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Biomedical subjects

J Midtgaard

Publications and source records attributed to J Midtgaard.

At least 19 recordsLinked to original sources

The group matters: an explorative study of group cohesion and quality of life in cancer patients participating in physical exercise intervention during treatment.

A series of studies have shown that physical activity improves cancer patients functional capacity and quality of life (QOL). Few of these studies have included physical exercise carried out in a group setting. However, patient's experience with the in-group processes remains unexplored. This study investigated group cohesion and changes in QOL in 55 cancer patients undergoing chemotherapy who participated in a 9 h weekly group exercise programme for 6 weeks. The study used a method triangulation component design. Seven qualitative group interviews were conducted post-intervention. QOL (SF-36; EORTC QLQ-C30) was assessed at baseline and after Week 6. The interviews revealed that group cohesion was an interim goal aimed to maximize peak performance potential by patients. Group cohesion was characterized by a special 'esprit de corps' and enabled the group members to feel like sport teams. The programme made purposeful togetherness possible while allowing the patients an opportunity to let their illness fade into the background. Questionnaire data showed significant improvements in mental health, social and emotional functioning. This study identified a conceptualization of group cohesion that forms a valuable basis for a larger randomized controlled trial to conclude whether the observed changes are a result of this specific intervention.

Adult↗

High-intensity resistance and cardiovascular training improve physical capacity in cancer patients undergoing chemotherapy.

The purpose of the study was to examine the effects of a supervised high- and low-intensity structured training program in cancer patients concurrently undergoing chemotherapy. Seventy patients, in different stages of the disease and with different diagnoses (48 females, 22 males), between 18 and 65 years of age (mean age 42.8) participated in a 9-h weekly training program over 6 weeks. The intervention involved physical exercise, relaxation, massage, and body-awareness training. Physical capacity (one-repetition maximum tests (1RM), VO2max) and body composition (weight, skin-fold) were compared before and after the exercise intervention. The average increase in muscular strength was 41.3% (P<0.001) and 14.5% in aerobic fitness (pre: 2.27+/-0.597 L/min, post: 2.56+/-0.644 L/min, (P<0.001). The exercise intervention significantly increased the weight of the subjects by 1% (pre: 72.62+/-13.42 kg, post: 73.25+/-13.44 kg, P=0.016). There was a significant decrease in skin-fold measurements by 3% (P=0.031). The exercise intervention was well tolerated, provided that daily screening criteria were adhered to. The effects of resistance and cardiovascular training observed in this short-term study support the theory that exercise is a beneficial intervention strategy for increasing muscle strength and aerobic fitness during antineoplastic chemotherapy. This type of exercise program can be an important component of complementary treatment for cancer patients undergoing chemotherapy.

Adolescent↗

Maximum physical capacity testing in cancer patients undergoing chemotherapy: qualitative findings from an exercise program.

BACKGROUND: Over the past few years there has been a growing interest in the field of physical exercise in rehabilitation of cancer patients, leading to requirements for objective maximum physical capacity measurement (maximum oxygen uptake (VO(2max)) and one-repetition maximum (1RM)) to determine dose-response levels in different cancer diagnoses. AIM: To explore the patients' experiences of maximum physical capacity testing while concurrently undergoing chemotherapy and participating in a 6-week, 9 h weekly multidimensional exercise program. DESIGN AND METHOD: Prospective, exploratory study using semi-structured qualitative interviews conducted prior to and at termination of the program. The study included 100 patients (18-65 years, median 42 years) with or without residual disease and with mixed diagnoses. RESULTS: Following the intervention, cancer patients felt significantly safer in performing maximum physical capacity tests as these motivated them through self-perceived competitiveness and set a standard that served to encourage peak performance. CONCLUSION: The positive attitudes in this sample towards maximum physical capacity open the possibility of introducing physical testing early in the treatment process. However, the patients were self-referred and thus highly motivated and as such are not necessarily representative of the whole population of cancer patients treated with chemotherapy.

Adolescent↗

Transforming the nature of fatigue through exercise: qualitative findings from a multidimensional exercise programme in cancer patients undergoing chemotherapy.

