Functional imaging in obese children responding to long-term sports therapy.

Functional imaging studies on responders and non-responders to therapeutic interventions in obese children are rare. We applied fMRI before and after a one-year sports therapy in 14 obese or overweight children aged 7-16 years. During scanning, participants observed a set of standardized pictures from food categories, sports, and pleasant and neutral images. We were interested in alterations of the cerebral activation to food images in association with changes in the BMI-standard deviation score (BMI-SDS) after therapy and therefore separated the observation group into two outcome subgroups. One with reduction of BMI-SDS >0.2 (responder group) and one without (non-responder group). Before therapy fMRI-activation between groups did not differ. After therapy we found the following results: in response to food images, obese children of the responder group showed increased activation in the left putamen when compared with the non-responder group. Pleasant images evoked increased insula activation in the responder group. Only the responder group showed enhanced activity within areas known to store trained motor patterns in response to sports images. Both the putamen and the insula are involved in the processing of emotional valence and were only active for the therapy responders during the observation of food or pleasant stimuli. Elevated activity in these regions might possibly be seen in the context of an increase of dopaminergic response to emotional positive stimuli during intervention. In addition, sport images activated motor representations only in those subjects who profited from the sports therapy. Overall, an altered response to rewarding and pleasant images and an increased recruitment of motor engrams during observations of sports pictures indicates a more normal cerebral processing in response to these stimuli after successful sports therapy in obese children.

Demonstration of spontaneous and stretch induced urinary bladder EMG in the living rabbit.

Spontaneous bladder EMG was recorded in the living rabbit from an isovolumetric bladder without chemical or electrical stimulation. Mechanical intervention, either by lifting the bladder out of the abdomen or by rapid filling, resulted in stretch induced bladder EMG. A self made epoxy resin electrode device that embedded 32 EMG recording electrodes in a matrix like pattern, each electrode Ag/AgCl, d = 0.6 mm with an interdistance of 2.3 mm, was used for registration. The recorder used a common average reference technique and a sample frequency of 400 Hz. A signal bandwidth of 0.05 to 108 Hz was available for analysis. Spontaneous EMG consisted of single spikes and bursts (2-20 spikes), but not of continuous activity. The shape of spikes was triphasic. Single spikes appeared with and without burst activity. Small (2-5 spikes) and large bursts (6-20 spikes) were discerned; small bursts not necessarily propagated across electrodes, large bursts did and were able to organize, suggesting that they were under short neuron system control. Spontaneous EMG was probably related to both contraction and relaxation. Stretch induced EMG was characterised by continuous activity on all electrodes, spikes that followed each other immediately, slowly fading away. The spikes had an elongated third phase when compared to the shape of spontaneous activity. Highest activity and amplitudes were found after lifting the bladder out of the abdomen and placing it on the electrode device. A concept is put forward in which the continuous activity is not unequivocally related to muscle shortening, but where the current stress and strain situation of the bladder tissue can cause a muscle fibre elongation upon the appearance of electrical activity. The EMG activity found was in many aspects similar to results of a previous study using mortalized rabbits. Artifact sources like the heart, respiration, or local movement between electrode and bladder could easily be identified due to the new experimental methodology used.

Validity of a non-invasive determination of the isovolumetric bladder pressure during voiding in men with LUTS.

Invasive pressure flow analysis is the gold standard for discriminating between hypocontractile bladder muscle function and infravesical obstruction in male patients with lower urinary tract symptoms. Here a non-invasive method to determine the isovolumetric bladder pressure to judge contractility is presented. This is based on interruption of urine flow by sudden occlusion of a specially fixed condom catheter. The pressure inside the condom is recorded and used to estimate the isovolumetric bladder pressure. Combined with, for example, home uroflowmetry, this non-invasive method may overcome some of the disadvantages (e.g., invasiveness, cost) of the conventional pressure flow test. To determine the isovolumetric bladder pressure reliably with this non-invasive method, two constraints have to be met. First, the bladder neck and urethra have to remain open after occlusion of the condom catheter. This was tested combining the non-invasive test with radiography in five patients. Second, a steady state has to be reached, i.e., the flow in the urethra, due to the elastic properties of the biological and the condom systems, should come to a stop when the bladder pressure and the condom pressure equilibrate. This was investigated by comparing the non-invasively recorded condom pressure with the simultaneously invasively recorded intravesical pressure in 52 patients. In these patients, three different methods of condom fixation were evaluated. The results show that the bladder neck and urethra remain open during the test. However, a steady state is often not reached. In more than 80% of the cases with the best condom fixation, the bladder pressure has not stabilized, although the condom pressure reached a plateau. Therefore, this method of sudden occlusion is not yet clinically applicable for determining the isovolumetric bladder pressure. Neurourol. Urodynam. 18:477-486, 1999.

