Quantification of push-off and collision work during step-to-step transition in amputees walking at self-selected speed: Effect of amputation level.

Maintaining forward walking during human locomotion requires mechanical joint work, mainly provided by the ankle-foot in non-amputees. In lower-limb amputees, their metabolic overconsumption is generally attributed to reduced propulsion. However, it remains unclear how altered walking patterns resulting from amputation affect energy exchange. The purpose of this retrospective study was to investigate the impact of self-selected walking speed (SSWS) on mechanical works generated by the ankle-foot and by the entire lower limbs depending on the level of amputation. 155 participants, including 47 non-amputees (NAs), 40 unilateral transtibial amputees (TTs) and 68 unilateral transfemoral amputees (TFs), walked at their SSWS. Positive push-off work done by the trailing limb (WStS+) and its associated ankle-foot (Wankle-foot+), as well as negative collision work done by the leading limb (WStS-) were analysed during the transition from prosthetic limb to contralateral limb. An ANCOVA was performed to assess the effect of amputation level on mechanical works, while controlling for SSWS effect. After adjusting for SSWS, NAs produce more push-off work with both their biological ankle-foot and trailing limb than amputees do on prosthetic side. Using the same type of prosthetic feet, TTs and TFs can generate the same amount of prosthetic Wankle-foot+, while prosthetic WStS+ is significantly higher for TTs and remains constant with SSWS for TFs. Surprisingly and contrary to theoretical expectations, the lack of propulsion at TFs' prosthetic limb did not affect their contralateral WStS-, for which a difference is significant only between NAs and TTs. Further studies should investigate the relationship between the TFs' inability to increase prosthetic limb push-off work and metabolic expenditure.

A High-throughput Screening of a Chemical Compound Library in Ovarian Cancer Stem Cells.

BACKGROUND: Epithelial ovarian cancer has a poor prognosis, mostly due to its late diagnosis and the development of drug resistance after a first platinum-based regimen. The presence of a specific population of "cancer stem cells" could be responsible of the relapse of the tumor and the development of resistance to therapy. For this reason, it would be important to specifically target this subpopulation of tumor cells in order to increase the response to therapy. METHOD: We screened a chemical compound library assembled during the COST CM1106 action to search for compound classes active in targeting ovarian stem cells. We here report the results of the high-throughput screening assay in two ovarian cancer stem cells and the differentiated cells derived from them. RESULTS AND CONCLUSION: Interestingly, there were compounds active only on stem cells, only on differentiated cells, and compounds active on both cell populations. Even if these data need to be validated in ad hoc dose response cytotoxic experiments, the ongoing analysis of the compound structures will open up to mechanistic drug studies to select compounds able to improve the prognosis of ovarian cancer patients.

Phantom hand and wrist movements in upper limb amputees are slow but naturally controlled movements.

After limb amputation, patients often wake up with a vivid perception of the presence of the missing limb, called "phantom limb". Phantom limbs have mostly been studied with respect to pain sensation. But patients can experience many other phantom sensations, including voluntary movements. The goal of the present study was to quantify phantom movement kinematics and relate these to intact limb kinematics and to the time elapsed since amputation. Six upper arm and two forearm amputees with various delays since amputation (6months to 32years) performed phantom finger, hand and wrist movements at self-chosen comfortable velocities. The kinematics of the phantom movements was indirectly obtained via the intact limb that synchronously mimicked the phantom limb movements, using a Cyberglove® for measuring finger movements and an inertial measurement unit for wrist movements. Results show that the execution of phantom movements is perceived as "natural" but effortful. The types of phantom movements that can be performed are variable between the patients but they could all perform thumb flexion/extension and global hand opening/closure. Finger extension movements appeared to be 24% faster than finger flexion movements. Neither the number of types of phantom movements that can be executed nor the kinematic characteristics were related to the elapsed time since amputation, highlighting the persistence of post-amputation neural adaptation. We hypothesize that the perceived slowness of phantom movements is related to altered proprioceptive feedback that cannot be recalibrated by lack of visual feedback during phantom movement execution.

