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Biomedical subjects

Anders Lund

Publications and source records attributed to Anders Lund.

29 records · Page 2Linked to original sources

Altered dopamine D2 receptor function in fibromyalgia patients: a neuroendocrine study with buspirone in women with fibromyalgia compared to female population based controls.

BACKGROUND: To what extent fibromyalgia belongs to affective spectrum disorders or anxiety spectrum disorders remains disputed. Buspirone induces a hypothermic response, which most likely is due to 5-HT(1A) autoreceptor stimulation, and growth hormone (GH) release, which probably is related to postsynaptic 5-HT(1A) receptor stimulation. The prolactin response to buspirone has been suggested to be mediated through dopamine (DA) antagonistic effects. OBJECTIVES: Based on the assumption that fibromyalgia is more strongly related to stress and anxiety than affective spectrum disorders, we hypothesized that compared to population controls, fibromyalgia patients should demonstrate an increased prolactin response (DA sensitivity) to buspirone challenge test, but no difference in hypothermic response or GH release (5HT sensitivity). METHOD: A 60-mg dose of buspirone was given orally to 22 premenopausal women with fibromyalgia and 14 age and sex matched healthy control subjects. Core body temperature, growth hormone and prolactin levels were analyzed at baseline and after 60, 90, and 150 min. RESULTS: Fibromyalgia patients showed an augmented prolactin response to buspirone compared to controls. Temperature and growth hormone responses did not differ from controls. CONCLUSIONS: Dopaminergic rather than serotonergic neurotransmission is altered in fibromyalgia, suggesting increased sensitivity or density of dopamine D(2) receptors in fibromyalgia patients. Stress and anxiety is an important modulator of dopaminergic neurotransmission. Our results suggest that fibromyalgia is related to anxiety and associated with disturbance in the stress response systems.

Anxiety↗

Selective impairment in effortful information processing in major depression.

Automatic and effortful information processing in depressed patients was investigated by a visual search paradigm, in order to examine dysfunctional effortful processing in depressed patients. Twenty-one patients with major depression, according to the DSM-IV, and with a moderate depression measured by the Hamilton Rating Scale score at >18 participated in the study. The healthy control group was matched for age, gender, and level of education. Half of the trials involved only one type of distractor, and the other half of the trials involved two types of distractors being presented. The results show that the performance of the depressed patients was equal to the control group when the target was easily recognized with only one type of distractor present. However, when target detection required a more difficult and complex attentive search strategy, effortful information processing, the depressed patients needed longer visual search time compared to the controls. Depressed patients seem to have impaired performance on effortful but not automatic information processing.

Adult↗

Sensitivity and specificity of memory dysfunction in schizophrenia: a comparison with major depression.

Fifty-three schizophrenic subjects were compared to 50 patients with major depression and 50 normal controls on measures of working memory, declarative memory and malingering. The schizophrenic group scored 1-2 SDs below controls on all measures, while depressive patients exposed only lesser deficits in working memory and free recall. The memory deficit of the schizophrenic subjects was disproportionately greater than their intellectual decline. Differences between clinical groups could not be explained by differences in IQ, clinical symptom load or demographic characteristics. This indicates that impaired memory is a particular sensitive symptom of schizophrenia and that the impairment is specific to the illness. Working memory failure was prominent in both clinical groups. The schizophrenic subjects displayed primarily an acquisition failure, while the depressed group showed retrieval difficulties.

Adult↗

The monopulsed nature of sperm whale clicks.

Traditionally, sperm whale clicks have been described as multipulsed, long duration, nondirectional signals of moderate intensity and with a spectrum peaking below 10 kHz. Such properties are counterindicative of a sonar function, and quite different from the properties of dolphin sonar clicks. Here, data are presented suggesting that the traditional view of sperm whale clicks is incomplete and derived from off-axis recordings of a highly directional source. A limited number of assumed on-axis clicks were recorded and found to be essentially monopulsed clicks, with durations of 100 micros, with a composite directionality index of 27 dB, with source levels up to 236 dB re: 1 microPa (rms), and with centroid frequencies of 15 kHz. Such clicks meet the requirements for long-range biosonar purposes. Data were obtained with a large-aperture, GPS-synchronized array in July 2000 in the Bleik Canyon off Vesterålen, Norway (69 degrees 28' N, 15 degrees 40' E). A total of 14 h of sound recordings was collected from five to ten independent, simultaneously operating recording units. The sound levels measured make sperm whale clicks by far the loudest of sounds recorded from any biological source. On-axis click properties support previous work proposing the nose of sperm whales to operate as a generator of sound.

