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Objective: To determine whether laparoscopic sacrocolpopexy (LSC) or vaginal sacrospinous fixation (VSF) is the most optimal surgical treatment in patients with POP-Q stage =2 vaginal vault prolapse (VVP).Design: Multicentre randomised controlled trial (RCT) and prospective cohort study alongside.Setting: Seven non-university teaching hospitals and two university hospitals in the Netherlands.Population : Patients with symptomatic post-hysterectomy vaginal vault prolapse, requiring surgical treatment.Methods: Randomisation in a 1:1 ratio to LSC or VSF. Evaluation of prolapse was done using the pelvic organ prolapse quantification (POP-Q). All participants were asked to fill in various Dutch validated questionnaires 12 months postoperatively.Main outcome measures: Primary outcome was disease-specific quality of life. Secondary outcomes included composite outcome of success and anatomical failure. Furthermore, we examined peri-operative data, complications and sexual function.Results: A total of 179 women, 64 women randomised and 115 women, participated in a prospective cohort. Disease-specific quality of life did not differ after 12 months between the LSC and VSF group in the RCT and the cohort (RCT: P = 0.887; cohort: P = 0.704). The composite outcomes of success for the apical compartment, in the RCT and cohort, were 89.3% and 90.3% in the LSC group and 86.2% and 87.8% in the VSF group, respectively (RCT: P = 0.810; cohort: P = 0.905). There were no differences in number of reinterventions and complications between both groups (reinterventions RCT: P = 0.934; cohort: P = 0.120; complications RCT: P = 0.395; cohort: P = 0.129).Conclusions: LSC and VSF are both effective treatments for vaginal vault prolapse, after a follow-up period of 12 months.

Background: Cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) is a treatment option for selected patients with colorectal peritoneal metastases (PM). This report provides an overview of treatment and survival outcomes for patients deemed ineligible for CRS-HIPEC. Methods: Colorectal PM patients referred to a tertiary center from 2014 to 2020 that were ineligible for CRS-HIPEC were included. Patient, tumor, and treatment characteristics were provided. Survival analyses were performed using the Kaplan-Meier method. Results: Of 476 patients referred for CRS-HIPEC, 227 (48%) were deemed ineligible. Median follow-up was 15 months [IQR 10–22]. Data on follow-up treatment was available for 198 patients, of which 73% received systemic therapy. These patients had a median overall survival (OS) of 17 months [IQR 9–25]. For patients receiving best supportive care (BSC) median OS was 4 months [IQR 2–9]. The main reason for ineligibility was extensive PM (42%), with a median OS of 11 months [IQR 5–18]. Patients deemed ineligible due to (extensive) liver (9%) or lung metastases (8%) showed longer OS (median 22 months, IQR 8–27, and 24 months, IQR 12–29, respectively) than patients with extensive PM (median 11 months, IQR 5–18) or distant lymph node metastases (median 14 months, IQR 4–25). Conclusion: The main reason for CRS-HIPEC ineligibility was extensive PM. The majority of patients received systemic therapy. Patients deemed ineligible due to extra-peritoneal metastases had better survival outcomes than patients deemed ineligible due to extensive PM.

Background Cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) is a potentially curative treatment for peritoneal metastases from colorectal cancer (CRC) or pseudomyxoma peritonei (PMP). Because of the considerable morbidity of this treatment, optimal patient selection is key. This study aimed to assess the impact of low skeletal muscle mass (SMM) on outcomes after CRS-HIPEC. Methods Patients who underwent CRS-HIPEC between 2014 and 2020 at a tertiary center were included. SMM was measured on computed tomography by means of the L3 muscle index. Postoperative complications and survival outcomes were compared between groups by use of logistic regression and Kaplan-Meier survival analyses. Results Of 284 included patients, 149 had low SMM. Occurrence of severe postoperative complications did not differ between groups (28.9% for patients with low vs. 34.1% for patients with normal SMM). Low SMM was not associated with postoperative complications (p = 0.344). For CRC patients, no significant differences were observed in disease-free (DFS) or overall survival (OS) between patients with low (median DFS 7 months [IQR 4–14], median OS 33 months [IQR 14–NR]) and patients with normal SMM (median DFS 8 months [IQR 5–20], median OS 35 months [IQR 18–NR]). Regarding PMP, survival outcomes did not significantly differ between groups (3-year DFS 47.3% for patients with low SMM vs. 54.5% for patients with normal SMM, p = 0.676; 3-year OS 70.8% vs. 90.9% respectively, p = 0.172). Conclusions Low SMM could not be identified as a predictor of severe complications or survival outcomes after CRS-HIPEC.

