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Biomedical subjects

K Rasmussen

Publications and source records attributed to K Rasmussen.

At least 163 records · Page 9Linked to original sources
PubMed1994

Insulin secretion, insulin action and non-insulin-dependent glucose uptake in pancreas transplant recipients.

To assess individual factors responsible of overall glucose tolerance after successful pancreas transplantation, an i.v. glucose tolerance test, with frequent blood sampling and tolbutamide administration to elicit a second insulin response was used to estimate insulin sensitivity (SI) and glucose effectiveness (SG) with Bergman's minimal model. Insulin secretion was calculated from the combined insulin-C-peptide kinetics method. These parameters were quantified in identically immunosupressed transplants: ISPx, four segmental pancreas recipients with impaired glucose tolerance; TSPx, five segmental pancrease recipients with normal glucose tolerance; WPx, five whole pancreas recipients with normal glucose tolerance; and in two controls groups, Kx, eight nondiabetic kidney recipients, and Ns, eight normal subjects. All participants had normal fasting plasma glucose and normal glycosylated hemoglobin A1C levels. The glucose tolerance KG value was significantly reduced only in ISPx compared with Ns (P < 0.05). SI was reduced by 60% in ISPx, WPx, and Kx compared with normal subjects (P < 0.05), whereas SI was reduced by 30% in TSPx compared with normal controls (P = NS). The reduction in SG was the same in all pancreas transplanted groups, as compared to Kx and Ns (by 33% and 40%, respectively, P < 0.05). The first-phase insulin secretion (0-5 min) was markedly reduced in ISPx and TSPx compared with Ns (by 76% and 50%), to Kx (by 84% and 66%) and to WPx (by 73% and 45%), respectively (P < 0.05), but similar to Ns in WPx. The overall incremental insulin secretion was reduced in ISPx compared with Ns, WPx, and Kx (by 38%, 62%, and 73%, respectively, P < 0.05) and reduced in TSPx compared to WPx and Kx (by 47% and 67%, respectively, P < 0.05) Ns secreted 43% of the total amount of insulin during the first phase the corresponding value was only 13% in ISPx vs. 24% in TSPx, 24% in Kx, and 25% in WPx, respectively (P < 0.05). In conclusion, after pancreas transplantation, the overall glucose tolerance is determined by the net effect of reductions in insulin sensitivity and glucose effectiveness and in the adaptability of the beta-cells to ensure sufficient insulin secretion. beta-cell function was impaired in both the whole pancreas and segmental transplant recipients, and the failure to increase insulin secretion sufficiently leads to glucose intolerance.

Adult↗
PubMed1994

Long-term topical nitrogen mustard treatment does not induce pulmonary fibrosis in MF patients.

Eleven patients with mycosis fungoides had X-ray examinations of their lungs before, during and after topical treatment with mechlorethamine. The mean number of treatments was 163, ranging from 28 to 300 treatments within a period of 1 to 13 years (mean 7.8 years). Each exposure to the skin of mechlorethamine was between 20 and 40 mg giving a cumulative dosage in the range from 1.120 mg to a maximum of 12.000 mg. We looked for potential lung damage from mechlorethamine vapours, such as fibrosis of the lungs, but found none. Thus, we conclude that topical treatment with mechlorethamine of patients with mycosis fungoides is not only an effective treatment, but also a safe therapy.

Administration, Cutaneous↗
PubMed1994

How to diagnose cobalamin deficiency.

Cobalamin deficiency must be suspected in all patients with unexplained neuropsychiatric symptoms or unexplained anemia. Special attention should be paid to patients at risk of developing cobalamin deficiency such as elderly people, vegetarians, HIV-infected patients, patients with gastrointestinal diseases and patients with autoimmunity or a family history of pernicious anemia. The assays aimed to answer the question: does this patient suffer from cobalamin deficiency, include analysis of P--cobalamins and analyses of the metabolites that accumulate upon cellular cobalamin deficiency, P--methylmalonate and P--homocysteine. P--cobalamins or especially a fraction of P--cobalamins, P--TC cobalamins are markers for latent cobalamin deficiency. An increased concentration of P--methylmalonate that decreases upon injection of cobalamin indicates overt metabolic cobalamin deficiency. The same holds for P--homocysteine but this analysis is less specific than P--methylmalonate. We suggest that either assay of P--cobalamins or P--methylmalonate is employed as screening test for cobalamin deficiency, and that further tests are performed only if the initial test in combination with the clinical picture gives an unclear answer. Once cobalamin deficiency has been diagnosed, the cause for the deficiency should be sought and the patient should be treated for life. Cobalamin absorption tests such as the Schilling test are considered of limited use. Gastric atrophy is likely to be present in patients with increased P--gastrin or decreased P--pepsinogen A. However, this condition can be diagnosed also by upper gastrointestinal endoscopy.

