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K Rasmussen

Publications and source records attributed to K Rasmussen.

At least 109 records · Page 6Linked to original sources
PubMed1997

An external quality assessment study on the analysis of methylmalonic acid and total homocysteine in plasma.

In spite of the increasing interest in the analysis of methylmalonic acid and total homocysteine in plasma, data on interlaboratory variation is lacking. We report the results of an external quality assessment study with the participation of 15 laboratories in the Scandinavian countries performing these analyses on a regular basis. For methylmalonic acid, using serum, heparin fluoride plasma and an aqueous sample, CVs were found in the range of 11-17%. For total homocysteine using EDTA plasma, heparin fluoride plasma and an aqueous sample, CVs were in the range of 6-12%. For both analytes, a significant correlation between the individual recoveries of added analyte and the results for the aqueous sample was found, suggesting that the use of inconsistent calibrations in the participating laboratories are contributing to the interlaboratory variation. An acceptable range for results from the individual laboratory was calculated using data on the biological within-subject and between-subject variations reported in the literature. These ranges were violated by several laboratories when using the consensus mean or median as target values. Even if the results of the present study document a reasonable standard in the measurement of methylmalonic acid and total homocysteine in plasma in the participating laboratories there is room for improvement and a permanent scheme of external quality assessment using relevant samples is essential. From 1997, a regular scheme has been available from our laboratory.

Anticoagulants↗
PubMed1997

Metabolic cobalamin deficiency in patients with low to low-normal plasma cobalamins.

Over a 2-year period, we examined 48 patients with P-cobalamin levels in the difficult "grey zone" at the lower reference limit detected by a competitive protein binding assay using intrinsic factor as binder. In 21 of 30 patients (70%) with low P-cobalamins we could not establish the diagnosis of metabolic cobalamin deficiency, but 1 of 18 patients (6%) with low-normal P-cobalamin values was confirmed metabolically cobalamin-deficient. Half of these 30 patients with low P-cobalamins had neuropsychiatric disorders, but only one-third of the latter patients had metabolic cobalamin deficiency. Ten of the remaining 15 patients (67%) were characterized as non-deficient. In patients with low-normal P-cobalamin level, we found neuropsychiatric disorders in 5 of the 18 (28%), but none of these had metabolic cobalamin deficiency. We conclude that P-cobalamins below the reference interval combined with typical neuropsychiatric symptoms or findings are not diagnostic of cobalamin deficiency and that further analyses are necessary.

Adult↗
PubMed1997

In vitro and in vivo biochemistry of olanzapine: a novel, atypical antipsychotic drug.

BACKGROUND: Classical (typical) antipsychotic drugs are in wide use clinically, but some patients do not respond at all to treatment, while in others, negative symptoms and cognitive deficits fail to respond. Also, these drugs often cause serious motor disturbances. Clozapine, an atypical antipsychotic, appears to correct many of these deficiencies, but has a significant incidence of potentially fatal agranulocytosis. Accordingly, we attempted to develop a prototype of a new generation of antipsychotics that is both more efficacious and safe. Our strategy was to create a compound that is not only active in behavioral tests that predict antipsychotic action but also shares the rich, multifaceted receptor pharmacology of clozapine without its side effects. To this end, Eli Lilly and Co. developed olanzapine. In this article we characterize the in vitro and in vivo receptor pharmacology of olanzapine. METHOD: We evaluated olanzapine interactions with neuronal receptors using standard assays of radioreceptor binding in vitro and well-established in vivo (functional) assays. RESULTS: Binding studies showed that olanzapine interacts with key receptors of interest in schizophrenia, having a nanomolar affinity for dopaminergic, serotonergic, alpha 1-adrenergic, and muscarinic receptors. In vivo olanzapine is a potent antagonist at DA receptors (DOPAC levels; pergolide-stimulated increases in plasma corticosterone) and 5-HT receptors (quipazine-stimulated increases in corticosterone), but is weaker at alpha-adrenergic and muscarinic receptors. Olanzapine has little or no effect at other receptors, enzymes, or key proteins in neuronal function. Olanzapine has a receptor profile that is similar to that of clozapine: it is relatively nonselective at dopamine receptor subtypes and it shows selectivity for mesolimbic and mesocortical over striatal dopamine tracts (electrophysiology; Fos). CONCLUSION: The binding and functional profile of olanzapine (1) is similar to that of clozapine, (2) indicates that olanzapine is an atypical antipsychotic drug, and (3) is consistent with clinical efficacy. If olanzapine also proves to be safe, then it will have high potential to become a more ideal antipsychotic drug.

Animals↗
PubMed1996

[Preimplantation genetic diagnosis. Technical and ethical aspects and international experiences].

