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PubMed2005

Effect of chronic intake of sweet substance on nociceptive thresholds and feeding behavior of Rattus norvegicus (Rodentia, Muridae).

The investigation of the influence of sweetened food on feeding behavior targeted to non-sucrose nutrients as well as the sensitivity to painful stimuli in isolated and grouped animals is the aim of the present work. The tail withdrawal latencies in the tail-flick test (a spinal reflex) were measured before and immediately after the treatment with tap water or sucrose (62, 125 or 250 g/l). Our findings suggest that: (a) The analgesic effect of sucrose intake depends on the concentration of sucrose solution and on the time during which the solution is consumed; (b) the most effective concentration of sucrose followed by antinociceptive effect was the one of 250 g/l in both isolated and grouped animals; (c) considering the individually caged rats, the intake of sucrose in the highest concentration (250 g/l) was the smallest as compared with the consumption of sucrose in more diluted solutions (62.5 and 125 g/l), but this higher sweetened solution was followed by antinociception; (d) animals treated with concentrated sucrose solution ate smaller quantities of pellets than animals treated with tap water; (e) tonic intake of highly concentrated sweet substance seems to be crucial for the increase of the nociceptive threshold in our model of sweet substance-induced antinociception.

Analgesia↗

PubMed2002

Differential effects of cigarette price on youth smoking intensity.

OBJECTIVES: Data from the 1992, 1993, and 1994 Monitoring the Future Surveys were used to investigate the differential effects of cigarette price on the intensity of youth cigarette smoking. METHODS: Respondents were classified into non-smokers; individuals who smoked less than one cigarette per day; individuals who smoked one to five cigarettes per day; individuals who smoked one-half pack a day; and individuals who smoked one pack or more a day. A Threshold of Change Model was estimated with information on cigarette prices as the main explanatory variables. RESULTS: Dummy variables indicating medium and high prices were found to have varying effects on different levels of smoking intensity, even though higher prices were associated with lower smoking in all cases. The differences are more striking in the high-price case. The effects of higher prices are largest at the heaviest smoking levels. CONCLUSION: Cigarette prices are an effective tool to discourage youth smoking. The differential effects of cigarette price on smoking intensity warrant further investigation.

Adolescent↗

PubMed1992

The relative contributions of occupational noise and aging in individual cases of hearing loss.

A method is proposed for allocation of hearing handicap between noise and aging in individual cases when noise exposure level and duration are known or can be estimated. A recently published international standard (ISO-1999, 1990) provides statistical models for hearing threshold changes associated with aging and noise exposure. When an individual's hearing threshold level exceeds the sum of the median levels expected given that individual's age, gender, exposure level, and exposure duration, the appropriate allocation depends on the correlation between age-related and noise-induced changes. However, the differences in allocation between assumptions of perfect and absent correlation are small. Only very small errors result from calculating the allocation based on median expectations for noise and aging. In most cases, age-related changes exceed noise-induced changes for the 0.5, 1, 2, and 3 kHz pure-tone average; for men age 65, this is true for all exposure levels below 100 dBA.

Age Factors↗

PubMed2002

Clinical implications of cardiac (123)I-meta-iodobenzylguanidine scintigraphy and cardiac natriuretic peptides in patients with heart disease.

The purpose of this study was to evaluate whether or not cardiac sympathetic nerve activity, using (123)I-meta-iodobenzylguanidine ((123)I-MIBG) imaging, and cardiac natriuretic peptides (atrial and brain, ANP and BNP) were independent predictors of cardiac events, and, if so, which was the stronger predictor. Planar (123)I-MIBG images were obtained from 62 patients with heart disease. Plasma ANP and BNP levels, left ventricular ejection fraction (LVEF) by echocardiography, serum total cholesterol and triglyceride were measured. (123)I-MIBG was assessed as the heart-to-mediastinum (H/M) ratio of the delayed image and the washout rate (WoR) from the early to the delayed image. Patients were followed up for an average of 16.2 months, and 12 of 62 patients had cardiac events. Patients with events had significantly lower LVEF and H/M ratio compared with those without events. They had significantly higher WoR, ANP and BNP. By multivariate Cox proportional hazard analysis, (123)I-MIBG (H/M or WoR), ANP and BNP were independent predictors for cardiac events. Event-free survival using a Kaplan-Meier model, with a threshold value of 2.0 for H/M and 45% for WoR, showed that patients with H/M<2.0 and/or WoR>45% had a significantly poorer prognosis. These results suggest that (123)I-MIBG imaging and cardiac natriuretic peptides are useful tools for the evaluation of patients with heart disease, and that cardiac sympathetic nerve activity is a stronger predictor of cardiac events.