Mitochondrial cytochrome c oxidase (CcO) or respiratory chain complex IV is a heme aa3-copper oxygen reductase containing metal centers essential for holo-complex biogenesis and enzymatic function that are assembled by subunit-specific metallochaperones. The enzyme has two copper sites located in the catalytic core subunits. The COX1 subunit harbors the CuB site that tightly associates with heme a3 while the COX2 subunit contains the binuclear CuA site. Here, we report that in human cells the CcO copper chaperones form macromolecular assemblies and cooperate with several twin CX9C proteins to control heme a biosynthesis and coordinate copper transfer sequentially to the CuA and CuB sites. These data on CcO illustrate a mechanism that regulates the biogenesis of macromolecular enzymatic assemblies with several catalytic metal redox centers and prevents the accumulation of cytotoxic reactive assembly intermediates.

Cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) is a treatment option for selected patients with colorectal peritoneal metastases (PM). This report provides an overview of treatment and survival outcomes for patients deemed ineligible for CRS-HIPEC.Colorectal PM patients referred to a tertiary center from 2014 to 2020 that were ineligible for CRS-HIPEC were included. Patient, tumor, and treatment characteristics were provided. Survival analyses were performed using the Kaplan-Meier method.Of 476 patients referred for CRS-HIPEC, 227 (48%) were deemed ineligible. Median follow-up was 15 months [IQR 10-22]. Data on follow-up treatment was available for 198 patients, of which 73% received systemic therapy. These patients had a median overall survival (OS) of 17 months [IQR 9-25]. For patients receiving best supportive care (BSC) median OS was 4 months [IQR 2-9]. The main reason for ineligibility was extensive PM (42%), with a median OS of 11 months [IQR 5-18]. Patients deemed ineligible due to (extensive) liver (9%) or lung metastases (8%) showed longer OS (median 22 months, IQR 8-27, and 24 months, IQR 12-29, respectively) than patients with extensive PM (median 11 months, IQR 5-18) or distant lymph node metastases (median 14 months, IQR 4-25).The main reason for CRS-HIPEC ineligibility was extensive PM. The majority of patients received systemic therapy. Patients deemed ineligible due to extra-peritoneal metastases had better survival outcomes than patients deemed ineligible due to extensive PM.

IntroductionMalignant peritoneal mesothelioma (MPM) is a rare, aggressive tumour arising primarily from the peritoneum. The only potentially curative treatment is cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC). However, the majority of patients are not eligible to undergo this treatment. The benefit of systemic treatment for these patients is limited at the cost of considerable morbidity. Hence, there is a need for appropriate palliative treatment options for patients with MPM. As MPM rarely disseminates outside the abdominal cavity, these patients might benefit from local treatment. A higher, more effective dose of chemotherapy can directly be delivered at the site of the disease. Systemic uptake will be limited, likely resulting in less toxicity. The aim of the INTERACT MESO trial is to determine the maximum tolerable dose of intraperitoneal paclitaxel monotherapy in patients with MPM. Secondary endpoints are to assess safety and toxicity, feasibility and the pharmacokinetic profile of this treatment.Methods and analysisThe INTERACT MESO trial is a prospective, open-label, single-centre, phase I study with a classic three-plus-three dose escalation design. The study population consists of adult patients with primary MPM, without extra-abdominal disease, who are not eligible to undergo CRS-HIPEC. According to standard of care work-up for CRS-HIPEC, patients will undergo diagnostic laparoscopy to determine the feasibility of CRS-HIPEC. In case CRS-HIPEC is not considered feasible, a peritoneal port-a-cath (PAC) system will be placed. Through this PAC, 8–16 weekly cycles of intraperitoneal chemotherapy will be administered.Ethics and disseminationThe Central Committee on Research Involving Human Subjects (CCMO, The Hague, The Netherlands) and the Medical Research Ethics Committee (METC, Rotterdam, The Netherlands) have granted permission to carry out this study protocol. The results of this trial will be submitted for publication in a peer-reviewed scientific journal.Trial registration numberNL9718. EudraCT: 2021-003637-11.

Cellular iron homeostasis and mitochondrial iron homeostasis are interdependent. Mitochondria must import iron to form iron–sulfur clusters and heme, and to incorporate these cofactors along with iron ions into mitochondrial proteins that support essential functions, including cellular respiration. In turn, mitochondria supply the cell with heme and enable the biogenesis of cytosolic and nuclear proteins containing iron–sulfur clusters. Impairment in cellular or mitochondrial iron homeostasis is deleterious and can result in numerous human diseases. Due to its reactivity, iron is stored and trafficked through the body, intracellularly, and within mitochondria via carefully orchestrated processes. Here, we focus on describing the processes of and components involved in mitochondrial iron trafficking and storage, as well as mitochondrial iron–sulfur cluster biogenesis and heme biosynthesis. Recent findings and the most pressing topics for future research are highlighted.

