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At least 1,405 records · Page 78Linked to original sources
PubMed2002

Computer simulation of the inverse problem of electrocardiography: use of properties of harmonic functions.

The problem of reconstructing the pattern of heart excitation from body surface potentials is simulated. The problem is well known as the inverse problem of electrocardiography and in a general case this problem has a non-unique solution. The relationship of the problem with the inverse problem of potential theory is shown. From this relationship a new excitation propagation model for the heart ventricles is developed. The model is based on a classical multidipole cardiogenerator, but is stable, flexible, and provides a unique solution for the inverse problem of electrocardiography.

Body Surface Potential Mapping↗
PubMed1997

Inverse localization of electric dipole current sources in finite element models of the human head.

The paper describes finite element related procedures for inverse localization of multiple sources in realistically shaped head models. Dipole sources are modeled by placing proper monopole sources on neighboring nodes. Lead field operators are established for dipole sources. Two different strategies for the solution of inverse problems, namely combinatorial optimization techniques and regularization methods are discussed and applied to visually evoked potentials, for which exemplary results are shown. Most of the procedures described are fully automatic and require only proper input preparation. The overall work for the example presented (from EEG recording to visual inspection of the results) can be performed in roughly a week, most of which is waiting time for the computation of the lead field matrix or inverse calculations on a standard and affordable engineering workstation.

Cerebral Cortex↗
PubMed2000

The putative < > 5-HT(1A) receptor antagonist, WAY 100635, has inverse agonist properties at cloned human 5-HT(1A) receptors.

Agonist binding to G protein-coupled receptors induces the formation of a receptor-G protein complex and subsequent guanosine 5'-diphosphate/guanosine 5'-triphosphate (GDP/GTP) exchange. Some receptors, however, form receptor-G protein complexes and promote GDP/GTP exchange even when not occupied by agonists. Such receptors preferentially activate pertussis toxin-sensitive G proteins (i.e., G(i)/G(o)), and the interactions of receptors and G proteins are affected by monovalent cations (most notably Na(+)), both in the occupied and unoccupied state. We investigated the effects of Na(+) on the intrinsic activity of 5-hydroxytryptamine(1A) (5-HT(1A)) receptor ligands, measured as maximal effect (E(MAX)), using guanosine 5'-0-(3-[35S]thio)-triphosphate ([35S]GTPgammaS) binding to membranes prepared from human epithelioid carcinoma (HeLa) cells, expressing 500 fmol/mg protein of cloned human 5-HT(1A) receptor (HA7 cells). A decrease of the NaCl concentration decreased the maximal effect of serotonin, increased basal [35S]GTPgammaS binding, and increased the negative intrinsic activity of spiperone and N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]-N-(2-pyridinyl)cyclohexaneca rboxamide (WAY 100635). This ability of WAY 100635 to decrease basal [35S]GTPgammaS binding was antagonized by (s)-N-tert-butyl-3-(4-(2-methoxyphenyl)piperazine-1-yl)-2-phenylpropa namide ((s)-WAY 100135) (pA(2)=7.77). Further, WAY 100635 was able to antagonize carboxamidotryptamine (5-CT)-stimulated [35S]GTPgammaS binding with a pA(2) of 9.9, in standard NaCl conditions, and of 9.7, in the absence of NaCl. Changes in membrane concentration did not affect the ability of WAY 100635 to decrease [35S]GTPgammaS binding. WAY 100635 did not affect basal [35S]GTPgammaS binding to membranes from untransfected HeLa cells. Pertussis toxin (200 ng/ml) prevented WAY 100635 and spiperone to decrease [35S]GTPgammaS binding, showing that their effects were mediated by G proteins of the G(i)/G(o) family. In conclusion, the constitutive and stimulated activity of human 5-HT(1A) receptors expressed in HA7 cells is sodium-dependent, which allowed to confirm the 5-HT(1A) inverse agonist properties of spiperone, and to show that WAY 100635 is an inverse agonist at 5-HT(1A) receptors that inhibits basal [35S]GTPgammaS binding to a lesser extent than spiperone. [35S]GTPgammaS binding to membranes from HA7 cells under low NaCl conditions appears to be especially suitable to evidence and pharmacologically analyze the inverse agonist properties of 5-HT(1A) receptor ligands.

Binding, Competitive↗
PubMed2000

Inverse agonism by Dmt-Tic analogues and HS 378, a naltrindole analogue.

