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At least 685 records · Page 38Linked to original sources
PubMed2001

A computational model of mechanisms controlling experience-dependent reorganization of representational maps in auditory cortex.

Cortical representations of sound can be modified by repeatedly pairing presentation of a pure tone with electrical stimulation of neuromodulatory neurons located in the basal forebrain (Bakin & Weinberger, 1996; Kilgard & Merzenich, 1998a). We developed a computational model to investigate the possible effects of basal forebrain modulation on map reorganization in the auditory cortex. The model is a self-organizing map with acoustic response characteristics mimicking those observed in the mammalian auditory cortex. We simulated the effects of basal forebrain modulation, using parameters intrinsic to the self-organizing map, such as the learning rate (controlling the adaptability of map nodes) and the neighborhood function (controlling the excitability of map nodes). Previous research has suggested that both parameters can be useful for characterizing the effects of neuromodulation on plasticity (Kohonen, 1993; Myers et al., 1996; Myers, Ermita, Hasselmo, & Gluck, 1998). The model successfully accounts for experimentally observed effects of pairing basal forebrain stimulation with the presentation of a single tone, but not of two tones, suggesting that auditory cortical plasticity is constrained in ways not accounted for by current theories. Despite this limitation, the model provides a useful framework for describing experience-induced changes in auditory representations and for relating such changes to variations in the excitability and adaptability of cortical neurons produced by neuromodulation.

Animals↗
PubMedDate not supplied

Optimizing heat shock protein expression induced by prostate cancer laser therapy through predictive computational models.

Thermal therapy efficacy can be diminished due to heat shock protein (HSP) induction in regions of a tumor where temperatures are insufficient to coagulate proteins. HSP expression enhances tumor cell viability and imparts resistance to chemotherapy and radiation treatments, which are generally employed in conjunction with hyperthermia. Therefore, an understanding of the thermally induced HSP expression within the targeted tumor must be incorporated into the treatment plan to optimize the thermal dose delivery and permit prediction of the overall tissue response. A treatment planning computational model capable of predicting the temperature, HSP27 and HSP70 expression, and damage fraction distributions associated with laser heating in healthy prostate tissue and tumors is presented. Measured thermally induced HSP27 and HSP70 expression kinetics and injury data for normal and cancerous prostate cells and prostate tumors are employed to create the first HSP expression predictive model and formulate an Arrhenius damage model. The correlation coefficients between measured and model predicted temperature, HSP27, and HSP70 were 0.98, 0.99, and 0.99, respectively, confirming the accuracy of the model. Utilization of the treatment planning model in the design of prostate cancer thermal therapies can enable optimization of the treatment outcome by controlling HSP expression and injury.

Animals↗
PubMedDate not supplied

Computational models for identifying potential P-glycoprotein substrates and inhibitors.

Multidrug resistance mediated by ATP binding cassette (ABC) transporters such as P-glycoprotein (P-gp) represents a serious problem for the development of effective anticancer drugs. In addition, P-gp has been shown to reduce oral absorption, modulate hepatic, renal, or intestinal elimination, and restrict blood-brain barrier penetration of several drugs. Consequently, there is a great interest in anticipating whether drug candidates are P-gp substrates or inhibitors. In this respect, two different computational models have been developed. A method for discriminating P-gp substrates and nonsubstrates has been set up based on calculated molecular descriptors and multivariate analysis using a training set of 53 diverse drugs. These compounds were previously classified as P-gp substrates or nonsubstrates on the basis of the efflux ratio from Caco-2 permeability measurements. The program Volsurf was used to compute the compounds' molecular descriptors. The descriptors were correlated to the experimental classes using partial least squares discriminant analysis (PLSD). The model was able to predict correctly the behavior of 72% of an external set of 272 proprietary compounds. Thirty of the 53 previously mentioned drugs were also evaluated for P-gp inhibition using a calcein-AM (CAM) assay. On the basis of these additional P-gp functional data, a PLSD analysis using GRIND-pharmacophore-based descriptors was performed to model P-gp substrates having poor or no inhibitory activity versus inhibitors having no evidence of significant transport. The model was able to discriminate between 69 substrates and 56 inhibitors taken from the literature with an average accuracy of 82%. The model allowed also the identification of some key molecular features that differentiate a substrate from an inhibitor, which should be taken into consideration in the design of new candidate drugs. These two models can be implemented in a virtual screening funnel.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2004

Spiral artery associated restricted growth (SPAARG): a computer model of pathophysiology resulting from low intervillous pressure having fetal programming implications.