Gastrins↗
PubMed1994

Pharmacological characterization of LY293284: A 5-HT1A receptor agonist with high potency and selectivity.

(-)-LY293284, (-)-4R-6-acetyl-4-(di-n-propylamino)1,3,4,5- tetrahydrobenz[c,d]indole, is a conformationally restricted tryptamine derivative with an acetyl group serving as a protophilic substitution for the hydroxyl in serotonin (5-HT). In ligand displacement studies, LY293284 had a Ki of 0.07 nM for the 5-HT1A receptor but no affinity for other monoaminergic receptors within 3 orders of magnitude. LY293284 was evaluated in in vivo models, which have been used as markers for presynaptic and postsynaptic 5-HT1A receptor activity. LY293284 decreased hypothalamic 5-hydroxyindoleacetic acid levels (ED50, 2.9 micrograms/kg s.c.) and dorsal raphe serotonergic neuron firing rate (ED50, 0.08 micrograms/kg s.c.), which are accepted indices of presynaptic activity. LY293284 also induced a reduction in body temperature in rats (ED50, 3.6 micrograms/kg s.c.), which was blocked by pretreatment with (+/-)-pindolol. Hypothermic responses of rats to 5-HT1A agonists have had both pre- and postsynaptic characteristics in previous studies. The ED50 values for 8-hydroxy-2-(di-n-propylamino)-tetralin (8-OH-DPAT) in these tests were 15 to 45 times higher than those observed for LY293284. In models for postsynaptic activity, the ED50 for LY293284 for elevating serum corticosterone levels was 9.7 micrograms/kg s.c. and the minimum effective doses to induce lower lip retraction and flat posture were 3 micrograms/kg s.c. For comparison, the same indices obtained for 8-OH-DPAT were 222.4 and 100 micrograms/kg, respectively. The 5-HT syndrome responses induced by LY293284 were also attenuated by pretreatment with (+/-)-pindolol. LY293284 was 10 times more potent than 8-OH-DPAT in a drug discrimination test that used pigeons trained to identify 8-OH-DPAT. In sexual behavior tests with male rats, LY293284 induced a maximal reduction in ejaculatory latency at 0.01 micrograms/kg s.c., which was approximately 10 times higher potency than 8-OH-DPAT. In the pigeon conflict model for anxiolytic activity, LY293284 was 100 times more potent than 8-OH-DPAT in increasing punished responding. In the rat forced swim model for antidepressant-like activity, LY293284 was 30 and 35 times more potent than 8-OH-DPAT in decreasing immobility time and defecation rate. These studies have demonstrated that LY293284 is a highly selective and extremely potent 5-HT1A receptor agonist and represents a useful pharmacological tool for studying 5-HT1A receptor-mediated effects.

Animals↗
PubMed1994

Visually determined high-frequency seizure activity.

The duration of high-frequency electroconvulsive therapy (ECT) seizure activity, the "spike seizure duration," was rated by two experienced clinicians from the paper EEG recording, along with total EEG seizure duration. The spike seizure duration, taken together with other seizure duration measurements, has shown differences between ECT methods of apparently different efficacy, such as unilateral and bilateral ECT. Close correspondence between the raters demonstrated high reliability for the determination of spike seizure duration, with interrater reliability kappa of 0.92 (p < 10(-6), although the raters employed different rules for selecting the end point.

Electroconvulsive Therapy↗
PubMed1994

Computer automated versus visually determined electroencephalographic and electromyographic seizure duration.

