fold increase in the risk of developing DDD and endplate herniations at 40 to 49 years. Affected Trp2 individuals had more severe degeneration. The Trp3 allele was absent from the Southern Chinese population. CONCLUSION: This largest-ever population study using MRI to define DDD demonstrates for the first time that the Trp2 allele is a significant risk factor for the development and severity of degeneration. The association is age- dependent as it is more prevalent in some age groups than in others. The contrasting Trp allele frequencies between the Finns and the Chinese are the first indication that the genetic risk factors for DDD varies between ethnic groups.

Adolescent↗

The effect of pinealectomy on scoliosis development in young nonhuman primates.

STUDY DESIGN: Prospective study on pinealectomy in primates. OBJECTIVE: To evaluate whether pinealectomy in a bipedal nonhuman primate model will result in the development of scoliosis. SUMMARY OF BACKGROUND DATA: Pinealectomy in newborn chickens consistently resulted in scoliosis development. Published data suggest that the surgical removal of the pineal, loss of melatonin secretion, and a bipedal posture are important elements in the development of scoliosis in lower animal models. METHOD: There were 18 rhesus monkeys between 8 and 11 months old that underwent pineal excision. All monkeys were kept in a regulated 12-hour light-dark cycle. Monthly radiographs assessed scoliosis development. Completeness of pineal excision was assessed by measurement of a major metabolite of melatonin in the urine, 6-sulfatoxymelatonin, using an enzyme-linked immunosorbent assay assessed. RESULTS: Mean follow-up was 28 months (range 10-41). Seven monkeys died prematurely, and 11 survived to date; the data from those that died could still be used, although follow-up was shortened. At the latest follow-up or death, scoliosis did not develop in any of the monkeys. Urinary 6-sulfatoxymelatonin measurements revealed 3 patterns. Group 1 consisted of 10 monkeys, which showed definite evidence of complete pineal excision. Group 2 consisted of an uncertain group of 2 monkeys in which the nighttime melatonin level is slightly high. Group 3 consisted of 6 monkeys that had incomplete pineal excision or ectopic melatonin production. CONCLUSIONS: To our knowledge, this is the first report of pinealectomy in nonhuman primates. Of the 18 monkeys, 10 had a loss of melatonin secretion, for a mean of 29 months after surgery. Because none of the monkeys had scoliosis develop, this study strongly suggests that the possible etiologic factors producing idiopathic scoliosis in lower animals are different from primates, and findings in lower animals cannot necessarily be extrapolated to human beings.

Animals↗

Vertebroplasty by use of a strontium-containing bioactive bone cement.

STUDY DESIGN: A review of the laboratory and clinical data for a new strontium-containing hydroxyapatite bioactive bone cement. OBJECTIVES: To compare the properties of the strontium-containing bioactive bone cement with those of polymethyl methacrylate (PMMA) and hydroxyapatite (HA) bone cements. SUMMARY OF BACKGROUND DATA: Vertebroplasty and kyphoplasty using conventional PMMA bone cements have been effectively used to treat osteoporotic spine fractures with good short- and medium-term results. However, PMMA has some undesirable properties, including its high setting temperature, lack of osseointegration, and large stiffness mismatch with osteoporotic bone. These properties are responsible for some postoperative complications. METHODS: Strontium-containing hydroxyapatite (Sr-HA) bioactive bone cement consists of a filler blend of strontium-containing hydroxyapatite, fumed silica and benzoyl peroxide; and a resin blend of bisphenol A diglycidylether methacrylate, triethylene glycol dimethacrylate, poly(ethylene glycol) methacrylate, and N, N-dimethyl-p-toluidine. Its properties, including mechanical strength, setting temperature, biocompatibility, and osseoinduction, were compared with other cements in vitro and in vivo. Early clinical results are presented. RESULTS: The Sr-HA cement has a setting time of 15 to 18 minutes, a maximum setting temperature of 58 degrees C, a compressive strength of 40.9 MPa, bending strength of 31.3 MPa, and a bending modulus of 1,408 MPa. The bending strength and modulus are closer to human cancellous bone. Sr-HA cement promotes osteoblast attachment and mineralization in vitro and bone growth and osseointegration in vivo. In a pilot study, 23 cases of osteoporotic fractures treated with this cement with a mean follow-up of 18 months suggest that it is as effective as PMMA in relieving pain. DISCUSSIONS: Oral strontium has been shown to induce new bone formation and is effective in reducing fracture risk in osteoporosis. Our data suggest that strontium delivered locally has the same effect; thus, the combination of strontium with HA in a cement with a low setting temperature, adequate stiffness, and low viscosity makes this a good bioactive cement for vertebroplasty and kyphoplasty.

Animals↗

A new operative classification of idiopathic scoliosis: a peking union medical college method.