Heme is an essential cofactor required for a plethora of cellular processes in eukaryotes. In metazoans the heme biosynthetic pathway is typically partitioned between the cytosol and mitochondria, with the first and final steps taking place in the mitochondrion. The pathway has been extensively studied and its biosynthetic enzymes structurally characterized to varying extents. Nevertheless, understanding of the regulation of heme synthesis and factors that influence this process in metazoans remains incomplete. Therefore, we investigated the molecular organization as well as the physical and genetic interactions of the terminal pathway enzyme, ferrochelatase (Hem15), in the yeast Saccharomyces cerevisiae. Biochemical and genetic analyses revealed dynamic association of Hem15 with Mic60, a core component of the mitochondrial contact site and cristae organizing system (MICOS). Loss of MICOS negatively impacts Hem15 activity, affects the size of the Hem15 high-mass complex, and results in accumulation of reactive and potentially toxic tetrapyrrole precursors that may cause oxidative damage. Restoring intermembrane connectivity in MICOS-deficient cells mitigates these cytotoxic effects. These data provide new insights into how heme biosynthetic machinery is organized and regulated, linking mitochondrial architecture-organizing factors to heme homeostasis., Graphical abstract Image 1

For high stress deformed specimens containing dislocations in a nonequilibrium dissociation state the relaxation of the splitting width by annealing at very low temperatures (100°C to 140°C) is investigated by TEM measurements. As the formation of new double kinks is prevented by the low temperature, the motion of the partials is a result of the motion of existing kinks. Assuming the kink migration energy being equal for the 30° and for the 90° partial its value is found between 1 and 1.2 eV. Additional TEM observations of relaxation phenomena changing the dislocation arrangement at higher annealing temperatures are reported.

The planetary boundaries concept has profoundly changed the vocabulary and representation of global environmental issues. We bring a critical social science perspective to this framework through the notion of societal boundaries and aim to provide a more nuanced understanding of the social nature of thresholds. We start by highlighting the strengths and weaknesses of planetary boundaries from a social science perspective. We then focus on capitalist societies as a heuristic for discussing the expansionary dynamics, power relations, and lock-ins of modern societies that impel highly unsustainable societal relations with nature. While formulating societal boundaries implies a controversial process ‒ based on normative judgments, ethical concerns, and socio-political struggles ‒ it has the potential to offer guidelines for a just, social-ecological transformation. Collective autonomy and the politics of self-limitation are key elements of societal boundaries and are linked to important proposals and pluriverse experiences to integrate well-being and boundaries. The role of the state and propositions for radical alternative approaches to well-being have particular importance. We conclude with reflections on social freedom, defined as the right not to live at others’ expense. Toward the aim of defining boundaries through transdisciplinary and democratic processes, we seek to open a dialogue on these issues. © 2021 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.

Heme is a cofactor and signaling molecule that is essential for much of aerobic life. All heme-dependent processes in eukaryotes require that heme is trafficked from its site of synthesis in the mitochondria to hemoproteins located throughout the cell. However, the mechanisms governing the mobilization of heme out of the mitochondria, and the spatio-temporal dynamics of these processes, are poorly understood. Herein, using genetically encoded fluorescent heme sensors, we developed a live cell assay to monitor heme distribution dynamics between the mitochondrial inner-membrane, where heme is synthesized, and the mitochondrial matrix, cytosol, and nucleus. Surprisingly, heme trafficking to the nucleus is ∼25% faster than to the cytosol or mitochondrial matrix, which are nearly identical, potentially supporting a role for heme as a mitochondrial-nuclear retrograde signal. Moreover, we discovered that the heme synthetic enzyme, 5-aminolevulinic acid synthase (ALAS), and GTPases in control of the mitochondrial dynamics machinery, Mgm1 and Dnm1, and ER contact sites, Gem1, regulate the flow of heme between the mitochondria and nucleus. Overall, our results indicate that there are parallel pathways for the distribution of bioavailable heme.

Spatiotemporal changes in the abundance, shape, and cellular localization of the mitochondrial network, also known as mitochondrial dynamics, are now widely recognized to play a key role in mitochondrial and cellular physiology as well as disease states. This process involves coordinated remodeling of the outer and inner mitochondrial membranes by conserved dynamin-like guanosine triphosphatases and their partner molecules in response to various physiological and stress stimuli. Although the core machineries that mediate fusion and partitioning of the mitochondrial network have been extensively characterized, many aspects of their function and regulation are incompletely understood and only beginning to emerge. In the present review we briefly summarize current knowledge about how the key mitochondrial dynamics-mediating factors are regulated via selective proteolysis by mitochondrial and cellular proteolytic machineries.