3-Iodobenzylguanidine↗

PubMed2004

How shunting inhibition affects the discharge of lumbar motoneurones: a dynamic clamp study in anaesthetized cats.

In the present work, dynamic clamp was used to inject a current that mimicked tonic synaptic activity in the soma of cat lumbar motoneurones with a microelectrode. The reversal potential of this current could be set at the resting potential so as to prevent membrane depolarization or hyperpolarization. The only effect of the dynamic clamp was then to elicit a constant and calibrated increase of the motoneurone input conductance. The effect of the resulting shunt was investigated on repetitive discharges elicited by current pulses. Shunting inhibition reduced very substantially the firing frequency in the primary range without changing the slope of the current-frequency curves. The shift of the I-f curve was proportional to the conductance increase imposed by the dynamic clamp and depended on an intrinsic property of the motoneurone that we called the shunt potential. The shunt potential ranged between 11 and 37 mV above the resting potential, indicating that the sensitivity of motoneurones to shunting inhibition was quite variable. The shunt potential was always near or above the action potential voltage threshold. A theoretical model allowed us to interpret these experimental results. The shunt potential was shown to be a weighted time average of membrane voltage. The weighting factor is the phase response function of the neurone that peaks at the end of the interspike interval. The shunt potential indicates whether mixed synaptic inputs have an excitatory or inhibitory effect on the ongoing discharge of the motoneurone.

Action Potentials↗

PubMed1998

Effective dose in diagnostic radiology as a function of x-ray beam filtration for a constant exit dose and constant film density.

Individual organ absorbed dose and total effective dose for nine common radiographic projections were investigated as a function of half-value-layer, HVL, and total equivalent filtration for the following cases: (1) with the patient exit dose held constant and (2) with the film density held constant. As expected, the absorbed dose to organs proximal to the x-ray beam entry point tracked with skin dose as a function of HVL, whereas organ dose distal to the x-ray beam entry point was almost independent of HVL. Dose to organs near mid-line showed an intermediate HVL dependence. For the nine radiographic projections, increasing the total filtration from 1.5 to 4.0 mm Al while holding the kVp fixed resulted in mean decreases in the effective dose of 17% for the case of a constant exit dose, and 25% for a constant film density with a "400 speed" rare-earth screen-film system. The decreases in the mean skin entrance doses were 38% and 45%, respectively. With the screen-film system, the average effective dose decreased at 16% per mm of added Al between 1.5 and 2.5 mm Al total filtration, and at 7% per mm between 2.5 and 4.0 mm. These results partially support the NCRP Report No. 102 recommendation that the minimum filtration be 2.5 mm Al for general diagnostic x-ray tubes. They also suggest, using the linear no-threshold radiation risk model, that further significant reductions in stochastic risk to the U.S. population can be achieved by raising the minimum beyond 2.5 mm. Experience over a 12 year period in our tertiary care teaching hospital indicates that adding 1-1.5 mm Al filtration beyond the 2.5 mm minimum does not pose a problem in terms of additional tube loading or reduction in image quality. However, these issues need to be more formally addressed.

Abdomen↗

PubMed1985

Prior stimulation and the masking-level difference.

Signal detection in diotic (NoSo) and dichotic (NoS pi) conditions was measured as a function of the stimulus parameters of the noise that preceded the signal-plus-masker. When the signal and masker were both pulsed, dichotic signal detection was worse than when the masker was continuous or when the onset of the masker preceded the signal-plus-masker by at least 500 ms. The dichotic detection thresholds decreased as the duration of the pulsed signal plus pulsed masker was increased. The level, spectrum, interaural configuration, duration, and temporal proximity of the prior noise (forward fringe) relative to the masker and/or signal and masker were all investigated. Almost any difference between the parameters of the fringe and the masker resulted in poorer signal detection in the dichotic conditions. These same stimulus conditions produced small (less than 2.2 dB) changes in the diotic detection thresholds. The various models of the Masking-Level Difference (MLD) may be modified to qualitatively describe some of these results.

