Hypersensitivity of trunk biomechanical model predictions to errors in image-based kinematics when using fully displacement-control techniques.

Recent advances in medical imaging techniques have allowed pure displacement-control trunk models to estimate spinal loads with no need to calculate muscle forces. Sensitivity of these models to the errors in post-imaging evaluation of displacements (reported to be ∼0.4-0.9° and 0.2-0.3 mm in vertebral displacements) has not yet been investigated. A Monte Carlo analysis was therefore used to assess the sensitivity of results in both musculoskeletal (MS) and passive finite element (FE) spine models to errors in measured displacements. Six static activities in upright standing, flexed, and extended postures were initially simulated using a force-control hybrid MS-FE model. Computed vertebral displacements were subsequently used to drive two distinct fully displacement-control MS and FE models. Effects of alterations in the reference vertebral displacements (at 3 error levels with SD (standard deviation) = 0.1, 0.2, and 0.3 mm in input translations together with, respectively, 0.2, 0.4, and 0.6° in input rotations) were investigated on the model predictions. Results indicated that outputs of both models had substantial task-dependent sensitivities to errors in the measured vertebral translations. For instance, L5-S1 intradiscal pressures (IDPs) were considerably affected (SD values reaching 1.05 MPa) and axial compression and shear forces even reversed directions as translation errors increased to 0.3 mm. Outputs were however generally much less sensitive to errors in measured vertebral rotations. Accounting for the accuracies in image-based kinematics measurements, therefore, it is concluded that the current measured vertebral translation errors at and beyond 0.1 mm are too large to drive biomechanical models of the spine.

Effects of eight different ligament property datasets on biomechanics of a lumbar L4-L5 finite element model.

Ligaments assist trunk muscles in balancing external moments and providing spinal stability. In absence of the personalized material properties for ligaments, finite element (FE) models use dispersed data from the literature. This study aims to investigate the relative effects of eight different ligament property datasets on FE model responses. Eight L4-L5 models distinct only in ligament properties were constructed and loaded under moment (15Nm) alone or combined with a compressive follower load (FL). Range of motions (RoM) of the disc-alone model matched well in vitro data. Ligament properties significantly affected only sagittal RoMs (∼3.0-7.1° in flexion and ∼3.8-5.8° in extension at 10Nm). Sequential removal of ligaments shifted sagittal RoMs in and out of the corresponding in vitro ranges. When moment was combined with FL, center of rotation matched in vivo data for all models (3.8±0.9mm and 4.3±1.8mm posterior to the disc center in flexion and extension, respectively). Under 15Nm sagittal moments, ligament strains were often smaller or within the in vitro range in flexion whereas some posterior ligament forces approached their failure forces in some models. Ligament forces varied substantially within the models and affected the moment-sharing and internal forces on the disc and facet joints. Intradiscal pressure (IDP) had the greatest variation between models in extension. None of the datasets yielded results in agreement with all reported measurements. Results emphasized the important role of ligaments especially under larger moments and the need for their accurate representation in search for valid spinal models.

Subject-specific 2D/3D image registration and kinematics-driven musculoskeletal model of the spine.

An essential input to the musculoskeletal (MS) trunk models that estimate muscle and spine forces is kinematics of the thorax, pelvis, and lumbar vertebrae. While thorax and pelvis kinematics are usually measured via skin motion capture devices (with inherent errors on the proper identification of the underlying bony landmarks and the relative skin-sensor-bone movements), those of the intervening lumbar vertebrae are commonly approximated at fixed proportions based on the thorax-pelvis kinematics. This study proposes an image-based kinematics measurement approach to drive subject-specific (musculature, geometry, mass, and center of masses) MS models. Kinematics of the thorax, pelvis, and individual lumbar vertebrae as well as disc inclinations, gravity loading, and musculature were all measured via different imaging techniques. The model estimated muscle and lumbar forces in various upright and flexed postures in which kinematics were obtained using upright fluoroscopy via 2D/3D image registration. Predictions of this novel image-kinematics-driven model (Img-KD) were compared with those of the traditional kinematics-driven (T-KD) model in which individual lumbar vertebral rotations were assumed based on thorax-pelvis orientations. Results indicated that while differences between Img-KD and T-KD models remained small for the force in the global muscles (attached to the thoracic cage) (<15%), L4-S1 compression (<15%), and shear (<20%) forces in average for all the simulated tasks, they were relatively larger for the force in the local muscles (attached to the lumbar vertebrae). Assuming that the skin-based measurements of thorax and pelvis kinematics are accurate enough, the T-KD model predictions of spinal forces remain reliable.