Seizure durations were determined during electroconvulsive therapy (ECT) by a computer-automated procedure for interpreting electroencephalographic (EEG) and electromyographic (EMG) signals. These seizure durations were compared with durations determined by two experienced clinicians from simultaneous paper recordings of EEG and EMG and with independently recorded observations of cuffed-limb motor movements. The computer EEG seizure end point was programmed as the point where the moving average EEG voltage first fell below the pre-ECT value and remained there for at least 2 s. The computer EMG seizure end point was programmed as the point where the moving average EMG voltage first fell below 200 mV and remained there for at least 2 s. Close correspondence between seizure durations rated from EEG recordings and computer-automated EEG measurements demonstrated validity and high reliability of the computer procedure. Likewise, validity and reliability were demonstrated for motor seizure durations both computer-derived and interpreted from the paper EMG recording by their close correspondence with cuffed-limb motor seizure durations.

Anesthesia↗
PubMed1993

Lipopolysaccharide induced monocyte thromboplastin synthesis and coagulation responses in patients undergoing coronary bypass surgery after preoperative supplementation with n-3 fatty acids.

Twenty patients with coronary heart disease (CHD) and elevated serum lipids were randomized into 2 groups of 10 to receive encapsulated preparations of either a concentrated ethylester form of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) or corn oil in doses of 6 g per day, given double blindly for approximately two months prior to coronary bypass surgery. Lipopolysaccharide (LPS) induced monocyte thromboplastin synthesis was studied during the preoperative period and one week following surgery. The ability of n-3 fatty acids to modify tissue factor pathway inhibitor (TFPI) and tissue plasminogen activator inhibitor (PAI-1) was also evaluated along with fibrinogen and thrombin-antithrombin III (TAT) complexes. No significant changes were noted preoperatively. Monocyte reactivity, PAI-1, fibrinogen and TAT increased significantly after surgery. These changes were not modified by preoperative loading with n-3 fatty acids.

Acute-Phase Reaction↗
PubMed1993

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

In order to explore the potential clinical utility of CCK-B antagonists for the treatment of benzodiazepine withdrawal symptoms, the auditory startle reflex was examined in rats undergoing withdrawal from the chronic administration of diazepam. Animals were exposed to diazepam continuously for 12 days (20 mg kg-1 per day) via osmotic minipumps. After 12 days the pumps were removed and the animals were allowed to go through spontaneous withdrawal for 4 days. Acute pretreatment with either diazepam or the selective CCK-B antagonist LY288513 dose-dependently blocked withdrawal-induced increases in the auditory startle response. These results support the hypothesis that the selective CCK-B antagonist LY288513 may be an effective treatment for alleviating at least some benzodiazepine withdrawal symptoms in man.

Acoustic Stimulation↗
PubMed1993

[Medical research in Finnmark].

Finnmark county, the most northern in Norway, has suffered from a severe shortage of specialist health services. In order to recruit specialist doctors to Finnmark and to keep them there, a programme for creating opportunities to do medical research in Finnmark was launched by the University of Tromsø. From 1986 to 1992 the Ministry of Health and Social Affairs has contributed a total of 8.5 mill. NOK to the programme, which is administered by the Medical Faculty at the University of Tromsø, in cooperation with the two hospitals in Finnmark. The programme has led to a substantial recruitment of doctors, both for specialist training as well as fully educated specialists. The percentage of unfilled positions has fallen from 81 to 29 in the period. 41 scientific papers have been published from the programme, 22 of them in international journals. The programme seems to have fulfilled its aims, both as regards stabilizing the specialist health service, and in a scientific context. We propose decentralized research programmes as a means of establishing cooperation between university hospitals and remote health care systems.

Arctic Regions↗
PubMed1993

[Cardiac events after myocardial infarction treated with streptokinase. The prognostic value of symptom-limited ECG on day 7].

One hundred and forty-seven consecutive patients admitted with suspected acute myocardial infarction (AMI) were treated with streptokinase. On day 7 after AMI 107 patients performed a symptom-limited exercise test (bicycle ergometer). Thirty-four of the tested patients developed at least one cardiac event (reinfarction, cardiac death, decided myocardial revascularization) during follow-up (30 months). Exercise induced ST-depression was more frequent among patients with cardiac events than among those without cardiac events (chi 2-test, p < 0.05). With multiple logistic regression analysis (BMPD) the following variables were found to have independent prognostic value for the development of new cardiac events: low maximal heart-rate during the exercise test, long duration of acute symptoms before streptokinase treatment and male sex. Exercise-induced ST-depression had no prognostic value in the BMPD-analysis. Exercise testing can be carried out with safety and supplies prognostic information concerning future cardiac events in patients with streptokinase-treated AMI.