Heme is an essential cofactor and signaling molecule. All heme-dependent processes require that heme is trafficked from its site of synthesis in the mitochondria to hemoproteins in virtually every subcellular compartment. However, the mechanisms governing the mobilization of heme out of the mitochondria, and the spatio-temporal dynamics of these processes, are poorly understood. To address this, we developed a pulse-chase assay in which, upon the initiation of heme synthesis, heme mobilization into the mitochondrial matrix, cytosol and nucleus is monitored using fluorescent heme sensors. Surprisingly, we found that heme trafficking to the nucleus occurs at a faster rate than to the matrix or cytosol. Further, we demonstrate that GTPases in control of mitochondrial fusion, Mgm1, and fission, Dnm1, are positive and negative regulators of mitochondrial-nuclear heme trafficking, respectively. We also find that heme controls mitochondrial network morphology. Altogether, our results indicate that mitochondrial dynamics and heme trafficking are integrally coupled.

Well-maintained mitochondrial functioning is crucial for cellular physiology. Thus, multiple mechanisms are in place to preserve mitochondrial welfare upon homeostatic challenges. One such mechanism - known as protein quality control (PQC) - comprises a network of conserved proteases distributed across mitochondrial compartments. An emerging key PQC component is the ATP-independent metalloprotease Oma1, which has been identified as a key regulator of mitochondrial dynamics under normal and pathological states. Oma1 is activated by various stress stimuli - likely via conformational changes within the Oma1 homo-oligomeric complex. Here we provide evidence for the presence of a redox-dependent mechanism of Oma1 activation that appears to involve two conserved cysteine residues. First, we show that Oma1 oligomerization and protein stability are significantly impaired by the C332A mutation. Additional mutation of the conserved Cys-272 residue stabilizes the latter producing a functional Oma1 complex. However, this complex displays a lower activation threshold, likely due to altered conformational state. Second, the proteolytic activity of Oma1 is negatively regulated by the presence of thiol-containing reducing agents, but is not affected by non-thiol reductants. Consistently, proteolysis by the enzyme harboring both mutated cysteine residues displays lower sensitivity towards thioreduction. Lastly, the analyses in yeast model indicate that the Cys-272 and Cys-332 residues are in the oxidized state, which remains largely unchanged upon stress-activation. The human Oma1 appears to be following the same trend. Our data suggest a novel redox-sensitive mechanism for Oma1 activation and highlight an important role of the enzyme’s intermembrane space-exposed cysteines in this process.

Heme is an essential cofactor involved in a plethora of vital functions. Heme is required to be in most subcellular compartments, but the way, in which it is transported from the mitochondria - its site of synthesis - to those compartments is poorly understood. Utilizing ratiometric, fluorescent heme sensors, we found that the GTPases in control of mitochondrial fusion, Mgm1 and fission, Dnm1, are positive and negative regulators of heme trafficking to the nucleus, respectively. Furthermore, we discovered that mitochondrial network morphology is under the control of heme biosynthesis. Our results indicate that mitochondrial dynamics and heme trafficking are integrally coupled.

Quadrupedal limb coordination during human walking was recently shown to be upregulated during obstacle stepping. An anticipatory activity of coupled cervico-thoraco-lumbar interneuronal circuits is followed by an appropriate executory activation of leg and arm muscles during task performance. This mechanism was studied in subjects with Parkinson's disease and age-matched controls walking on a treadmill with a randomly approaching obstacle. Spinal reflex (SR) responses, evoked by tibial nerve stimulation during mid-stance, were present in all arm and leg muscles investigated. They were larger before execution of obstacle avoidance compared with normal steps in both subject groups. The performance of obstacle stepping was slightly worse in Parkinson's disease than in control subjects. The anticipatory SR in the arm muscles prior to normal and obstacle steps was larger in Parkinson's disease compared with age-matched subjects, but smaller in the tibialis anterior. The arm and leg muscle activation was stronger during obstacle compared with normal swing but did not differ between Parkinson's disease and age-matched subjects. These observations indicate that quadrupedal limb coordination is basically preserved in Parkinson's disease subjects. Our data are consistent with the proposal that in Parkinson's disease subjects the enhanced anticipatory spinal neuronal activity (reflected in the SR) in the arm muscles is required to achieve an appropriate muscle activation for the automatic control of body equilibrium during the performance of the task. In the tibialis anterior the SR is attenuated presumably because of a stronger voluntary (i.e. cortical) control of leg movements.