Acoustic Stimulation↗

PubMed2003

Abrupt climate change.

Large, abrupt, and widespread climate changes with major impacts have occurred repeatedly in the past, when the Earth system was forced across thresholds. Although abrupt climate changes can occur for many reasons, it is conceivable that human forcing of climate change is increasing the probability of large, abrupt events. Were such an event to recur, the economic and ecological impacts could be large and potentially serious. Unpredictability exhibited near climate thresholds in simple models shows that some uncertainty will always be associated with projections. In light of these uncertainties, policy-makers should consider expanding research into abrupt climate change, improving monitoring systems, and taking actions designed to enhance the adaptability and resilience of ecosystems and economies.

Journal Article↗

PubMed1962

Fourier treatment of some experiments in visual flicker.

This report analyzes some experiments in visual flicker recently described by Forsyth and Brown. The assumption that only the first Fourier component of their stimuli is at the flicker threshold, the other components being below threshold, provides a model that accurately predicts their data. Hence, contrary to the conclusions drawn by Forsyth and Brown, no new nonlinear property of the visual system has been demonstrated.

Flicker Fusion↗

PubMed1996

Proarrhythmic and antiarrhythmic actions of ion channel blockers on arrhythmias in the heart: model study.

We explain why 1) some class I and IV antiarrhythmia drugs could exert proarrhythmic action, 2) some class III drugs are effective in controlling reentrant arrhythmias, and 3) cycle length (CL) oscillation is involved in the termination or initiation of reentry. To explain these phenomena, we employ the following three means: bifurcation analysis, simulation, and model construction. Antiarrhythmia drugs are modeled by varying maximal conductances of Na+, Ca2+, and time-dependent delayed rectifying and time-independent inward rectifying K+ channels in the Beeler-Reuter model, where the model cells are arranged in a ring. Bifurcation analysis predicts that there is a critical ring size (CRS) at which infinite ring behavior suddenly breaks down. Channel blockers can affect CRS in different manners: Na+ and Ca2+ blockers shorten CRS, whereas delayed rectifying K+ channel blockers and the inward K+ channel blockers lengthen CRS. This differential explains why some antiarrhythmia drugs are proarrhythmic (i.e., shorten CRS) whereas others are antiarrhythmic (i.e., lengthen CRS). Simulation is then used to investigate how the drugs affect reentrant rhythms in the neighborhood of the CRS. We find that, in this region, CL, conduction velocity, and action potential duration become oscillatory. As ring size shrinks, the pattern of the oscillation becomes more complex. When the ring shrinks to a certain size, reentry can no longer be sustained, and it terminates after a few oscillatory cycles. To explain the basic mechanism involved in CL oscillation, we then construct a minimal model that contains a low-threshold fast inward current and a high-threshold slow inward current. With this model, we show that the two inward currents, with vastly different activation and inactivation kinetics, cause CL oscillations. Our results thus give theoretical explanations for the experimental finding of Frame's group in canine atrial tricuspid ring in vitro that class IC drugs can bring about stable reentry from nonsustained transient reentry, whereas class III drugs transform stable reentry to complex oscillations in CL. Our results also support the result of Frame's group, in that, in "adjustable" tricuspid rings, CL oscillation becomes more complex and its period becomes shorter as an excitable gap is shortened.

Animals↗

PubMed1989

Osmoregulation of thirst and vasopressin release in pregnancy.