The neuronal control of the lower urinary tract: A model of architecture and control mechanisms.

The human micturition cycle is controlled by central and peripheral nervous structures and connections. In literature, no complete or generally accepted model describes the principles of micturition control. In this paper, the integration of (neuro-)anatomy, (neuro-)physiology and control theory is used to describe and model the neuronal control of the lower urinary tract. Neuroanatomy supplies the most basic information necessary for the modellation of the peripheral pathways and central connections involved in the control of the uropoetic system. It is found that not all the nervous structures and connections have been identified as such yet. The linking up between several nervous structures (e.g., the presence of central and peripheral relay stations) is not completely clear. A s a consequence, each model to describe the micturition cycle from the perspective of control theory is yet of limited physiological value as it cannot exceed a rather general level of modellation. Adding functional considerations (neurophysiology and control theory) to the neuroanatomical skeleton completes the model. Some control mechanisms active during the micturition cycle can still not be revealed in detail. Crucial questions on the neuronal innervation of the human uropoetic system and the control mechanisms active during the micturition cycle remain, like how the supraspinal trigger mechanisms for micturition are organised, or how the voluntary cessation of voiding is realised. A simplified version of the model discussed in this paper can already be used for mathematical modelling, e.g., neural network simulations.

Three dimensional registration of mechanical bladder activity using polystyrene fluorescent spheres: A technical note.

Optical marker tracing methods have been applied successfully in recent years to quantify local material deformation of heart tissue, skin and striated muscles. In this study, polystyrene fluorescent spheres (d = 0.6 mm) are glued to the ventral serosal bladder wall in the rabbit. Three dimensional video registration of the polystyrene spheres is used to calculate two directions of principal strain (epsilon (1), epsilon (2) ) on the bladder surface in vivo. The aim is to investigate the feasibility of the technique for this new application in two experimental circumstances: during spontaneous bladder wall activity and after electrical stimulation of bladder innervating nerve fibers. During spontaneous activity, random contraction and relaxation occurred simultaneously and separately across the bladder wall for the two principal strains epsilon (1) and epsilon (2). After extradural electrical stimulation of sacral nerve root S2, the principal strains epsilon ( 1) and epsilon (2) synchronized in time in such a way that epsilon ( 1) and epsilon (2) both represented contraction or both represented relaxation. One and the same bladder wall area passed through phases of contraction followed by relaxation and vice versa. After multiple stimulation periods, the coordination between the two principal strains during stimulation was reduced. This technique allows to identify local areas of contraction and relaxation in the intact bladder wall in vivo. Three dimensional video registration of polystyrene fluorescent spheres to study bladder wall contraction and its relaxation proved to be a feasible technique, with which electrical stimulation effects and spontaneous activity could be measured.

A non-invasive method for bladder electromyography in humans.

No convincing correlation of bladder EMG in humans to simultaneously measured intravesical pressure has been reported in the literature. In most studies on bladder EMG the electrodes contact the bladder wall itself. This causes problems in the discrimination between very small extracellular signals, reflecting actual membrane potential changes of bladder muscle cells, and large electro-mechanical artefact caused by electrode movement as the tissue contracts. Aim of this study is to investigate whether bladder EMG can be performed non-invasively with Ag-AgCl surface electrodes that are placed on the abdominal skin of healthy volunteers. Bipolar electrode signals are obtained in a diagonal, vertical and horizontal direction of the abdominal electrodes. A conventional urodynamic investigation is performed according to International Continence Society standards simultaneously with bladder EMG. This new method shows that voiding is accompanied by a slow voltage change in bipolar electrode signals. The contribution of abdominal and other striated muscle activity to the bipolar electrode signals can clearly be distinguished from the slow voltage changes related to voiding. Free flowmetry shows that the electrical activity picked up by the abdominal electrodes is related to bladder emptying. In pressure/flow studies a relation between the electrical activity and the detrusor pressure is found. The present results suggest that the slow voltage changes found during bladder contraction are caused by summed membrane potential changes of bladder muscle cells, but this concept needs further testing. Also, validation for clinical use remains to be established.