Objective Knowledge about the long-term course of spinal neuronal function after spinal cord injury (SCI) is important if regeneration therapies become available in the future. The objective of this study was to examine the behavior of locomotor EMG activity and of spinal reflexes in patients with chronic motor-complete SCI. Methods EMG activity from rectus femoris (RF), biceps femoris (BF), medial gastrocnemius (GM) and tibialis anterior (TA) of both sides was investigated during locomotor movements assisted by a robotic device in 10 chronic (>1 year after accident) complete SCI and 5 healthy subjects. H-reflexes (recorded from GM) were induced during the onset and flexion reflexes (recorded from BF and TA) at the end of the stance phase. Results Only in the chronic SCI subjects an exhaustion of EMG activity—i.e. a decrease in amplitude—occurred within a few minutes in all leg muscles. The EMG exhaustion was not associated with a change in the H- or flexion reflex amplitude during a walking session. Conclusions Exhaustion of neuronal function in chronic complete SCI might be restricted to unused motor tasks, i.e. locomotion. The fact that H- and flexion reflexes show a normal behavior might be due to the fact that they still become activated. Significance Training/pharmalogical approaches may be required to maintain neuronal function of unused tasks as a basis for future successful regeneration therapies.

During human gait, electrical stimulation of the foot elicits facilitatory P2 (medium latency) responses in TA (tibialis anterior) at the onset of the swing phase, while the same stimuli cause suppressive responses at the end of swing phase, along with facilitatory responses in antagonists. This phenomenon is called phase-dependent reflex reversal. The suppressive responses can be evoked from a variety of skin sites in the leg and from stimulation of some muscles such as rectus femoris (RF). This paper reviews the data on reflex reversal and adds new data on this topic, using a split-belt paradigm. So far, the reflex reversal in TA could only be studied for the onset and end phases of the step cycle, simply because suppression can only be demonstrated when there is background activity. Normally there are only 2 TA bursts in the step cycle, whereas TA is normally silent during most of the stance phase. To know what happens in the stance phase, one needs to have a means to evoke some background activity during the stance phase. For this purpose, new experiments were carried out in which subjects were asked to walk on a treadmill with a split-belt. When the subject was walking with unequal leg speeds, the walking pattern was adapted to a gait pattern resembling limping. The TA then remained active throughout most of the stance phase of the slow-moving leg, which was used as the primary support. This activity was a result of coactivation of agonistic and antagonistic leg muscles in the supporting leg, and represented one of the ways to stabilize the body. Electrical stimulation was given to a cutaneous nerve (sural) at the ankle at twice the perception threshold. Nine of the 12 subjects showed increased TA activity during stance phase while walking on split-belts, and 5 of them showed pronounced suppressions during the first part of stance when stimuli were given on the slow side. It was concluded that a TA suppressive pathway remains open throughout most of the stance phase in the majority of subjects. The suggestion was made that the TA suppression increases loading of the ankle plantar flexors during the loading phase of stance.Key words: human gait, cutaneous reflexes, sural nerve, tibialis anterior, split belt, reflex reversal.

An experimental setup to directly monitor the rates of light induced dry etching reactions is presented. We use an etching cell kept inside an ultrahigh vacuum chamber which allows in situ sample preparation and the combination with a vacuum ultraviolet monochromator for synchrotron radiation. The sample material is evaporated on a polished quartz crystal which serves to monitor the reaction rates via the frequency changes. As a model system measurements for Cu samples are presented with Cl2 as etching gas and Ar as carrier gas. We distinguish between processes originating from gas phase excitation (non-selective) and from surface excitation (selective). In addition the dark reaction is separated.

The aim of this study was to evaluate the influence of vestibulo-spinal drive on the performance of various locomotor-like movements. The extent of body rotation was assessed during walking (1 Hz and 2 Hz), running and hopping in place after vestibular stimulation (10 body rotations; 0.5 Hz). Compared to the controls, body rotations with eyes closed were larger during hopping than while running and smallest during walking independent of stepping frequency. A close correlation existed between the absolute duration of stance phase of the two legs and the rotation of the body. It is suggested that the amount of proprioceptive feedback from the legs determines the influence of vestibulo-spinal input on body movement.

Purpose:: We investigated whether recording the perineal sympathetic skin response, which reflects the sympathetic function of the thoracolumbar spinal cord, represents a reliable and accurate diagnostic tool for assessing bladder neck competence and incompetence.Materials and Methods:: We compared the sympathetic skin response recorded from the hand, foot and perineal skin with urodynamic findings in 90 patients with neurogenic bladder dysfunction, including 66 with spinal cord injury and 24 with cauda equina lesions.Results:: Video urodynamics revealed an incompetent bladder neck in 11 of 32 patients (34%) with complete and 7 of 34 (21%) with incomplete spinal cord injury but in only 1 of 24 (4%) with the conus-cauda equina syndrome. This association significantly correlated with the lesion level at T10 to L2 in 12 of 26 cases (46%) as well as with the loss of perineal but preserved hand and foot sympathetic skin response in 13 of 18 (72%).Conclusions:: Recording the perineal sympathetic skin response i...