The potent delta-opioid receptor antagonist H-2',6-L-tyrosine(Dmt)-1, 2,3,4-tetrahydroisoquinoline-3-carboxylic acid (Tic-OH) exhibited partial inverse agonism (EC(50)=6.35 nM, E(max)=-18.87%) for [35S]GTPgammaS binding and H-Dmt-Tic-NH(2) was a neutral antagonist (no effect up to 30 microM). In contrast N,N(CH(3))(2)-Dmt-Tic-NH(2) was a full inverse agonist (EC(50)=2.66 nM, E(max)=-35.95%) similar to ICI 174864 ([N,N-diallyl-Tyr(1),Aib(2,3),Leu(5)]enkephaline) but with a 3.5-fold higher EC(50). In comparison, naltrindole was a neutral antagonist while its analogue HS 378 was a partial inverse agonist (E(max)=-12.99%).

Benzamides↗
PubMed1998

Assessing the cause of T wave inversion in precordial leads with ECG mapping.

Inversion of the T wave in precordial leads in patients with angina pectoris is a predictor of coronary disease; however, it may also be seen in normal adults. The aim of this study was to assess the cause of T wave inversion by carrying out precordial electrocardiographic (ECG) mapping in 51 patients, who also underwent echocardiography and coronary angiography. The 37 patients in group A had atypical symptoms. They included 11 patients who showed M pattern mapping, of whom 7 had noncoronary cardiac disease and 4 were normal. In 23 other group A patients, whose mappings were in the N pattern, the angiography was normal. In the remaining three patients of this group, mappings were in the I pattern, with angiography revealing coronary disease in two of them and no disease in the third. The 14 group B patients all had typical angina; mappings were in the I pattern in 8 of the patients and in the N pattern in the remaining 6. Angiography revealed coronary artery disease in all patients with the I pattern mapping, while all those with the N pattern were found to be normal. Sensitivity, specificity, and positive predictive value for detecting normal subjects were all 100% for N pattern mapping; for detecting coronary disease, they were 100%, 90%, and 90% for I pattern mapping, respectively. It is concluded that precordial ECG mapping is an accurate method for the assessment of T wave inversion in precordial leads.

Adult↗
PubMed2002

Contribution of the alpha1-GABA(A) receptor subtype to the pharmacological actions of benzodiazepine site inverse agonists.

A histidine-to-arginine point-mutation at position 101 in the alpha1-subunit of gamma-aminobutyric acid (GABA)(A) receptors has been shown to switch the in vitro efficacy of Ro 15-4513 from inverse agonism to agonism. In order to assess the consequences of this pharmacological switch in vivo, the motor and proconvulsant effects of Ro 15-4513 were analyzed in knock-in mice containing point-mutated alpha1(H101R)-GABA(A) receptors. Furthermore the influence of the alpha1(H101R) substitution on the efficacy of the beta-carboline inverse agonist DMCM was examined both in vitro and in vivo. Ro 15-4513 (10 mg/kg) increased baseline locomotion and potentiated the convulsant effect of pentylenetetrazole in wild type mice. In alpha1(H101R) mice, Ro 15-4513 decreased locomotion and, at a higher dose (30 mg/kg) it displayed an anticonvulsant action. In vitro, DMCM acted as an inverse agonist at recombinant alpha1beta2gamma2 receptors whereas it potentiated GABA-evoked chloride currents at alpha1(H101R)beta2gamma2 receptors. DMCM was inactive as a convulsant in alpha1(H101R) mice. In keeping with the major contribution of these receptors to the sedative and anticonvulsant properties of benzodiazepine site agonists, the present findings identify the alpha1-GABA(A) receptors as the molecular targets for the allosteric modulation by benzodiazepine site ligands in either direction with regard to the behavioral outputs, sedation/motor stimulation and anticonvulsion/proconvulsion.

Animals↗
PubMed1996

Systemic pressor response during hindlimb ischemia is inversely related to femoral artery pressure and fractional inspired oxygen.

