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Biomedical subjects

D Heck

Publications and source records attributed to D Heck.

At least 19 recordsLinked to original sources
PubMed2006

C57BL/6J and DBA/2J mice vary in lick rate and ingestive microstructure.

Fluid licking in mice is an example of a rhythmic behavior thought to be under the control of a central pattern generator. Inbred strains of mice have been shown to differ in mean or modal interlick interval (ILI) duration, suggesting a genetic-based variation. We investigated water licking in the commonly used inbred strains C57BL/6J (B6) and DBA/2J (D2), using a commercially available contact lickometer. Results from 20-min test sessions indicated that D2 mice lick at a faster rate than B6 mice (10.6 licks/s vs. 8.5 licks/s), based on analysis of the distribution of short-duration ILIs (50-160 ms). This strain difference was independent of sex, extent of water deprivation or total number of licks. D2 mice also displayed a faster lick rate when the strains were tested with a series of brief (5 s) trials. However, when ingestion over the entire 20-min session was analyzed, it was evident that D2 mice had an overall slower rate of ingestion than B6 mice. This was because of the tendency for D2 mice to have more very long pauses (>30 s) between sequences of licking bursts. Overall, it appeared that D2 mice licked more efficiently, ingesting more rapidly during excursions to the spout that were fewer and farther between.

Animals↗
PubMed2005

Upper limit on the photon fraction in highest-energy cosmic rays from AGASA data.

A new method to derive an upper limit on photon primaries from small data sets of air showers is developed which accounts for shower properties varying with the primary energy and arrival direction. Applying this method to the highest-energy showers recorded by the AGASA experiment, an upper limit on the photon fraction of 51% (67%) at a confidence level of 90% (95%) for primary energies above 1.25 x 10(20) eV is set. This new limit on the photon fraction above the Greisen-Zatsepin-Kuzmin cutoff energy constrains the -burst model of the origin of highest-energy cosmic rays.

Journal Article↗
PubMed2005

Detection and imaging of atmospheric radio flashes from cosmic ray air showers.

The nature of ultrahigh-energy cosmic rays (UHECRs) at energies >10(20) eV remains a mystery. They are likely to be of extragalactic origin, but should be absorbed within approximately 50 Mpc through interactions with the cosmic microwave background. As there are no sufficiently powerful accelerators within this distance from the Galaxy, explanations for UHECRs range from unusual astrophysical sources to exotic string physics. Also unclear is whether UHECRs consist of protons, heavy nuclei, neutrinos or gamma-rays. To resolve these questions, larger detectors with higher duty cycles and which combine multiple detection techniques are needed. Radio emission from UHECRs, on the other hand, is unaffected by attenuation, has a high duty cycle, gives calorimetric measurements and provides high directional accuracy. Here we report the detection of radio flashes from cosmic-ray air showers using low-cost digital radio receivers. We show that the radiation can be understood in terms of the geosynchrotron effect. Our results show that it should be possible to determine the nature and composition of UHECRs with combined radio and particle detectors, and to detect the ultrahigh-energy neutrinos expected from flavour mixing.

Journal Article↗
PubMed2001

Two-dimensional monitoring of spiking networks in acute brain slices.

To understand spatiotemporally coordinated activity in neural networks and interaction between different areas or layers in brain tissue, simultaneous multisite recording is a prerequisite. For in vitro studies pursuing these goals, substrate integrated, planar microelectrode arrays (MEAs) have been developed to monitor spikes and local field potentials. Here we report for the first time recordings of single-unit spike activity with MEAs in acute slice preparations of the rat cerebellum. We compare these recordings to results of conventional techniques, and discuss the recording conditions in view of the equivalent circuits commonly used. Simultaneous recordings with tungsten microelectrodes and MEAs verified that recording characteristics and signal-to-noise ratios of MEA electrodes were comparable to those of conventional extracellular electrodes. Spike shapes were identical on both electrodes. We found no detectable overlap between spike signals recorded at neighboring MEA electrodes (200 microm spacing). Neuronal spike activity was detected with MEA electrodes at distances of up to 100 microm from the site of spike generation. We conclude that extracellular recording of independent single-unit spike activity with MEAs is indeed suitable to monitor network activity in acute slices, making MEAs an exceptionally useful tool for the assessment of fast network dynamics in acute slices.

