From twitch to tetanus for human muscle - experimental data and model predictions for m. triceps surae

In models describing the excitation of muscle by the central nervous system, it is often assumed that excitation during a tetanic contraction can be obtained by the linear summation of responses to individual stimuli, from which the active state of the muscle is calculated. We investigate here the extent to which such a model describes the excitation of human muscle in vivo. For this purpose, experiments were performed on the calf muscles of four healthy subjects. Values of parameters in the model describing the behaviour of the contractile element (CE) and the series elastic element (SEE) of this muscle group were derived on the basis of a set of isokinetic release contractions performed on a special-purpose dynamometer as well as on the basis of morphological data. Parameter values describing the excitation of the calf muscles were optimized such that the model correctly predicted plantar flexion moment histories in an isometric twitch, elicited by stimulation of the tibial nerve. For all subjects, the model using these muscle parameters was able to make reasonable predictions of isometric moment histories at higher stimulation frequencies. These results suggest that the linear summation of responses to individual stimuli can indeed give an adequate description of the process of human muscle excitation in vivo

Dynamic spasticity of plantar flexor muscles in cerebral palsy gait

Objective: To quantify dynamic spasticity, i.e. the coupling between muscle-tendon stretch velocity and muscle activity during gait, of the gastrocnemius and soleus muscles in children with spastic cerebral palsy. Design: Prospective, cross-sectional study. Subjects: Seventeen ambulatory children with cerebral palsy with spastic calf muscles, and H matched typically developing children. Methods: The children walked at 3 different speeds. Threedimensional kinematic and electromyographic data were collected. Muscle-tendon velocities of the gastrocnemius medialis and soleus were calculated using musculoskeletal modelling. Results: In typically developing children, muscles were stretched fast in swing without subsequent muscle activity, while spastic muscles were stretched more slowly for the same walking speed, followed by an increase in muscle activity. The mean ratio between peak activity and peak stretch velocity in swing was approximately 4 times higher in spastic muscles, and increased with walking speed. In stance, the stretch of muscles in typically developing children was followed by an increase in muscle activity. Spastic muscles were stretched fast in loading response, but since muscle activity was already built up in swing, no clear dynamic spasticity effect was present. Conclusion: Spastic calf muscles showed increased coupling between muscle-tendon stretch velocity and muscle activity, especially during the swing phase of gait. © 2010 Foundation of Rehabilitation Information

How Crouch Gait Can Dynamically Induce Stiff-Knee Gait

Children with cerebral palsy frequently experience foot dragging and tripping during walking due to a lack of adequate knee flexion in swing (stiff-knee gait). Stiff-knee gait is often accompanied by an overly flexed knee during stance (crouch gait). Studies on stiff-knee gait have mostly focused on excessive knee muscle activity during (pre)swing, but the passive dynamics of the limbs may also have an important effect. To examine the effects of a crouched posture on swing knee flexion, we developed a forward-dynamic model of human walking with a passive swing knee, capable of stable cyclic walking for a range of stance knee crouch angles. As crouch angle during stance was increased, the knee naturally flexed much less during swing, resulting in a 'stiff-knee' gait pattern and reduced foot clearance. Reduced swing knee flexion was primarily due to altered gravitational moments around the joints during initial swing. We also considered the effects of increased push-off strength and swing hip flexion torque, which both increased swing knee flexion, but the effect of crouch angle was dominant. These findings demonstrate that decreased knee flexion during swing can occur purely as the dynamical result of crouch, rather than from altered muscle function or pathoneurological control alone. © 2010 The Author(s)

The role of preoperative iron deficiency in colorectal cancer patients: prevalence and treatment

Background: In preoperative blood management of colorectal cancer patients, intravenous iron therapy is increasingly used to treat anaemia and prevent red blood cell transfusions. However, while iron deficiency is the most common cause of anaemia, little is known about the prevalence and namely type of iron deficiency in this population, whereas both types of iron deficiency (i.e. absolute and functional iron deficiency) are recommended to be treated differently by international cancer guidelines. Objective: The aim of present study is to investigate the prevalence and namely type of iron deficiency in colorectal cancer patients, and to assess its clinical relevance. Methods: Preoperative iron status, clinical parameters (i.e. age, ASA classification, tumour location, tumour stage) and postoperative complications were retrospectively collected for all newly diagnosed colorectal cancer patients in our institution over a 3-year period. Results: Iron deficiency was observed in 163 (48.1%) of 339 patients. Of these iron-deficient patients, 3.7% had an isolated absolute iron deficiency (AID) and 15.3% a functional iron deficiency (FID), while the rest had a combination of AID and FID. Anaemia was present in 66.1% of iron-deficient patients. Iron deficiency was significantly associated with an increased postoperative complication rate (univariable OR 1.94, p = 0.03, multivariable OR 1.84, p = 0.07), with right-sided tumours (p < 0.001), high ASA classification (p = 0.002), advanced tumour stage (p = 0.01) and advanced age (p = 0.04). In comparing clinical parameters between patients with AID and FID, advanced age was significantly associated with FID (p = 0.03), and the presence of anaemia with AID (p = 0.02). Conclusion: In preoperative colorectal cancer patients, there is a high prevalence of iron deficiency, including a high percentage of patients with—a component of—functional iron deficiency, associated with the increased postoperative complication rate. As both types of iron deficiency require a different treatment strategy, our results illustrate the therapeutic potential of especially intravenous iron supplementation in patients with severe iron deficiency and stress the urgency of routinely monitoring preoperative iron status and differentiation between types of iron deficiency. As iron therapy may also be potentially harmful in respect to stimulation of tumour growth, future clinical trials assessing the long-term effect of iron therapy are necessary