The objective of this study was to explore the nature of fatigue in cancer patients with advanced stages of disease undergoing chemotherapy and concurrently participating in a 6-week multidimensional exercise programme (physical exercise, relaxation, massage and body-awareness training). Semi-structured qualitative interviews were conducted with 23 patients between 18 and 65 years of age prior to, during, and at termination of the programme. The findings endorsed that physical debilitation, fatigue, and uncertainty of physical capacity were the patients' motivation for participation. Throughout the programme the patients experienced exercise-induced fatigue, which they associated with a sense of increased physical strength, improvement in energy and physical well-being. This positive sense of fatigue can be seen as a contrast to the negative chemotherapy-induced fatigue, which is characterized by physical discomfort and uncontrollable exhaustion. The patients learned to manoeuvre through periods of intense fatigue by using exercise as a strategy to adjust their sense of physical debilitation. Visibility of fatigue's qualitative aspects is necessary if patients are to be encouraged to stay active and to set realistic goals. The transformation process of fatigue identified in this study supports the theory of exercise as a beneficial intervention strategy in the treatment of cancer-related fatigue.

Activities of Daily Living↗

Computational analysis of action potential initiation in mitral cell soma and dendrites based on dual patch recordings.

In olfactory mitral cells, dual patch recordings show that the site of action potential initiation can shift between soma and distal primary dendrite and that the shift is dependent on the location and strength of electrode current injection. We have analyzed the mechanisms underlying this shift, using a model of the mitral cell that takes advantage of the constraints available from the two recording sites. Starting with homogeneous Hodgkin-Huxley-like Na(+)-K(+) channel distribution in the soma-dendritic region and much higher sodium channel density in the axonal region, the model's channel kinetics and density were adjusted by a fitting algorithm so that the model response was virtually identical to the experimental data. The combination of loading effects and much higher sodium channel density in the axon relative to the soma-dendritic region results in significantly lower "voltage threshold" for action potential initiation in the axon; the axon therefore fires first unless the voltage gradient in the primary dendrite is steep enough for it to reach its higher threshold. The results thus provide a quantitative explanation for the stimulus strength and position dependence of the site of action potential initiation in the mitral cell.

Action Potentials↗

Forward and backward propagation of dendritic impulses and their synaptic control in mitral cells.

The site of impulse initiation is crucial for the integrative actions of mammalian central neurons, but this question is currently controversial. Some recent studies support classical evidence that the impulse always arises in the soma-axon hillock region, with back-propagation through excitable dendrites, whereas others indicate that the dendrites are sufficiently excitable to initiate impulses that propagate forward along the dendrite to the soma-axon hillock. This issue has been addressed in the olfactory mitral cell, in which excitatory synaptic input is restricted to the distal tuft of a single primary dendrite. In rat olfactory bulb slices, dual whole cell recordings were made at or near the soma and from distal sites on the primary dendrite. The results show that the impulse can be initiated in either the soma-axon hillock or in the distal primary dendrite, and that the initiation site is controlled physiologically by the excitatory synaptic inputs to the distal tuft and inhibitory synaptic inputs near the soma.

Action Potentials↗

Spatial synaptic integration in Purkinje cell dendrites.

Synaptic integration occurs within a framework of synaptic connections, and cell type-specific, intrinsic and transmitter-gated ion channels. These components are differentially distributed over the somato-dendritic membrane. Recent results from Purkinje cells and pyramidal cells exemplify some of these mechanisms of spatial synaptic integration. This paper focusses on the cerebellar Purkinje cell. In these neurons, the amplitude and distribution of single climbing fibre and parallel fibre EPSP-evoked Ca2+ influx were regulated by the transient outward, IA-like current in the distal (spiny) dendrites. The synaptically evoked Ca2+ influx was graded from a local response involving only a few terminal spiny dendrites to a propagated Ca2+ spike. The climbing fibre-evoked Ca2+ influx in the spiny dendrites was finely graded by parallel fibre-induced depolarization. Climbing fibre and parallel fibre-evoked Ca2+ influx elicited a short lasting afterhyperpolarization that affected subsequent dendritic Ca2+ influx. In addition, inhibitory synaptic input controlled dendritic Ca2+ influx. Interaction between information from different sources along the dendrites is thus controlled by intrinsic potassium conductances and IPSPs. Different electrophysiological properties are found in the cerebellar neurons. Thus, Golgi cells, stellate cells and granule cells seem to integrate on a shorter intrinsic timescale than do Purkinje cells, the output neuron of the cerebellar cortex. The specific mechanisms by which different types of presynaptic neurons specifically innervate a given dendritic compartment remain to be elucidated, but recent results provide some experimental evidence of a differential distribution of cell adhesion molecules between the axonal and the somato-dendritic membrane, suggesting one mechanism contributing to the ordered distribution of synapses during synaptogenesis.