The influence of new reciprocating link medial linkage orthosis on walking and independence in a spinal cord injury patient.

OBJECTIVES: The purpose of this paper is to describe the development and evaluation of a new medial linkage reciprocating gait orthosis (MLRGO) that incorporates a reciprocal mechanism and is sensitive to pelvic motion to potentially assist paraplegic patients to walk and provide functional independence. CASE DESCRIPTION AND METHODS: The new orthosis was constructed and tested by a 20-year-old female paraplegic subject with transverse myelitis at T10 level, who was 4 years post injury and had also been an isocentric reciprocating gait orthosis (IRGO) user for 2 years. She received gait training for 12 weeks before undertaking gait analysis, and also completed a questionnaire that was designed to assess the perceived functionality of the new MLRGO when compared with an IRGO. RESULTS: The results demonstrated improvements in gait velocity, step length and cadence, and also improvement in functional independence with the new orthosis compared with an IRGO. CONCLUSION: The results demonstrated that this new MLRGO could be used for paraplegic patients who would like an improvement in functional independence and ambulation.

Design and analysis of a new medial reciprocal linkage using a lower limb paralysis simulator.

STUDY DESIGN: A feasibility study on the effect of a new reciprocating orthosis on specific gait parameters for use by people with spinal cord injury. OBJECTIVES: The aim of this study was to design and develop a new medial linkage orthosis (MLO) mechanism incorporating a reciprocating motion and to determine its efficacy in improving specific spatiotemporal, kinematic and kinetic parameters while ambulating when worn by healthy subjects. This was achieved via the use of a lower limb paralysis simulator (LLPS). METHODS: A reciprocating joint with a remote center of motion was designed for use as an MLO. A prototype was fabricated and incorporated into an orthosis and equipped with a saddle to make the reciprocating motion possible. The efficacy of the orthosis was evaluated on four able-bodied healthy subjects who were trained to walk with the MLO attached to the LLPS. RESULTS: Mean walking speed, stride length, stride time and cadence was 0.09±0.007 m s(-1), 0.42±0.01 m, 4.89±0.45 s and 29.54±4.32 steps min(-1), respectively, when healthy subjects walked with the new orthosis. The mean hip joint torque produced was 0.36±0.13 Nm. CONCLUSION: In this study a new MLO was designed and fabricated that provided a reciprocating mechanism using a four-bar mechanism to set the virtual axis of the mechanism in a more proximal position than hinge-type joints. Further investigation is currently underway to assess its effect on gait parameters and energy expenditure in paraplegic patients.

Comparison of new medial linkage reciprocating gait orthosis and isocentric reciprocating gait orthosis on energy consumption in paraplegic patients: a case series.

OBJECTIVES: As energy consumption during orthotics walking has main role in rehabilitation of walking in individuals with spinal cord injury (SCI), the aim of this study was comparison between new medial linkage orthosis (new MLO) and isocentric reciprocating gait orthosis (IRGO) on energy consumption in paraplegic patients. METHODS: Four people with motor incomplete SCI (mean age 34.5 years, mass 73 kg and height 175 cm with injury levels ranging from T8-T12) participated in this study. Gait evaluation was performed using new MLO compared with using conventional IRGO. Walking speed and heart rate were measured to calculate the physiological cost index (PCI) to estimate metabolic energy consumption. RESULTS: Reductions in energy consumption were observed using new MLO compared with using IRGO, but the difference was not statistically significant. However, walking distance and walking speed also improved, but not significantly. CONCLUSION: All subjects had faster speeds of walking, walked longer distances and had lower PCI when using new MLO compared to walking with IRGO. Consequently, this orthosis should be examined and considered with larger sample size.