Integrin and cadherin synergy regulates contact inhibition of migration and motile activity.

Integrin receptors play a central role in cell migration through their roles as adhesive receptors for both other cells and extracellular matrix components. In this study, we demonstrate that integrin and cadherin receptors coordinately regulate contact-mediated inhibition of cell migration. In addition to promoting proliferation (Sastry, S., M. Lakonishok, D. Thomas, J. Muschler, and A. Horwitz. 1996. J. Cell Biol. 133:169-184), ectopic expression of the alpha5 integrin in cultures of primary quail myoblasts promotes a striking contact-mediated inhibition of cell migration. Myoblasts ectopically expressing alpha5 integrin (alpha5 myoblasts) move normally when not in contact, but upon contact, they show inhibition of migration and motile activity (i.e., extension and retraction of membrane protrusions). As a consequence, these cells tend to grow in aggregates and do not migrate to close a wound. This phenotype is also seen with ectopic expression of beta1 integrin, paxillin, or activated FAK (CD2 FAK) and therefore appears to result from enhanced integrin-mediated signaling. The contact inhibition observed in the alpha5 myoblasts is mediated by N-cadherin, whose expression is upregulated more than fivefold. Perturbation studies using low calcium conditions, antibody inhibition, and ectopic expression of wild-type and mutant N-cadherins all implicate N-cadherin in the contact inhibition of migration. Ectopic expression of N-cadherin also produces cells that show inhibited migration upon contact; however, they do not show suppressed motile activity, suggesting that integrins and cadherins coordinately regulate motile activity. These observations have potential importance to normal and pathologic processes during embryonic development and tumor metastasis.

Inhibitory activity of 3'-fluoro-2' deoxythymidine and related nucleoside analogues against adenoviruses in vitro.

Antiviral effects of nucleoside analogues against human adenoviruses (ADV) belonging to subgroup B (ADV3) and C (ADV2) were comparatively analysed using focus reduction assay on Fogh and Lund (FL) cells. 3'-Fluoro-2'-deoxythymidine (FTdR), 3'-fluoro-2'-deoxyuridine (FUdR), 2',3'-dideoxycytidine (ddC) and 3'-fluoro-2'-deoxyguanosine (FGdR) emerged as potent and selective inhibitors. They were nontoxic for the FL cells at the tested doses. FTdR was proved to be the most effective inhibitor against both serotypes ADV2 and ADV3 (0.05 microM/0.02 microM). The inhibitory effect of FTdR was also analyzed on the level of viral proteins and viral DNA synthesis using radioimmunoprecipitation and PCR, respectively. Neither the main structural protein of ADV, the hexon, nor viral DNA could be detected in ADV-infected FL cells that had been exposed to FTdR.

A method for the electromyographic mapping of the detrusor smooth muscle.