Animals↗

Processing of information from different sources: spatial synaptic integration in the dendrites of vertebrate CNS neurons.

Most synapses on a neuron are distributed along the dendrites. Inputs from different types of presynaptic neurons often distribute to different dendritic compartments. This provides an anatomical framework for spatial synaptic integration. At the same time, a plethora of time- and voltage-dependent responses are present, usually with a distinct distribution over the somato-dendritic membrane. These intrinsic conductances shape the local dendritic response to ligand-gated conductances, and provide the dendrites with a dynamic way of regulating the interaction between synapses. Recent results from neurons in the vertebrate CNS exemplify these mechanisms of dendritic integration.

6-Cyano-7-nitroquinoxaline-2,3-dione↗

Synaptic integration in a model of cerebellar granule cells.

1. We have developed a compartmental model of a turtle cerebellar granule cell consisting of 13 compartments that represent the soma and 4 dendrites. We used this model to investigate the synaptic integration of mossy fiber inputs in granule cells. 2. The somatic compartment contained six active ionic conductances: a sodium conductance with fast activation and inactivation kinetics, gNa; a high-voltage-activated calcium conductance, gCa(HVA); a delayed potassium conductance, gK(DR); a transient potassium conductance, gK(A); a slowly relaxing mixed Na+/K+ conductance activating at hyperpolarized membrane potentials, gH, and a calcium- and voltage-dependent potassium conductance, gK(Ca). The kinetics of these conductances was derived from electrophysiological studies in a variety of preparations, including turtle and rat granule cells. 3. In the soma, dynamics of intracellular free Ca2+ was modeled by incorporation of a Na+/Ca2+ exchanger, radial diffusion, and binding sites for Ca2+. 4. The model of the turtle granule cell exhibited depolarization-induced action potential firing with properties closely resembling those seen with intracellular recordings in turtle granule cells in vitro. 5. In the most distal compartments of the dendrites, mossy fiber activity induced synaptic currents mediated by alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)- and N-methyl-D-aspartate (NMDA)-type of glutamate receptors. The strength of synaptic inputs chosen was such that the synaptic potential induced by synchronous activation of two mossy fiber synapses reached threshold for induction of a single action potential. 6. The slow time course of the NMDA synaptic current together with the slow relaxation kinetics of gH significantly affected the temporal summation of excitatory synaptic potentials. A priming action potential evoked by mossy fiber stimulation increased the maximal time interval between two synaptic potentials capable to reach again threshold for a subsequent action potential. This time interval then decreased in parallel with the decay of the NMDA synaptic current, reached a minimum after 200 ms, and slowly recovered with reactivation of gH. 7. Repetitive, steady activation of synaptic conductances by a single mossy fiber at different frequencies induced action potential firing with a sharp threshold at 12 Hz. Activity of a single or of several mossy fibers induced firing of the granule cell at a frequency close to that induced when the average synaptic current was directly injected into the cell. The mossy fiber activity-granule cell firing frequency curve was close to linear with a slope of about one-half for input frequencies < or = 400 Hz.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Spatial distribution of Ca2+ influx in turtle Purkinje cell dendrites in vitro: role of a transient outward current.