Applying Stretch to Evoke Hyperreflexia in Spasticity Testing: Velocity vs. Acceleration

\ua9 Copyright \ua9 2021 Sloot, Weide, van der Krogt, Desloovere, Harlaar, Buizer and Bar-On. In neurological diseases, muscles often become hyper-resistant to stretch due to hyperreflexia, an exaggerated stretch reflex response that is considered to primarily depend on the muscle\u27s stretch velocity. However, there is still limited understanding of how different biomechanical triggers applied during clinical tests evoke these reflex responses. We examined the effect of imposing a rotation with increasing velocity vs. increasing acceleration on triceps surae muscle repsonse in children with spastic paresis (SP) and compared the responses to those measured in typically developing (TD) children. A motor-operated ankle manipulator was used to apply different bell-shaped movement profiles, with three levels of maximum velocity (70, 110, and 150\ub0/s) and three levels of maximum acceleration (500, 750, and 1,000\ub0/s2). For each profile and both groups, we evaluated the amount of evoked triceps surae muscle activation. In SP, we evaluated two additional characteristics: the intensity of the response (peak EMG burst) and the time from movement initiation to onset of the EMG burst. As expected, the amount of evoked muscle activation was larger in SP compared to TD (all muscles: p &lt; 0.001) and only sensitive to biomechanical triggers in SP. Further investigation of the responses in SP showed that peak EMG bursts increased in profiles with higher peak velocity (lateral gastrocnemius: p = 0.04), which was emphasized by fair correlations with increased velocity at EMG burst onset (all muscles: r &gt; 0.33–0.36, p ≤ 0.008), but showed no significant effect for acceleration. However, the EMG burst was evoked faster with higher peak acceleration (all muscles p &lt; 0.001) whereas it was delayed in profiles with higher peak velocity (medial gastrocnemius and soleus: p &lt; 0.006). We conclude that while exaggerated response intensity (peak EMG burst) seems linked to stretch velocity, higher accelerations seem to evoke faster responses (time to EMG burst onset) in triceps surae muscles in SP. Understanding and controlling for the distinct effects of different biological triggers, including velocity, acceleration but also length and force of the applied movement, will contribute to the development of more precise clinical measurement tools. This is especially important when aiming to understand the role of hyperreflexia during functional movements where the biomechanical inputs are multiple and changing

Multispectral Optoacoustic Tomography of Matrix Metalloproteinase Activity in Vulnerable Human Carotid Plaques

Elevated expression of cathepsins, integrins and matrix metalloproteinases (MMPs) is typically associated with atherosclerotic plaque instability. While fluorescent tagging of such molecules has been amply demonstrated, no imaging method was so far shown capable of resolving these inflammation-associated tags with high fidelity and resolution beyond microscopic depths. This study is aimed at demonstrating a new method with high potential for noninvasive clinical cardiovascular diagnostics of vulnerable plaques using high-resolution deep-tissue multispectral optoacoustic tomography (MSOT) technology. MMP-sensitive activatable fluorescent probe (MMPSense (TM) 680) was applied to human carotid plaques from symptomatic patients. Atherosclerotic activity was detected by tuning MSOT wavelengths to activation-dependent absorption changes of the molecules, structurally modified in the presence of enzymes. MSOT analysis simultaneously provided morphology along with heterogeneous MMP activity with better than 200 micron resolution throughout the intact plaque tissue. The results corresponded well with epi-fluorescence images made from thin cryosections. Elevated MMP activity was further confirmed by zymography, accompanied by increased macrophage influx. We demonstrated, for the first time to our knowledge, the ability of MSOT to provide volumetric images of activatable molecular probe distribution deep within optically diffuse tissues. High-resolution mapping of MMP activity was achieved deep in the vulnerable plaque of intact human carotid specimens. This performance directly relates to pre-clinical screening applications in animal models and to clinical decision potential as it might eventually allow for highly specific visualization and staging of plaque vulnerability thus impacting therapeutic clinical decision making

Iron therapy as treatment of anemia: A potentially detrimental and hazardous strategy in colorectal cancer patients

Stemcel biology/Regenerative medicine (incl. bloodtransfusion