Objectives: To evaluate the diagnostic and prognostic contribution of motor nerve conduction studies (NCS) in addition to neurological examination in patients with acute paraplegia. Methods: In 79 patients with acute onset of paraplegia due to traumatic or ischaemic damage of the conus medullaris/cauda equina (conus/cauda) or lesion of the mid-thoracic spinal cord (epiconal) neurological (initial and follow-up clinical motor and sensory scores; outcome of ambulatory capacity determined at least 6 months post-trauma) and electrophysiological examinations (motor nerve conduction velocity (MNCV) and compound motor action potential (CMAP) of tibial and peroneal nerves) were performed in parallel. Results: Severe axonal motor neuropathies were significantly caused by conus/cauda lesions (loss of tibial CMAP in 71% and of peroneal CMAP in 68%) compared to patients with epiconal lesion (no loss of tibial CMAP and abolished peroneal CMAP in 14%). The CMAPs were deemed acutely pathological 4–14 days post-trauma and were indicative of the severity of conus/cauda lesion while the MNCV remained normal. Follow-up recordings (up to 1 year post trauma) revealed no significant change in the CMAP values. The clinical examination according to the American Spinal Injury Association (ASIA protocol) in contrast to the CMAP values was significantly related to the outcome of ambulatory capacity. Conclusions: In contrast to patients with an epiconal SCI almost all patients with damage of the conus/cauda present a severe axonal neuropathy of the tibial and peroneal nerves. Pathological CMAPs develop as early as 1–2 weeks after onset of acute paraplegia. They allow, at an early stage, to differentiate between conus/cauda or epiconal lesion and to assess the severity of conus/cauda lesion. Thereafter follow-up examinations remain stable and a developing worsening of peripheral nerve or spinal cord function, eg due to post-traumatic syringomyelia, may be indicated by a secondary deterioration of CMAP values. The clinical examination, according to the ASIA protocol, in acute paraplegia patients, in contrast to the motor nerve conduction studies, is of prognostic value in predicting the outcome of ambulatory capacity. Spinal Cord (2000) 38, 203–210

Introduction Using EMG and tension recordings during treadmill walking in spastic patients, the authors provide arguments that changes in mechanical muscle fibre properties contribute to spastic muscle hypertonia. Material and methods EMG activity and tension of the gastrocnemius and tibialis anterior muscles are registered in 15 hemiplegic patients during treadmill walking with and without disturbances. Results In the unaffected leg, tension and EMG activity were closely related. On the contrary, in the hemiplegic leg, the tension is increased throughout the stance phase while the EMG activity is depressed. When the foot is displaced backward, short and polysynaptic reflexes are presented in the unaffected leg while the polysynaptic reflexes are depressed in the hemiplegic leg. Discussion and conclusion The data suggest that the increased stretch reflexes are not the main mechanism responsible for the spastic movement disorder and that at least part of the impaired function is due to changes in mechanical muscle fibre properties.

We put forward the hypothesis that synchronous muscle activation would be less frequent with increasingly more complex grip tasks. Six subjects performed a visuo-motor step-tracking task using the precision and the power grip. During the experiment transcranial magnetic stimuli were applied. Electromyographic activity was recorded from the hand muscles active in both tasks. Muscle synchronization was found to be enhanced during the power grip as compared to the precision grip. Magnetic stimulation had a stronger effect during the precision grip than during the power grip. Our findings are in favour of a variable organization of muscle activation in hand muscles during various tasks and support the stronger contribution of the corticomotoneuronal system in the precision than the power grip.

Spasticity develops as a consequence of damage to the central nervous system (CNS). Clinically, spasticity is characterized by muscle hypertension and exaggerated reflexes and is associated with varying degrees of paresis. Together this results in the syndrome of spastic paresis. Patients suffer from impeded and retarded movement ability. Electrophysiological investigations of functional arm and leg movements (e.g. in walking) show a reduced activation of arm and leg muscles which can be explained by the loss of activating signals from motor brain centers and functional reflex systems. This effect predominates over the increased tendon-reflex activity. The reduced muscle activation caused by paresis is partially compensated by structural alterations of the muscle fibers (e.g. loss of sarcomeres). For this reason a functional improvement mostly cannot be achieved by antispastic medication which targets the deactivation of tendon-reflexes. However, they are useful in immobilized patients. In mobile patients functional improvement can be achieved by functional training which is accompanied by an adapted, i.e. reduced, spastic muscle tone.