In vitro fertilisation (IVF) is now an established treatment for infertility, and therefore preimplantation genetic diagnosis (PGD) has become an attractive diagnostic possibility on embryos at risk of having serious genetic and chromosomal abnormalities. PGD enables screening of certain genetic and chromosomal abnormalities before a pregnancy is established. In Denmark, The Minister of Health has in a recently proposed law on assisted reproduction recommended the implementation of pre-implantation genetic diagnosis on pre-embryos at risk of having serious genetic disorders. The aim of this review is to summarize international experience with the method and discuss its advantages and disadvantages. We conclude, that it is too early to implement the method as a routine clinical diagnostic analysis in Denmark, and that further research on the reliability of the method, the economy as well as other alternatives is recommended.

Embryonic Development↗
PubMed1996

[Formaldehyde in the occupational environment. A possible cause of chemically induced reactive arthritis].

A case is presented of a farmer aged 33 years who developed polyarthritis four to five days after having used formaldehyde for fumigation of his piggery. The farmer was admitted to the General Hospital in Herning for treatment. The course of the treatment was several months. Furthermore, two farm assistants and a bricklayer were exposed to formaldehyde in the piggery. They developed acute intoxication symptoms and, a few days after the exposure, arthralgia. There was no other collective exposure. Apart from the formaldehyde, there was a great amount of water in the piggery, leading to the conclusion that the exposure was due to the formaldehyde being absorbed in the water with following evaporation. In conclusion, a relationship between these particular circumstances of formaldehyde exposure and reactive arthritis is found to be likely.

Adult↗
PubMed1996

[P-methylmalonate and P-homocysteine: metabolic markers of vitamin deficiencies. Background, validity and applications].

The clinical value of measuring concentrations of methylmalonate and total homocysteine in plasma as an aid in the diagnosis of cobalamin, folate and pyridoxine deficiencies has recently aroused interest. This review describes factors which affect the validity and interpretation of plasma (p-) methylmalonate and p-homocysteine. P-methylmalonate is not affected by preanalytical variables, there are no age- or sex-related differences and the intra-individual variation is negligible. The only important limitation to the specificity of an increased p-methylmalonate for cobalamin deficiency appears to be secondary accumulation due to impaired renal function. However, an elevated p-methylmalonate, which normalizes following cobalamin injections proves cobalamin deficiency, irrespective of renal function. P-homocysteine is affected by several preanalytical factors, so the utmost care is required in blood collection. Furthermore, p-homocysteine is dependent on age and sex. An elevated p-homocysteine is a less specific parameter for cobalamin deficiency, for which reason measurement in patients with suspected cobalamin deficiency is indicated only if p-methylmalonate is normal. Homocysteine is also increased in folate and pyridoxine deficiencies. Recently, moderate hyperhomocysteinaemia has become an established independent and significant risk factor for premature atherosclerotic cardiovascular diseases, suggesting a large future demand for p-homocysteine determinations.

Amino Acids↗
PubMed1996

The CCK-B antagonist LY288513 blocks the effects of nicotine withdrawal on auditory startle.

In order to explore the potential clinical utility of CCK-B antagonists for the treatment of nicotine withdrawal symptoms, the auditory startle reflex was examined in rats undergoing withdrawal from the chronic administration of nicotine. Rats were exposed to nicotine continuously for 12 days (6 mg kg-1 day-1) via osmotic minipumps. After 12 days the pumps were removed and the animals allowed to go through spontaneous withdrawal for several days. Acute treatment with the CCK-B antagonist LY288513, at doses that have no effect on startle responses in naive rats, blocked the nicotine withdrawal-induced increase in the acoustic startle reflex. These results indicate that CCK-B antagonists may be an efficacious treatment for some nicotine withdrawal symptoms in man and may represent a novel pharmacotherapy for smoking cessation.

Animals↗
PubMed1996

Olanzapine, a novel atypical antipsychotic, reverses d-amphetamine-induced inhibition of midbrain dopamine cells.

This study compared the ability of the novel atypical antipsychotic olanzapine with that of clozapine to reverse the d-amphetamine-induced inhibition of substantia nigra (A9) and ventral tegmental area (A10) dopamine (DA) cells. Extracellular single-unit recordings were made from A9 and A10 DA cells in anesthetized rats. When administered alone, neither olanzapine nor clozapine altered the firing rate of A9 or A10 DA cells. Administration of d-amphetamine (0.5, 1.0 and 2.0 mg/kg, IV, decreased the firing rate of A9 and A10 DA cells. Olanzapine completely reversed the inhibitory effects of d-amphetamine on A10 DA cells (ED100 = 0.18 mg/kg, IV) and on A9 DA cells (ED100 = 1.0 mg/mg, IV). Clozapine completely reversed the inhibitory effects of d-amphetamine on A10 DA cells (ED100 = 3.8 mg/kg, IV), but only partially reversed the effects of d-amphetamine on A9 DA cells at the highest dose tested (8.0 mg/kg, IV). Thus, olanzapine, like clozapine, was more potent in reversing the effects of d-amphetamine on A10 than A9 DA cells. In addition, olanzapine was more potent than clozapine in the reversal of d-amphetamine effects on A9 and A10 DA cells. These results indicate that olanzapine and clozapine have similar effects on DA unit activity and predict that olanzapine should have an atypical antipsychotic profile in man.