1. Intracellular recordings were made from Purkinje cells in a slice preparation of the turtle cerebellum. Simultaneously, changes in [Ca2+]i in all regions of the cell were detected with high-speed fluorescence imaging of injected fura-2. Cells were stimulated either intrasomatically or synaptically. In addition, the cells were polarized locally with an external electrical field aligned parallel to the soma-dendritic axis. 2. The soma, smooth dendrites, and spiny dendrites displayed voltage-dependent changes in [Ca2+]i. Changes in the somatic region were correlated with Na+ spike firing and local depolarization. Small [Ca2+]i changes in the spiny dendrites were correlated with graded potentials and larger changes with Ca2+ action potentials. Individual Ca2+ spike transients sometimes occurred separately in different dendritic regions demonstrating localized firing. 3. The amplitude and spatial extent of spike-related [Ca2+]i transients were increased with intrasomatic depolarizing prestimulus membrane potentials and reduced by hyperpolarizing prestimulus potentials. This dependence and the latency to Ca2+ spike activation were strongly reduced by 4-aminopyridine (4-AP). These results suggest that a transient A-like current regulates the generation of Ca2+ spikes and the localization of Ca2+ influx in turtle Purkinje cell dendrites. 4. Both electric field depolarization and intrasomatic depolarization affected the generation of Ca2+ spikes and [Ca2+]i signals in a similar manner. Strong field stimulation could evoke focal depolarization at the tips of the spiny dendrites and cause local Ca2+ spike generation near the pial surface. When both stimuli were used, their effects were additive. 5. Climbing fiber (CF) or parallel fiber (PF) stimulation were associated with the generation of dendritic Ca2+ transients. In some experiments the PF-induced Ca2+ transients were confined to a small part of the spiny dendrites. The spatial distribution and the amplitude of these transients were influenced by somatic depolarization or field stimulation in a manner similar to their effect on directly evoked Ca2+ spikes and consistent with the involvement of a transient outward current in the control of the synaptically induced Ca2+ influx. 6. These results suggest that the intrinsic potassium conductances dynamically modulate spatial integration and influence the compartmentalization of Ca2+ spikes and [Ca2+]i changes in the dendrites.

Animals↗

Membrane properties and synaptic responses of Golgi cells and stellate cells in the turtle cerebellum in vitro.

1. Intracellular recordings from anatomically identified Golgi cells and deep stellate cells were obtained in a slice preparation of the turtle cerebellar cortex. 2. Golgi cells and stellate cells had very similar firing patterns, which differed from those of Purkinje cells. In the interneurones, a short time constant and a high input resistance ensured a short response time. A pronounced spike after-hyperpolarization (spike AHP) participated in the rapid repolarization following a depolarizing input. The active and passive membrane properties of the interneurones ensured a very tight temporal coupling between input and output. 3. TTX abolished both the action potentials and a subthreshold depolarizing response. The Na+ excitability was increased by addition of Mn2+ or Co2+ to block calcium channels, or by addition of potassium channel blockers. 4. Ca2+ spikes and a Ca2+ plateau could be evoked following addition of potassium channel blockers. A partly 4-aminopyridine (4-AP)-sensitive transient hyperpolarization was found to control Ca2+ excitability in Golgi cells. It is suggested that this hyperpolarization is due to an A-like conductance. 5. A strong anomalous rectification was activated just below spike threshold, and dominated the subthreshold membrane potential at time scales longer than ca 100 ms. The anomalous rectification was partly blocked by Cs+. 6. Temporal integration over time scales up to ca 25 s was provided by activity-dependent adaptation in firing frequency and a long-lasting after-hyperpolarization (AHPL), which had both TTX-sensitive, Ca(2+)-independent, and Ca(2+)-dependent components. 7. Spontaneous IPSPs and EPSPs were abundant. The IPSPs were abolished by bicuculline. EPSPs were easily evoked by parallel fibre stimulation, had a shorter time course than in Purkinje cells, and were suppressed by the spike AHP. 8. Due to a short response time and a relatively short overall time frame for temporal integration, cerebellar interneurones operate on a faster time scale than the Purkinje cells, the output neurones of the cerebellar cortex. 9. It is suggested that information from shared sources, e.g. the parallel fibres, is distributed onto dynamically different cellular populations based on differences in the intrinsic membrane properties of the postsynaptic neurones.

Action Potentials↗

Stellate cell inhibition of Purkinje cells in the turtle cerebellum in vitro.