Osmoregulation is altered in human gestation, body tonicity declining to a nadir early in pregnancy after which a new steady-state plasma osmolality is maintained until term. Development of precise, sensitive, and specific radioimmunoassays for arginine vasopressin (AVP), which permit clearer definitions of functional properties of the osmoregulatory system, have led to a formulation of how these changes occur (both in women as well as in a gravid rat model). The osmotic thresholds for thirst and antidiuretic hormone release each decrease approximately 10 mosmol/kg during the initial weeks of human gestation. Lowering the threshold to drink stimulates increased water intake and dilution of body fluids. Because AVP release is not suppressed at the usual levels of tonicity, it still circulates and water is retained. Osmolality declines until it decreases below the osmotic thirst threshold (situated several mosmol/kg above that for hormone secretion), and a new steady state, with little change in water turnover, is established. The metabolic clearance rate of AVP is also altered, increasing three- to fourfold between gestational week 10 and midtrimester, paralleling the appearance and rapid rise in circulating cystine-aminopeptidase (vasopressinase), an observation that may explain several disorders of water handling that complicate human pregnancy. Finally, mechanisms responsible for the altered osmoregulation are obscure but chorionic gonadotropin may be involved in the changes during human gestation.

Animals↗

PubMed2006

Temporal measures and neural strategies for detection of tones in noise based on responses in anteroventral cochlear nucleus.

To examine possible neural strategies for the detection of tones in broadband noise, single-neuron extracellular recordings were obtained from the anteroventral cochlear nucleus (AVCN) in anesthetized gerbils. Detection thresholds determined by average discharge rate and several temporal metrics were compared with previously reported psychophysical detection thresholds in cats (Costalupes 1985). Because of their limited dynamic range, the average discharge rates of single neurons failed to predict psychophysical detection thresholds for relatively high-level noise at all measured characteristic frequencies (CFs). However, temporal responses changed significantly when a tone was added to a noise, even for neurons with flat masked rate-level functions. Three specific temporal analyses were applied to neural responses to tones in noise. First, temporal reliability, a measure of discharge time consistency across stimulus repetitions, decreased with increasing tone level for most AVCN neurons at all measured CFs. Second, synchronization to the tone frequency, a measure of phase-locking to the tone, increased with tone level for low-CF neurons. Third, rapid fluctuations in the poststimulus time histograms (PSTHs) decreased with tone level for a number of neurons at all CFs. For each of the three temporal measures, some neurons had detection thresholds at or below psychophysical thresholds. A physiological model of a higher-stage auditory neuron that received simple excitatory and inhibitory inputs from AVCN neurons was able to extract the PSTH fluctuation information in a form of decreased rate with tone level.

Acoustic Stimulation↗

PubMed1995

Directionally selective motion detection in the sustaining fibers of the crayfish optic nerve: linear and nonlinear mechanisms.

1. Directional selectivity of crayfish sustaining fibers was examined with drifting sine wave gratings and with intracellular and extracellular recordings. Directionality was measured for variations in stimulus contrast, spatial frequency, and temporal frequency. 2. Sustaining fibers exhibit directional selectivity in the magnitude of the compound postsynaptic potential (PSP), the impulse frequency modulation response, and the mean firing rate. The mean synaptic potential is insensitive to direction. The directionality of the mean impulse rate appears to arise by rectification in the voltage-to-impulse transduction. 3. The preferred directions of three identified sustaining fibers are similar to those of head-down optomotor neurons to which these sustaining fibers project. 4. The modulatory response, elicited by gratings drifting in the preferred direction, increased linearly with contrast until saturation (typically at a contrast of 0.5), where maximum directional selectivity obtains. 5. The magnitude of the directional response is a band-pass function of spatial and temporal frequency and exhibits reversal of directionality (i.e., aliasing) at high spatial and temporal frequencies. The results imply a spatial sampling interval of 4.5 degrees and a temperature-dependent inhibitory delay of 40-90 ms. The PSP modulation response shares several features with that of neighboring tangential (Tan1) neurons. 6. A qualitative model is proposed for the transformation of a phase-sensitive, linear directional response to a phase-insensitive and nonlinear time-averaged response, based on the functional connections from Tan1 neurons to sustaining fibers to optomotor neurons. The model includes a threshold rectification, a synaptic band-pass filter, and differences in temporal phase among converging modulatory signals.

Animals↗

PubMed2001

Middle cerebral artery occlusion and reperfusion in primates monitored by microdialysis and sequential positron emission tomography.