BACKGROUND: Delayed-onset reflex increases in mean arterial pressure (MAP) occur during clamping of the infrarenal aorta. This study investigated the afferent limb of the reflex by independently altering femoral artery blood pressure (FBP) or fractional concentration of inspired oxygen (FIO2) while monitoring systemic arterial blood pressure. METHODS: The infrarenal aorta was divided, and an occlusive roller pump delivered incremental flow to the distal aorta thus controlling FBP. In six dogs the FBP was reduced in random order to 50, 40, 30, 20, and 10 mm Hg and held constant for 30 minutes. In another six dogs the FBP was held at 20 mm Hg, whereas the FIO2 was randomly varied among 0.13, 0.21, and 1.0 for 30-minute intervals. RESULTS: Under these conditions MAP was significantly and inversely correlated with FBP (MAP was 172 +/- 8 mm Hg when FBP was 10 mm Hg, p < 0.0001; MAP was 158 +/- 8 mm Hg when FBP was 20 mm Hg, p = 0.0001; MAP was 138 +/- 7 mm Hg when FBP was 30 mm Hg, p = 0.0048; and MAP was 130 +/- 7 mm Hg when FBP was 40 mm Hg, p = 0.0045). MAP was significantly and inversely related to the FIO2 value when FBP was fixed at 20 mm Hg (MAP of 186 +/- 9 mm Hg at FIO2 of 0.13 and was significantly higher than MAP of 163 +/- 11 mm Hg at FIO2 of 0.21, p = 0.01; and MAP of 157 +/- 10 mm Hg at FIO2 of 1.0, p = 0.0001). CONCLUSIONS: The magnitude of the delayed systemic pressor response is inversely proportional to the FBP. We suggest that this pressor response is also particularly sensitive, in part, to arterial blood oxygen tension when hindlimb perfusion pressure is low.

Animals↗
PubMed2001

Inversion of synthetic and experimental acoustical scattering data for the comparison of two reconstruction methods employing the Born approximation.

This work is concerned with the reconstruction, from measured (synthetic or real) data, of a 2D penetrable fluid-like object of arbitrary cross-section embedded in a fluid of infinite extent and insonified by a plane acoustic wave. Green's theorem is used to provide a domain integral representation of the scattered field. The introduction therein of the Born approximation gives rise to a linearized form of the inverse problem. The actual inversion is carried out by two methods. The first diffraction tomography (DT), exhibits the contrast function very conveniently and explicitly in the form of a wave number/incident angle Fourier transform of the far backscattered field and thus requires measurements of this field for incident waves all around the object and at all frequencies. The second discretized domain integral equation with Born approximation method, is numerically more intensive, but enables a wider choice of configurations and requires less measurements (one or several frequencies, one or several incident waves, choice of measurement points) than the DT method. A comparison of the two methods is carried out by inversion of both simulated and experimental scattered field data.

Acoustics↗
PubMed1998

Inversion superiority in visual agnosia may be common to a variety of orientation polarised objects besides faces.

Selective impairment in recognition of faces (prosopagnosia) resulting from certain localized cortical lesions has been advanced as an argument for a face specific brain module. The argument is claimed to be strengthened by the discovery of an inversion superiority effect in the recognition of faces by a prosopagnosic patient (Farah et al., Vis Res 1995b;35:2089-2093). The present paper reports an inversion superiority effect in the recognition of faces and shoes in a visual agnosic patient. The finding raises the possibility that several classes of orientationally polarized objects, of which shoes and faces are examples, will exhibit inversion superiority.

Aged↗
PubMed2000

Linear inverse filtering improves spatial separation of nonlinear brain dynamics: a simulation study.

We examined topographic variations in nonlinear measures based on scalp voltages, which were generated by two simulated current dipoles each placed in a different hemisphere of a spherical volume conductor (three-shell model). Dipole dynamics were that of a three-torus and the x-component of the Lorenz-system and scalp voltage were calculated for a configuration of 29 electrode positions. Although estimates for correlation dimension D2 and Lyapunov exponent L1 were close to the theoretical values for the original time series, the simulated scalp voltage data showed almost no topographic resolution of dipole positions. In order to enhance topographic differentiation, we constructed linear inverse filters, to focus on brain activity from a specified brain region. It turned out that the nonlinear measures for the inversely filtered time series were much closer to the expected values (with respect to the location of the dipoles used in the simulation) than when using unfiltered data. Our preliminary results indicate that inverse filtering can improve the topographic resolution of nonlinear scalp EEG estimates.

Brain↗
PubMed2002

Mechanically induced ankle inversion during human walking and jumping.

A new method to study sudden ankle inversions during human walking and jumping is presented. Ankle inversions of 25 degrees were elicited using a box containing a trap door. During the gait task, subjects walked at a speed of 4 km/h. At a pre-programmed delay after left heel strike, an electromagnet released the box on the treadmill. This delay enabled the subject to step on the box without having to change the walking cadence. During the jumping task, subjects jumped from a 30 cm high platform on the box in a standardised way. In both tasks 20 stimulus and 20 control trials were presented randomly. The average tilting velocity of the trap door during the stimulus trials was 403 degrees /s during the walking task and 595 degrees /s during the jumping task. For the control trials a tilting of 0 degrees was used. With this method it is possible to evoke reproducible ankle inversions causing characteristic EMG responses in six lower leg muscles.

