Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “modulators”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,045 records · Page 58Linked to original sources
PubMed1983

Role of the modulator protein in the interconversion of rabbit skeletal muscle protein phosphatase.

The major active protein phosphatase present in a rabbit skeletal muscle extract is associated with the glycogen particle and migrates in sucrose density gradient centrifugation as a Mr = 70,000 protein and contains modulator activity. Addition of extra modulator protein causes a time- and concentration-dependent conversion of the enzyme to an inactive FA-ATP, Mg-dependent form. The intrinsic modulator in the active phosphatase is destroyed by limited proteolysis without an appreciable change in the phosphatase activity. The proteolyzed active enzyme has a lower molecular weight (Mr = 40,000) and it reassociates with the modulator producing a FA-ATP, Mg-dependent enzyme form (Mr = 60,000). The modulator protein is used stoichiometrically in the activation of the ATP, Mg-dependent phosphatase. This is in agreement with the presence of one unit of modulator activity per unit of native spontaneously active phosphatase.

Adenosine Triphosphate↗
PubMed1997

Dual modulation of 5-fluorouracil cytotoxicity using folinic acid with a dihydropyrimidine dehydrogenase inhibitor.

Dihydropyrimidine dehydrogenase (DPD) is the key enzyme of the fluorouracil (FU) catabolic pathway. We have shown that tumor cells expressing a high DPD activity are resistant to FU (Eur J Cancer 30: 1517, 1994), and that 5-ethynyluracil (776C), a very potent DPD inactivator, markedly enhances the FU cytotoxic effect (Clin Cancer Res 1: 991, 1995). Both experimental background and clinical experience have demonstrated the role of folinic acid (FA) in increasing FU efficacy. The aim of the present study was to investigate the dual FU pharmacomodulation based on the combination of FU with 776C and/or FA on 7 human cancer cell lines (2 head and neck, 3 breast, 1 colon, 1 duodenum) expressing a spontaneous FU sensitivity. These cell lines were chosen according to their ability to respond to FU modulation by FA and/or 776C. The potency of FU modulation was evaluated by the ratio between FU IC50 and FU IC50 in the presence of the tested biomodulator(s), defined as factor F. In cell lines sensitive to FU modulation by 776C only (median F value with 1 microM of 776C = 2.5), the addition of FA did not enhance FU-776C cytotoxicity. In contrast, for cell lines resistant to FU modulation by 776C, the FU-FA-776C combination led to a significant cytotoxicity enhancement as compared to FU-FA (median F values were 3.6 and 2.6 respectively). In cell lines responsive to FU modulation by FA and 776C, the median F values were 2.3 and 1.8 with FA and 776C, respectively. Interestingly, the dual modulation by FA + 776C led to a median F value at 6.3, suggesting more than the additive effects of FA and 776C. This synergistic interaction was statistically confirmed by multivariate ANOVA (FA x 776C interaction). The present study points out that FA plus 776C could prove to be a very attractive combination for future strategies in FU biomodulation.

Cell Survival↗
PubMed2002

A specific tryptophan in the I-II linker is a key determinant of beta-subunit binding and modulation in Ca(V)2.3 calcium channels.

The ancillary beta subunits modulate the activation and inactivation properties of high-voltage activated (HVA) Ca(2+) channels in an isoform-specific manner. The beta subunits bind to a high-affinity interaction site, alpha-interaction domain (AID), located in the I-II linker of HVA alpha1 subunits. Nine residues in the AID motif are absolutely conserved in all HVA channels (QQxExxLxGYxxWIxxxE), but their contribution to beta-subunit binding and modulation remains to be established in Ca(V)2.3. Mutations of W386 to either A, G, Q, R, E, F, or Y in Ca(V)2.3 disrupted [(35)S]beta3-subunit overlay binding to glutathione S-transferase fusion proteins containing the mutated I-II linker, whereas mutations (single or multiple) of nonconserved residues did not affect the protein-protein interaction with beta3. The tryptophan residue at position 386 appears to be an essential determinant as substitutions with hydrophobic (A and G), hydrophilic (Q, R, and E), or aromatic (F and Y) residues yielded the same results. beta-Subunit modulation of W386 (A, G, Q, R, E, F, and Y) and Y383 (A and S) mutants was investigated after heterologous expression in Xenopus oocytes. All mutant channels expressed large inward Ba(2+) currents with typical current-voltage properties. Nonetheless, the typical hallmarks of beta-subunit modulation, namely the increase in peak currents, the hyperpolarization of peak voltages, and the modulation of the kinetics and voltage dependence of inactivation, were eliminated in all W386 mutants, although they were preserved in part in Y383 (A and S) mutants. Altogether these results suggest that W386 is critical for beta-subunit binding and modulation of HVA Ca(2+) channels.