Amphetamine↗
PubMed1996

Central nervous system characterization of the new cholecystokininB antagonist LY288513.

The activity of LY288513, an investigational cholecystokinin (CCK)B antagonist, was evaluated in a wide range of pharmacological tests in mice and rats. The anxiolytic benzodiazepine, diazepam, served as a reference standard for LY288513 in many of the tests. In the elevated plus-maze, LY288513 (3, 10 mg/kg, IP; 10, 30 mg/kg, PO) produced an anxiolytic-like action in mice with a magnitude of effect similar to that of diazepam. However, unlike diazepam, LY288513 produced no overt clinical signs and did not affect muscle tone, neuromuscular coordination, or sensorimotor reactivity. Also, in contrast to diazepam, LY288513 did not produce changes in the thresholds for electroshock- or pentylenetetrazol-induced convulsions. High doses of LY288513 (1000 mg/kg, PO) were required to reduce spontaneous activity levels, decrease body temperature, or potentiate the CNS-depressant effects of hexobarbital. LY288513 had no analgesic activity in mouse writhing or tail-flick tests. Electrophysiological studies in anesthetized rats showed that acute administration of LY288513 decreased the number of spontaneously active dopamine neurons in the substantia nigra and ventral tegmental area. However, LY288513 did not produce catalepsy. These data indicate that LY288513 possess both anxiolytic and antipsychotic potential.

Animals↗
PubMed1996

Some epidemiologic features of canine neosporosis in Denmark.

From a serological survey of 98 dogs, the overall prevalence of subclinical neosporosis among dogs in Denmark was estimated as 15.3%. From a questionnaire completed at the time of blood sampling in 87 dogs, it was found that exposure to cats could be a risk factor for the infection in dogs (odds ratio 3.46; 95% confidence limit 1.1-11.4). Further, it was shown that the antibody response in a pregnant dog increased markedly during gestation, suggesting that the parasite may be reactivated during pregnancy in a manner resembling that of Toxocara canis.

Animals↗
PubMed1996

Combination therapy with metoprolol and nifedipine versus monotherapy in patients with stable angina pectoris. Results of the International Multicenter Angina Exercise (IMAGE) Study.

OBJECTIVES: This study was designed to investigate whether combination therapy with metoprolol and nifedipine provides a greater anti-ischemic effect than does monotherapy in individual patients with stable angina pectoris. BACKGROUND: Combination therapy with a beta-adrenergic blocking agent (which reduces myocardial oxygen consumption) and a dihydropyridine calcium antagonist (which increases coronary blood flow) is a logical approach to the treatment of stable angina pectoris. However, it is not clear whether, in individual patients, this combined therapy is more effective than monotherapy. METHODS: Two hundred eighty patients with stable angina pectoris were enrolled in a double-blind trial in 25 European centers. Patients were randomized (week 0) to metoprolol (controlled release, 200 mg once daily) or nifedipine (Retard, 20 mg twice daily) for 6 weeks; placebo or the alternative drug was then added for a further 4 weeks. Exercise tests were performed at weeks 0, 6 and 10. RESULTS: At week 6, both metoprolol and nifedipine increased the mean exercise time to 1-mm ST segment depression in comparison with week 0 (both p < 0.01); metoprolol was more effective than nifedipine (p < 0.05). At week 10, the groups randomized to combination therapy had a further increase in time to 1-mm ST segment depression (p < 0.05 vs. placebo). Analysis of the results in individual patients revealed that 7 (11%) of 63 patients adding nifedipine to metoprolol and 17 (29%) of 59 patients (p < 0.0001) adding metoprolol to nifedipine showed an increase in exercise tolerance that was greater than the 90th percentile of the distribution of the changes observed in the corresponding monotherapy + placebo groups. However, among these patients, an additive effect was observed only in 1 (14%) of the 7 patients treated with metoprolol + nifedipine and in 4 (24%) of the 17 treated with nifedipine + metoprolol. CONCLUSIONS: The mean additive anti-ischemic effect shown by combination therapy with metoprolol and nifedipine in patients with stable angina pectoris is not the result of an additive effect in individual patients. Rather, it may be attributed to the recruitment by the second drug of patients not responding to monotherapy.

Adrenergic beta-Antagonists↗
PubMed1996

Electrophysiological effects of olanzapine, a novel atypical antipsychotic, on A9 and A10 dopamine neurons.