Failure of adequate trophoblastic conversion of maternal spiral arteries is associated with intrauterine growth restriction (IUGR). In addition to poor oxygen delivery, raised spiral artery resistance reduces placental intervillous pressure. An iterative type computer model was formed by linking an existing model of the fetus and a new nine cotyledon placental model. Simulation of compression cuffing of the spiral arteries to progressively restrict uteroplacental flow was performed, while observing various fetal and placental variables. Water moved to the fetus in the cotyledonary core villi, and to the mother in the outer villous layers. While the fetus could match villous capillary pressure to changes in intervillous pressure, net transplacental water movement was minimal, but when spiral artery resistance was increased sufficiently to cause mean intervillous pressure to fall below that which the fetus could match, a net flow to the mother appeared. That continued until the resulting fetal blood hemoconcentration produced a sufficient increase in colloid osmotic pressure to restrict further loss. All cells within the fetal-placental unit are then required to operate in an abnormal ionic environment, which may significantly affect systems such as the renin-angiotensin set-point, with implications for post-natal homeostasis such as control of adult blood pressure. Furthermore, in vivo, cells of the feto-placental unit respond to the increased intravascular osmotic pressure by production of intracellular osmolytes in order to match intracellular and vascular/interstitial osmotic pressures. This may explain the observed effects on postnatal water balance in growth restricted infants and could also provide a possible mechanism for the association of the systemic maternal complications associated with impaired placentation and reduced intervillus flow.

Journal Article↗
PubMed2005

The impact of anatomic manipulations on pharyngeal collapse: results from a computational model of the normal human upper airway.

Obstructive sleep apnea (OSA) is a common disease with important neurocognitive and cardiovascular sequelae. Existing therapies are unsatisfactory, leading investigators to seek alternative forms of anatomic manipulation to influence pharyngeal mechanics. We have developed a two-dimensional computational model of the normal human upper airway based on signal averaging of MRI. Using the finite element method, we can perform various anatomic perturbations on the structure in order to assess the impact of these manipulations on pharyngeal mechanics and collapse. By design, the normal sleeping upper airway model collapses at -13 cm H2O. This closing pressure becomes more negative (ie, less collapsible) when we perform mandibular advancement (-21 cm H2O), palatal resection (-18 cm H2O), or palatal stiffening (-17 cm H2O). Where clinical data are available in the literature, the results of our model correspond reasonably well. Furthermore, our model provides information regarding the site of obstruction and provides hypotheses for clinical studies that can be undertaken in the future (eg, combination therapies). We believe that, in the future, finite element modeling will provide a useful tool to help advance our understanding of OSA and its response to various therapies.

Airway Obstruction↗
PubMed1991

Study on the genesis of giant negative T wave in apical hypertrophic cardiomyopathy using a three-dimensional computer model.

Apical hypertrophic cardiomyopathy is characterized by a spade-like left ventricular cavity and by both giant negative T waves and tall R waves in the electrocardiogram. However, the mechanisms of these ECG abnormalities have not been satisfactorily clarified. We have recently developed a three-dimensional computer model of ventricular depolarization and repolarization processes. This model has successfully simulated normal QRST waves and changes characterizing some abnormal conditions. A model of apical hypertrophic cardiomyopathy was constructed by adding model units to the endocardium of the left ventricular apex. The surface ECG was then calculated by assuming different gradients of action potential durations and different proportions of the hypertrophic cells in the apical segment. A negative T wave of -1.45 mV in lead V4, similar to the clinically reported ECG, was obtained by assuming: (1) diffusely distributed hypertrophic cells at the apex and (2) uniform, long action potential durations of hypertrophic cells. It is suggested that these properties may account for the distinctive ECG abnormalities in apical hypertrophic cardiomyopathy.

Cardiomyopathy, Hypertrophic↗
PubMed1997

A prognostic computer model to predict individual outcome in interventional cardiology. The INTERVENT Project.