Action Potentials↗
PubMed1999

Sequential stimulation of rat and guinea pig cerebellar granular cells in vitro leads to increasing population activity in parallel fibers.

Sequential stimulation of the granular layer of the cerebellar cortex in vitro using 11 linearly aligned stimulating electrodes leads to massive population activity in the parallel fiber system and to spike activity in Purkinje cells (Heck, D., Neurosci. Lett., 157 (1993) 95-98; Heck, D., Naturwissenschaften, 82 (1995) 201-2030). The induced parallel fiber activity, however, might have been a result of direct stimulation of parallel fibers themselves and not of stimulation of granular cells or their ascending axons. We report here that using sequential 'moving' stimuli and varying the distance covered by the 'movement', parallel fiber population spike amplitude increases with distance and saturates for distances longer than 1.0 mm. This effect cannot be explained if parallel fibers are directly stimulated, but requires stimulation of the granular cells or their ascending axons. We conclude that the population spike activity and Purkinje cell responses induced by sequential stimulation of the granular layer of the cerebellar cortex slices in this and earlier experiments consists of orthodromic parallel fiber spikes.

Animals↗
PubMed1998

Health-related quality of life after knee replacement.

A cross-sectional, community-based survey of a random sample of 1750 of 242,311 Medicare recipients was performed. The patients were at least sixty-five years old and had had a primary or revision knee replacement (either unilaterally or bilaterally) between 1985 and 1989. Three samples were surveyed separately: a national sample (to reflect the United States as a whole) and samples from Indiana and the western part of Pennsylvania (sites chosen for convenience to assess the validity of the findings for the national sample on a regional level). Each sample was stratified by race, age, residence (urban or rural), and the year of the procedure. Valid and reliable questionnaires were used to elicit the participants' assessments of pain, physical function, and satisfaction two to seven years after the knee replacement. Of the 1486 patients who were eligible for inclusion in the survey, 1193 (80.3 per cent) responded. The mean age of the respondents was 72.6 years. Eight hundred and forty-nine respondents (71.2 per cent) were white, and 849 (71.2 per cent) were women. The participants reported that they had little or no pain in the knee at the time of the survey, regardless of the age at the time of the knee replacement, the body-mass index, or the length of time since the knee replacement. After adjustment for potential confounding variables, predictors of better physical function after the replacement were an absence of problems with the contralateral knee, primary knee replacement (rather than revision) (Indiana sample only), and a lower body-mass index (Indiana and western Pennsylvania samples). Four hundred and fifteen (85.2 per cent) of the 487 patients in the national sample were satisfied with the result of the knee replacement. In what we believe to be the first community-based study of the outcome of knee replacement, patients reported having significant (p = 0.0001) and persistent relief of pain, improved physical function, and satisfaction with the result two to seven years postoperatively. The findings of the present study suggest that age and obesity do not have a negative impact on patient-relevant outcomes (pain and physical function). Dissemination of these findings has the potential to increase appropriate referrals for knee replacement and thereby reduce the pain and functional disability due to osteoarthrosis of the knee.

Aged↗
PubMed1998

Closed fractures of the tibial shaft. A meta-analysis of three methods of treatment.

We reviewed the literature to determine the clinical outcomes of the treatment of closed fractures of the tibial shaft with immobilization in a cast, open reduction with internal fixation, or fixation with an intramedullary rod. We reviewed 2372 reports of comparative trials and uncontrolled studies of series of patients published between 1966 and 1993. Nineteen reports, involving six controlled trials and twenty-seven groups of patients, met our inclusion criteria. A structured questionnaire was used to assess the quality of the literature in terms of the experimental design and the method of assessment of outcome. Outcomes from controlled trials were summarized with odds ratios and risk differences, and outcomes from case series were summarized by the medians of the reported results. The studies that were reviewed generally had few subjects and were poorly designed. The comparative trials showed treatment with a cast to be associated with a lower rate of superficial infection than open reduction and internal fixation (mean difference, -5.81 per cent; p = 0.02) and open reduction and internal fixation to be associated with a higher rate of union by twenty weeks than treatment with a cast (mean difference, -18.07 per cent; p = 0.008). There were no other significant associations. There were insufficient data for us to evaluate any aspect of functional status, level of pain, or other patient-reported outcomes of any of the methods of treatment. The results of the present review suggest that the data from the published literature are inadequate for decision-making with regard to the treatment of closed fractures of the tibia.

