Cycle-to-cycle control of swing phase of paraplegic gait induced by surface electrical stimulation

Parameterised swing phase of gait in paraplegics was obtained using surface electrical stimulation of the hip flexors, hamstrings and quadriceps; the hip flexors were stimulated to obtain a desired hip angle range, the hamstrings to provide foot clearance in the forward swing, and the quadriceps to acquire knee extension at the end of the swing phase. We report on two main aspects; optimisation of the initial stimulation parameters, and parameter adaption (control). The initial stimulation patterns were experimentally optimised in two paraplegic subjects using a controlled stand device, resulting in an initial satisfactory swinging motion in both subjects. Intersubject differences appeared in the mechanical output (torque joint) per muscle group. During a prolonged open-loop controlled trial with the optimised but unregulated stimulation onsets and burst duration for the three muscle groups, the hip angle range per cycle initially increased above the desired value and subsequently decreased below it. The mechanical performance of the hamstrings and quadriceps remained relatively unaffected. A cycle-to-cycle controller was then designed, operating on the basis of the hip angle ranges obtained in previous swings. This controller successfully adapted the burst duration of the hip flexors to maintain the desired hip angle range

The influence of the reciprocal cable linkage in the advanced reciprocating gait orthosis on paraplegic gait performance

A wide variety of mechanical orthoses is available to provide ambulation to paraplegic patients. Evaluation of energy cost during walking in each of these devices has been acknowledged as an important topic in this field of research. In order to investigate the benefits of a ballistic swing on gait performance in the Advanced Reciprocating Gait Orthosis (ARGO) a study was conducted in which the ARGO was compared with an orthosis with freely swinging legs. This Non Reciprocally linked Orthosis (NRO) was obtained by removing the reciprocal linkage in the subjects' own ARGOs. Subsequently, flexion/extension limits were mounted to permit adjustment of stride length. Six male paraplegic subjects with lesions ranging from T4 to T12 were included in the study. A single case experimental design (B-A-B-A) was conducted in order to improve internal validity. Biomechanical and physiological parameters were assessed and the subjects' preference for either ARGO or NRO was determined.\ud \ud It was found that large inter-individual differences produced insufficient evidence in this study to draw general conclusions about difference in energy expenditure between both orthoses. However, individual analysis of the results showed a reduction of oxygen cost (range: 4%-14%) in the NRO in T9 and T12 lesions, while oxygen cost in subjects with T4 lesions increased markedly (22% and 40%). It is concluded that patients with low level lesions could benefit in terms of oxygen lost from removing the reciprocal cable linkage in the ARGO. However, only one subject preferred the NRO for walking, whereas none of the subject chose the NRO for use in daily living activities. Removal of the reciprocal cable linkage in the ARGO may not be desirable for these patients

The influence of frontal alignment in the advanced reciprocating gait orthosis on energy cost and crutch force requirements during paraplegic gait

Reduction of energy cost and upper body load during paraplegic walking is considered to be an important criterion in future developments of walking systems. A high energy cost limits the maximum walking distance in the current devices, whereas wrist and shoulder pathology can deteriorate because of the high upper body load. A change in alignment of the mechanical brace in the frontal plane, i.e. abduction, can contribute to a more efficient gait pattern with sufficient foot clearance with less pelvic lateral sway. A decrease in pelvic lateral sway after aligning in abduction results in a shift of the centre of mass to the swing leg crutch which may result in a decrease in required crutch force on stance side to maintain foot clearance. Five paraplegic subjects were provided with a standard Advanced Reciprocating Gait Orthosis (ARGO) and an ARGO aligned in 4 different degrees of abduction (0°, 3°, 6° and 9°). After determining an optimal abduction angle for each of the subjects, a cross over design was used to compare the ARGO with the individually optimised abducted orthosis. An abduction angle between 0° and 3° was chosen as optimal abduction angle. Subjects were not able to walk satisfactory with abduction angles 6° and 9°. A significant reduction in crutch peak force on stance side was found (approx. 12% , p < 0.01) in the abducted orthosis. Reduction in crutch force time integral (15%) as well as crutch peak force on swing side (5%) was not significant. No differences in oxygen uptake as well as oxygen cost was found. We concluded that an abduction angle between 0° and 3° is beneficial with respect to upper boHy load, whereas energy requirements did not change

Differential effects of tissue plasminogen activator and streptokinase on infarct size and on rate of enzyme release: influence of early infarct related artery patency: The GUSTO Enzyme Substudy