It is not yet possible to predict an individual's outcome from percutaneous transluminal coronary angioplasty or alternative/adjunctive coronary interventional techniques. The purpose of the INTERVENT project is to redefine complications associated with coronary interventions, to set up a prognostic computer model to predict individual outcome and to compare the results to those of conventional statistical techniques. 2500 data items were analysed in 455 consecutive patients (mean age: 61.1 +/- 8.3 years; range 33-84 years; 80.4% male, 16.7% unstable angina, 5.1%/10.1% acute/subacute myocardial infarction) undergoing coronary interventions at three university centres. In-lab/out-of-lab complication rates were 0.4%/0.9% (death), 1.8%/0.2% (abrupt vessel closure with myocardial infarction) and 5.5%/4.0% (haemodynamic complications). Computer algorithms derived by applying techniques from artificial intelligence were able (1) to reduce the set of possible relevant risk factors from 2500 to about 40, (2) to predict individual risk with an accuracy of > 95% and (3) to explain the structural relationship between outcome and risk factors. Patient data from two centres were used to construct and test the algorithm. Data from a third centre were used to evaluate the algorithm. The most important predictors-were acute myocardial infarction, heart failure (NYHA class > II), unstable angina, complex lesions, high low density lipoprotein cholesterol and duration of coronary heart disease. Neither age nor gender impaired the percutaneous transluminal coronary angioplasty results in acute ischaemic syndromes; however, for stable angina, procedural risk increased with age. There was little risk from primary percutaneous transluminal coronary angioplasty in acute myocardial infarction in patients with NYHA heart failure classes I-II; however, the risk was high for patients in NYHA classes > II, either with or without additional thrombolysis. Alternative/adjunctive intervention techniques were no predictors for in-lab-, but were predictors for post-procedural complications.

Adult↗
PubMed1986

A computer model of slipped capital femoral epiphysis. Causes of fixation error and chondrolysis.

Penetration of the joint by metal pins can occur when treating slipped capital femoral epiphysis. Predisposing factors are present in the usual surgical methods. These include x-ray detail loss secondary to the pelvic projection and failure to obtain specific x-ray orientation to the axis of the capital epiphysis. One operative strategy to reduce these predispositions is presented. A probable mechanism of how chondrolysis can occur without joint penetration following extra capsular osteotomy is described with a theoretical remedy. Computer disease modeling and treatment simulation are the basis of this study. The computer model, which closely simulates all degrees of the disease, suggests that SCFE deformation is caused by hip extension against anterior hip capsule contracture. The latter is also the proposed cause of chondrolysis following realignment procedures.

Biomechanical Phenomena↗
PubMedDate not supplied

Examination of the potential structure of human salivary cystatins based on computer modelling.

The cystatin family of proteins exists in both excreted and intracellular forms, and appears to be involved in protective and regulatory roles, inhibiting a variety of bacterial, viral and intracellular proteases. The amino acid sequences of several human forms of cystatin are known, but currently only the structure of chicken cystatin (approx. 40% homologous to the human forms) has been experimentally determined. The objective of this study was to use the X-ray coordinates of chicken cystatin to construct computer models of the structures of three human salivary forms (SN, S and SA). These structures were energy-minimized and subjected to dynamic simulations. The resultant structures were compared to determine conformational differences. Global root mean square deviations between equivalent atoms ranged from 1.4 A to 3.9 A. The closest structural similarity to chicken cystatin involved cystatin SN, which also showed the highest (68%) functional sequence homology. Local secondary structure was examined in more detail. In comparisons of alpha-carbon position the third beta-strand (77% functional sequence conservation) and its preceding loop (60% conserved) showed the highest structural conservation in S, while beta-strand 4 showed the highest structural conservation in SN and SA. Throughout their structures, SN and SA were more structurally similar to chicken cystatin than to salivary cystatin S. There are two regions of conserved, negatively charged residues in the salivary cystatins, which appear to be spaced so that they are capable of interaction with hydroxypatite. It is concluded that not only does structural modelling by analogy provide detailed models of salivary cystatins that can be tested by future experimentation, but also that examination of the models has revealed potential sites of interaction with hydroxyapatite.

Amino Acid Sequence↗
PubMed2001

150 mM HCO3(-)--how does the pancreas do it? Clues from computer modelling of the duct cell.