Various methods for detrusor EMG in the living mammal have been described in the literature. These methods do insufficiently take into account signal components that are caused by movement between the electrodes and the bladder wall. Reliable detrusor EMG has not been achieved yet. This study investigates the feasibility of a new experimental set-up, in which the electrical activity of the detrusor smooth muscle can be examined. In six rabbits, after cervical dislocation, laparotomy and after excision of the heart, electrical signals of the detrusor muscle are measured with 240 electrodes. The electrodes are positioned on the serosal surface of the filled and isovolumetric bladder. During the recordings, no bladder contractions are deliberately evoked by any stimulus. Consistent results in all six animals show a repetitive spike pattern on multiple electrodes with a repetition frequency of 1.2 Hz. Spikes are triphasic and have a mean duration of 0.47 s (STD = 0.15 s, n = 40) and a mean amplitude of 0.29 mV (STD = 0.07 mV, n = 40). On adjacent electrodes a time shift between the spikes is found, suggesting the propagation of electrical activity across the detrusor surface. The maximum conduction velocity of an arbitrary spike front in the direction of propagation is approximately 30 mm/s. In two animals slow waves are found on the edge of the highpass filter setting. Extensive control experiments are executed to validate the set-up and to interpret the data obtained by the animal experiments. The bladder is still able to contract thirty minutes post mortem. The heart, as a distant signal source, generates a signal that is present on all electrodes and shows no detectable time shift from one electrode to any other. Motion imposed on the electrodes relative to the bladder wall does not reproduce the slow waves and spikes found in the animal experiments. The control experiments support that the results of the animal experiments show electrical activity originating from the detrusor muscle itself. With the experimental set-up described in this paper, nearly artefact free detrusor EMG can be recorded. An electromyographic map of a considerable detrusor smooth muscle area can be obtained.

Neuronal circuitry of the lower urinary tract; central and peripheral neuronal control of the micturition cycle.

A new presentation technique is introduce to describe the neuronal circuitry involved in the control of the uropoëtic system and its control mechanisms during the micturition cycle. This method is based on the preparation of flow charts and is applied to the discussion of four qualitative models which are derived from the literature. Opinions concerning the reflex arcs and supraspinal connections said to be involved in micturition and continence are different and sometimes contradictory. Little is known about supraspinal (inter)connections and their function in micturition control is still fragmentary. The control mechanisms which terminate voiding are not totally clear. Moreover, the role of the pelvic floor musculature in the control of the lower urinary tract is probably underestimated. The flow charts presented in this paper contribute to the future design of a single complete qualitative model representing the general central and peripheral nervous connections and control mechanisms. Such a model would provide an approach for future research in neuromodulation and neurostimulation of the uropoëtic system and a reduced version could be used for quantitative modelling, e.g. in neural network simulations.

[Evaluation of 3 automatic systems for measurement of the erythrocyte sedimentation rate]. / Valoración de tres sistemas automáticos para la determinación de la velocidad de sedimentación globular.

PURPOSE: To evaluate three automated devices for measuring the erythrocyte sedimentation rate (ESR) (VES-MATIC 60, Menarini(R); SEDISCAN Becton-Dickinson(R) y SEDIMATIC, Ral(R)) by comparison with the Westergren method (WM). MATERIAL AND METHODS: A total of 1576 whole blood samples (VM: 694, SC: 316 and SM: 566) from patients of the Hospital Clínic i Provincial de Barcelona were included in this study. In all the specimens, the ESR was determined following the ICSH recommendations (WM). The Student's t test for paired data and linear regression analysis were used for inaccuracy study. Reproducibility was assessed after five measurements of three different samples and establishing the coefficient of variation (CV). RESULTS: Significant correlation was found between the systems studied and th WM. Moreover, for ESR > 21 mm/h (groups II, III and IV) the results provided by VM system were not significantly different from those of WM. Finally, all the systems presented a good reproducibility, although the lower values of CV were obtained with the VM method. CONCLUSIONS: The automatic systems for measurements of the ESR demonstrate important advantages and, from this analysis, we concluded that the VM could be the alternative method to conventional Westergren for the ESR determination.

[Lezius nailing under controversy? Experiences with Lezius-Herzer curved nailing in 1,062 pertrochanteric femoral fractures]. / Lezius-Nagelung im Widerstreit? Erfahrungen mit der Rundnagelung nach Lezius-Herzer bei 1062 pertrochanteren Oberschenkelfrakturen.

Curved nailing according to Lezius and Herzer was applied to 700 of 1,062 cases of pertrochanteric fractures of the femur at the Surgical Department of the "Carl Gustav Carus" Medical Academy, Dresden, between 1964 and 1985. Complications are described, and results are generally compared with other surgical techniques used to handle pertrochanteric fractures of the femur. Lezius nailing, when compared to other methods, has proved to be a simple and reliable approach, primarily under the aspect of geriatric traumatology, and should be used on a much wider scale.