Amino Acid Motifs↗
PubMed1997

Movement-related modulation across the receptive field of neurons in the primary somatosensory cortex of the monkey.

Cutaneous signals are modulated at the various relays just preceding and during voluntary movements. In these conditions, neuronal discharge in the primary somatosensory cortex (SI) related to movement per se is still evident while discharge to air puff stimulation on the skin is diminished. This selective modulation could be explained by rapid movement-related changes in receptive field (RF) configuration. We tested this hypothesis by giving air puff stimuli at different sites within and at the edges of the RF of SI cells during rest and elbow flexions in one awake monkey. For 40 cells, analysis of the global response yielded four different types of modulation: non-modulated cells, completely gated cells, partially and uniformly modulated cells, and non-uniformly modulated cells. Cell discharge for successive 5-ms intervals was also analyzed at the different sites and showed that response uniformity across time is more robust at the RF center than at peripheral sites in the RF. While this study did not show any clear RF displacement, intra-RF excitability seems to be affected by movement in various ways at the level of the cortex. These facts could have implications for information processing during movement.

Acoustic Stimulation↗
PubMed1998

The H-reflex in the passive human soleus muscle is modulated faster than predicted from post-activation depression.

The purpose of the present study was to investigate the influence of afferent activity (mainly homonymous Ia-afferent activity) on the modulation (post-activation depression) of the soleus H-reflex during isolated and passive sinusoidal ankle joint rotations at a speed and amplitude comparable to slow walking. The H-reflex modulation was measured in the relaxed soleus muscle on human subjects during different imposed patterns of 20 degrees haversine ankle joint rotations (0.5-0.6 Hz) while they were sitting comfortably in a chair. Eighteen healthy males and four male patients with clinically complete spinal cord lesion above the soleus motoneuron pool participated in the study. During a single dorsi-plantar flexion rotation the H-reflex was depressed to 27+/-7% (mean+/-S.E.M.) of the initial level within 600 ms. The course of this depression was reversed when the dorsi-flexion velocity started to decrease. At the end of the dorsi-flexion movement the depression was already relieved to a level of 73+/-6% of the initial level. The H-reflex returned more slowly to the initial level within 2 s after the end of the movement cycle. During two consecutive ankle joint rotations and continuous ankle joint rotations both at 0.5 Hz the H-reflex was modulated but also generally depressed while the movement was imposed. The reflex only returned to the reference level after the movements were stopped. These observations indicate the action of a fast and a slow mechanism in the post-activation depression of the soleus H-reflex. The H-reflex modulations observed in the spinal cord injured patients were comparable to the reflex modulations observed in the healthy subjects, except the depressions were smaller. This suggests that a major part of the amplitude of the H-reflex modulation observed in healthy subjects was caused by peripheral and spinal influences. The fast 500 ms recovery of the H-reflex had a time course comparable to presynaptic inhibition. The slow 2 s recovery after the end of a given imposed movement may be explained by a change in the probability of transmitter release from the homonymous soleus Ia-afferent synaptic terminals after repeated activations.

Adult↗
PubMed2003

Gaze modulation of visual aftereffects.

Physiological studies of non-human primates have suggested that the direction of gaze can modulate the gain of neuronal responses to visual stimuli in many cortical areas including V1. The neural gaze modulation is suggested to subserve the conversion from gaze-independent (eye-centered) to dependent (e.g., head-centered) representations. However, it has not been established whether the gaze modulation has significant influences on human visual perception. Here we show that gaze direction modestly but significantly modulates the magnitudes of the motion aftereffect, the tilt aftereffect and the size aftereffect. These aftereffects were stronger when the adaptation and test patterns were presented in the same gaze direction, than when they were presented in different gaze directions, even though the patterns always stimulated the same retinal location. The gaze modulation effect was not statistically significant for the post-adaptation elevation of contrast detection thresholds. The gaze modulation of visual aftereffects provides a useful psychophysical tool to analyze human cortical processes for coordinate transformations of visual space.