This study examined the effects of the novel atypical antipsychotic olanzapine (LY170053) on the activity of substantia nigra pars compacta (A9) and ventral tegmental area (A10) dopamine cells in anesthetized rats. Acute administration of olanzapine (10, 20 mg/kg sc) increased the number of spontaneously active A10, but not A9, dopamine cells. Chronic administration of olanzapine (10, 20 mg/kg/day x 21 days) decreased the number of spontaneously active A10, but not A9, dopamine cells. Administration of the dopamine agonist apomorphine reversed the effects of chronic olanzapine on A10 cells, indicating a possible depolarization-inactivation mechanism. In conclusion, olanzapine has selective effects on A10 versus A9 dopamine cells following acute and chronic administration. These effects of olanzapine on dopamine cells are similar to the effects observed with clozapine and may play an important role in the atypical antipsychotic profile of olanzapine.

Anesthesia↗
PubMed1996

A selective AMPA antagonist, LY293558, suppresses morphine withdrawal-induced activation of locus coeruleus neurons and behavioral signs of morphine withdrawal.

The glutamate receptor subtype that mediates the morphine withdrawal-induced activation of locus coeruleus (LC) neurons was examined in this study using in vitro and in vivo single-unit electrophysiologic recordings. For LC neurons recorded in vitro in rat brain slices, the selective alpha-amino-3-hydroxy-5-methyl-4-isoxazole proprionic acid (AMPA) antagonist, LY293558, showed a greater than 10-fold selectivity for inhibiting the excitatory effects of AMPA vs kainate, and a greater than 30-fold selectivity for inhibiting the excitatory effects of AMPA vs NMDA. LY293558 also greatly reduced the response of LC neurons to glutamate in a concentration-dependent manner. In in vivo recordings in anesthetized rats, pretreatment with LY293558 (0.1 to 10 mg/kg, i.p.) dose dependently suppressed the morphine withdrawal-induced activation of LC neurons. In unanesthetized, morphine-dependent animals, pretreatment with LY293558 (1 to 30 mg/kg, i.p.) dose dependently suppressed naltrexone-precipitated morphine withdrawal signs. These results indicate: (1) AMPA receptors mediate a large component of the excitatory effects of glutamate on LC neurons; (2) activation of AMPA receptors plays an important role in the morphine withdrawal-induced activation of LC neurons; (3) AMPA antagonists can suppress many signs of morphine withdrawal in awake animals; and (4) AMPA antagonists may have therapeutic effects in humans for the treatment of opiate withdrawal.

Animals↗
PubMed1996

Comparison of the deoxyuridine suppression test with serum levels of methylmalonic acid and homocysteine in mild cobalamin deficiency.

Both the deoxyuridine suppression test (dUST) and the cobalamin-dependent metabolites, methylmalonic acid (MMA) and homocysteine, are valuable tools for identifying clinical cobalamin deficiency. Examination of these metabolic changes in mild or marginal deficiency can provide useful comparisons of diagnostic frequencies and sensitivities and help define the sequence of metabolic changes in early deficiency. These tests were therefore compared directly with each other in 50 patients with low cobalamin levels and few or no obvious signs of deficiency. Serum homocysteine (P=0.0003) and MMA levels (P=0.0004) correlated with dUST results. However, the dUST results were abnormal significantly more often (38/50 patients) when matched against levels of homocysteine (25 abnormal results of 50; P=0.007) or MMA (20/50; P=0.008). Abnormalities of one or both serum metabolite levels (30/50 patients) occurred almost as often as dUST abnormalities (P=0.059). Metabolite levels, even when originally 'normal', fell with cobalamin therapy in many cases. The results indicate that both the dUST and serum metabolite levels become abnormal before macrocytic anaemia develops in mild cobalamin deficiency. The dUST appears to be most frequently abnormal of the tests; metabolite levels appear to rise almost concurrently but they do not become diagnostically abnormal as soon.

Bone Marrow↗
PubMed1996

Palpitations and lifestyle: impact of depression and self-rated health. The Nordland Health Study.

On the basis of a questionnaire in a population study in the county of Nordland, Norway, the prevalence of palpitations and its associations to some lifestyle factors, depression and self-rated health were analysed. All the 10,497 residents aged 40 to 42 years were invited to participate, 82% attended, 87% of the attenders returned a questionnaire by mail, and 6436 subjects were included in this report. The prevalence of palpitations was 15% in men and 25% in women. Palpitations were significantly associated with coffee consumption, smoking, alcohol intoxication, physical inactivity, depression and poor self-rated health in the univariate analyses. In a logistic regression analysis, the relations between palpitations and lifestyle were weakened. Significant predictors for palpitations were depression and poor self-rated health in both sexes, in addition to heavy coffee drinking and physical inactivity in men and alcohol intoxication in women. In conclusion, palpitations were more firmly linked to depression and self-evaluated health than to lifestyle.

Adult↗