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Biomedical subjects

K Rasmussen

Publications and source records attributed to K Rasmussen.

At least 199 records · Page 11Linked to original sources
PubMed1992

[Determination of vitamin b12 deficiency].

Development of cobalamin deficiency in the tissues is considered to be a process which lasts for years. Macrocytic anaemia and/or neurological symptoms do not occur until late in this process. Serum cobalamins as the only parameter have proved less suitable for differentiation between healthy individuals with low serum cobalamin values and patients who require cobalamin for the remainder of their lives. The need for a better indicator for cobalamin deficiency has been emphasized. Recently developed methods of measurement have rendered determinations of serum methylmalonic acid possible. This value is raised in cases of cobalamin deficiency in the tissues. The serum methylmalonic values have proved both sensitive and specific to determine the extent to which genuine cobalamin deficiency is present or not and may also be employed for monitoring the effect of treatment as the raised values becomes normalized following substitution therapy with vitamin B12.

Humans↗
PubMed1992

[Laboratory diagnosis of cobalamin deficiency. A comparative study of 2 serum cobalamin methods and serum methylmalonic acid].

The diagnosis of cobalamin deficiency is established traditionally by demonstration of lowered serum cobalamin, but, for many reasons it cannot be anticipated that the concentrations of cobalamins in the serum reflect the relationship between blood cobalamin and tissue cobalamin accurately. The blood methylmalonic acid which cannot be metabolized in cases of cellular cobalamin deficiency should, on the other hand, indicate the cobalamin available for the tissues. A blind, prospective, controlled investigation was undertaken to compare the clinical employability of a recently developed method for measurement of the concentration of methylmalonic acid in the serum with older and more recent methods of measuring serum cobalamins. The three methods classified 94, 72 and 74% of the patients correctly, respectively (n = 50). The results reveal that serum methylmalonic acid is a more sensitive and specific analysis for demonstrating whether cobalamin deficiency was present or not. Serum cobalamins measured by both methods are relatively insensitive and unspecific markers for cobalamin deficiency in the tissue. Low cobalamin concentrations do not indicate that the patient in question has cobalamin deficiency, and values in the lower half of the reference interval do not exclude cobalamin deficiency. Measurement of methylmalonic acid in the serum is recommended in patients with low-normal or low serum cobalamin.

Adolescent↗
PubMed1992

[Cobalamin deficiency despite normal serum cobalamins].

In a man aged 77 years with normal concentrations of cobalamins in the serum, the concentration of methylmalonic acid in the serum was raised (2,920 nmol/l; 50-370 nmol/l). (The serum cobalamin concentrations were measured both by an old R-binder method (400 pmol/l; reference interval 200-800 pmol/l) and by a more recent S-binder method (164 pmol/l; 95-585 pmol/l)). Following a saturation dose of vitamin B12, the serum concentration of methylmalonic acid became normal (215 nmol/l) indicating that the patient had had functional cobalamin deficiency. The clinician should never let himself be deceived by a normal concentration of cobalamins in the serum and thus discard a suspicion of cobalamin deficiency. Measurement of serum methyl-malonic acid, which is a sensitive and specific analysis to differentiate between the presence or absence of cobalamin deficiency, is recommended to elucidate cases of doubt.

Aged↗
PubMed1992

Glucocorticoid regulation of alkaline phosphatase, osteocalcin, and proto-oncogenes in normal human osteoblast-like cells.

In humans, glucocorticoids are known to have marked effects on bone metabolism and function, including the significant regulation of osteoblast cells. To aid in the understanding of the mechanism of glucocorticoid action on normal human osteoblasts (hOB), confluent cells were analyzed for the presence of glucocorticoid receptors (GR) as well as for the effects of the glucocorticoid dexamethasone (Dex) on the expression of both the rapid responding nuclear proto-oncogenes and the late responding structural genes for bone matrix proteins. The interactions between Dex and 1,25 dihydroxy vitamin D3 (1,25 D3) on the gene expression in these cells were also examined. Using a functional receptor assay, a mean of 11,600 functional nuclear bound glucocorticoid receptors (range 6,000-22,000) was measured in fifteen separate cell strains. Northern blot analysis with a cDNA probe to the human GR was used to demonstrate the presence of a 7Kb transcript which is a candidate mRNA for GR in these cells. In agreement with previous studies, treatment of the hOB cells with Dex increased the steady state mRNA levels for alkaline phosphatase (AP) but displayed little or no effect on the mRNA levels for osteocalcin (OC) and glyceraldehyde phosphate dehydrogenase (GAPDH). Interestingly, the 1,25 D3 inductions of mRNA levels for OC were blocked by Dex but enhanced for AP. The above effects of Dex on AP and OC gene expression, including the interaction with 1,25 D3, were also shown to occur at the level of protein. The effect of Dex on the mRNA levels of the nuclear proto-oncogenes c-myc, c-fos, and c-jun was also investigated, since the oncoproteins (Fos/Jun) appear to play a role in the delayed glucocorticoid regulation of structural genes. Interestingly, Dex increased the steady state levels of c-myc, c-fos, and c-jun mRNAs in nonproliferating (confluent) hOB cells by 3.5-, 10-, and 2.0-fold, respectively, over control (untreated cells) values within one h of steroid treatment. The Dex-induced mRNA levels were transient and returned to basal values within 24 h of the steroid treatment. A reduced but qualitatively similar pattern of response was found in proliferating hOB cells. The pattern of response of these genes to glucocorticoids in hOB cells mimics the response in avian liver cells but not in reproductive cells. These results support the theory that hOB cells are target cells for glucocorticoids, and that as a primary event glucocorticoids rapidly regulate the expression of the nuclear oncoproteins Fos/Jun in these cells.