A novel stability and kinematics-driven trunk biomechanical model to estimate muscle and spinal forces.

An anatomically detailed eighteen-rotational-degrees-of-freedom model of the human spine using optimization constrained to equilibrium and stability requirements is developed and used to simulate several symmetric tasks in upright and flexed standing postures. Predictions of this stability and kinematics-driven (S+KD) model for trunk muscle forces and spine compressive/shear loads are compared to those of our existing kinematics-driven (KD) model where both translational and rotational degrees-of-freedom are included but redundancy is resolved using equilibrium conditions alone. Unlike the KD model, the S+KD model predicted abdominal co-contractions that, in agreement with electromyography data, increased as lifting height increased at a constant horizontal moment arm. The S+KD model, however, could not fully explain the CNS strategy in activating antagonistic muscles for most of the remaining tasks. Despite quite distinct activities in individual muscles, both models predicted L4-L5 intradiscal pressure that matched the in vivo data, the L4-S1 compression loads, and the sum of all trunk muscle forces. For modeling applications in ergonomics, where the compressive spine loads are of interest, the two models yielded <15% difference. In the field of rehabilitation, where detailed muscle forces are required, the S+KD model explained more properly the CNS strategy in activating the antagonistic muscles for some tasks.

The impingement-dislocation risk of total hip replacement: effects of cup orientation and patient maneuvers.

Hip dislocation is one of the most frequent complications after total hip arthroplasty. Impingement and dislocation might be caused due to misalignment of the acetabular cup during surgery, or performing dislocation-prone activities afterwards. A finite element model was developed to predict the impingement and dislocation behavior of the prosthetic joint, for different combinations of cup orientation and patient maneuver. Four dislocation-prone activities of daily life and 25 cup orientations were analyzed to determine how close they are to the impingement and subsequent dislocation events. The angular margin results obtained indicated that the sit-to-stand and standing while bending at the waist are prone to dislocation, in particular when the cup anteversion angle is small.

NOD2 sequencing in Iranian children with Crohn's disease.

Crohn's disease (CD) is a chronic inflammatory disease of the gastrointestinal tract. Although the exact etiology of disease is still unknown, mutations in the CARD15/NOD2 gene have been reported in association with CD in several studies. This study was performed to determine whether the CARD15/NOD2 gene confers susceptibility to Iranian pediatric patients with CD. All 12 coding exons of the CARD15/NOD2 gene were sequenced in 16 enrolled pediatric onset CD patients. Sequencing of the CARD15/NOD2 gene showed no mutation. However, two patients harbored polymorphisms within this gene. A heterozygous single nucleotide polymorphism rs3135500 C > Y in the exon 12.3 was detected in a 10-year-old girl with mild severity of CD and history of rectovaginal and perianal fistula, and multiple skin tags. The other 5-year-old boy with moderate to severe CD and a history of perianal fissures and oral candidiasis harbored heterozygous single nucleotide polymorphisms in exons 4.1 and 12.1. The results of the present study show that the CARD15/NOD2 mutations in Iranian patients with pediatric onset CD are not responsible for the pathogenesis of disease.

Response to induction therapy in a pediatric population of inflammatory bowel disease.