Casts, Surgical↗
PubMed1997

Voltage signals of individual Purkinje cell dendrites in rat cerebellar slices.

For investigating neuronal information processing at the cellular level, a technique which visualizes the voltage distribution within single neurons in situ would be extremely useful. Voltage-sensitive dyes are, in principle, capable of reporting membrane potential [Cohen, L.B. and Salzberg, B.M., Rev. Physiol. Biochem. Pharmacol., 83 (1978) 35-88; Grinvald, A., Lieke, E.E., Frostig, R.D. and Hildesheim, R., J. Neurosci., 14 (1994) 2545-2568; Kleinfeld, D., Delaney, K.R., Fee, M.S., Flores, J.A., Tank, D.W. and Gelperin, A., J. Neurophysiol., 72 (1994) 1402-1419]. However, their application to single cells internally is technically difficult [Antic, S. and Zecevic, D., J. Neurosci., 15 (1995) 1392-1405; Grinvald, A., Salzberg, B.M., Lev-Ram, V. and Hildesheim, R., Biophys. J., 51 (1987) 643-651; Kogan, A., Ross, W.N., Zecevic, D. and Lasser-Ross, N., Brain Res., 700 (1995) 235-239; Zecevic, D., Nature, 381 (1996) 322-325]. An alternative strategy consists in applying the dye from the outside to all cells in the tissue, while manipulating a single cell by current injection [Krauthamer, V. and Ross, W.N., J. Neurosci., 4 (1984) 673-682; Ross, W.N. and Krauthamer, V., J. Neurosci., 4 (1984) 659-672]. Here, we modify this technique to further enhance spatial at the cost of temporal resolution [Borst, A., Z. Naturforsch., 50 (1995) 435-438]. Applied to rat cerebellar slices we demonstrate that the potential spread in individual Purkinje cells can be imaged up to even fine dendritic branches. The acquired optical signals suggest that steadily hyperpolarized Purkinje cells are electrically compact. When permanently depolarized, the somatic input resistance is significantly diminished, yet the spatial voltage drop along the dendrites remains unchanged. As demonstrated by compartmental modeling, this hints to a concentration of outward rectifying currents at the soma of the cells.

Animals↗
PubMed1997

Effects of the volatile anesthetic enflurane on spontaneous discharge rate and GABA(A)-mediated inhibition of Purkinje cells in rat cerebellar slices.

The effects of the volatile anesthetic enflurane on the spontaneous action potential firing and on gamma-aminobutyric acid-A (GABA(A))-mediated synaptic inhibition of Purkinje cells were investigated in sagittal cerebellar slices. The anesthetic shifted the discharge patterns from continuous spiking toward burst firing and decreased the frequency of extracellularly recorded spontaneous action potentials in a concentration-dependent manner. Half-maximal reduction was observed at a concentration corresponding to 2 MAC (1 MAC induces general anesthesia in 50% of patients and rats). When the GABA(A) antagonist bicuculline was present, 2 MAC enflurane reduced action potential firing only by 13 +/- 8% (mean +/- SE). In further experiments, inhibitory postsynaptic currents (IPSCs) were monitored in the whole cell patch-clamp configuration from cells voltage clamped close to -80 mV. At 1 MAC, enflurane attenuated the mean amplitude of IPSCs by 54 +/- 3% while simultaneously prolonging the time courses of monoexponential current decays by 413 +/- 69%. These effects were similar when presynaptic action potentials were suppressed by 1 microM tetrodotoxin. At 1-2 MAC, enflurane increased GABA(A)-mediated inhibition of Purkinje cells by 97 +/- 20% to 159 +/- 38%. During current-clamp recordings, the anesthetic (2 MAC) hyperpolarized the membrane potential by 5.2 +/- 1.1 mV in the absence, but only by 1.6 +/- 1.2 mV in the presence, of bicuculline. These results suggest that enflurane-induced membrane hyperpolarizations, as well as the reduction of spike rates, were partly caused by an increase in synaptic inhibition. Induction of burst firing was related to other actions of the anesthetic, probably an accelerated activation of an inwardly directed cationic current and a depression of spike afterhyperpolarizations.

