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[Liver transplantation after exertion-induced heat stroke associated with fulminant liver failure].

OBJECTIVES: Describe the course of fulminant liver failure after exertional heat stroke. CASE REPORT: A 30-year-old man acclimated to the tropical climate, collapsed and became comatose with hyperthermia during a commando march in Gabon. Thirty-six hours later, the biological examination revealed moderate rhabdomyolysis and fulminant liver failure. An orthotoptic liver transplantation was performed at the 48th hour. Acute renal failure with severe rhabdomyolysis developed on the 4th day post-surgery while the patient was perfectly alert. His condition thereafter deteriorated and he died of chronic rejection 11 months after liver transplantation. DISCUSSION: In its most serious forms exertional heat stroke is a multiple organ dysfunction syndrome of poorly understood pathogenesis. The reported case suggests that exertional heat stroke can cause fulminant liver failure, resulting either from the direct effect of heat on the hepatic parenchyma, or from acute hepatic ischemia due to blood redistribution made worse by the hypersecretion of antidiuretic hormone, a potent portal vasoconstrictor, which occurs in the heat acclimated subject.

Adult↗

Th1 and Th2 cytokines exert regulatory effects upon islet microvascular areas in the NOD mouse.

In this study, we show that intra- and peri-islet microvascular areas undergo different changes during the islet inflammation in the nonobese diabetes-prone female mice. Actually, although the islet vascular area (IVA) considerably decreases while the infiltration progresses, at 15 weeks of age, the peri-islet vascular bed is unexpectedly and significantly increased. On the contrary, the intra-IVA is significantly decreased, due to vessel dilation. Later, by 20-25 weeks of age, a decrease of both IVA occur, due to a significant islet beta cell loss. Moreover, a dramatic fall of natural free radical scavenger values, which, in turn, exert an influence upon vessels, is observed. These effects are completely counteracted by the administration of IL-4, a Th2 protective cytokine; IL-10, another putative Th2 cytokine, exerts direct effects upon endothelial cell (EC) function, as shown by the increase of endothelial nitric oxide synthase (eNOS) mRNA transcripts and by the release of endothelial NO which, in turn, exert vasodilatory effects; moreover, this cytokine significantly upregulates adhesion molecules on endothelia. On the other hand, IL-1beta, a Th1 proinflammatory cytokine, dramatically increases nitrite and nitrate levels, as well as inducible nitric oxide synthase (iNOS) transcripts and also upregulates islet ICAM-1 expression as well as circulating ICAM-1 levels. Taken together, our findings clearly show that cytokines and islet endothelia are directly involved in the pathophysiology of the disease. Their reciprocal influence gives new insight to understand the role of microvasculature during islet beta cell attack.

Animals↗

Calcium indirectly increases the control exerted by the adenine nucleotide translocator over 2-oxoglutarate oxidation in rat heart mitochondria.

The effect of calcium on the control exerted by the adenine nucleotide translocator over respiration in isolated heart mitochondria was investigated in order to determine whether calcium directly stimulates the translocator. At respiration rates intermediate between states 3 and 4, Ca2+ is shown to increase the control over 2-oxoglutarate oxidation exerted by the adenine nucleotide translocator in rat heart mitochondria. This did not occur when succinate was the respiratory substrate, even though the control exerted by the translocator was substantial, indicating that Ca2+ does not have a direct effect on the adenine nucleotide translocator. Ca2+ increased the uncoupled oxidation rate of 2-oxoglutarate, but not succinate. Using the summation theorem for flux control, the effect of Ca2+ is explained by a shift of the control over respiration rate toward the adenine nucleotide translocator, from the respiratory chain, presumably as the result of the activation of the 2-oxoglutarate dehydrogenase complex.

Adenosine Triphosphate↗

Neural computations underlying the exertion of force: a model.

We have developed a model that simulates possible mechanisms by which supraspinal neuronal signals coding forces could converge in the spinal cord and provide an ongoing integrated signal to the motoneuronal pools whose activation results in the exertion of force. The model consists of a three-layered neural network connected to a two-joint-six-muscle model of the arm. The network layers represent supraspinal populations, spinal cord interneurons, and motoneuronal pools. We propose an approach to train the network so that, after the synaptic connections between the layers are adjusted, the performance of the model is consistent with experimental data obtained on different organisms using different experimental paradigms: the stiffness characteristics of human arm; the structure of force fields generated by the stimulation of the frog's spinal cord; and a correlation between motor cortical activity and force exerted by monkey against an immovable object. The model predicts a specific pattern of connections between supraspinal populations coding forces and spinal cord interneurons: the weight of connection should be correlated with directional preference of interconnected units. Finally, our simulations demonstrate that the force generated by the sum of neural signals can be nearly equal to the vector sum of forces generated by each signal independently, in spite of the complex nonlinearities intervening between supraspinal commands and forces exerted by the arm in response to these commands.