Cystic fibrosis (CF) takes its name from the pathological changes that occur in the pancreas. Cystic fibrosis transmembrane conductance regulator (CFTR) is highly expressed in the pancreatic ductal epithelium and plays a key role in ductal HCO(3)(-) secretion. In humans, the pancreatic duct secretes near isotonic NaHCO(3). Experimental data suggests that HCO(3)(-) secretion occurs via apical Cl(-)/HCO(3)(-) exchangers working in parallel with Cl(-) channels (CFTR and calcium activated chloride channels, CaCC). Programming the currently available experimental data into our computer model (based on network thermodynamics) shows that while the anion exchanger/Cl(-) channel mechanism will produce a relatively large volume of a HCO(3)(-)-rich fluid, it can only raise the luminal HCO(3)(-) concentration up to about 70 mM. To achieve secretion of about 150 mM NaHCO(3) it is necessary to modulate the properties of the apical membrane transporters as the secreted fluid flows down the ductal system. On the basis of our computer simulations, we propose that HCO(3)(-) secretion occurs mainly via the exchanger in duct segments near the acini (luminal HCO(3)(-) concentration up to about 70 mM), but mainly via channels further down the ductal tree (raising luminal HCO(3)(-) to about 150 mM). We speculate that the switch between these two secretory mechanisms is controlled by a series of luminal signals (e.g. pH, HCO(3)(-) concentration) acting on the apical membrane transporters in the duct cell.

Animals↗
PubMed1996

The antiarrhythmic effect of verapamil on atrioventricular re-entry in the Wolff-Parkinson-White syndrome: a computer model study.

Verapamil is supposed to suppress the initiation of circus movement supraventricular tachycardia by affecting the atrioventricular node. In electrophysiological tests, programmed stimulation is usually performed by using the same location for pacing and premature stimulus. Spontaneous ectopic activity starts from a different location than the sinus node and can therefore find altered re-entry conditions. In this study a 3D computer model based on Huygen's principle is used for simulation of the spread of excitation in the human heart in combination with a posterobasal, right or left lateral accessory pathway (AP). The effect of verapamil on properties of the atrioventricular node were modelled by prolonging the effective refractory period and basal conduction time. For each of the three APs, ectopic foci at the atrial base and between sinus node and AP were modelled at various coupling intervals for investigating re-entrant activation. In the control state (without verapamil) only orthodromic echoes were found. The maximum echo zone (EZ) range was found near the AP. If stimuli were selected further away from the AP on the atrial basis, the EZ range decreased until no EZ was found. The EZ range decreased from it's maximum value near the AP, towards the difference of the effective refractory periods between AP and AV-node near the sinus node Verapamil abolished the EZ in case of a posteroseptal AP. For a lateral AP the administration of verapamil resulted in an orthodromic and antidromic EZ depending on the atrial premature activation site. A maximum orthodromic EZ was found for premature stimuli near the AP. As stimulus site moved away from the AP, the EZ range first decreased continuously to zero leading eventually to an antidromic EZ. These findings suggest the important influence of the site of premature stimuli with respect to the accessory pathway and AV-node on the inducibility of atrial re-entry.

Anti-Arrhythmia Agents↗
PubMed2003

ARMADA--a computer model of the impact of environmental factors on health.

Environmental impact assessments are conducted on many developments as part of the planning process. There is currently wide interest in developing tools for assessing the impact on the health of the local population of proposed developments that will cause environmental changes. A computer model called ARMADA (Age Related Morbidity And Death Analysis) is described that provides a framework for investigating such health impacts. ARMADA generates estimates of age-related patterns of morbidity and mortality within the local population. These estimates incorporate the demographic features of the population in question and base-line information about the incidence of the disease classes being considered.

Age Factors↗
PubMed1985

Tensorial computer model of gaze--I. Oculomotor activity is expressed in non-orthogonal natural coordinates.