BACKGROUND AND PURPOSE: In a previous investigation concerning the hemodynamic and metabolic changes over time displayed by sequential positron emission tomography (PET) in a middle cerebral artery (MCA) occlusion/reperfusion primate model, a metabolic threshold for irreversible ischemia could be identified (reduction of metabolic rate of oxygen [CMRO(2)] to approximately 60% of the contralateral hemisphere). To evaluate the potential of microdialysis (MD) as an instrument for chemical brain monitoring, the aim of this subsequent study was to relate the chemical changes in MD levels directly to the regional metabolic status (CMRO(2) above or below the metabolic threshold) and the occurrence of reperfusion, as assessed by PET. METHODS: Continuous MD (2 probes in each brain) and sequential PET measurements were performed during MCA occlusion (2 hours) and 18 hours (mean) of reperfusion in 8 monkeys (Macaca mulatta). Energy-related metabolites (lactate, pyruvate, and hypoxanthine) and glutamate were analyzed. The MD probe regions were divided into 3 categories on the basis of whether CMRO(2) was below or above 60% of the contralateral region (metabolic threshold level) during MCA occlusion and whether reperfusion was obtained: severe ischemia with reperfusion (n=4), severe ischemia without reperfusion (n=4), and penumbra with reperfusion (n=5). RESULTS: The lactate/pyruvate ratio, hypoxanthine, and glutamate showed similar patterns. MD probe regions with severe ischemia and reperfusion and probe regions with severe ischemia and no reperfusion displayed high and broad peaks, respectively, during MCA occlusion, and the levels almost never decreased to baseline. Penumbra MD probe regions displayed only slight transient increases during MCA occlusion and returned to baseline. CONCLUSIONS: This experimental study of focal ischemia showed that the extracellular changes of energy-related metabolites and glutamate differed depending on the ischemic state of the brain during MCA occlusion and depending on whether reperfusion occurred. If MD proves to be beneficial in clinical practice, it appears important to observe relative changes over time.

Animals↗

PubMed2003

Modulation of remifentanil-induced analgesia, hyperalgesia, and tolerance by small-dose ketamine in humans.

UNLABELLED: Adding a small dose of ketamine to opioids may increase the analgesic effect and prevent opioid-induced hyperalgesia and acute tolerance to opioids. In this randomized, double-blinded, placebo-controlled crossover study, we investigated the effect of remifentanil combined with small concentrations of ketamine on different experimental pain models. Pain detection thresholds to single and repeated IM electrical stimulation and to repeated transcutaneous electrical stimulation, pressure pain tolerance threshold, and sedative, respiratory, and cardiovascular side effects were assessed in 14 healthy volunteers. Saline, remifentanil alone, and remifentanil combined with ketamine at target plasma concentrations of 50 or 100 ng/mL were administered in four study sessions. The ketamine infusion was started after baseline testing at a constant target concentration. Remifentanil was started after testing with ketamine alone at an initial target concentration of 1 ng/mL and then increased to 2 ng/mL and decreased to 1 ng/mL. The last test series were started 10 min after discontinuation of remifentanil. Acute remifentanil-induced hyperalgesia and tolerance were detected only by the pressure pain test and were not suppressed by ketamine. Remifentanil alone induced significant analgesia with all pain tests. Ketamine further increased the remifentanil effect only on IM electrical pain. Remifentanil at a 2 ng/mL target concentration induced a slight respiratory depression that was antagonized by ketamine. We conclude that ketamine effects on opioid analgesia are pain-modality specific. IMPLICATIONS: Coadministration of ketamine and morphine for pain relief is still controversial. Our experimental pain study with volunteers showed that ketamine enhances opioid analgesia without increasing sedation and reduces respiratory depression. Opioid-induced hyperalgesia and tolerance were not affected by ketamine and depended on the type of nociceptive stimulus. This may explain the conflicting results on opioid tolerance in previous studies.

Adult↗

PubMed2003

Further validation of a questionnaire to identify women likely to have low bone density.