Adult↗
PubMed1997

Inverse dynamics as a tool for motion analysis: arm tracking movements in cerebellar patients.

Kinematic analysis of limb movements can be used to evaluate motion of patients with movement disorders. Those with clinically mild to moderate impairment, however, often show only small, insignificant deviations in the measured trajectories compared to those of healthy controls. Furthermore, kinematic data alone do not give sufficient information about internal quantities such as muscle activation or joint moments. In order to improve the sensitivity of motion analysis of limb movements, we propose the use of inverse dynamics, since it allows biomechanical quantities to be determined without restricting movement. We developed an inverse dynamic model of the upper limb with 9 degrees of freedom. Spatial positions (Cartesian coordinates) of anatomical landmarks, which were recorded by an infrared video-based three-dimensional motion analysis system, are transformed into body-related Cardan angles. The model determines joint moments and powers at the shoulder, elbow, and wrist. Arm tracking movements in a patient with a mild cerebellar ataxia and a healthy control demonstrate that the model allows a clear differentiation between normal and abnormal limb movements, even if no significant differences are noted in the recorded trajectories. We conlude that inverse dynamic modeling can be an effective tool for motion analysis in patients with cerebellar disorders. It also gives further insight into the parameters that may be controlled by the central nervous system.

Arm↗
PubMed1997

Does central serotonergic function correlate inversely with aggression? A study using D-fenfluramine in healthy subjects.

Much research has investigated possible links between serotonergic function and aggression in violent or personality disordered populations, but few studies have looked at healthy subjects. In this study we administered 30 mg of the specific 5-HT releasing agent D-fenfluramine to 35 healthy subjects, along with questionnaire measures of hostility and aggression. Prolactin and cortisol responses were used as indices of central 5-HT function. In males, there were significant inverse correlations between 5-HT mediated cortisol responses and both the Buss-Durkee Hostility Inventory total score and the aggression factor. There were no such relations in female subjects or using prolactin responses. There was also an inverse relation between basal cortisol levels and both prolactin and cortisol responses, but no relation between basal cortisol levels and aggressive measures. These results provide some support for the existence of an inverse relationship between central serotonin function and aggression/hostility in healthy males, similar to that seen in previous studies using violent or highly aggressive populations.

Adult↗
PubMed2002

Mechanisms of inverse agonism at G-protein-coupled receptors.

Many drugs with important therapeutic actions that had been assumed to be antagonists at G-protein-coupled receptors (GPCRs) have been shown to be inverse agonists. For both basic pharmacology and drug design it is important to understand the mechanisms whereby these drugs achieve their effects. It had been assumed that these drugs achieved their effects by stabilizing an inactive state of the receptor (R) at the expense of a partially activated state (R*). In this article, I consider this and other mechanisms that could explain inverse agonist actions, and conclude that more than one mechanism can apply to inverse agonism at GPCRs.

Animals↗
PubMed2001

Inverse association between sense of humor and coronary heart disease.

Prospective studies have suggested that antisocial Type A personality traits may be associated with an increased incidence of coronary heart disease (CHD). However, few data have addressed whether more favorable personality characteristics may be inversely correlated with CHD. Therefore, two standardized questionnaires designed to either assess anger and hostility or to measure the propensity to laugh under a variety of situations encountered in everyday life, were administered to 300 consecutive subjects. Compared to controls, CHD subjects were significantly less likely to experience laughter during daily activities, surprise situations or social interactions (P<0.005). Logistic regression analysis revealed an inverse correlation between humor and CHD, even after adjustment for other covariates, including hypercholesterolemia, hypertension and diabetes mellitus (P=0.03). A significant inverse association was also observed between humor production and antisocial Type A personality traits (P=0.0001). These data extend previous observations linking antisocial Type A personality traits to CHD and raise the possibility that the propensity to laugh may contribute to cardioprotection.

Analysis of Variance↗
PubMed2003

Stereotactic intensity modulated radiation therapy and inverse treatment planning for tumors of the head and neck region: clinical implementation of the step and shoot approach and first clinical results.