Compensatory mechanism involving the hip joint of the intact limb during gait in unilateral trans-tibial amputees.

Hip dynamics in the intact limb during the beginning of stance phase in unilateral trans-tibial amputees (TTA) was studied to evaluate its contribution to compensatory function. We hypothesized (1) an increase in hip total work during H1 power phase (0-30% of gait cycle) including an initial negative phase and (2) an intensification of the hip work in response to uncomfortable gait induced by prosthesis misalignment. Three-dimensional gait analysis was conducted in 17 unilateral TTA and 15 healthy subjects walking at the same self-selected speed in three prosthetic alignments: initial alignment (IA); IA altered either by 6 degrees of internal rotation (IR) or by 6 degrees of external rotation. Patients reported best comfort of gait in IA condition and discomfort mainly in IR condition. During the H1 power phase, in intact limbs a consistent initial flexion movement of the hip (0-8% gait cycle) was associated to negative work and was followed by hip extension and positive work whereas in both prosthetic and control limbs only hip extension and positive work occurred (except in one healthy individual). Absolute value of hip work during H1 phase was significantly higher in intact and prosthetic limbs compared to control limbs in IA condition and was further significantly increased in IR condition only in intact limbs demonstrating a compensatory function of the latter. In intact limbs, early hip negative work contributed to energy absorption in addition to the knee joint probably to compensate the lower energy absorption exerted by the prosthetic limbs.

[Muscles of the below-knee amputees]. / Les muscles de l'amputé tibial.

OBJECTIVE: The objective of this article is to review anatomical, histological and physiological muscle changes following below-knee amputation. MATERIALS AND METHODS: We searched the PubMed and Reedoc databases for studies evaluating modifications of the below-knee stump and changes over time in its anatomy, volume and histology. We also looked at postamputation modifications in gait and balance. RESULTS: Below-knee amputees show muscular atrophy on both the amputated side and nonamputated side, with fewer and smaller muscle fibres (particularly slow-twitch fibres). This amyotrophy varies in magnitude and distribution and can reach about 25% for the quadriceps (predominantly on the medial side), but is nonsignificant for the hamstrings. This amyotrophy results from the anatomical consequences of the surgical act. The loss of one or more of a muscle's insertions or reimplantation into a nonphysiological site prompts greater atrophy. Changes in muscle activation patterns also lead to atrophy. The hamstrings replace the triceps as the main muscles for propulsion and the remaining stump muscles contract so as to ensure a good fit with the prosthesis. The below-knee amputee must adapt to a new muscular state: gait symmetry is altered, energy expenditure for walking is higher and training is needed in order to achieve optimal balance control.

Compensatory mechanism involving the knee joint of the intact limb during gait in unilateral below-knee amputees.

This study evaluated the asymmetry of knee kinetics during uncomfortable gait induced by prosthesis misalignment to further demonstrate the compensatory function of the knee joint of the intact limb during gait. Three-dimensional gait analysis including knee kinematics and kinetics at the beginning of stance phase was conducted in 15 healthy subjects and 17 unilateral trans-tibial amputees (TTA) walking at self-selected speed in three conditions of prosthetic alignment: initial alignment (IA); initial alignment altered either by 6 degrees of internal rotation (IR) or by 6 degrees of external rotation (ER) applied on the pylon. Patients reported best comfort of gait in IA condition and discomfort mainly in IR condition. Maximum knee flexion and knee total work at power phases K0-K2 were significantly higher in intact limbs compared to prosthetic and control limbs. In intact limbs, these variables had significantly higher values (+10-35%, p<0.05) in IR condition than IA condition whereas these were not altered across conditions in prosthetic limbs. In trans-tibial amputees, inducing uncomfortable gait by internally rotating the prosthetic foot did not alter the knee kinetics of the prosthetic limb, which suggests a protective mechanism. Knee kinetics of the intact limb did alter, which suggests a compensatory mechanism.