Background The recent international GUSTO trial of 41 021 patients with acute myocardial infarction demonstrated improved 90-mm infarct related artery patency as well as reduced mortality in patients treated with an accelerated regimen of tissue plasminogen activator, compared to patients treated with streptokinase. A regimen combining tissue plasminogen activator and streptokinase yielded intermediate results. The present study investigated the effects of treatment on infarct size and enzyme release kinetics in a subgroup of these patients. Methods A total of 553 patients from 15 hospitals were enrolled in the study. Four thrombolytic strategies were compared: streptokinase with subcutaneous heparin, streptokinase with intravenous (iv.) heparin, tissue plasminogen activator with iv. heparin, and streptokinase plus tissue plasminogen activator with i.v. heparin. The activity of alpha-hydroxybutyrate dehydrogenase (HBDH) in plasma was centrally analysed and infarct size was defined as cumulative HBDH release per litre of plasma within 72 h of the first symptoms (Q(72)). Patency of the infarct-related vessel was determined by angiography in 159 patients, 90 mm after treatment. Results Infarct size was 3·72 g-eq . 1−1 in patients with adequate coronary perfusion (TIMI-3) at the 90 mm angi-ogram and larger in patients with TIMI-2 (4·35 g-eq . 1−1) or TIMI 0-1 (5·07 g-eq . 1−1)flow (P=0·024). In this subset of the GUSTO angiographic study, early coronary patency rates (TIMI 2+3) were similar in the two streptokinase groups (53 and 46%). Higher, but similar, patency rates were observed in the tissue plasminogen activator and combination therapy groups (87 and 90%). Median infarct size for the four treatment groups, expressed in gram- equivalents (g-eq) of myocardium, was 4·4, 4·5, 3·9 and 3·9 g-eq per litre of plasma (P=0·04 for streptokinase vs tissue plasminogen activator). Six hours after the first symptoms, respectively 5·3, 6·6, 14·0 and 13·6% of total HBDH release was complete (P<0·000l for streptokinase vs tissue plasminogen activator). Conclusions Rapid and complete coronary reperfusion salvages myocardial tissue, resulting in limitation of infarct size and accelerated release of proteins from the myocardium. Treatment with tissue plasminogen activator, resulting in earlier reperfusion was more effective in reducing infarct size than the streptokinase regimens, which contributes to the differences in survival between treatment groups in the GUSTO tria

The influence of the reciprocal hip joint link in the advanced reciprocating gait orthosis on standing performance in paraplegia

The effect of reciprocally linking the hip hinges of a hip-knee-ankle-foot orthosis on standing performance was studied in a comparative trial of the Advanced Reciprocating Gait Orthosis (ARGO) and an ARGO in which the Bowden cable was removed (A_GO). Six male subjects with spinal cord injury (SCI) at T4 to T12 level participated in the study, which was conducted using a single case experimental design. Standing balance, the ability to handle balance disturbances (standing stability), and the performance of a functional hand task during standing were assessed in both orthosis configurations in the order A_GO-ARGO-A_GO-ARGO. No significant differences with respect to standing performance were found for the two orthosis configurations. However, the results indicate that the crutch force needed for maintaining balance during various tasks, especially for quiet standing with two crutches, may be much higher in the orthosis without Bowden cable. Therefore, it is very likely that the reciprocal hip joint link in the ARGO provides a substantial and clinically relevant reduction of upper body effort required for standing under functional conditions

Novel insights into the epidemiology of epidermolysis bullosa (EB) from the Dutch EB Registry:EB more common than previously assumed?

Background Epidermolysis bullosa (EB) is a heterogeneous group of rare and incurable genetic disorders characterized by fragility of the skin and mucosae, resulting in blisters and erosions. Several epidemiological studies in other populations have been carried out, reporting varying and sometimes inconclusive figures, highlighting the need for standardized epidemiological analyses in well-characterized cohorts. Objectives To evaluate the epidemiological data on EB in the Netherlands, extracted from the molecularly well-characterized cohort in the Dutch EB Registry. Methods In this observational study all EB-patients that were based in the Netherlands and captured in the Dutch EB Registry between 1988 and 2018 were included. The epidemiological outcomes were based on complete diagnostic data (clinical features, immunofluorescence, electron microscopy and mutation analysis), with longitudinal follow-up. Results A total of 464 EB-patients (287 families) were included. The incidence and point-prevalence of EB in the Netherlands were 41.3 per million live births and 22.4 per million population, respectively. EB Simplex (EBS), Junctional EB (JEB), Dystrophic EB (DEB) and Kindler EB were diagnosed in 45.7%, 18.8%, 34.7% and 0.9% of the EB-patients, respectively, with an incidence and point-prevalence of 17.5 and 11.9 (EBS), 9.3 and 2.1 (JEB), 14.1 and 8.3 (DEB), 0.5 and 0.2 (Kindler EB). In 90.5% of the EB-patients the diagnosis was genetically confirmed. During the investigated time period 73 EB-patients died, 72.6% of whom as a direct consequence of their EB. Conclusion The epidemiological outcomes of EB in the Netherlands are high, attributed to a high detection rate in a well-organized set-up, indicating that EB might be more common than previously assumed. These epidemiological data help to understand the extensive need for (specialized) medical care of EB-patients and is invaluable for the design and execution of therapeutic trials. This study emphasizes the importance of thorough reporting systems and registries worldwide

A Defective Pentose Phosphate Pathway Reduces Inflammatory Macrophage Responses during Hypercholesterolemia

Metabolic reprogramming has emerged as a crucial regulator of immune cell activation, but how systemic metabolism influences immune cell metabolism and function remains to be investigated. To investigate the effect of dyslipidemia on immune cell metabolism, we performed in-depth transcriptional, metabolic, and functional characterization of macrophages isolated from hypercholesterolemic mice. Systemic metabolic changes in such mice alter cellular macrophage metabolism and attenuate inflammatory macrophage responses. In addition to diminished maximal mitochondrial respiration, hypercholesterolemia reduces the LPS-mediated induction of the pentose phosphate pathway (PPP) and the Nrf2-mediated oxidative stress response. Our observation that suppression of the PPP diminishes LPS-induced cytokine secretion supports the notion that this pathway contributes to inflammatory macrophage responses. Overall, this study reveals that systemic and cellular metabolism are strongly interconnected, together dictating macrophage phenotype and function