Alkaline Phosphatase↗
PubMed1992

Lidocaine to prevent ventricular fibrillation in the prehospital phase of suspected acute myocardial infarction: the North-Norwegian Lidocaine Intervention Trial.

The efficacy of lidocaine to prevent ventricular fibrillation during the prehospital phase of suspected acute myocardial infarction was assessed 3 hours after administration in a randomized controlled trial. A total of 204 patients examined within 6 hours after onset of symptoms were included, and acute myocardial infarction was later confirmed in 63% of these. Lidocaine, administered as a 100 mg intravenous bolus dose followed by a 300 mg intramuscular injection, failed to prevent ventricular fibrillation, which was observed in 2 (2.1%) of 96 patients in the lidocaine group and in 3 (3.0%) of 101 patients in the placebo group (p = 0.95; odds ratio 0.7, 95% confidence interval 0.4 to 1.3). In addition, sudden cardiac collapse with unknown heart rhythm was observed in three patients who received lidocaine (3.1%) compared with none in the placebo group (p = 0.23; odds ratio 7.6, 95% confidence interval 2.8 to 22.1). The results of this small study suggest that lidocaine, even when given in a high dose, is ineffective in preventing ventricular fibrillation when administered before hospitalization for suspected acute myocardial infarction. Prophylactic use of lidocaine in this situation may therefore not be warranted or advisable.

Adult↗
PubMed1992

Serum methylmalonic acid in uraemia.

During a 3 month period we measured serum methylmalonic acid concentrations monthly in 37 patients, all on chronic haemodialysis because of end-stage kidney disease. Concentrations of methylmalonic acid in serum were above the upper reference limit in 36 of the 37 subjects. All patients were in regular cobalamin therapy, with intramuscular injections every third month, and all had normal to very high values of serum cobalamin. We found no normalization of serum methylmalonic acid during the examination period after cobalamin injections, and we could not demonstrate any relationship between concentrations of methylmalonic acid and creatinine, cobalamin and creatinine or methylmalonic acid and cobalamin in serum of these subjects. We conclude that an elevated serum methylmalonic acid concentration is a general finding in uraemic patients, and so the assay cannot be used to establish the diagnosis of tissue cobalamin deficiency in these patients.

Adolescent↗
PubMed1992

Coordinate regulation of the cyclic AMP system with firing rate and expression of tyrosine hydroxylase in the rat locus coeruleus: effects of chronic stress and drug treatments.

Recent studies have demonstrated that chronic stress increases the firing rate and expression of tyrosine hydroxylase (TH) in neurons of the locus coeruleus (LC), the major noradrenergic nucleus in brain. The present study was undertaken to examine the influence of chronic stress and other treatments known to influence the activity of LC neurons on the cyclic AMP (cAMP) second messenger system in these neurons. Chronic (5 days) cold exposure significantly increased levels of TH immunoreactivity in the LC, as previously reported, but not in substantia nigra (SN) or ventral tegmentum (VT), two dopaminergic nuclei studied for comparison. Chronic cold exposure increased levels of cAMP-dependent protein kinase activity in soluble, but not particulate, fractions of the LC, and increased basal and GTP- and forskolin-stimulated adenylate cyclase activity in this brain region. In contrast, levels of the protein kinase and adenylate cyclase in VT, SN, and frontal cortex were not significantly influenced by cold exposure. To study further the relationship between regulation of LC firing rate, TH expression, and the cAMP system in the LC, other treatments known to influence TH were examined. Reserpine treatment, shown previously to increase levels of TH, was found to increase both LC firing rate and levels of soluble cAMP-dependent protein kinase activity in the LC. 6-Hydroxydopamine, shown previously to increase levels of TH and firing rate of LC neurons, also increased soluble levels of protein kinase activity. Other treatments known to either increase (adrenalectomy) or decrease (chronic imipramine) levels of TH in the LC were also found to increase or decrease, respectively, levels of cAMP-dependent protein kinase activity in this brain region.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenalectomy↗
PubMed1992

The Tromsø study: physical fitness, self reported physical activity, and their relationship to other coronary risk factors.