Acoustics↗

Factors explaining variance in perceived pain in women with fibromyalgia.

BACKGROUND: We hypothesized that a substantial proportion of the subjectively experienced variance in pain in fibromyalgia patients would be explained by psychological factors alone, but that a combined model, including neuroendocrine and autonomic factors, would give the most parsimonious explanation of variance in pain. METHODS: Psychometric assessment included McGill Pain Questionnaire, General Health Questionnaire, Hospital Anxiety and Depression Rating Scale, Eysenck personality Inventory, Neuroticism and Lie subscales, Toronto Alexithymia Scale, and Multidimensional Health Locus of Control Scale and was performed in 42 female patients with fibromyalgia and 48 female age matched random sample population controls. A subgroup of the original sample (22 fibromyalgia patients and 13 controls) underwent a pharmacological challenge test with buspirone to assess autonomic and adrenocortical reactivity to serotonergic challenge. RESULTS: Although fibromyalgia patients scored high on neuroticism, anxiety, depression and general distress, only a minor part of variance in pain was explained by psychological factors alone. High pain score was associated with high neuroticism, low baseline cortisol level and small drop in systolic blood pressure after buspirone challenge test. This model explained 41.5% of total pain in fibromyalgia patients. In population controls, psychological factors alone were significant predictors for variance in pain. CONCLUSION: Fibromyalgia patients may have reduced reactivity in the central sympathetic system or perturbations in the sympathetic-parasympathetic balance. This study shows that a biopsychosocial model, including psychological factors as well as factors related to perturbations of the autonomic nervous system and hypothalamic-pituitary-adrenal axis, is needed to explain perceived pain in fibromyalgia patients.

Journal Article↗

EPR dosimetric properties of 2-methylalanine: EPR, ENDOR and FT-EPR investigations.

To find an EPR dosimeter material that is sensitive enough for clinical use, the substance 2-methylalanine (2MA) with the chemical structure (CH(3))(2)C(NH(3)(+))COO(-) was tested for its sensitivity to ionizing radiation, dose response, and radical stability over time. At equal and moderate settings of microwave power and modulation amplitude, 2MA was found to be 70% more sensitive than L-alpha-alanine, which is the most common EPR dosimeter material today. The dose response is linear, at least in the dose range of interest (0.5-00 Gy), and the time-dependent variations in signal intensity are very small and may be corrected for easily. The energy dependence of the stopping power and energy absorption was calculated and was found to be similar to that of alanine. The dependence of the signal intensity on microwave power and modulation amplitude was investigated, and the optimal settings were found to be 25 mW (Bruker ER 4102ST) and 12 gauss, respectively. Single crystals of 2MA were analyzed using ENDOR and ENDOR-induced EPR to identify the radiation-induced radicals that formed. Only one radical, in which the amino group is detached from the original molecule, was identified. This radical is obviously dominating and is apparently the only one relevant for dosimetry purposes. The complete set of coupling parameters for three hyperfine couplings is reported. The power saturation properties and spectral line width are ruled by the relaxation times T(1) and T(2). To determine the relaxation times of 2MA, pulsed EPR experiments were performed on single crystals. Two different values of T(1) were obtained, one in the range 1-3 micros, shown to be of importance for the dosimetry properties, and another that is strongly anisotropic with a value between 10 and 35 micros that does not seem to affect the saturation behavior. T(2) was estimated to be of the order of 200-300 ns.

Alanine↗

Intrathecal co-administration of substance P and NMDA augments nociceptive responses in the formalin test.

The effects of intrathecal administration of substance P and N-methyl-D-aspartate (NMDA) were studied in the formalin test in mice. Both substances were administered 5 min before injection of formalin into the hind paw. Co-administration of substance P and NMDA intensified the response in both the 1st (0-10 min) and the 2nd phase (20-30 min) of the formalin test, and increased the duration of the response. The increase in the response to formalin depended on the formalin concentration and was significant with 1% and 5% concentrations of formalin but not with a 0.05% concentration. No increase in the response was observed when NMDA or substance P was given alone. These findings indicate that concurrent activation of spinal NMDA and substance P receptors induces an enhancement of spinal transmission of nociception, and that this enhancement is dependent on the intensity or the quality of the peripheral stimulus.