Action Potentials↗
PubMed1997

The detection and generation of sequences as a key to cerebellar function: experiments and theory.

Starting from macroscopic and microscopic facts of cerebellar histology, we propose a new functional interpretation that may elucidate the role of the cerebellum in movement control. The idea is that the cerebellum is a large collection of individual lines (Eccles's "beams": Eccles et al. 1967a) that respond specifically to certain sequences of events in the input and in turn produce sequences of signals in the output. We believe that the sequence-in/sequence-out mode of operation is as typical for the cerebellar cortex as the transformation of sets into sets of active neurons is typical for the cerebral cortex, and that both the histological differences between the two and their reciprocal functional interactions become understandable in the light of this dichotomy. The response of Purkinje cells to sequences of stimuli in the mossy fiber system was shown experimentally by Heck on surviving slices of rat and guinea pig cerebellum. Sequential activation of a row of eleven stimulating electrodes in the granular layer, imitating a "movement" of the stimuli along the folium, produces a powerful volley in the parallel fibers that strongly excites Purkinje cells, as evidenced by intracellular recording. The volley, or "tidal wave," has maximal amplitude when the stimulus moves toward the recording site at the speed of conduction in parallel fibers, and much smaller amplitudes for lower or higher "velocities." The succession of stimuli has no effect when they "move" in the opposite direction. Synchronous activation of the stimulus electrodes also had hardly any effect. We believe that the sequences of mossy fiber activation that normally produce this effect in the intact cerebellum are a combination of motor planning relayed to the cerebellum by the cerebral cortex, and information about ongoing movement, reaching the cerebellum from the spinal cord. The output elicited by the specific sequence to which a "beam" is tuned may well be a succession of well timed inhibitory volleys "sculpting" the motor sequences so as to adapt them to the complicated requirements of the physics of a multijointed system.

Animals↗
PubMed1995

Variation in orthopedic surgeons' perceptions of the indications for and outcomes of knee replacement.

OBJECTIVE: To determine the agreement among orthopedic surgeons' indications for knee replacement, their perceptions of the usefulness of various treatments for osteoarthritis of the knee and their expected outcomes of knee replacement, and to determine the relation between these opinions and the number of knee replacement procedures performed by individual surgeons. DESIGN: Survey. SETTING: Ontario. PARTICIPANTS: All 392 orthopedic surgeons in the province. Of the 325 practising traceable surgeons 234 (72.0%) responded. OUTCOME MEASURES: Indications for knee replacement, perceived usefulness of treatments for osteoarthritis, perceived outcomes of knee replacement and number of knee replacement procedures performed by individual surgeons. RESULTS: The respondents disagreed on how 20 of 34 patient characteristics affected their decision to perform knee replacement surgery. They also disagreed on the usefulness of seven of eight treatments for arthritis of the knee. The respondents demonstrated variation in their expected outcomes of knee replacement. The surgeons who performed more procedures judged, on average, the outcomes to be better and to have fewer complications than the surgeons who performed fewer procedures. CONCLUSIONS: Orthopedic surgeons demonstrated disagreement about some of the indications for knee replacement, the usefulness of treatments for arthritis of the knee and the perceived outcomes of knee replacement. The areas of greatest disagreement should be the focus of future research and the development of practice guidelines.

Adult↗
PubMed1995

Investigating dynamic aspects of brain function in slice preparations: spatiotemporal stimulus patterns generated with an easy-to-build multi-electrode array.

Electrical stimulation of nervous tissue with single stimulating electrodes is a technique widely used for the investigation of nervous system function. While it has proved to be useful in all kinds of experiments, single electrode stimuli are, however, far from being 'natural'. In most parts of the living brain, incoming activity results from the firing of a large number of presynaptic neurons, thus reflecting a complex combination of space and time aspects of neural activity. In this paper, a multi-electrode stimulating system is introduced which allows for the generation of fast space-time stimulus patterns. An example for the application of dynamic input patterns to the cerebellar cortex in vitro is given. The corresponding experiments revealed aspects of cerebellar function which cannot be seen using static or single electrode stimulation.