Figural Aftereffect↗
PubMedDate not supplied

Aquatic modules for bioregenerative life support systems based on the C.E.B.A.S. biotechnology [correction of biotechnilogy].

Most concepts for bioregenerative life support systems are based on edible higher land plants which create some problems with growth and seed generation under space conditions. Animal protein production is mostly neglected because of the tremendous waste management problems with tetrapods under reduced weightlessness. Therefore, the "Closed Equilibrated Biological Aquatic System" (C.E.B.A.S.) was developed which represents an artificial aquatic ecosystem containing aquatic organisms which are adapted at all to "near weightlessness conditions" (fishes Xiphophorus helleri, water snails Biomphalaria glabrata, ammonia oxidizing bacteria and the rootless non-gravitropic edible water plant Ceratophyllum demersum). Basically the C.E.B.A.S. consists of 4 subsystems: a ZOOLOGICAL (correction of ZOOLOGICASL) COMPONENT (animal aquarium), a BOTANICAL COMPONENT (aquatic plant bioreactor), a MICROBIAL COMPONENT (bacteria filter) and an ELECTRONICAL COMPONENT (data acquisition and control unit). Superficially, the function principle appears simple: the plants convert light energy into chemical energy via photosynthesis thus producing biomass and oxygen. The animals and microorganisms use the oxygen for respiration and produce the carbon dioxide which is essential for plant photosynthesis. The ammonia ions excreted by the animals are converted by the bacteria to nitrite and then to nitrate ions which serve as a nitrogen source for the plants. Other essential ions derive from biological degradation of animal waste products and dead organic matter. The C.E.B.A.S. exists in 2 basic versions: the original C.E.B.A.S. with a volume of 150 liters and a self-sustaining standing time of more than 13 month and the so-called C.E.B.A.S. MINI MODULE with a volume of about 8.5 liters. In the latter there is no closed food loop by reasons of available space so that animal food has to be provided via an automated feeder. This device was flown already successfully on the STS-89 and STS-90 spaceshuttle missions and the working hypothesis was verified that aquatic organisms are nearly not affected at all by space conditions, i.e. that the plants exhibited biomass production rates identical to the sound controls and that as well the reproductive, and the immune system as the embryonic and ontogenic development of the animals remained undisturbed. Currently the C.E.B.A.S. MINI MODLULE is prepared for a third spaceshuttle flight (STS-107) in spring 2001. Based on the results of the space experiments a series of prototypes of aquatic food production modules for the implementation into BLSS were developed. This paper describes the scientific disposition of the STS-107 experiment and of open and closed aquaculture systems based on another aquatic plant species, the Lemnacean Wolffia arrhiza which is cultured as a vegetable in Southeastern Asia. This plant can be grown in suspension culture and several special bioreactors were developed for this purpose. W. arrhiza reproduces mainly vegetatively by buds but also sexually from time to time and is therefore especially suitable for genetic engineering, too. Therefore it was used, in addition, to optimize the C.E.B.A.S. MINI MODULE to allow experiments with a duration of 4 month in the International Space Station the basic principle of which will be explained. In the context of aquaculture systems for BLSS the continuous replacement of removed fish biomass is an essential demand. Although fish reproduction seems not to be affected in the shortterm space experiments with the C.E.B.A.S. MINI MODULE a functional and reliable hatchery for the production of siblings under reduced weightlessness is connected with some serious problems. Therefore an automated "reproduction module" for the herbivorous fish Tilapia rendalli was developed as a laboratory prototype. It is concluded that aquatic modules of different degrees of complexity can optimize the productivity of BLSS based on higher land plants and that they offer an unique opportunity for the production of animal protein in lunar or planetary bases.

Ammonia↗
PubMed1996

Two distinct mechanisms generate the respiratory modulation in fibre activity of the rat cervical sympathetic trunk.