[Exercise training for lower limb amputees]. / Le réentraînement à l'effort chez l'amputé de membre inférieur.

Lower limb amputee have lower exercise capacities, proportionally to the delay necessary to use their well-fitted prosthesis. Exercise training is a valid therapeutic to improve local factors (residual limb), muscle strength and endurance, locomotor performance and to decrease the cardiovascular risk factors. The programs for exercise training used for amputees are derivate from the vascular diseases and adapted (upper limb ergometer, cycloergometer with intact limb, pharmacological stress). Exercise training must be personalised because the population with lower limb amputation is very heterogeneous for deficiency and capacity (orthopaedic, vascular and cardiac) and for their socioprofessional project.

[Capacity and performance: ambulatory monitoring under controlled and real-life conditions]. / Evaluation des capacités et des performances: contribution des monitorages de la locomotion en situation d'exercice et de vie réelle.

OBJECTIVES: To determine the value of ambulatory monitoring in assessing human gait. To describe the sensors, the parameters and the ambulatory devices. MATERIALS AND METHODS: Literature review and practical experience about techniques, principles, objectives and limits. RESULTS: Accelerometry is the main technique for ambulatory monitoring because of its reliability, pertinence of signals and software developed for interpretation. Simultaneous monitoring of heart rate response is clinically relevant. Pedometers and actimeters can answer precise clinical questions about amount of walking activity. CONCLUSION: Ambulatory monitoring during long periods (one day or more) is important, especially for rehabilitation medicine because it measures the actual patient activity performed and participation. The simultaneous monitoring of environmental conditions of activity should improve the interpretation of the data collected.

[Optoelectronic gait analysis after metatarsophalangeal arthrodesis of the hallux: fifteen cases]. / Analyse opto-électronique de la marche après arthrodèse métatarso-phalangienne de l'hallux: à propos de 15 cas.

PURPOSE OF THE STUDY: Degeneration of the metatarsophalangeal joint of the hallux is a frequent secondary lesion of the first ray subsequent to hallux valgus. Different surgical techniques have been proposed for cure, including metatarsophalangeal arthrodesis. Joint fusion relieves pain but sacrifices joint motion. The purpose of this work was to assess changes observed in gait after metatarsophalangeal arthrodesis of the hallux using a three-dimensional optoelectronic system. MATERIAL AND METHODS: Gait analysis was performed with a Vicon 3D system with five cameras and two AMTI force platforms in twelve patients who had undergone metatarsophalangeal arthrodesis more than six months earlier. The kinetic and kinematic curves and ground reaction forces were analyzed. Changes in the gait cycle and any compensations observed in the talocrural and interphalangeal joints were noted in the three dimensions. Wilcoxon test for paired series was applied for the statistical analysis. RESULTS: The general gait parameters and kinetic and kinematic values were not modified (excepting a non-significant decline in maximal dorsiflexion of the ankle joint). There was a significant decrease in propulsion force in the anteroposterior and vertical planes, with significantly later heal lift-off and systematic displacement of ground reaction forces anterior to the metatarsophalangeal joint on the arthrodesis side. Reflectors positioned on the distal extremity of the hallux demonstrated that the essential part of compensation occurred at the level of the interphalangeal joint. DISCUSSION: Gait analysis after tibiotalar arthrodesis has been widely reported in the literature. The consequence of joint fusion on the rear foot and/or the torsion couple have also been studied. However, to our knowledge, there has been only one report using a different methodology devoted to metatarsophalaneal arthrodesis of the hallux. In this study, only step length and interphalangeal moment as well as ankle force were found to be decreased. Function of the interphalangeal joint was not assessed. The Vicon system enabled an adapted study of gait after metatarsophalangeal arthrodesis. This method offers several perspectives: study of the effect of the position of the arthrodesis in the sagittal plane on gait, changes over time in interphalangeal joint motion, or consequences of fusion on walking up and down stairs. CONCLUSION: Metatarsophalangeal arthrodesis of the hallux does not modify general gait parameters nor the kinetic and kinematic values. Compensation is achieved via the interphalangeal joint.