Crohn's disease (CD) and ulcerative colitis (UC) are two inflammatory bowel diseases (IBD) characterized by chronic intestinal inflammation. In this study, the clinical characteristics of a cohort of pediatric patients with IBD are reviewed and their responses to induction therapy are evaluated. The severity of disease for 43 patients (20 with CD and 23 with UC) was determined using the PCDAI and PUCAI and based on the initial severity, before treatment was started. Following treatment, the severity of disease was re-evaluated at 6 months after the initial diagnosis. The patients in both groups had mild-to-severe disease. The mean PCDAI and PUCAI values were 60.62 +/- 16.48 and 50.95 +/- 9.35, for CD and UC patients, respectively. Most patients (83.7 %) responded to standard treatments with a significant reduction in the PCDAI and PUCAI scores from baseline (p value < 0.001). At the primary endpoint of 24 weeks, 54 % of all patients were in clinical remission; 16 of 23 in the UC group (70 %) and 6 of 20 in the CD group (30 %). The results of this study provide evidence that subgrouping pediatric patients with IBD into distinct clinical phenotypes based on severity of the initial presentation may provide better means of management of this group. This approach can result in a better response to treatment and reduce the side effects of unnecessary therapy.

The effect of pectin on swelling and permeability characteristics of free films containing Eudragit RL and/or RS as a coating formulation aimed for colonic drug delivery.

BACKGROUND AND THE PURPOSE OF THE STUDY: The potential of pectin as a bacterially degradable polysaccharide for colon drug delivery has been demonstrated. Due to the high solubility and swelling properties of pectin in aqueous media, it is frequently used in combination with water insoluble polymers for targeting drugs to the colon. The aim of this study was to evaluate free films containing pectin as a bacterially-degradable polysaccharide in combination with Eudragit RL (ERL) and/or RS (ERS) as a coating formulation for colonic drug delivery. METHODS: Isolated free films comprising 20% pectin and 80% ERL or ERS and their combination in 1:1 ratio were prepared by casting method. Then, free films were evaluated by water vapor transmission (WVT), swelling and permeability experiments for theophylline and indomethacin in different media. RESULTS: Formulations containing ERL exhibited higher WVT, swelling and permeability compared with formulations containing ERS. The permeability of theophylline through free films composed of pectin and eudragit polymers in simulated colonic media was not significantly different from those obtained in other media. However indomethacin free films containing pectin and ERL showed higher permeation in simulated colonic fluid (SCF) compared to the other media. MAJOR CONCLUSION: Formulation containing pectin and ERL may be suitable as a coating formulation for colon targeted delivery of drugs of low solubility such as indomethacin.

Design and development of a hand robotic rehabilitation device for post stroke patients.

Robot-mediated rehabilitation is a rapidly advancing discipline that seeks to develop improved treatment procedures using new technologies, e.g., robotics, coupled with modern theories in neuroscience and rehabilitation. A robotic device was designed and developed for rehabilitation of upper limbs of post stroke patients. A novel force feedback bimanual working mode provided real-time dynamic sensation of the paretic hand. Results of the preliminary clinical tests revealed a quantitative evaluation of the patient's level of paresis and disability.

Design and implementation of series elastic actuators for a haptic laparoscopic device.

The design of a laparoscopic haptic device based on a 4-DOFs mechanism and Series Elastic Actuators (SEA) is described and the results of the theoretical and experimental examinations are presented. With a sufficient bandwidth and low impedance, the system provided a stable interaction with soft tissues, e.g., human liver, in virtual environments.

Design and evaluation of a novel triaxial isometric trunk muscle strength measurement system.

Maximal strength measurements of the trunk have been used to evaluate the maximum functional capacity of muscles and the potential mechanical overload or overuse of the lumbar spine tissues in order to estimate the risk of developing musculoskeletal injuries. A new triaxial isometric trunk strength measurement system was designed and developed in the present study, and its reliability and performance was investigated. The system consisted of three main revolute joints, equipped with torque sensors, which intersect at L5-S1 and adjustment facilities to fit the body anthropometry and to accommodate both symmetric and asymmetric postures in both seated and standing positions. The dynamics of the system was formulated to resolve validly the moment generated by trunk muscles in the three anatomic planes. The optimal gain and offset of the system were obtained using deadweights based on the least-squares linear regression analysis. The R2 results of calibration for all loading courses of all joints were higher than 0.99, which indicated an excellent linear correlation. The results of the validation analysis of the regression model suggested that the mean absolute error and the r.m.s. error were less than 2 per cent of the applied load. The maximum value of the minimum detectable change was found to be 1.63 Nm for the sagittal plane torque measurement, 0.8 per cent of the full-scale load. The trial-to-trial variability analysis of the device using deadweights provided intra-class correlation coefficients of higher than 0.99, suggesting excellent reliability. The cross-talk analysis of the device indicated maximum cross-talks of 1.7 per cent and 3.4 per cent when the system was subjected to flexion-extension and lateral bending torques respectively. The trial-to-trial variability of the system during in-vivo strength measurement tests resulted in good to excellent reliability, with intra-class correlation coefficients ranging from 0.69 to 0.91. The results of the maximum voluntary isometric torques exertion measurements for 30 subjects indicated good agreement with the previously published data in the literature. The extensive capabilities and high reliability of the system are promising for more comprehensive investigations on the trunk biomechanics in future, e.g. isometric strength measurement at symmetric and asymmetric postures, muscle endurance, and recruitment pattern analysis.