Arm↗

Peroxovanadate but not vanadate exerts insulin-like effects in human adipocytes.

Vanadate and peroxovanadate were recently reported to exert maximal or even supramaximal (peroxovanadate) insulin-like effects in rat adipocytes. To evaluate the response in human cells, isolated human adipocytes were exposed to insulin or various concentrations of vanadate (0-10 mmol/l) or peroxovanadate (0-5 mmol/l). Neither vanadate nor peroxovanadate affected 125I-insulin binding and insulin sensitivity. Vanadate exerted no apparent effect on 14C-U-glucose uptake, whereas 0.1 mmol/l peroxovanadate exerted a full insulin-like response (p < 0.001). No additive response was observed by combining either vanadate or peroxovanadate with insulin. Peroxovanadate at 0.1 mmol/l was as effective as insulin in inhibiting isoproterenol-stimulated lipolysis. Neither peroxovanadate nor insulin-inhibited lipolysis stimulated by N6-monobutyryl-cAMP, an analogue which is not hydrolysed by the cAMP-phosphodiesterase. It is concluded that peroxovanadate, but not vanadate, elicits a full insulin-like response in human adipocytes.

Adipose Tissue↗

Twenty-four hour effects of oxprenolol Oros and atenolol on heart rate, blood pressure, exercise tolerance and perceived exertion.

The effects of oxprenolol, a non-selective beta-blocker with moderate intrinsic sympathomimetic activity (ISA), given by the Oros delivery system, on resting and exercise heart rate and blood pressure have been compared over a 24-h period with those of atenolol, a beta 1-selective blocker without ISA. The effects on maximal and submaximal exercise tolerance and perceived exertion were studied in relation to the level of beta-blockade. 9 healthy subjects were treated with placebo, atenolol, 100 mg/day and oxprenolol Oros, 16/260 mg/day in random order, each for 5 days. Progressive maximal exercise tests and submaximal endurance tests at 80% of maximum aerobic exercise capacity were performed 2, 5 and 24 h after intake of the drugs. The reduction of blood pressure 2 and 5 h after drug intake was less pronounced after oxprenolol Oros than after atenolol, but by 24 h after the last dose the effects were similar. The peak level of beta-blockade (i.e. reduction in maximal exercise heart rate) was similar after oxprenolol Oros and atenolol. The minimal level of beta-blockade 24 h after the last dose was greater after oxprenolol Oros than after atenolol. Maximal exercise capacity and submaximal exercise tolerance were impaired after both beta-blockers. The subjective feeling of exertion did not differ between placebo, atenolol and oxprenolol Oros when related to the relative work load, except after the first minute of exercise, when the rating of perceived exertion was higher after atenolol.

Adult↗

Non-cytotoxic asialo-GM1-positive cells exert antimetastatic activity.

Metastasis can be inhibited by asialo-GM1-positive spleen cells, and in this paper we show that there are two such spleen cell populations. One population is adherent and non-cytotoxic to YAC cells, whereas the other population is non-adherent and cytotoxic to YAC cells. Both cell populations exert an antimetastatic activity in cyclophosphamide-treated mice that are inoculated with LL2 Lewis lung carcinoma cells. We conclude that the antimetastatic activity is not only exerted by cytotoxic asialo-GM1-positive cells (apparently natural killer cells), but also by adherent, non-cytotoxic asialo-GM1+, Thy1.2-, IgG- cells. This means that the latter exert their antimetastatic activity by a non-cytotoxic mechanism.

Animals↗

Biomechanics of the hip: forces exerted during walking.

Since the work of Pauwels, the forces exerted on the coxofemoral joint during walking have been studied either in different spatial planes (frontal, sagittal and horizontal) or by three-dimensional spatial analysis. Starting from the findings of our own studies, our aim was to compare the two methods of analysis (two-dimensional and three-dimensional) in order to provide a better understanding of the benefits and limitations of each method. In pursuit of this aim, we studied the pressure forces exerted on the coxofemoral joint, using a geometric plane technique following a method similar to that of Pauwels [20], and with a three-dimensional modelling technique using the finite element method. The material, taken from the published literature, was the same in both our studies. The results are expressed in terms of the size and orientation of the pressure force exerted on the coxofemoral joint during the monopodal weightbearing phase of walking. A comparison of these two methods of analysis clearly demonstrates the simplicity of two-dimensional analysis (which must incorporate as a minimum the frontal plane and the sagittal plane) and the richness of the three-dimensional analysis. The latter method, by appropriate manipulation of the information obtained, provides a starting point for computer simulations performed with the aim of testing a biomechanical or therapeutic hypothesis.