Animals↗
PubMed1995

Use of antibiotic-impregnated cement during hip and knee arthroplasty in the United States.

A survey of practicing orthopaedists regarding their use of antibiotic(s) in bone-cement (ABC) was carried out. The initial sampling of 2,139 orthopaedists spanned the continental United States. Responses that passed fail-edit criteria were obtained from 1,015 physicians. Clinical practice patterns are highly variable. Adult reconstructive orthopaedic practitioners' belief in antibiotic(s) in bone-cement for the treatment of patients with previous sepsis is favorable. This opinion can be supported at the guideline level. Guidelines suggesting that liquid antibiotics should not be used as additions to polymethyl methacrylate are also supportable. The need for careful scientific inquiry and cost-effectiveness evaluation of the benefits and risks relating to the use of antibiotic additions to polymethyl methacrylate cement in joint arthroplasty exists. On the basis of such inquiry, educational dissemination to reduce practice variation would be indicated.

Anti-Bacterial Agents↗
PubMed1995

Rates of tibial osteotomies in Canada and the United States.

This study determined the temporal trends and factors associated with the rates of performance of tibial osteotomies from 1985 to 1990 in Ontario, Canada and the United States. The Health Care Financing Administration, Ontario Health Insurance Plan, and National Hospital Discharge Survey databases were used to determine the number of osteotomies from 1985 to 1990. Osteotomy rates decreased in both countries approximately by 11% to 14% per year in patients 65 years and older and by 3% to 4% per year in patients younger than 65 years. Men received twice as many osteotomies as women in both countries. In the United States, the average rate of tibial osteotomies was 2 to 3 times lower than in Ontario.

Age Factors↗
PubMed1993

Rat cerebellar cortex in vitro responds specifically to moving stimuli.

In spite of the detailed anatomical knowledge available, the functional significance of the cerebellar wiring diagram is still obscure. Since there are no variations in the anatomy throughout the whole cortical plane, it is plausible to assume that the basic operation is the same in all parts of the cerebellum. The 'wiring' suggests that local activity must depend on the spatio-temporal organization of the inputs. Neocortical input reaches the cerebellar cortex from nearly all cortical areas via mossy fibers terminating on the granular cells. We simulated such an input to the granular layer in acute slices of rat cerebellar cortex using an array of 11 stimulating electrodes. By successively switching the stimulus current from one electrode to the next, a 'moving' input to the granular layer is simulated. Our experiments show that the cerebellar cortex is specifically activated by 'moving' stimuli applied to the granular layer. The activation is a function of 'movement' direction and velocity. Thus, it enables the cerebellar cortex to act as a movement detector. Such behavior has previously been postulated on anatomical grounds [Braitenberg, J. Theoret. Neurobiol., 2 (1983) 237-241; Braitenberg, In Glickstein et al. (Eds.), Cerebellum and Neuronal Plasticity, Plenum, 1987, pp. 193-207].

6-Cyano-7-nitroquinoxaline-2,3-dione↗
PubMed1992

Modulation of effects of lipopolysaccharide on macrophages by a major outer membrane protein of Proteus mirabilis as measured in a chemiluminescence assay.

Our previous studies have shown that a major protein isolated from purified cell walls of Proteus mirabilis (39-kDa protein) is a strong modulator of the specific immune responses to lipopolysaccharide (LPS) from this bacterium. When the protein is mixed with LPS before immunization of mice, the responses of antibody-producing cells specific for LPS are greatly enhanced and converted predominantly to the immunoglobulin G isotype. In the present study, the immunomodulating effects of the 39-kDa protein were tested at the level of interaction of LPS with macrophages. Activation of macrophages was determined by measuring the production of oxygen radicals in a chemiluminescence assay with lucigenin as the amplifier. LPS from P. mirabilis induced strong oxidative metabolism in both peritoneal and bone marrow-derived murine macrophages. These responses were inhibited in a dose-dependent manner by mixing LPS with increasing amounts of the protein. In contrast, bovine serum albumin and methylated bovine serum albumin enhanced the response of macrophages dramatically when complexed with LPS. The inhibiting activity of the 39-kDa protein was also observed with LPS from Escherichia coli K-12.

Animals↗