Cyproheptadine for the treatment of functional abdominal pain in childhood: a double-blinded randomized placebo-controlled trial.

AIM: The management of functional abdominal pain (FAP) in children and adolescents is challenging for health care professionals, and there are only limited or inconclusive studies of pharmacologic or behavioral therapy in childhood FAP. The objective of this randomized placebo-controlled clinical trial was to determine the potential efficacy and safety of cyproheptadine in the treatment of pediatric FAP. METHODS: Between January 2006 and March 2007, 29 clinically referred children and adolescents with FAP (aged 4.5 to 12 years) completed a 2-week, double-blinded randomized placebo-controlled trial of cyprohetadine. Primary outcome measure was the self-reported change of frequency and duration of abdominal pain by using a 6-point scale, and the parents' impression or assessment of the children's improvement. RESULTS: By week 1 and 2 of the intervention, the intensity and frequency of abdominal pain among the patients treated with cyproheptadine, were rated as complete resolved and very much improved or improved for 3 (20%), 10 (66.6%), respectively. However, in the placebo-receiver children, these scales had no change in 7 (50%), rated as improved or very much improved in 5 (35.7%), and become worse in 2 (14.3%). The patients' self-reported and the parents' impression in the cyproheptadine group were significantly better than it in the placebo group (P=0.003). CONCLUSION: Among children with functional abdominal pain, cyproheptadine is enough effective to improve the intensity and frequency of abdominal pain in a short-term period.

The effects of trochlear groove geometry on patellofemoral joint stability--a computer model study.

The effect of the variation in the femoral groove geometry on patellofemoral joint stability was studied using a two-dimensional transverse plane model with deformable articular surfaces. The femoral and patellar bony structures were modelled as rigid bodies with their profiles expressed by splines. The articular cartilage was discretized into compression springs, distributed along the femoral and patellar profiles, based on the rigid-body spring model. The medial and lateral retinacula were modelled as linear tensile springs, and the quadriceps muscles and patellar tendon as strings with known tension. The anatomical data were obtained from the transverse plane magnetic resonance images of a normal knee flexed at 20 degrees and from the literature. A dynamic analysis approach was employed to solve the governing equations of the model, i.e. three static equilibrium equations of the patella and a constraint equation for each cartilage spring, explicitly. The results of the model suggest that alteration of the sulcus angle from 139 degrees to 169 degrees causes a lateral shift and tilt of less than 3 mm and 4 degrees. This effect increased slightly with increasing total quadriceps force, however, to significantly more than 7 mm and 18 degrees respectively when the medial retinaculum was released. It was suggested that this might be the combined effect of the medial retinaculum deficiency and trochlear dysplasia that is responsible for patellar subluxation and, particularly, dislocation disorders.

A new approach to C2 continuous piecewise bicubic representation of the articular surfaces of diarthrodial joints.