[Evaluation of amputees]. / Evaluation des amputés.

INTRODUCTION: Review of the literature about evaluation of amputees. MATERIALS AND METHODS: A search of the Medline and Reedoc databases with the key words lower limb amputee, upper limb amputee, evaluation of lower limb amputee, evaluation of upper limb amputee, survey of lower limb amputee, survey of upper limb and the same words in French for reports on the evaluation of amputees. RESULTS: Evaluations of amputees differ according to the level of amputation (lower or upper limb) and age (adult or child). They concern standing balance, walking (lower limb) and the mono- or bimanual prehensile capacities with or without prostheses in daily living activities and leisure (upper limb) as well as quality of life, personal satisfaction, psychological impact and, in particular, coping strategies. DISCUSSION: For lower-limb amputees, tools to evaluate include scales of deambulation, of which few are valid in French, and global scales (on locomotor capacities, quality of life and satisfaction), which have been recently validated, but only one of them is valid in French. For upper-limb amputees, specific and valid tools are not available for adults; however, for children some functional capacity scales in daily activities have been validated and take into account psychomotor development. None of these tools are valid in French, and their use is scattered and limited to validation studies. CONCLUSION: Only a few tools to evaluate amputees are valid in French for adults, and they concern lower-limb amputees only. Validating some of these tools in French is necessary.

[Clinical and three-dimensional kinematic features of the upper limb after replantation of the hand]. / Evaluation clinique et cinématique 3D du membre supérieur après réimplantation de la main.

INTRODUCTION: Functional assessments of hand replantation after traumatic amputation are considered as good although frequent deficits of long fingers mobility and hand sensitiveness occur. AIMS: To evaluate the capability of handling and the compensatory mechanisms involved in handling. METHODS: Prospective study in eight right-handed males who had distal amputation of the left upper limb with hand replantation for more than two years. Eight males with paired age and handedness served as control. Skin sensitiveness (thread test), mobility (TAM), functional capability (Box and Blocks test, 400 points test) and occupational outcome were assessed. Three-dimensional analysis (opto-electronic device) of the motion of the trunk and the upper limbs (arm, forearm, hand) was made during a pointing and gripping-shifting maneuver and the time of the related phases was measured (dynamometric cube device). Correlation between clinical assessments and three-dimensional analysis were tested. RESULTS: Patients with replantation had a remarkable recovery of the absolute and relative times of the various phases of the handling maneuver. Only the gripping phase was significantly prolonged in patients, this result was correlated with the deficit in motor function and sensitiveness of the replanted hand. The visual control was higher because of the lack of superficial and deep sensitiveness. Compensatory mechanisms involved a lateral shift of the replanted limb segments, probably attributed to the lateral shift of the trunk. CONCLUSION: Patient with a replanted hand develops a homogenesis displacement of the trunk and the pectoral girdle to compensate the shortening and the reduction in active mobility of the hand. This compensatory mechanism, observed in a small scale in healthy too, is efficient with respect to the handling phases.

Functional asymmetries of the lower limbs. A comparison between clinical assessment of laterality, isokinetic evaluation and electrogoniometric monitoring of knees during walking.

We used bilateral electrogoniometric gait monitoring of the knees to demonstrate the existence of an angular asymmetry between the two legs in healthy subjects. We also searched for correlations between this asymmetry and handedness, footedness and ocular laterality and isokinetic strength of the flexor-extensor muscles of the two knees. Among the 40 subjects studied, 25 (62.5%) showed an asymmetric maximal knee flexion: the difference being superior or equal to 5 degrees between the knees. There was no correlation between this asymmetry and the lateralities studied. We termed this type of asymmetry 'angular preponderance' to differentiate it from the laterality defined by clinical tests. Isokinetic strength of the knee flexors and extensors was correlated with the gender and speed, but not with side or laterality. Appropriate interpretation of lower limb examination should take into consideration angular gait asymmetry in the healthy subject.