Biomechanical Phenomena↗

Evaluation of acute and chronic hepatotoxic effects exerted by anabolic-androgenic steroid stanozolol in adult male rats.

Stanozolol (ST) is a 17alpha-alkyl anabolic-androgenic steroid (17alpha-AAS) often misused by athletes and bodybuilders. The use of anabolic-steroids by sportsmen and teenagers has increased dramatically, thus raising the question about their hepatotoxicity, specially those such as ST which are orally administered. Previously, we have reported diverse in vivo effects exerted by this steroid and published the existence of a highly specific ST-binding site in male rat liver microsomes. The existence of this binding site, the reported hepatic effects exerted in humans, and the very limited information about its potential hepatotoxicity led us to treat adult male rats acutely and chronically with ST and study different parameters that could indicate liver damage: serum levels of transaminases, concentration of monooxygenase enzymes in liver, liver membrane lipid peroxidation products, liver histopathology, and cell cycle/ploidy status of liver cells. In our study, no changes in serum transaminases or lipid peroxidation levels were obtained. However, acute stanozolol treatment significantly decreased the levels of cytochrome P450 (Cyt. P450) and cytochrome b5 (Cyt. b5) during the first 48 h of treatment, while subsequently, at 72 and 96 h, these microsomal enzymes underwent a significant increase in their levels. In sharp contrast with this response to acute treatment, the content of these two enzymes during chronic treatment showed an important decrease. Interestingly, acutely and chronically ST-treated livers showed slight to moderate inflammatory or degenerative lesions in centrilobular hepatocytes. Flow cytometric analysis demonstrated that both acute and chronic ST treatment were capable of increasing the percentage of S-phase fraction (%SPF) of liver cells. These findings taken together clearly show that this steroid is capable of altering the liver capacity for metabolizing xenobiotics and indicate that high doses of ST could exert a proliferative effect on liver cells. Such data should be considered in risk evaluations for this compound.

Acute Disease↗

An iterative method to calculate forces exerted by single cells and multicellular assemblies from the detection of deformations of flexible substrates.

We present a new method for quantification of traction forces exerted by migrating single cells and multicellular assemblies from deformations of flexible substrate. It is based on an iterative biconjugate gradient inversion method. We show how the iteration and the solution are influenced by experimental parameters such as the noise on deformations sigma ( XY ), and the mean depth of recorded deformations Z (M). In order to find the validity range of our computational method, we simulated two different patterns of force. The first artificial force pattern mimics the forces exerted by a migrating Dictyostelium slug at a spatial resolution of Delta=20 mum (Rieu et al. in Biophys J 89:3563-3576, 2005) and corresponds to a large and spread force field. The second simulated force pattern mimics forces exerted by a polarized fibroblast at discrete focal adhesion sites separated by Delta=4 microm. Our iterative method allows, without using explicit regularization, the detailed reconstruction of the two investigated patterns when noise is not too high (sigma ( XY )/u (max)< or =6%, where u (max )is the maximal deformation), and when the plane of recorded deformations is close to the surface (Delta/Z (M)> or =4). The method and the required range of parameters are particularly suitable to study forces over large fields such as those observed in multicellular assemblies.

Algorithms↗

The effects of an ergonomic-educational course. Postural load, perceived physical exertion, and biomechanical errors in nursing.

OBJECTIVES: To evaluate the results of an ergonomic-educational course for nurses we assessed the number and percentage of harmful postures and of ergonomic and biomechanical errors made before and after the course. We also studied the perceived physical exertion. MEANS AND METHODS: In all, 12 nurses who had participated in the course (trainees) and 12 who had not (controls) were recorded on video while performing standardized nursing tasks. The wards from which the two groups of nurses came were comparable, as were the patient populations. The nurses were also comparable in some personal characteristics. The tasks they performed included washing, lifting, and repositioning a patient as well as certain tasks other than patient handling. Video recordings were made once before (1-2 weeks) and twice after the course (after 3 months and after 15 months). The harmful postures, the errors made, and the ratings of perceived exertion were measured by means of the Ovako Working-posture Analysis System (OWAS), a checklist, and Borg scores, respectively. RESULTS: When the first and last measurements of all the above tasks taken as a whole were analyzed the trainees showed a significant improvement in the number and percentage of harmful postures and errors, whereas the controls did not. The same could be concluded for lifting alone. After the course the new work routine did not appear to have caused any extra perceived physical exertion. CONCLUSION: It can be concluded that the course was successful, although it should be carefully investigated as to whether nurses remain capable of working safely in daily practice. The work pressure that nurses experience during their normal duties could prevent them from working safely during everyday work.