The central nervous system expresses its function in natural frames of reference. A most conspicuous feature of such frames is their non-orthogonality. Gaze stabilization and, in particular, the sensorimotor transformations performed by the vestibulo-ocular reflex, are prime examples of such general coordinate transformations between and within multidimensional non-orthogonal frames. Since such operations can be described by tensor formalisms in an abstract manner, this methodology is applied here to develop a tensorial computer model of gaze stabilization. The representation of sensorimotor transformations by a reference-frame independent method obviates the necessity to simplify the intrinsic coordinate systems either by a reduction of the dimensionality or by a presumption of orthogonality. The frames of reference intrinsic to vestibulo-ocular reflex transformation (the vestibular semicircular canals and extraocular muscles) as well as the covariant character of the sensory input and the contravariant character of the motor output are physically obvious. A model built on these intrinsic systems of coordinates first serves to quantitate the degree of non-orthogonality in the extraocular muscle system, and thus to demonstrate both the necessity and the applicability of representing them by a formalism suitable for non-orthogonal systems, such as tensor network theory. The actual non-orthogonality of the gaze-stabilization system can be quantitated on the basis of the difference of covariant and contravariant expressions as follows. Tensor network theory describes sensorimotor transformations by employing a covariant embedding procedure. This, however, yields a covariant intention-type motor vector. If the central nervous system were to transmit these sensory-type components directly to the extraocular muscle motor mechanism, an error-angle would occur since covariants do not physically compose the intended movement. The error in every direction of gaze would be zero only if the extraocular muscle system would constitute an orthogonal set of rotation axes. Otherwise, the error, called refraction angle, is a measure of non-orthogonality. The complexity of the quantitation of non-orthogonality is compounded by the fact that these rotation axes change with the moving eye. Calculation of eye movements, executed both by covariant and contravariant vectors from primary and secondary eye positions, is based on the simplest assumption that the central nervous system establishes the covariant-contravariant transformation in the retinal tangent plane.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1998

Determination and analysis of antigenic epitopes of prostate specific antigen (PSA) and human glandular kallikrein 2 (hK2) using synthetic peptides and computer modeling.

Prostate specific antigen (PSA) and human glandular kallikrein 2 (hK2), produced essentially by the prostate gland, are 237-amino acid monomeric proteins, with 79% identity in primary structure. Twenty-five anti-PSA monoclonal antibodies (Mabs) were studied for binding to a large array of synthetic linear peptides selected from computer models of PSA and hK2, as well as to biotinylated peptides covering the entire PSA sequence. Sixteen of the Mabs were bound to linear peptides forming four independent binding regions (I-IV). Binding region I was localized to amino acid residues 1-13 (identical sequence for PSA and hK2), II (a and b) was localized to residues 53-64, III (a and b) was localized to residues 80-91 (= kallikrein loop), and IV was localized to residues 151-164. Mabs binding to regions I and IIa were reactive with free PSA, PSA-ACT complex, and with hK2; Mabs binding to regions IIb, IIIa, and IV were reactive with free PSA and PSA-ACT complex, but unreactive with hK2; Mabs binding to region IIIb detected free PSA only. All Mabs tested (n = 7) specific for free PSA reacted with kallikrein loop (binding region IIIb). The presence of Mabs interacting with binding region I did not inhibit the catalytic activity of PSA, whereas Mabs interacting with other binding regions inhibited the catalysis. Theoretical model structures of PSA, hK2, and the PSA-ACT complex were combined with the presented data to suggest an overall orientation of PSA with regard to ACT.

Amino Acid Sequence↗
PubMed1999

A prognostic computer model to individually predict post-procedural complications in interventional cardiology: the INTERVENT Project.

AIMS: The purpose of this part of the INTERVENT project was (1) to redefine and individually predict post-procedural complications associated with coronary interventions, including alternative/adjunctive techniques to PTCA and (2) to employ the prognostic INTERVENT computer model to clarify the structural relationship between (pre)-procedural risk factors and post-procedural outcome. METHODS AND RESULTS: In a multicentre study, 2500 data items of 455 consecutive patients (mean age: 61.1+/-8.3 years: 33-84 years) undergoing coronary interventions at three university centres were analysed. 80.4% of the patients were male, 16.7% had unstable angina, and 5.1%/10.1% acute/subacute myocardial infarction. There were multiple or multivessel stenoses in 16.0%, vessel bending >90 degrees in 14.5%, irregular vessel contours in 65.0%, moderate calcifications in 20.9%, moderate/severe vessel tortuosity in 53.2% and a diameter stenosis of 90%-99% in 44.4% of cases. The in-lab (out-of-lab) complications were: 0.4% (0.9%) death, 1.8% (0.2%) abrupt vessel closure with myocardial infarction and 5.5% (4.0) haemodynamic disorders. CONCLUSION: Computer algorithms derived from artificial intelligence were able to predict the individual risk of these post-procedural complications with an accuracy of >95% and to explain the structural relationship between risk factors and post-procedural complications. The most important prognostic factors were: heart failure (NYHA class), use of adjunctive/alternative techniques (rotablation, atherectomy, laser), acute coronary ischaemia, pre-existent cardiac medication, stenosis length, stenosis morphology (calcification), gender, age, amount of contrast agent and smoker status. Pre-medication with aspirin or other cardiac medication had a beneficial effect. Techniques, such as laser angioplasty or atherectomy were predictors for post-procedural complications. Single predictors alone were not able to describe the individual outcome completely.