PURPOSE/OBJECTIVE: The aim of this analysis is to evaluate the feasibility of inverse treatment planning and intensity modulated radiation therapy (IMRT) for head and neck cancer in daily clinical routine. A step and shoot IMRT approach was developed which allows the treatment of large target volumes without the need to use a split beam technique. By using the IMRT approach better protection of different organs at risk in the head and neck region may be achieved and an escalation of the dose in the tumor should be possible. We evaluated the feasibility of the treatment technique and the patient tolerance to the treatment. First clinical results are reported. MATERIALS AND METHODS: Between 1999 and 2002, 48 patients with a carcinoma of the head and neck region were treated with curative intention. All patients were treated in a patient-specific Scotch-Cast mask. Patients who required treatment of the lymph node levels I-VI, were additionally positioned by a vacuum pillow in order to immobilize the upper part of the thorax. For inverse treatment planning, the software module KonRad was used which was integrated into the VIRTUOS planning system. Each treatment plan was verified using quantitative film dosimetry in a head and neck phantom. The step and shoot IMRT technique with a multileaf collimator integrated in a Primus (Siemens) accelerator was used for treatment. For all target volumes the whole target including the lymph nodes were covered completely by the IMRT treatment. RESULTS: The mean total dose for the target volumes of macroscopic disease ranged between 63.0 and 64.1 Gy. The mean total dose of microscopic disease ranged between 55.2 and 60.1 Gy. The mean percentage of planning target volume receiving <90% of the prescribed dose ranged between 3.0 and 11.5%. For the treatment, the median number of beams was seven (range: five to nine). The time to deliver the treatment ranged between 9 and 18 min. The results of the verification revealed a mean deviation between measured and calculated absolute doses for the 48 patients of 0.1+/-1.4%. Including the phantom verification the IMRT treatment of the patients could be started approximately after five working days. The treatment was well tolerated by all patients. The 2-year actuarial overall survival was 92% and the 2-year actuarial local control rate was 93%. According to the Radiation Therapy Oncology Group (RTOG), no higher acute toxicity than Grade 3 was seen. Observation of the late effects revealed only one transient Grade 4 toxicity of the bone and only four patients had a xerostomia higher than Grade 1. CONCLUSION: The use of an inversely-planned and intensity-modulated step and shoot approach is feasible in clinical routine for head and neck tumors. Treatment could be applied as planned and no increased toxicity was found. Compared to other IMRT approaches for the head and neck region the used technique allows the treatment of the primary tumor and the lymph nodes level I-VI with only one intensity modulated treatment volume. The presented technique avoids to match conventional radiotherapy fields and IMRT fields, and therefore, reduce the risk of overdosage or underdosage at the matching line. Compared to conventional treatment techniques IMRT shows advantages in tumor dose and dose at the organs at risk.

Adult↗
PubMed1999

Phase inversion dynamics of PLGA solutions related to drug delivery. Part II. The role of solution thermodynamics and bath-side mass transfer.

The role of solvent properties and bath-side composition on the phase inversion dynamics and in vitro protein release kinetics of polylactic-co-glycolic acid (PLGA) solutions has been examined using dark ground imaging, in vitro release rate, and SEM techniques. Thermodynamic phase diagrams for three model systems (PLGA in 1-methyl-2-pyrrolidinone (NMP), triacetin, and ethyl benzoate) suggest two general classes of precipitation behavior, depending on the relative solvent strength and water miscibility. Drug release from the NMP-based system is primarily governed by the dynamics of phase inversion and exhibits a distinct burst region followed by a much slower release. Alternatively, depots with low solvent/water affinity (PLGA in triacetin or ethyl benzoate) undergo much slower phase inversion, resulting in a less porous, more fluid, two-phase structure that also releases protein more uniformly. Addition of a small chain triglyceride or organic salt to the aqueous receptor bath also evokes a significant increase in the mass transfer rate of protein from the low solvent/non-solvent affinity depots. An interpretation of these results in terms of a qualitative model for the protein release mechanism is also given.

Absorption↗
PubMed1998

Analytical validation of the BEM--application of the BEM to the electrocardiographic forward and inverse problem.

The objective of this study is to analytically validate a boundary element (BE) formulation for the relationship between the transmembrane potential on the heart's surface and the potential on the body surface applying a concentric spherical test geometry. The relative difference (reldif) between the potential on the outer sphere of the test geometry computed analytically and numerically is determined by 3.59% for the coarse discretization (48 BEs) and by 0.46% in the case of the finer subdivision (192 BEs). In the inverse problem, the transmembrane potential on the inner sphere is estimated numerically from the electric potential on the outer sphere by using a minimum-norm least-square approach. The relative differences found are 20.2% when no measurement noise is added and 26.4% in the presence of 2% additional Gaussian noise. The BE formulation is also applied to real world data for solving the electrocardiographic inverse problem. A normal volunteer's inhomogeneous thorax (outer thorax surface, surfaces of the lungs, epicardial heart surface) is modelled by 424 BEs. The same inverse method is then applied in order to reconstruct the transmembrane potential on the epicardium from the measured body surface potential (BSP) data during normal ventricular depolarisation.

Electrocardiography↗