STUDY DESIGN: A retrospective radiographic study on the type of surgically treated idiopathic scoliosis, with a prospective study on the reliability of the type-related fusion guide. OBJECTIVES: To identify and classify surgically treated idiopathic scoliosis, and define its related fusion levels by a new classification system. SUMMARY OF BACKGROUND DATA: Some classification methods for idiopathic scoliosis have been suggested. However, poor intraobserver reproducibility and interobserver reliability were experienced in these studies, and were not appropriate for guiding surgical planning. METHODS: A total of 427 surgically treated idiopathic scoliosis cases were reviewed. Preoperative and postoperative standing anteroposterior, lateral, and preoperative supine side-bending radiograph were analyzed using the Scoliosis Research Society definition of scoliosis and curve apex. The resulting classification was tested for intraobserver reliability and interobserver reliability, and by 6 surgeons. Apical frequencies were determined for each type, and prospective surgical testing of the new type and its related fusion guide was performed. RESULTS: Three major types and 13 subtypes were identified, of which the Peking Union Medical College type I accounted for 56.62%, type II 42.16%, and type III 1.22%. The interobserver reliability testing was 85% (kappa coefficient 0.832), while intraobserver reproducibility was 91% (kappa coefficient 0.898). Each type had its corresponding fusion levels. A prospective study of 152 cases was performed according to the classification. All of these cases were followed over 18 months, and no postoperative decompensation was noted. CONCLUSION: The Peking Union Medical College classification of idiopathic scoliosis is one system to combine each type with its corresponding fusion level, and it had much higher interobserver reliability and intraobserver reproducibility than the King system. Further prospectivestudies would help to clarify and expand this system.

Adolescent↗

Pure shear properties of lumbar spinal joints and the effect of tissue sectioning on load sharing.

STUDY DESIGN: An in vitro biomechanical study on lumbar intervertebral joints. OBJECTIVES: To examine the mechanical properties of lumbar motion segments under pure shear loading and establish whether a simple model for functional differentiation between the anterior column and the posterior elements is applicable. SUMMARY OF BACKGROUND DATA: Anteroposterior shear has been implicated as a major factor in spinal instability. There is a substantial amount of data on shear motion as a coupled part of flexion-extension; data on the pure shear properties of intervertebral joints is limited. METHODS: Eighteen human cadaver lumbar motion segments were subject to nondestructive testing under pure shear loads (anterior shear and posterior shear). An MTS standard testing machine was used to record the load-deformation characteristics of specimens subject to deformation at a constant rate to a maximum shear load of approximately 250 N. Tissue sectioning was then performed with the specimen mounted in the testing machine. Eight specimens were sectioned through the intervertebral disc, including the anterior and posterior longitudinal ligaments, and 8 specimens were sectioned through the pedicles to remove the posterior elements. The same deformation pattern applied to the intact specimen was then reapplied to the sectioned specimen, and the load-deformation characteristics following sectioning were evaluated. RESULTS: The shear stiffness of the intact segments were found to be higher in anterior shear (mean group A = 583.8, B = 607 N/mm) than in posterior shear (mean group A = 469, B = 438.4 N/mm). Section of the anterior column and adjacent longitudinal ligaments resulted in a mean stiffness decreased by 22.8% of the intact value under anterior shear and 23.9% under posterior shear. Much larger change in shear stiffness was seen, and the mean sectioned stiffness dropped by 77.7% in anterior shear and 79% in posterior shear after removal of the posterior elements. After the anterior column was sectioned, 12% and 18% increases in the deformation for anterior and posterior directions were seen, whereas a distinct increase in the deformations was found after posterior elements sectioned. CONCLUSIONS: The posterior elements of the lumbar spine are more efficient in resisting anterior and posterior shear loads. However, the anterior column will exhibit similar load-displacement characteristics if subject to greater deformations. The sum of the normalized mean shear loads of the anterior column and posterior elements sustained at maximum intact deformation is significantly different from the shear load sustained by the intact spine at the same deformation. A simple concept of load sharing between the anterior column and the posterior elements may not be valid.

Adult↗

A stronger bicortical sacral pedicle screw fixation through the s1 endplate: an in vitro cyclic loading and pull-out force evaluation.