Adult↗

Reversal of exertional hypotension after coronary bypass grafting.

A decrease in systolic blood pressure that occurs with treadmill exercise testing may be a sign of reversible ischemic left ventricular dysfunction. To test this hypothesis, we examined retrospectively the postoperative treadmill responses of 37 patients who had exertional hypotension (end exercise systolic blood pressure less than or equal to initial preexercise levels) before coronary arterial bypass grafting. This group of 37 patients was characterized preoperatively by an abnormal exercise electrocardiogram (36 patients), multiple vessel occlusive disease (36 patients) and a normal ejection fraction at rest (32 patients). Postoperative exercise tests showed improvement in hemodynamic and electrocardiographic changes with reversal of exertional hypotension (33 patients), and conversion to a normal exercise electrocardiogram (29 patients). Coronary bypass surgery can be expected to reverse exertional hypotension in patients with symptomatic angina pectoris and evidence of ischemia in the exercise electrocardiogram.

Adult↗

Usefulness of the hyperventilation test in stable exertional angina pectoris in selecting medical therapy.

To assess the prevalence of abnormal coronary vasoconstriction in stable exertional angina and to evaluate whether the presence of increased coronary tone may have therapeutic implications, we studied 83 consecutive patients with typical exertional angina, positive response to exercise stress testing and documented coronary artery disease. Abnormal coronary vasoconstriction was induced by a hyperventilation test in 16 patients (group I) while the remaining 67 had a negative response (group II). No differences were observed between the 2 groups with regard to clinical, exercise and angiographic data. All group I patients and 16 patients in group II repeated hyperventilation and exercise tests after the administration of dihydropyridine-type calcium antagonists (7 patients nifedipine, 9 patients felodipine). After treatment 15 of 16 group I patients had a negative response to the hyperventilation test. The total exercise duration was significantly increased (278 +/- 183 vs 554 +/- 248 seconds; p less than 0.001) with higher values of rate pressure product at peak exercise (168 +/- 47 vs 235 +/- 67 mm Hg x beats/min/100; p less than 0.0025). In group II no significant differences were observed between pre- and posttreatment values for total exercise duration (244 +/- 210 vs 308 +/- 243 seconds) and rate pressure product at peak exercise (170 +/- 46 vs 188 +/- 56 mm Hg x beats/min/100). These data show that the hyperventilation test can be used to select a subset of patients with stable exertional angina and detectable abnormal coronary vasoconstriction who will improve their exercise tolerance with coronary vasodilator treatment.

Angina Pectoris↗

Observer ratings of perceived exertion in relation to self ratings and heart rate.

The results from a comparison made between observers' estimations of a bicycling subject's exertion and the self-raters' perceived exertion show that one can draw conclusions of an individual's exertion at physical work by using observer ratings. Six bicycling subjects (self-raters) cycled on a bicycle ergometer at six different power levels presented in random order. The estimations were made simultaneously by the observers and the self-rater during the last half minute at each power level. At the same time the self-rater's heart rate was registered. In accordance with earlier findings on physical work, the relation between heart rate and power level was linear. The estimations were made on a category-ratio scale as well as with magnitude estimation. The observers found the category-ratio scale easier to use and it seems as if the category-ratio scale is as reliable as magnitude estimation for these kinds of ratings.

Journal Article↗

Perceived exertion during a self-imposed pace of work for a group of cleaners.

Nine cleaners were monitored for four hours while performing their ordinary work. They rated their perceived exertion on Borg's CR-10 scale every five minutes and their heart rates were recorded every minute. It was found that the subjects worked on a physiological 'steady-state' level, meaning that their heart rates were about the same regardless of the work performed. Their ratings of perceived exertion varied, however, but were all 'fairly strong' or stronger. During more than 80% of the time, the work periods on the different tasks were shorter than 15 min. On the basis of the results of a bicycle ergometer test, it was determined that the actual level of exertion during the ordinary work corresponded to about 35% of the subjects' estimated maximal oxygen uptake. Most subjects had back symptoms and more than half of them reported symptoms involving the neck, shoulders, wrists and hands. The varying intensities indicate where the problems are most critical.