1. The stellate cell-mediated inhibition of Purkinje cells was studied by intracellular recordings in an in vitro slice preparation of the turtle cerebellar cortex. A graded inhibitory postsynaptic potential (IPSP) was recorded in Purkinje cells upon stimulation of the parallel fibre-stellate cell pathway. 2. The IPSP was abolished by bicuculline, and had a reversal potential around -75 mV, consistent with a GABAA receptor-operated Cl- conductance dominating the response investigated here. 3. Paired recordings from synaptically coupled stellate cells and Purkinje cells demonstrated that the inhibitory input from a single stellate cell is sufficient to reduce the firing in a Purkinje cell. 4. The extracellular-evoked IPSP interacted with the active postsynaptic membrane properties in the Purkinje cell. Interaction with both the Na+ plateau and the IA prolonged the responses to an IPSP, making the net effect of the inhibitory response dependent on the membrane potential in each postsynaptic neurone. 5. A precisely timed IPSP was particularly efficient in reducing dendritic Ca2+ influx. 6. The voltage-dependent Ca2+ component of a climbing fibre response (CFR) as well as of a parallel fibre (PF) input was reduced by the IPSP. 7. It is suggested that Ca2+ spike-mediated reduction in Purkinje cell excitability may be prevented by the stellate cell IPSP-mediated reduction in Ca2+ influx.

Action Potentials↗

Excitatory synaptic responses in turtle cerebellar Purkinje cells.

1. Climbing fibre responses (CFRs) and parallel fibre responses (PFRs) in Purkinje cells have been analysed in intracellular recordings obtained at various levels from cell body to terminal dendrites in the turtle cerebellum in vitro. 2. With increasing stimulus intensity, the PFR recorded in distal dendrites displayed an early regenerative component which was graded at rest and at hyperpolarized membrane potentials, but was all-or-none at depolarized membrane potentials. 3. The all-or-none component had the same characteristics as Ca2+ spikes triggered by passing depolarizing current through the recording electrode. 4. The repolarizing phase of the PFR had a fast component enhanced by depolarization and diminished by hyperpolarization. 5. In the mid-molecular layer the PFR also included a plateau component which was increasingly prolonged by depolarization and abolished by hyperpolarization. 6. CFRs recorded in the soma had a plateau component, prolonged by local depolarization and abolished by local hyperpolarization. 7. The CFR in distal dendrites included a regenerative component. In some cells this component appeared in an all-or-none manner with local depolarization. In other cells it was smoothly graded with local polarization. 8. In mid-molecular records the CFR was prolonged by local depolarization and presumably electrotonically affected by the configuration of the response more distally and proximally in the cell. 9. It is concluded that excitatory synaptic responses in Purkinje cells include a regenerative Ca2+-mediated spike component in the spiny dendrites and a plateau component located in the proximal dendrites and/or the cell body. It is shown that both responses are modulated in configuration by the local membrane potential. In the spiny dendrites activation and inactivation of the transient hyperpolarizing potential appear to govern the Ca2+ influx during the CFR.

Action Potentials↗

Synaptic control of excitability in turtle cerebellar Purkinje cells.

1. In turtle Purkinje cells in vitro successive climbing fibre responses (CFRs) gradually induced a hyperpolarization that persisted with maintained stimulation and decayed over minutes after climbing fibre stimulation was terminated. 2. The rate of development and the amplitude of this long-lasting hyperpolarization (LHP) increased with the frequency of CFRs. 3. The LHP was also induced by Ca2+ spikes evoked by current injection but not by Na+ spikes. The LHP was blocked by Co2+ but not by tetrodotoxin and could not be explained solely by an increased K+ conductance. 4. Depolarizing current during a train of CFRs enhanced the regenerative component of CFRs and promoted the LHP. Hyperpolarizing current during the stimulus train reduced the regenerative component of CFRs and attenuated the resulting LHP. 5. In the range of membrane potentials attained at different levels of climbing fibre activity the regenerative component of CFRs varied from being dominant at very low stimulus frequency (0.1 s-1) to being inconspicuous at high stimulus frequency (10 s-1). 6. It is concluded that successive CFRs induce a Ca2+-dependent, long-lasting hyperpolarization. The magnitude of the hyperpolarization is regulated by the rate of CFRs and by the voltage- and frequency-dependent configuration of each individual CFR. 7. The active, non-synaptic properties of turtle Purkinje cells make the Ca2+ influx during climbing fibre responses prone to regulation by on-going synaptic activity and by the after-effects of synaptic activity on a time scale of minutes. We suggest that this arrangement may enhance the capacity and complexity of spatial and temporal synaptic integration in Purkinje cells.

Action Potentials↗