STUDY DESIGN: The insertion torque and pull-out force after cyclic loading of the bicortical sacral pedicle screw through the S1 endplate were tested using human cadaveric specimens. OBJECTIVES: The purpose of this study was to (1) evaluate the effect of cyclic loading on the pull-out force of two different techniques of bicortical sacral pedicle screw fixation and (2) to correlate the pull-out force after cyclic loading with the screw insertion torque. SUMMARY OF BACKGROUND DATA: Biomechanical studies using conventional sacral pedicle screw fixation techniques have demonstrated reduction in stiffness and strength after cyclic loading. Technical difficulties with anterior sacral cortex penetration and frequent screw loosening have been reported in clinical studies. In the authors' center, a new method of sacral pedicle screw fixation bicortically through the S1 endplate has been used successfully in the clinical setting. However, the mechanical stability of this new technique after undergoing cyclic loading has not been documented in the literature. METHODS: Seven-millimeter compact Cotrel-Dubousset sacral screws were randomly assigned by side (left vs. right) and inserted bicortically either anteromedially through the anterior sacral cortex or superiorly through the S1 endplate of 17 fresh frozen human sacrum. The tk;4maximum insertion torque for each screw was measured. Cyclic loading from 40 N to 400 N was applied to each screw at a frequency of 2 Hz for 20,000 cycles. Pull-out tests were conducted after completion of the cyclic tests. RESULTS: The mean maximum insertion torque and mean pull-out force following cyclic loading were significantly higher for bicortical fixation through the S1 endplate (mean 3.17 N.m and 1457 N) than bicortical fixation through the anterior sacral cortex (mean 1.98 N.m and 1122 N). Both S1 endplate and anterior cortical fixation techniques demonstrated significant correlations between insertion torque and pull-out force following cyclic loading. CONCLUSIONS: In sacral pedicle screw fixation, screw trajectory through the S1 endplate was significantly stronger than screws penetrating the anterior sacral cortex. Insertion torque was a good intraoperative indicator of screw pull-out force after cyclic loading.

Adult↗

Adaptive signal enhancement of somatosensory evoked potential for spinal cord compression detection: an experimental study.

The objective of this study was to assess the efficacy of adaptive signal enhancement (ASE) as a means of indicating intraoperative spinal cord impingement. ASE technique was used to determine the changes in the somatosensory evoked potential (SEP) elicited from eighteen rats with varying levels of spinal cord compression. ASE technique was found to be able to effectively extract SEP signals for the detection of spinal cord injury. Furthermore, while the traditional ensemble averaging (EA) technique requires more than 500 trials for meaningful signal processing in severe noisy SEP recordings, the ASE method required only 50 trials to provide similar information. Because of its fast and reliable SEP detection, the ASE method is ideal for spinal cord monitoring in the clinical setting.

Algorithms↗

Multi-adaptive filtering technique for surface somatosensory evoked potentials processing.

Somatosensory evoked potential (SEP) testing has been widely applied to diagnosis of various neurological disorders. However, SEP recorded using surface electrodes is buried in noises, which makes the signal-to-noise ratio (SNR) very poor. Conventional averaging method usually requires up to thousands of raw SEP input trials to increase the SNR so that an identifiable waveform can be produced for latency and amplitude measurement. In this study, a multi-adaptive filtering (MAF) technique, emerging from the combination of well-developed adaptive noise canceller and adaptive signal enhancer, is introduced for fast and accurate surface SEP extraction. The MAF technique first processes the raw surface recorded SEP by the Canceller with a reference noise channel of background noise for adaptive subtraction before entering the Enhancer. The MAF was verified by filtering simulated SEP signals in which electroencephalography and Gaussian noise of different SNRs were added. It was found that the MAF could effectively suppress the noise and enhance the SEP components such that the SNR of the SEP is improved. Results showed that MAF with 50 input trials could provide similar performance in SEP detection to those extracted by the conventional averaging method with 1000 trials even at an SNR of -20 dB.

Algorithms↗

Combination of adeno-associated virus and adenovirus vectors expressing bone morphogenetic protein-2 produces enhanced osteogenic activity in immunocompetent rats.

We have previously shown that gene therapy using adeno-associated virus (AAV) carrying bone morphogenetic proteins (BMPs) is a promising strategy for new bone formation in vivo in SD rats. However, it had a relatively low transduction efficiency. We investigate here whether enhanced osteogenic activity can be achieved without eliciting a severe immune response, using a cocktail of AAV-BMP2 and adenovirus (Ad)-BMP2 as a vector system. The muscles of SD rats were injected with either AAV-BMP2, Ad-BMP2, or an AAV-BMP2/Ad-BMP2 cocktail, and the in vivo bone formation was determined at eight weeks post-injection. Radiographic examination demonstrated that the addition of a low level of Ad-BMP2 to AAV-BMP2 produced significantly higher new bone formation than the use of AAV-BMP2 alone. Histological and immunohistological analysis revealed an enlarged bone-forming area and a long-term BMP2 expression, without pronounced infiltration of lymphocytes. Our results provide the first evidence that the introduction of a low level of adenovirus in vivo in immunocompetent subjects can greatly enhance AAV-mediated gene transfer, without inducing severe immune responses. This cocktail vector system may offer an attractive way of improving the efficiency of AAV-based gene delivery.

Adenoviridae↗