UNLABELLED: A questionnaire instrument called the Simple Calculated Osteoporosis Risk Estimation (SCORE*) stratifies risk for osteoporosis, potentially reducing population-screening costs. SCORE is calculated using race, weight, age, history of estrogen use, fracture history, and presence/absence of rheumatoid arthritis. We tested SCORE in 912 postmenopausal women aged 45 yr or more using a Hologic QDR4500C densitometer for the total hip, femoral neck, and lumbar spine. National Health and Nutrition Examination Survey (NHANES III) norms were used to calculate hip T-scores. Low bone density (T-score < -2.0) was found in 29.6% of patients at the femoral neck, 17.7% at the total hip, 36.1% at the lumbar spine, and 46.1% at one or more sites. The sensitivity/specificity of the SCORE model (using a threshold of 6 points) was 0.97/0.36 for the femoral neck, 0.95/0.30 for the total hip, 0.86/0.35 for the spine, and 0.88/0.41 for any site (total hip, femoral neck, or spine). When used to detect low bone density at any site, SCORE would have deferred 27.6% of women referred for DXA scans, but 20.7% of these (5.7% of the entire population) would have been false-negatives, and thus inappropriately deferred. At a cutpoint of 3 instead of 6, sensitivity/specificity was 0.96/0.16. In those aged 50-60, the group with the greatest need for risk stratification, sensitivity/specificity for low density at any site was 0.72/0.54, and 46.1% would have been deferred, but 18.5% of this group would have been false-negatives. A cutpoint of 1 in this age group yielded sensitivity/specificity of 0.94/0.16. After age 65, few women would be deferred. CONCLUSION: When used to detect low bone density at any site with sufficient sensitivity for clinical practice, SCORE did not have sufficient discriminatory power to be broadly applicable.

Area Under Curve↗

PubMed1998

[Genetic and clinical diagnosis of infantile autism].

The main objectives of this study were to characterize the selected variables for a better understanding and diagnosis of infantile autism such as clinical and image findings, diagnostic criteria, frequency of neuropsychiatric disorders in the subjects' families, familial recurrence and occurrence of consangunity between the subjects' parents and between other couples in the family. The sample was composed of 36 subjects of both sexes, in the age group from 1 though 20 years old, members of 35 distinctive families, all of which presenting clinical diagnosis for infantile autism. Mental retardation was clinically observed in all subjects of the sample and convulsion in 27.8%; neuropsychiatric disorders were referred in at least one family member of the subjects (97.14% of the families); recurrent autism in 11.42% grandparents and great-grand-parents (2.86%); abnormal findings in computed tomography scan were observed in three subjects. These results support the suggestion of the multifactorial heredity model with differential threshold fold sex in infantile autism. The clinical evaluation of all infantile autism cases should always appraise the neurological, psychiatric and genetic features.

Adolescent↗

PubMed1993

Felbamate. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy in epilepsy.

Felbamate is currently being developed as an antiepileptic agent. Although its mechanism of action has yet to be fully elucidated, felbamate appears to inhibit both the spread of seizures and increase seizure threshold in animal models. Data available in the clinical setting provide evidence that, at doses of up to 3600 mg/day as an adjunct to existing antiepileptic therapy or as monotherapy following substitution for other medications, the drug reduces the frequency of partial onset seizures in adult patients refractory to conventional antiepileptic treatments. Felbamate is also effective in the treatment of Lennox-Gastaut syndrome in children, a severe epilepsy which is usually refractory to antiepileptic agents. The effect of felbamate in the treatment of generalised tonic-clonic seizures in adults with partial onset seizures which are secondarily generalised is promising but requires clarification in large-scale trials. The most common adverse effects occurring during administration of felbamate are mild to moderate gastrointestinal (nausea, vomiting and anorexia) and central nervous system (headache, somnolence, diplopia, dizziness and insomnia) disturbances. Drug interactions with other antiepileptic agents may prove problematic in terms of adverse effects. Thus, at this stage of its development, the antiepileptic efficacy of felbamate in treatment-refractory patients with partial onset seizures and Lennox-Gastaut syndrome has been proven but efficacy in generalised tonic-clonic seizures requires further substantiation in large well controlled and well designed clinical trials. In addition, a more comprehensive base of comparative clinical trials data is necessary to further clarify issues of relative efficacy and tolerability compared with other antiepileptic agents. The clinical implications of the drug interactions associated with felbamate also require more detailed investigation. These data will be awaited with interest and when available will help to place felbamate in perspective in the management of epilepsy.

Adolescent↗