Adult↗
PubMed1993

Solvent-induced chronic toxic encephalopathy.

Chlorinated solvents, especially trichloroethylene, have been extensively used for metal degreasing since the beginning of this century. There have been case reports of cranial nerve damage and symptoms of acute and reversible encephalopathy. However, another issue during the last decade is the possible existence of a syndrome of chronic cerebral dysfunction. Our study deals with the risk of developing a state of psychoorganic syndrome after long-term exposure to solvents, mainly trichloroethylene. In this historical cohort study, 96 metal degreasers participated in a clinical medical and psychological examination. The risk of developing psychoorganic syndrome was proportional to the exposure duration, to increasing age, and to decreasing primary intellectual level. Using logistic regression analysis, there was a significantly increased risk of developing psychoorganic syndrome from solvent exposure. There was an odds ratio of 5.6 (0.93-34.3) for psychoorganic syndrome in the medium-exposed group. In the most highly exposed group, with a mean full-time exposure duration of 11 years, there was a significantly increased risk of psychoorganic syndrome, the adjusted odds ratio was 11.2 (1.9-66.6). None of four other potential confounders (arteriosclerotic disease, neurologic/psychiatric disease, alcohol abuse, and current solvent exposure) had any significant associations to psychoorganic syndrome.

Adult↗
PubMed1993

Psychometric tests for assessment of brain function after solvent exposure.

Psychometric testing is a key issue in neuropsychological toxicology assessment. Evaluation of methods for assessing general intellectual impairment is necessary as conventional neurology has been shown to be insensitive to the neurotoxic effects of solvents and metals. This study presents an analysis of a psychometric test battery from an investigation of psycho-organic syndrome in a historical cohort of 96 metal degreasers with long-term exposure to solvents, particularly trichloroethylene. The neuropsychological test battery was a combination of Wechsler Adult Intelligence Scale (WAIS), Luria, and tests developed in Scandinavia. Linear regression analysis showed a significant dose-response relation between increasing cumulative solvent exposure and impaired psychometric test performance in 9 out of 15 tests. Multivariate analysis, however, suggests that much of the variance was due to confounding variables, especially age, and to a lesser degree, primary intellectual function and word blindness. After control for confounding factors the strongest association with solvent exposure occurred for the following three tests: acoustic-motor function, Paced Auditory Serial Addition Test (PASAT), and the visual gestalt test.

Brain Diseases↗
PubMed1993

Inhibition of A9 and A10 dopamine cells by the cholecystokinin-B antagonist LY262691: mediation through feedback pathways from forebrain sites.

The diphenylpyrazolidinone cholecystokinin-B (CCK-B) antagonist LY262691 has been shown to decrease the number of spontaneously active dopamine (DA) cells in the ventral tegmental area (A10) and substantia nigra (A9) of the anesthetized rat. In the present study, we examined the localization of the receptors mediating these effects of LY262691 on A9 and A10 DA cells. In one group of anesthetized rats, the effects of systemic administration of LY262691 on the number of spontaneously active A9 or A10 DA cells was determined using extracellular, single-unit recordings after radio frequency lesions were placed in the nucleus accumbens, caudate-putamen, or medial prefrontal cortex. Lesions of the caudate-putamen blocked the effects of systemically administered LY262691 on the number of spontaneously active A9, but not A10, DA cells. Conversely, lesions of the n. accumbens blocked the effects of systemically administered LY262691 on A10, but not A9, DA cells. Lesions of the medial prefrontal cortex blocked the effects of systemically administered LY262691 on both A9 and A10 DA cells. In a separate group of anesthetized rats, the number of spontaneously active A9 or A10 DA cells was determined after LY262691 was microinjected into the n. accumbens, caudate-putamen, or medial prefrontal cortex. Microinjection of LY262691 into the caudate-putamen led to a significant decrease in the number of spontaneously active A9, but not A10, DA cells. Conversely, microinjection of LY262691 into the n. accumbens or medial prefrontal cortex led to a significant decrease in the number of spontaneously active A10, but not A9, DA cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia↗