Preganglionic multifibre activity was recorded in the cervical sympathetic trunk of vagotomized Wistar rats and analysed for its respiratory modulation. The aim of the study was to investigate whether both a central and a reflex component of respiratory modulation are observed in sympathetic activity of rats as was previously demonstrated in cats. For this purpose, sympathetic activity was summed over several hundred cycles (i) with respect to phrenic nerve discharge as an indicator for central respiration and (ii) with respect to tracheal pressure as an indicator for artificial ventilation. As a consequence of vagotomy both cycles were desynchronized. Sympathetic activity which was analysed exhibited a central respiratory modulation with a minimum during inspiration and a broad peak during expiration. Additionally, in the activity of 44/49 filaments a ventilation-related modulation was seen in parallel with the falling phase of the blood pressure waves accompanying artificial ventilation. The analysis of the latter rhythm during central apnoea and after complete sino-aortic denervation proved its reflex origin and its independence of the central respiratory modulation. We conclude that in rats respiratory modulation of sympathetic activity is caused by two distinct mechanisms, one being of central and one being of reflex, probably baroreceptor, origin.

Adrenergic Fibers↗
PubMed1998

Reciprocal dopamine-glutamate modulation of release in the basal ganglia.

Dopaminergic and glutamatergic transmissions have long been known to interact at multiple levels in the basal ganglia to modulate motor and cognitive functions. One important aspect of their interactions is represented by the reciprocal modulation of release. This topic has been the object of interest since the late 70's, particularly in the striatum and in midbrain dopaminergic areas (substantia nigra and ventral tegmental area). Analysis of glutamate-dopamine interactions in the control of each other's release is complicated by the fact that both glutamate and dopamine act on multiple receptor subtypes which can exert different effects. Therefore, glutamatergic modulation of dopamine release has been reviewed by analyzing the effects of glutamatergic selective receptor agonists and antagonists in the striatum (both motor and limbic portions) and in midbrain dopaminergic areas, as revealed by in vitro (slices, cell cultures, synaptosomes) and in vivo (push-pull, microdialysis and voltammetry techniques) experimental approaches. The same approach has been followed for dopaminergic modulation of glutamate release. The facilitatory nature of glutamate modulating both presynaptic and dendritic dopamine release has clearly emerged from in vitro studies. However, evidence is presented that, at least in the striatum and in the nucleus accumbens of awake rats, glutamate-mediated inhibitory effects may also occur. In vitro and in vivo experiments in the striatum and midbrain dopaminergic areas mainly depict dopamine as an inhibitory modulator of glutamate release. However, in vivo studies reporting dopamine D1 receptor mediated facilitatory effects are also considered. Therefore, the general notion that glutamate and dopamine act oppositely to regulate each other's release, is only partly supported by the available data. Conversely, the nature of the interaction between the two neurotransmitters seems to vary depending on the experimental approach, the brain area considered and the subtype of receptor involved.

Animals↗
PubMed2001

Nitric oxide as modulator of neuronal function.

The gas NO is a messenger that modulates neuronal function. The use of NO donors and NO synthase inhibitors as pharmacological tools revealed that this free radical is probably implicated in the regulation of excitability and firing, in long-term potentiation and long-term depression, as well as in memory processes. Moreover, NO modulates neurotransmitter release. In vivo and in vitro studies have shown that, in all brain structures investigated, endogenous NO modulates the release of several neurotransmitters, such as acetylcholine, catecholamines, excitatory and inhibitory amino acids, serotonin, histamine, and adenosine. In most cases, enhanced NO level in the tissue increases the release of neurotransmitters, although decreasing effects have also been observed. Cyclic 3'-5' guanosine monophosphate and glutamate mediate the modulation of transmitter release by NO. Recent observations suggest that the release of some transmitters is dually influenced by NO. Thus, besides modulation by presynaptically located auto- and heteroreceptors, NO released from nitrergic neurons seems to play a universal role in modulating the release of transmitters in the brain.

Animals↗
PubMed2003

A second pathway for modulating glucocorticoid receptor transactivation properties.