Nottingham Health Profile: reliability in a sample of 542 subjects with major amputation of one or several limbs.

The reliability of a generic health-related quality of life measure was assessed for subjects with major amputation of one or several limbs. The Nottingham Health Profile was sent a first time to 1011 limb amputees, and a second time to the 542 respondents to the first inquiry. The intraclass correlation coefficient (ICC) between the answers to each survey was highest for the categories of distress caused by pain (ICC = 0.83), emotional reactions (ICC = 0.83) and mobility (ICC = 0.81). It was found satisfactory for energy level (ICC = 0.75), sleep (ICC = 0.75) and social isolation (ICC = 0.64). It is concluded that the NHP is a reliable health related quality of life measure for amputees.

Upregulation of nerve growth factor expression by human airway smooth muscle cells in inflammatory conditions.

Recent studies have suggested that nerve growth factor (NGF) may play a role in inflammation and bronchial hyperresponsiveness in asthma. Neither the types of cells that produce NGF in the human airways nor the effect of inflammation on NGF expression are clear. The two-fold aim of the present study was to determine whether airway smooth muscle produces NGF in vitro, and, if so, whether the pro-inflammatory cytokine interleukin-1beta (IL-1beta) affects this expression. Human airway smooth muscle cells in culture were incubated in the presence or absence of IL-1beta. NGF production was measured by enzyme-linked immunosorbent assay. NGF messenger ribonucleic acid (mRNA) was measured using a specific real-time fluorescent polymerase chain reaction technique, and expressed in relation to glyceraldehyde-3-phosphate dehydrogenase (GAPDH) mRNA levels. Human airway smooth muscle cells in vitro expressed NGF constitutively (21.4+/-7.8 pg x mL(-1); 14.6+/-5.4 pg NGF complementary deoxyribonucleic acid (cDNA) x pg GAPDH cDNA(-1) (mean+/-SEM)). Stimulation with IL-1beta (0.1-30 U x mL(-1)) for 24 h induced a dose-dependent increase in NGF production (22.1 pg x mL(-1) at 10 U x mL(-1); p<0.05). The IL-1beta (10 U x mL(-1))-induced increase in NGF expression was time-dependent. It was highest for NGF protein at 10 h (1.6-fold increase over control; p<0.001) and for NGF mRNA at 2.5 h (2.4-fold increase over control; p<0.05). In conclusion, the present study clearly shows that the human airway smooth muscle cell is a source of nerve growth factor, the expression of which is upregulated in inflammatory conditions, mimicked in vitro by the addition of interleukin-1beta.

[Classification and mechanisms of body perceptions in the amputees]. / Classification et mécanismes des perceptions et illusions corporelles des amputés.

OBJECTIVE: Amputees can experience several types of physical illusions and phantom limb phenomenon. The objective was to establish a synthetic classification of theses perceptions. METHOD: Prospective study in 75 amputees (group 1: amputation (n = 60), group 2: congenital defect). The subjects were asked first to report their perceptions spontaneously and then to detail the perception, if exist, of the missing limb: form recognition, posture, movement, reminiscence of a lost limb. RESULTS: Different types of perception were described besides the perception of the real state : normal, deformed or commemorative phantom limb and illusion of a normal body. DISCUSSION: Whatever the model (i.e.: neuro-matrix) which support the construction of the scheme and the body image, the representations related to identified perceptions, use various innate, autobiographic and identity frames of references as well as instantaneous peripheral information, treated by reorganized cerebral structures. Each type of perception is related to a particular representation pattern. CONCLUSION: This approach, in accordance with the literature, offers a better understanding of the differences between amelic and amputated subjects and of their perception of any prosthetic equipment.

Expression and function of proteinase-activated receptor 2 in human bronchial smooth muscle.