1. The effect of body immersion on postural adjustments was studied in ten healthy subjects. Reaction times, for pushing or pulling a rigid handle, in response to a visual stimulus were measured. In addition EMG recordings were taken from upper arm and lower leg muscles during three levels of body immersion while standing on a platform (immersed to spinal levels: lumbar nerve root 2 (L2); thoracic nerve root 4 (T4); and cervical nerve root 7 (C7)), while floating and while standing or sitting out of water. 2. With increasing levels of body immersion there was a near linear reduction in the amplitude of the gastrocnemius (GM) EMG activity before (200 ms) the onset of a force signal from pulling, but immersion had a significantly weaker effect on the amplitude of the tibialis anterior (TA) EMG during pushing movements. There was no significant difference in the effect of body immersion on biceps femoris (BF) and rectus femoris (RF). Under free-floating conditions postural adjustments did not occur in response to pull or push movements. There were no adaptational changes of EMG adjustments during successive trials at a given immersion level. 3. Under non-immersed conditions reaction times were significantly shorter during sitting than during standing. This difference is assumed to be due to the postural adjustments required while standing before the onset of a voluntary arm movement. While standing, reaction times were significantly longer for pull compared with push movements. Under all conditions of body immersion the reaction times remained longer compared with the sitting condition, even when no leg muscle EMG adjustments were present. 4. It is assumed that the differential effect of body immersion on the antagonistic leg muscles is due to the differential neuronal control of antagonistic leg muscles with a strong influence from proprioceptive input (most probably from load receptors) on the leg extensors. The longer reaction times seen during body immersion, where no postural adjustments were evident, suggests that a supraspinal command to the leg muscles precedes the voluntary arm movement. However, because of the changed/decreased afferent input no postural adjustments are generated.

The case of a patient with short history of unilateral hip pain due to compression of the lumbar plexus by a cyst arising from the hip joint is reported. Radiologically there were only mild signs of osteoarthritis of the affected hip but severe degenerative changes were found in the lumbar spine. There was atrophy of the quadriceps muscle of the affected limb with subsequent giving-way during gait and sensory loss on the lateral aspect of the thigh. The neurological and electromyographical examination suggested compression of the lumbar plexus. By sonography, computerized tomography and contrast radiographs, a finger shaped cyst was identified going from the ventromedial aspect of the hip joint between the iliopsoas, the pectineus, and the iliacus muscles respectively. After excision of the cyst, hip pain ceased and the signs of neural compression disappeared almost completely within 12 weeks. Histologically the specimen showed synovial tissue with cartilaginous debris. In cases of hip pain without sufficient radiological and clinical signs of osteoarthritis, femoral nerve compression should be excluded by neurological examination. To our knowledge, this is the first report about compression of the femoral nerve by an isolated extrapelvic cyst arising from the hip joint.

This chapter deals with the neuronal mechanisms underlying impaired gait. The aim is, first, a better understanding of the underlying pathophysiology and, second, the selection of an adequate treatment. One of the first symptoms of a lesion within the central motor system perceived by patients is a movement disorder, which is most characteristic during locomotion, e.g. in patients suffering spasticity after stroke or a spinal cord injury or Parkinson disease. By the recording and analysis of electrophysiological and biomechanical signals during a movement, the significance of impaired reflex behavior or muscle tone and its contribution to the movement disorder can reliably be assessed. Adequate treatment should not be restricted to the correction of an isolated clinical sign but should be based on the mechanisms underlying the movement disorder that impairs the patient. Therapy should be directed toward functional training, which takes advantage of the plasticity of the nervous system. In the future a combination of repair and functional training will further improve the mobility of disabled patients.

The adaptation of leg movements to split-belt conditions was studied during treadmill walking in 10 healthy subjects. Four different belt speeds (0.5/1.0/1.5/2.0 m/s) were offered in all possible combinations for the left and right leg. All subjects automatically adapted to split-belt conditions. Although in all subjects and in all conditions the adaptation of leg movements within the stride cycle resulted in a walking pattern, the stepping pattern in conditions with extreme speed differences could be best described as limping. Regardless of the speed combination offered to the left and right leg, the adaptation to differences in left and right belt speed always involved: (1) Changes in stride cycle duration. The stride frequency in split-belt conditions was always intermediate to the values found during normal walking at speeds corresponding to the left and right belt speeds. There was a tendency towards the normal value of the faster belt, however. (2) An asymmetrical adaptation of the amplitude of leg movements. The support length of a leg generally tended towards the normal value for the speed offered to this leg. Thus, within the same cycle duration, the leg on the faster moving belt always made larger amplitudes than the slower leg. (3) An altered timing of support, swing and double support durations within the stride cycle. An increase in the relative duration of the support phase of the slower leg and the swing phase of the faster leg allowed for the larger amplitude of leg movements of the faster leg. Contrary to the asymmetric adaptation in support and swing durations the adaptation in the durations of both double support periods were more or less symmetric. The results of this split-belt walking study point to a high degree of flexibility in the relative timing of leg movements during walking. It is argued that the adaptation to split-belt conditions involves the tuning of low level coordinative mechanisms to the specific task requirements during split-belt walking by means of the afferent feedback resulting from the movement pattern.