We recently reported that three factors (a cis-acting element and changing concentrations of receptor or coactivator TIF2) act at a common rate-limiting step to modulate the position of the dose-response curve and the partial agonist activity of glucocorticoid receptors (GRs). The ability of saturating levels of GR, and added inhibitors, to prevent the actions of the three modulators (cis-acting element, GR, and TIF2) but not the currently investigated C-terminal fragment of E1A-13S (E1A-133C) indicates that E1A-133C alters GR properties via a second pathway that is downstream of the common step for the original three modulators. hSur2 binds to E1A-133C. We find that hSur2 modulates GR transactivation properties, thus suggesting that the effects of E1A-133C are due to the recruitment of hSur2. hSur2 also modifies GR activities in the presence of saturating GR concentrations, which is consistent with hSur2 acting downstream of the common step for the original three modulators. The H160Y mutation, which eliminates hSur2 binding to E1A, blocks most of the activity of E1A-133C. This suggests that the modulatory activity of E1A-133C is largely due to the binding of hSur2, which is a component of the Mediator complex. Collectively, these data support the existence of a new pathway for modulating GR transactivation processes, thereby increasing the number of cellular mechanisms that permit differential control of gene expression by endogenous levels of glucocorticoid hormones.

Adenovirus E1A Proteins↗
PubMed2003

Imaging of central itch modulation in the human brain using positron emission tomography.

The unpleasantness of itching is reduced by cooling. Although previous research suggests the presence of a central itch modulation system, there is little documentation about the modulation system in the brain. In the present study, we investigated the modulating system of the itching sensation in human brains using positron emission tomography and H(2) (15)O. The significant increases of regional cerebral blood flow caused by histamine stimuli using iontophoresis were observed in the anterior cingulate cortex (BA24), the thalamus, the parietal cortex (BA40 and BA7), the dorsolateral prefrontal cortex (BA46) and the premotor cortex (BA6). We did not observe any changes in the secondary somatosensory cortex (S2) during the itching stimulus, corresponding to the previous imaging studies concerning itching. Activation in these areas related to itching stimuli was decreased by a simultaneous stimulation of itching and cold pain (the dual stimuli), as compared to itching alone. Interestingly, the midbrain, including periaqueductal gray matter (PAG), was only activated during the dual stimuli. PAG is well known to be a modulating noxious stimulus. Here we hypothesize that the activation of PAG may also be related to the itch modulation. These findings indicate that the modified brain activities in the PAG, the cingulate, the frontal and the parietal cortex might be associated with the itch modulation in the central nervous system and that the S2 might not be primarily involved in processing the itching perception in the brain since the activity of S2 was not observed in any concentration of itching stimuli.

Adult↗
PubMed1999

Dissociation of sensory and affective dimensions of pain using hypnotic modulation.

Understanding the complex nature of pain perception requires the ability to separately analyze its psychological dimensions and their interaction, and relate them to specific variables and responses. The present study, therefore, attempted to selectively modulate the sensory and affective dimensions of pain, using a cognitive intervention, and to assess the possible relationship between these psychological dimensions of pain and changes in physiological responses to the noxious stimuli. In three experiments, normal subjects trained in hypnosis rated pain intensity and pain unpleasantness produced by a tonic heat-pain stimulus (1-min immersion of the hand in 45.0-47.5 degrees C water). Two experiments were designed to test hypnotic suggestions to decrease (Experiment one (Section 2.5.1)), or increase and decrease (Experiment two (Section 2.5.2)) pain affect. Suggestions in Experiment three (Section 2.5.3) were directed towards an increase or decrease in pain sensation. In Experiments one and two (Sections 2.5.1 and 2.5.2), the significant modulation in pain unpleasantness ratings was largely independent of variations in perceived pain intensity. Moreover, in Experiment two (Section 2.5.2), there was a significant correlation between the stimulus-evoked heart-rate increase and ratings of pain unpleasantness, but not of pain intensity, suggesting a direct functional interaction between pain affect and autonomic activation. In Experiment three (Section 2.5.3), suggestions to modulate the sensory aspect of pain produced significant modulation of pain intensity ratings, with secondary changes in pain unpleasantness ratings. Hypnotic susceptibility (Stanford Hypnotic Susceptibility Scale form A) was specifically correlated to pain unpleasantness modulation in Experiment two (Section 2.5.2) and to pain intensity modulation in Experiment three (Section 2.5.3), suggesting that this factor relates to the primary process toward which hypnotic suggestions are directed. The specific pain dimension on which hypnotic suggestions act depends on the content of the instructions and is not a characteristic of hypnosis itself. Results are consistent with a successive-stage model of pain perception (e.g. Wade JB, Dougherty LM, Archer CR, Price DD. Assessing the stages of pain processing: a multivariate analytical approach. Pain 1996;68:157-167) which provides a conceptual framework necessary to study the cerebral representation of pain perception.