Animals↗

The role of descending noradrenergic systems in regulation of nociception: the effects of intrathecally administered alpha-adrenoceptor antagonists and clonidine.

It has been proposed that descending noradrenergic systems exercise a tonic inhibition of nociception at the spinal level. The recent finding that changes in tail skin temperature (TT) may have a strong effect on the tail-flick latency makes a reevaluation of this hypothesis necessary. The alpha-adrenoceptor agonist clonidine injected intrathecally (i.th.) in a dose of 60 micrograms increased the response temperature in the increasing hot plate test 10 min after injection, and prolonged the tail-flick latency 30-60 min after injection. A considerable part of the change in tail-flick latency was caused by a reduction in TT. The alpha 1-antagonist prazosin (30 and 60 micrograms) tended to increase the response temperature in the increasing hot plate test after 60 min, and to prolong the latency in the tail-flick test. These effects were not statistically significant. Clonidine and prazosin induced sensorimotor impairment and a reduction in body temperature after 30-60 min. The alpha 2-antagonist yohimbine had no effect in the increasing hot plate test, but reduced the tail-flick latency 10 min after drug administration. This reduction could be explained by an increase in TT. The results suggest that the reduced latency in the tail-flick test after i.th. injection of yohimbine is caused by an increase in the tail blood flow, and does not support the hypothesis of a tonic bulbospinal noradrenergic inhibition of nociception. The time course of response latencies suggests that supraspinal mechanisms may be involved in the effects of i.th. clonidine and prazosin in the tail-flick test, while there seems to be a spinally mediated antinociceptive effect of clonidine that can be demonstrated in the increasing hot plate test.

Animals↗

The apparent antinociceptive effect of desipramine and zimelidine in the tail flick test in rats is mainly caused by changes in tail skin temperature.

Tricyclic antidepressants have shown antinociceptive properties in some, but not in all, animal studies using the tail flick test. Tail flick latency has been found to be strongly negatively correlated to tail skin temperature with its highest correlation found when the temperature is measured close to the heated spot. The selective 5-HT reuptake inhibitor zimelidine, as well as the noradrenaline reuptake inhibitor desipramine, increased tail flick latencies. However, this increase could largely be explained by a concomitant reduction in tail skin temperature. The highest dose of desipramine investigated (25 mg/kg) seemed to possess antinociceptive properties in this test also after correction for the fall in tail skin temperature. Lower doses of desipramine (5 and 15 mg/kg) and zimelidine (5, 20 and 30 mg/kg) were either inactive or their effect on tail flick latency could be explained by the fall in tail skin temperature. The apparent antinociceptive effect of zimelidine in the tail flick test thus seems to be due to an effect on tail skin temperature. Desipramine also seems to have its main effect due to a similar mechanism; however, the highest dose of desipramine used induced significant antinociception.

Analgesics↗

EPR dosimetric properties of formates.

As a part of a program to develop an electron paramagnetic resonance (EPR) dosimeter suited for clinical use (doses in the cGy range), polycrystalline samples of lithium formate monohydrate (HCO2Li.H2O), magnesium formate dihydrate (C2H2O4Mg.2H2O), and calcium formate (C2H2O4Ca) have been examined. L-Alanine was included for comparison and reference. Samples were irradiated with 60Co gamma-rays and 60-220 kV X-rays. The dosimeter response was assessed using the peak-to-peak amplitude of the first-derivative EPR spectrum. Dose-response curves for the 60Co gamma-irradiated samples were constructed, and the dependences of the response on the photon energy, microwave power, and modulation amplitude were studied. Stability of the irradiation products upon storage (signal fading) was also investigated. Lithium formate monohydrate is by far the best candidate of the tested formates, suitable for measuring doses down to approximately 0.1 Gy. Lithium formate monohydrate is more sensitive than alanine by a factor of 5.6-6.8 in the tested photon energy range, it exhibits no zero-dose signal and shows a linear dose response in the dose range from 0.2 to 1000 Gy. Its EPR signal was found unchanged in shape and intensity 1 week after irradiation to 10 Gy. Various less favorable properties rendered the other formates generally unsuitable, although calcium formate exhibits some interesting EPR dosimetric properties.

Electron Spin Resonance Spectroscopy↗