Journal Article↗

A static dynamometer measuring multidirectional torques exerted simultaneously at the hip and knee.

The function of a static dynamometer measuring torques exerted simultaneously in the different anatomical planes of the hip (flexion-extension, abduction-adduction and internal-external rotation) and knee (flexion-extension) is described. Muscular torques were calculated in real time using a desktop computer from measurements of orthogonal forces applied at two locations and the lever arm values measured in each subject. The reliability of the force transducers was explored by examining their output, using calibrated weights, on three different days. The results were identical over this period of time, indicating that the transducers are highly reliable. A mechanical simulator of a lower limb was constructed to generate specific or combined torques of known values at the hip and knee. The torques measured by the dynamometer were found to be highly concordant with the known torques applied by the simulator, indicating that the torque measurements were valid. The usefulness of the dynamometer is demonstrated by evaluating the activity of the rectus femoris and biceps femoris muscles during static efforts exerted in various directions at the hip. In addition, the mechanical action of biarticular muscles at the hip was evaluated by quantification of hip torques during efforts exerted at the knee. From these results, it has been concluded that the present biarticular and multidirectional dynamometer is a valid, reliable and precise instrument that may prove to be useful in evaluating the muscular function of the lower limb.

Biophysics↗

How musculotendon architecture and joint geometry affect the capacity of muscles to move and exert force on objects: a review with application to arm and forearm tendon transfer design.

This commentary reviews musculotendon architecture and the relation between architectural parameters and the force, speed, and excursion capacity of musculotendon units. It is hoped that this review will help provide the framework within which to appreciate the importance of the data presented by Lieber et al. Muscle fiber pennation hardly affects musculotendon output of forearm and hand muscles. Instead, physiologic cross-sectional area and muscle fiber length affect force capacity and speed and excursion capacity, respectively. How muscles with equal mass can have different force, speed, and excursion capacities is explained. Since the moment arm of a muscle (the shortest distance from the musculotendon unit to the joint center of rotation) transforms muscle output into musculotendon output, it is shown why the capacity for a muscle to exert force on an object, as during grasping, is directly proportional to its moment arm and why the range of joint movement and speed over which muscles exert force is inversely proportional to the moment arm. Finally, tendon, being not stiff in forearm and hand musculotendon units, also affects their output. Criteria are given for designing tendon transfer reconstructions from architectural data and moment arm data to best replicate the biomechanical function of the replaced muscle. To have the same capacity for imparting movement to objects and exerting force on them, the donor muscle should have the same moment arm/physiologic cross-sectional area product, the same fiber length/moment arm ratio, and the same tendon length/muscle fiber length ratio as the replaced muscle.

Arm↗

Residual exertional ischemia and unfavorable left ventricular remodeling in patients with systolic dysfunction after anterior myocardial infarction.

OBJECTIVES: This study investigated whether exercise-induced myocardial ischemia influences left ventricular remodeling after anterior myocardial infarction. BACKGROUND: The effects of acute and recurrent ischemia on ventricular function are well established. However, to our knowledge the role of exertional ischemia in the remodeling response after infarction has not been investigated. METHODS: Ninety-one patients with a first anterior Q wave myocardial infarction were studied at 5 weeks by rest echocardiography and exercise scintigraphy. The echocardiographic examination was repeated 6 months later. On the basis of the presence and extent of reversible perfusion defects on exercise scintigraphy, patients were assigned to groups with no exertional ischemia (group 1, n = 20 [22%], mild to moderate ischemia (group 2, n = 45 [49%]) and severe exertional ischemia (group 3, n = 26 [29%]). RESULTS: Initial left ventricular volumes were similar, and no differences were found among the three groups in the remodeling response over the 6-month period of the study. However, patients in groups 2 and 3 with an ejection fraction < or = 40% showed significant (p < 0.01) ventricular enlargement over time, which was similar between the two groups (end-diastolic volume [mean +/- SD] from 74 +/- 13 to 80 +/- 17 ml/m2 in group 2 and from 72 +/- 11 to 81 +/- 19 ml/m2 in group 3; regional dilation from 42 +/- 16% to 52 +/- 22% in group 2 and from 38 +/- 18% to 46 +/- 27% in group 3). In contrast, ventricular dimensions did not change in group 1 patients with an ejection fraction < or = 40% as well as in patients in all three groups with an ejection fraction > 40%. CONCLUSIONS: Exercise-induced myocardial ischemia may contribute to progressive ventricular enlargement in patients with poor left ventricular function after a large anterior myocardial infarction.

Analysis of Variance↗