Affective Symptoms↗
PubMed2000

Redox modulation of recombinant human GABA(A) receptors.

We previously reported that GABA-evoked currents of rat retinal ganglion cells were modulated by redox agents. In this study, we further characterized the effects of redox modulation on GABA receptors using recombinant human subunits in the Xenopus oocyte expression system with two-electrode voltage-clamp recording. GABA receptors composed of subunits alpha(1-3), beta(1-3), gamma(1), gamma(2S,) and rho(1) were expressed. The sulfhydryl reducing agent dithiothreitol reversibly potentiated the responses of various combinations of functional recombinant GABA(A) subunits, whether expressed as triplets (alpha(1)beta(1-3)gamma(1,2S)), pairs (alpha(1-3)beta(1-3); beta(1-3)gamma(1,2S)), or singly (beta(2)). These effects of dithiothreitol were rapidly reversible, and the oxidizing agent 5-5'-dithiobis-2-nitrobenzoic acid exerted the opposite effect. In contrast to these effects on GABA(A) receptors, dithiothreitol had no effect on the responses of homomeric GABA rho(1) (GABA(C)) receptors. The degree of dithiothreitol potentiation of GABA(A) receptor responses depended on subunit composition. Co-expression of gamma(2S) with alpha(1)beta(1-3) subunits resulted in markedly less dithiothreitol potentiation of GABA-evoked currents than that observed for alpha(1-3)beta(1-3) subunits in the absence of gamma(2S). None the less, the magnitude of dithiothreitol potentiation could be restored by using a combination of lower GABA concentrations (5-10 microM) and higher dithiothreitol concentrations (5-20mM). N,N,N', N'-tetrakis(2-pyridyl-methyl)ethylenediamine, a high-affinity Zn(2+) chelator, also potentiated GABA(A) receptor currents. However, the potentiation produced by 10mM dithiothreitol was larger than that produced by saturating concentrations of N,N,N', N'-tetrakis(2-pyridyl-methyl)ethylenediamine (100 microM), implying that at least part of the effect of dithiothreitol was due to redox modulation rather than Zn(2+) chelation. Dithiothreitol also potentiated the spontaneous current of homomeric GABA(A) receptors composed of beta subunits. Mutation of a single cysteine residue in the M3 domain, yielding homomeric beta(3)(C313A) receptors, abrogated dithiothreitol potentiation of the spontaneous current. In summary, this study further characterizes the modulatory effects of redox agents on recombinant GABA(A) receptors. The degree of redox modulation of GABA(A) receptors depended on subunit composition. In contrast to their effect on GABA(A) receptors, redox agents were not found to modulate GABA(C) receptors composed of homomeric rho(1) subunits. Using site-directed mutagenesis, a cysteine residue was located in the beta(3) subunit which may comprise one of the redox-active sites that underlies the modulation of heteromeric GABA(A) receptors by reducing and oxidizing agents.

Animals↗
PubMed1997

Modulated beam conformal therapy for head and neck tumors.

PURPOSE: The goal of modulated-beam conformal therapy is to reduce the dose to healthy tissue and sensitive structures around a uniformly irradiated target volume. Multiple intensity-modulated fields offer improved tissue-sparing dose distributions. New computer-based systems for planning and delivering such treatments may soon be available from different commercial sources that will make the formulation of an intensity-modulated treatment plan and its execution widely available at any treatment facility that has the resources to acquire the necessary equipment. This work reports on a study of the integration of two such systems. METHODS AND MATERIALS: Treatment planning was done using a commercially available inverse planning algorithm based on simulated annealing. The plans arbitrarily assumed nine coplanar x-ray beams at nonopposed gantry angles. Intensity modulation was computed for each beam. The modulated field at each gantry angle was broken down into a series of uniform (nonmodulated) subfields, which could be delivered as a sequence to produce the desired dose distribution. Because a large number of subfields was delivered, a multileaf collimator (MLC) was used for field shaping. This allowed rapid and accurate field shaping for treatments made up of several hundred subfields. Computer control of the MLC and linear accelerator allowed delivery of doses less than .01 Gy per subfield. Treatment was delivered on a prototype, computer-controlled accelerator and MLC system. Resulting dose distributions were analyzed using film and an anatomically specific, homogeneous phantom. RESULTS: The treatment plans were evaluated using dose-volume histogram analysis. The plans provided acceptably uniform irradiation of the target volume without exceeding dose tolerances for nearby critical structures. The plans were successfully delivered by a prototype dynamic MLC. The time needed to deliver a sequence of subfields at one gantry angle ranged from 0.7 to 2.0 min. Isodoses from film agreed reasonably well with planned isodose distributions. CONCLUSIONS: It is feasible to plan and deliver fixed gantry, modulated-beam conformal therapy for head and neck tumors with systems being developed commercially. The planned dose distributions exhibit significant potential for sparing closely spaced normal tissue structures in the head and neck.