Adult↗
PubMed2004

Proarrhythmic consequences of a KCNQ1 AKAP-binding domain mutation: computational models of whole cells and heterogeneous tissue.

The KCNQ1-G589D gene mutation, associated with a long-QT syndrome, has been shown to disrupt yotiao-mediated targeting of protein kinase A and protein phosphatase-1 to the I(Ks) channel. To investigate how this defect may lead to ventricular arrhythmia during sympathetic stimulation, we use integrative computational models of beta-adrenergic signaling, myocyte excitation-contraction coupling, and action potential propagation in a rabbit ventricular wedge. Paradoxically, we find that the KCNQ1-G589D mutation alone does not prolong the QT interval. But when coupled with beta-adrenergic stimulation in a whole-cell model, the KCNQ1-G589D mutation induced QT prolongation and transient afterdepolarizations, known cellular mechanisms for arrhythmogenesis. These cellular mechanisms amplified tissue heterogeneities in a three-dimensional rabbit ventricular wedge model, elevating transmural dispersion of repolarization and creating other T-wave abnormalities on simulated electrocardiograms. Increasing heart rate protected both single myocyte and the coupled myocardium models from arrhythmic consequences. These findings suggest that the KCNQ1-G589D mutation disrupts a critical link between beta-adrenergic signaling and myocyte electrophysiology, creating both triggers of cardiac arrhythmia and a myocardial substrate vulnerable to such electrical disturbances.

Action Potentials↗
PubMed2004

Postmortem time estimation using body temperature and a finite-element computer model.

In the Netherlands most murder victims are found 2-24 h after the crime. During this period, body temperature decrease is the most reliable method to estimate the postmortem time (PMT). Recently, two murder cases were analysed in which currently available methods did not provide a sufficiently reliable estimate of the PMT. In both cases a study was performed to verify the statements of suspects. For this purpose a finite-element computer model was developed that simulates a human torso and its clothing. With this model, changes to the body and the environment can also be modelled; this was very relevant in one of the cases, as the body had been in the presence of a small fire. In both cases it was possible to falsify the statements of the suspects by improving the accuracy of the PMT estimate. The estimated PMT in both cases was within the range of Henssge's model. The standard deviation of the PMT estimate was 35 min in the first case and 45 min in the second case, compared to 168 min (2.8 h) in Henssge's model. In conclusion, the model as presented here can have additional value for improving the accuracy of the PMT estimate. In contrast to the simple model of Henssge, the current model allows for increased accuracy when more detailed information is available. Moreover, the sensitivity of the predicted PMT for uncertainty in the circumstances can be studied, which is crucial to the confidence of the judge in the results.

Autopsy↗
PubMed1994

Selective stimulation of sacral nerve roots for bladder control: a study by computer modeling.

The aim of this study was to investigate theoretically the conditions for the activation of the detrusor muscle without activation of the urethral sphincter and afferent fibers, when stimulating the related sacral roots. Therefore, the sensitivity of excitation and blocking thresholds of nerve fibers within a sacral root to geometric and electrical parameters in tripolar stimulation using a cuff electrode, have been stimulated by a computer model. A 3-D rotationally symmetrical model, representing the geometry and electrical conductivity of a nerve root surrounded by cerebrospinal fluid and a cuff was used, in combination with a model representing the electrical properties of a myelinated nerve fiber. The electric behavior of nerve fibers having different diameters and positions in a sacral root was analyzed and the optimal geometric and electrical parameters to be used for sacral root stimulation were determined. The model predicts that an asymmetrical tripolar cuff can generate unidirectional action potentials in small nerve fibers while blocking the large fibers bidirectionally. This result shows that selective activation of the detrusor may be possible without activation of the urethral sphincter and the afferent fibers.

Animals↗