To compare the effects of electrical bipolar vessel sealing and conventional suturing on postoperative pain, recovery, costs and micturition symptoms in women undergoing vaginal hysterectomy.Randomised controlled trial.Eight teaching hospitals in the Netherlands.One hundred women scheduled to undergo vaginal hysterectomy for benign conditions excluding pelvic organ prolapse.Women were randomised to vessel sealing or conventional surgery. The quality of life related to pelvic floor function was assessed using validated questionnaires before surgery and 6 months after surgery. Pain scores and recovery were assessed using a diary, including daily visual analogue scale scores, starting from the day before surgery until 6 weeks after surgery.Visual analogue scale pain scores, surgery time, blood loss, complications, quality of life related to pelvic floor function and costs.The evening after surgery, women in the vessel-sealing group reported significantly less pain (5.7 versus 4.5 on a scale of 0-10, P = 0.03), but after that pain scores were similar. Operation duration was shorter for vessel sealing (60 versus 71 minutes, P = 0.05). Blood loss and hospital stay did not differ. We observed no major difference in costs between the two interventions (2903 versus 3102 €, P = 0.26). Changes in micturition and defecation symptoms were not affected by the surgical technique used.Using vessel sealing during vaginal hysterectomy resulted in less pain on the first postoperative day, shorter operating time, similar morbidity and similar pelvic floor function. No major differences in costs were found between the two interventions.

Serial neurological examinations were analysed on 94 consecutive spinal cord injury (SCI) patients admitted for rehabilitation to the Swiss Paraplegic Center at the Clinic Balgrist Zurich, Switzerland between 1987 and 1992. Patients' data were examined adopting ASIA and modified Frankel definitions in order to compare the two classifications in terms of consistency and prognostic value. The modified Frankel definition was subdivided into five categories (A, B, C, D and E). On admission (discharge) 43 (37) patients were classified as Frankel A, 23 (11) patients in group B, 26 (42) patients in group C, 2 (2) patients as Frankel D and 0 (2) patients in group E. A qualitative analysis of the results on the base of a maximal score of 100 points (A = 0, B = 25, C = 50, D = 75 and E = 100 points) suggested a mean score improvement from 21.5 (+/- 22.5) to 29.0 (+/- 26.3) or 7.5 (+/- 7.1), regarding all 94 patients during follow up (admission/discharge). The median improvement was one modified Frankel grade (A/B to B/C). No detailed assessments were yielded concerning motor and sensory functions. Using ASIA definition, a continuous numerical score of motor and sensory function was observed. Recovery during follow up was determined by detailed motor and sensory function. For all 94 patients (quadriplegics and tetraplegics), the average motor recovery according to the ASIA definition was 9.4 (+/- 9.6). The mean ASIA motor score improved from 52.2 (+/- 17.3) on admission to 61.6 (+/- 17.9) on discharge.(ABSTRACT TRUNCATED AT 250 WORDS)

To assess in women with stress urinary incontinence (SUI) the value of urodynamics prior to treatment.We performed a multicenter non-inferiority randomized controlled trial. Women with SUI were randomly allocated to management based on a workup with or without urodynamics. The primary outcome was clinical reduction of complaints as measured with the Urogenital Distress Inventory urinary incontinence subscale (UDI-UI) at 12 months after the onset of treatment. A mean difference in improvement of less than 8 was considered non-inferior. The study was analyzed according to intention-to-treat.The trial was stopped prematurely because of slow recruitment. We randomly allocated 59 women to a strategy with (N = 31) or without (N = 28) urodynamics. The mean difference in improvement on the UDI-UI was 14 in favor of the group without urodynamics (48 SD ± 22 vs. 34 SD ± 22, 95% CI: -28 to -0.26), confirming non-inferiority. Addition of urodynamics did not result in a lower occurrence of de novo overactive bladder complaints compared to a workup without urodynamics (6/31 vs. 1/28; RR 5.4, 95% CI: 0.70-42). In the group allocated to urodynamics, initial surgical management was more often abandoned compared to the group not allocated to urodynamics (5/31 vs. 1/28; RR 4.5, 95% CI: 0.56-36).In this relatively small study, the omission of urodynamics was not inferior to the use of urodynamics in the preoperative workup of women with SUI. Women with SUI undergoing urodynamics had the risk of a choice for more prudent treatment, which seemed to result in a delay until effective treatment.