Algorithms↗
PubMed2002

The frequency-modulation following response in young and aged human subjects.

The frequency-modulation following response (FMFR) is a steady-state evoked response which may be a neural correlate of frequency discrimination. Aged subjects with normal hearing have abnormal frequency discrimination for low carrier frequencies and thus it might be predicted that aged individuals would have reduced FMFR amplitudes compared to young subjects. In this study, FMFR amplitudes were measured for frequency-modulated sinusoids with a carrier frequency of 0.5 kHz (80 dB SPL). In Experiment 1, the modulation depth was held constant (80%) and the modulation rate was varied (4-38 Hz), whereas in Experiment 2 the modulation rate was held constant (38 Hz) and the modulation depth was varied (0-80%). Aged subjects had significantly larger FMFR amplitudes than young subjects for certain stimulus parameters, although individual variability was large. Such results would not be predicted given previous data regarding frequency discrimination, but are consistent with several reports of larger-than-normal amplitudes of middle latency and late responses in aged subjects.

Acoustic Stimulation↗
PubMedDate not supplied

Intervention booster: adding a decision-making module to risk reduction and other health care programs for adolescents.

A generic adolescent intervention booster of the decision-making module, "Choices for Tomorrow: Decision Making as a Life Tool," is described for patient education. The intent of the intervention booster is refinement of adolescent decision-making skills by teaching a life tool for making lifestyle decisions (such as smoking and alcohol use) and other health-related decisions. An overview of the module is presented. The module includes a curriculum, a 17-minute life-action videocassette, a participant's workbook, and two instruments to measure outcomes. The theoretical framework is based on the health/choice model, the Janis and Mann conflict model of decision making, and the Piagetian cognitive framework related to adolescent development. The decision-making module can be used alone or as a "booster" to supplement the content of new or existing intervention programs that are aimed at health promotion and maintenance during adolescence. Because the module was originally developed for adolescents who have survived cancer, a population that often experiences cognitive impairment from treatment, it includes cognitive remediation strategies (such as memory aids). The decision-making module can also be used in other learning situations with healthy or chronically ill adolescents and/or their parents.

Adolescent↗
PubMed1999

The construction and testing of the EORTC colorectal cancer-specific quality of life questionnaire module (QLQ-CR38). European Organization for Research and Treatment of Cancer Study Group on Quality of Life.

The objectives of the current study were to construct a colorectal cancer-specific quality of life (QL) questionnaire module to be used in conjunction with the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 and to test its reliability and validity in The Netherlands. Module construction took place following the EORTC guidelines for module development. The module--the QLQ-CR38--consists of 38 items covering symptoms and side-effects related to different treatment modalities, body image, sexuality and future perspective. This module was tested among 117 colorectal cancer patients on several occasions. The timing was prior to treatment with radiotherapy or chemotherapy, during treatment and 3 months following the second assessment. For purposes of test-retest reliability, a subsample of patients completed the QLQ-CR38 1 week following the third assessment. Multitrait scaling analysis confirmed the hypothesised scale structure of the function scales but not of the symptom scales. Cronbach's alpha coefficients for seven of the nine scales exceeded the 0.70 criterion at one or both assessments. The test-retest reliability for all scales and one single item was 0.78 or higher. The stability of the two remaining single items was lower. On the basis of known-groups comparisons, selective scales distinguished clearly between patients differing in disease stage, initial and on-treatment performance status and the presence of a stoma. Additionally, selective scales detected change over time as a function of change in performance status and treatment-induced change. These results lend support to the clinical validity of the QLQ-CR38 as a supplementary questionnaire for assessing specific QL issues relevant to patients with colorectal cancer. Additional efforts to test the module's cross-cultural validity are needed.

Adult↗