Trypsin and mast cell tryptase cleave proteinase-activated receptor 2 (PAR2) to induce alterations in contraction of airway smooth muscle that have been implicated in asthma in experimental animals. Although tryptase inhibitors are under development for treatment of asthma, little is known about the localization and function of PAR2 in human airways. We detected PAR2 expression in primary cultures of human airway smooth muscle cells using reverse transcriptase/polymerase chain reaction (RT-PCR) and immunofluorescence. The PAR2 agonists trypsin, tryptase, and an activating peptide (SLIGKV-NH2) stimulated calcium mobilization in these cells. PAR2 agonists strongly desensitized responses to a second challenge of trypsin and SLIGKV-NH2, but not to thrombin, indicating that they activate a receptor distinct from the thrombin receptors. Immunoreactive PAR2 was detected in smooth muscle, epithelium, glands, and endothelium of human bronchi. Trypsin, SLIGKV-NH2, and tryptase stimulated contraction of isolated human bronchi. Contraction was increased by removal of the epithelium and diminished by indomethacin. Thus, PAR2 is expressed by human bronchial smooth muscle where its activation mobilizes intracellular Ca2+ and induces contraction. These results are consistent with the hypothesis that PAR2 agonists, including tryptase, induce bronchoconstriction of human airway by stimulating smooth muscle contraction. PAR2 antagonists may be useful drugs to prevent bronchoconstriction.

Temporary phantom limbs evoked by vestibular caloric stimulation in amputees.

OBJECTIVE: Relationships between the vestibular system and the body schema have been suggested but never demonstrated in amputees. We studied the effects of vestibular stimulation on body representation in amputees focusing on the phantom limb phenomenon. METHOD: Prospective study in 31 amputated subjects of one or several limbs before the age of 16 years. The amputees underwent a caloric vestibular stimulation test, ipsilateral (n = 31) and contralateral (n = 8) to the side of amputation. Amputees were asked to report their perceptions spontaneously and to answer open questions. Four types of perceptions were analyzed: normal phantom, deformed phantom, painful phantom, and no phantom, before, during, and after the vestibular stimulation test. Data were compared between the two groups for pre- and post-test perceptions (chi2 test). RESULTS: Vestibular caloric stimulation provoked temporary perception of a normal phantom limb in 16 of 17 amputees who previously did not experience phantoms. For 12 of 12 amputees who currently experienced deformed or painful phantom limbs, caloric stimulation led to temporary replacement of the abnormal phantom with a non-painful normal phantom. CONCLUSIONS: The phenomena observed: 1) throw light on assumed mechanisms controlling construction of static and dynamic engrams used to produce the body schema; 2) complete the neuromatrix theory proposed to explain the phantom limb phenomenon; and 3) suggest that the vestibular system triggers the procedure of reconstruction of the global body schema.

[Chemoprevention perspectives for bronchial cancer]. / Perspectives de chimioprévention du cancer bronchique.

Lung cancer, with a high incidence and a 14% survival rate at 5 years is the leading cause of death in France. Because of past and present smoking habits in the French population and the lack of real expectations for significant therapeutic progress within a short or mid-term delay, the only reasonable way to try to limit the predictable hecatomb in the next 2 decades is to reduce exposure to the main risk factors (tobacco smoke, asbestos.), implement an early and effective (radiographic and/or endoscopic) screening system, and/or determine an active chemoprevention scheme. The principle of chemoprevention is based on the fundamental concept that since lung cancer develops through several stages, subjects exposed to risk factors could be given a compound or compounds counteracting the deleterious effect of carcinogenic substances on DNA and/or blocking the subsequent cascade of molecular events. Two families of products have been considered as potential chemoprevention agents: antioxidants (selenium, beta-caroten, vitamin E, and N-acetyl-cystein) and vitamin A and its analogs. Unfortunately, despite promising experimental data, large-scale clinical trials have not evidenced any protective effect of these compounds that have even been observed to produce opposing effects. To date, no chemopreventive substance can be reasonable proposed for subjects at risk. Due to the lack of proof of the efficacy of the different screening systems proposed, the only preventive action with proven efficacy is to limit exposure to risk factors. All health care givers must actively participate in the fight against active and passive smoking.