Based on the force-deflection equation for a beam subjected to lateral point loads, a C2 continuous piecewise bicubic mathematical representation was proposed to model complicated geometrical surfaces, e.g. the articular surfaces of human joints. The method was then extended so that it could be used for mathematical modelling of incomplete nets of data points, as well as smoothing of noisy and/or filtering of erroneous data points. Mathematical techniques were also developed to calculate the required unknown parameters explicitly, with no need to solve the system of equations simultaneously. The performance of the proposed method was evaluated on a number of surface modelling problems, including two known analytical surfaces and the human femoral and patellar articular surfaces. The results indicate that the proposed method is precise, flexible, and easy to apply and has several advantages over the conventional smoothing methods, i.e. the B-spline approach.

Permeability and swelling studies on free films containing inulin in combination with different polymethacrylates aimed for colonic drug delivery.

The aim of this study was to assess some permeability and swelling characteristics of free films prepared by combination of inulin as a bacterially degradable system and time- or pH-dependent polymers as a coating formulation for colonic drug delivery. Different free films were prepared by casting and solvent evaporation method. Formulations containing inulin with Eudragit RS, Eudragit RL, Eudragit RS-Eudragit RL, Eudragit FS and Eudragit RS-Eudragit S with different ratios of inulin were prepared. After preparation, free films were evaluated by water vapor transmission test, swelling experiment and permeability to indomethacin and theophylline in different media. Formulations containing Eudragit FS had high resistance to water vapor permeation; but were unable to protect premature swelling and drug release in simulated small intestine media. Also, combination of Eudragit RS and Eudragit S had no suitable characteristics for colon delivery. However, Eudragit RS and Eudragit RL in combination with inulin made free films which had more swelling and permeation of drug in the colonic medium rather than the other media. It was shown that formulations containing sustained release polymethacrylates in combination with inulin have more potential as a coating system for specific colon delivery compared with pH-dependent polymers.

Heart sounds separation from lung sounds using independent component analysis.

Heart beat is an unavoidable source of interference during lung sound recording. This disturbance is more significant at low and medium breathing flow rates. Removing heart sounds (HS) from lung sound recordings or vice versa is a challenging task but of great interest for respiratory specialists and cardiologists. In this study, to separate the two signals, a novel HS separation method based on Independent Component Analysis (ICA) is developed. This method applies an ICA algorithm to the spectrograms of two simultaneous lung sound recordings obtained at two different locations on the chest and yields the independent spectrograms of the separated signals. Then, by implementing the Inverse Short Time Fourier Transform (ISTFT), the separated signals are reconstructed in the time domain. The method was applied to data of two healthy subjects. Analysis of the results as well as subjective inspections indicate the efficiency of the proposed method in terms of HS separation from lung sounds.

Antioxidant enzyme gene expression in congestive heart failure following myocardial infarction.

Increased oxidative stress and reduction in antioxidant enzymes have been suggested to be involved in the pathophysiology of congestive heart failure subsequent to myocardial infarction (MI). The objective of the present study was to characterize changes in the mRNA abundance and protein levels for the enzymatic antioxidants, superoxide dismutase (SOD), glutathione peroxidase (GSHPx) and catalase during the sequelae of congestive heart failure in rats. MI was produced by the ligation of the left coronary artery and hearts from controls and 1, 4 and 16 week PMI groups were analyzed. Losartan treatment (2 mg/ml in drinking water, daily) was started at 4 weeks and continued for 12 weeks. The mRNA levels for SOD were reduced by about 40% at 1-week PMI, were near to the control levels at 4-week PMI and at 16 weeks PMI, the levels were reduced by about 73% below the controls. GSHPx mRNA levels remained unchanged at all time points. The mRNA levels for catalase remained unchanged at 1 and 4 weeks PMI and were significantly reduced by about 44% at 16 weeks PMI as compared to the controls. The protein levels for MnSOD, CuZnSOD, GSHPx at 1 and 16 weeks remained unchanged in treated and untreated PMI groups. However, the protein levels for catalase was significantly increased in the control and PMI groups treated with Losartan. It is concluded that changes in the SOD and catalase activities during severe heart failure correlated with changes in mRNA for these enzymes. The precise mechanism/s for the improvement in antioxidant reserve and protein levels after Losartan treatment is/are unclear at this time.