STUDY OBJECTIVE: The aim was to investigate the associations between physical fitness, leisure physical activity, and coronary risk factors. DESIGN: This was a cross sectional study of a random sample of men and women, following a population survey. SETTING: The municipality of Tromsø, Norway in 1986-1987. PARTICIPANTS: All men born 1925-1966 and all women born 1930-1966 were invited to the survey; 21,826 subjects attended (81% of the eligible population): of these, 297 men and 312 women, randomly selected, attended the present study (attendance rates 94% in men and 89% in women). MEASUREMENTS AND MAIN RESULTS: Fitness was tested by bicycle ergometry. Physical activity was reported on a questionnaire. Multiple regression analysis was performed with fitness and leisure activity as dependent variables, and coronary risk factors as independent variables. Fitness and leisure activity were positively related (p less than 0.05). Prominent findings for fitness were negative associations with age and smoking (p less than 0.05), and positive associations with body mass index in both sexes (p less than 0.01). HDL cholesterol and systolic blood pressure were significant predictors of fitness in men (p less than 0.01). Smoking emerged as a strong negative predictor for leisure activity in women (p less than 0.01), and a negative relation between leisure activity and total cholesterol was found in men (p less than 0.01). CONCLUSIONS: The study indicates that coronary risk factors are more closely linked to physical fitness than to leisure physical activity.

Adult↗
PubMed1992

Serum methylmalonic acid before and after oral L-isoleucine loading in cobalamin-deficient patients.

Over a 1 1/2-year period, we measured concentrations of methylmalonic acid in serum before and after a standardized loading with oral L-isoleucine (100 mmol) in 13 patients admitted for evaluation of cobalamin deficiency. All patients had serum cobalamin values below 100 pmol l-1, but only 12 of the 13 patients were clinically confirmed cobalamin deficient. The clinically non-cobalamin-deficient patient had folate deficiency and was excluded. The serum methylmalonic acid concentrations before loading with isoleucine were above the upper reference limit (0.37 mumol l-1) in all the patients and L-isoleucine caused an increase in serum methylmalonic acid of more than 1.00 mumol l-1 in 11 of the 12 deficient patients. In the remaining patient the increase was 0.35 mumol l-1. The results show that a significant increase of an initially elevated serum methylmalonic acid concentration after isoleucine loading is a general finding in tissue cobalamin deficiency which strongly supports the diagnosis.

Administration, Oral↗
PubMed1992

Two novel nonradioactive polymerase chain reaction-based assays of dried blood spots, genomic DNA, or whole cells for fast, reliable detection of Z and S mutations in the alpha 1-antitrypsin gene.

Two new nonradioactive polymerase chain reaction (PCR)-based assays for the Z and S mutations in the alpha 1-antitrypsin gene are presented. The assays take advantage of PCR-mediated mutagenesis, creating new diagnostic restriction enzyme sites for unambiguous discrimination between test samples from individuals who are normal, heterozygous, or homozygous for the mutations. We show that the two assays can be performed with purified genomic DNA as well as with boiled blood spots. The new assays were validated by parallel testing with a technique in which PCR is combined with allele-specific oligonucleotide (ASO) probes. In all cases tested the results obtained by the different techniques were in accordance. The new assays can be used for prenatal diagnostics and can be performed directly with boiled tissue samples. Because the new assays are easy to perform and reliable, we conclude that they are well suited for routine diagnosis.

Base Sequence↗
PubMed1992

Non-invasive quantitative measurement of blood flow and estimation of vascular resistance by the Doppler ultrasound method. Methodological studies and clinical application on the fetus and the transplanted kidney allograft.

The introduction of ultrasound 25 years ago was an important improvement and represented a significant step forward in the examination of several organs, especially in the abdomen. During the last 10 years it has been possible to combine Real-Time ultrasound with Doppler ultrasound, thus gaining information on the blood flow and vascular resistance in several organs. The ultrasound method has great advantages; it is non-invasive, can be repeated whenever needed, can be performed bed-side and is inexpensive to use. The present study was undertaken to examine whether the method could be used to diagnose several pathological conditions relevant to the obstetrician and the nephrologist. Before clinical application was performed, the theories behind the ultrasound Doppler principle and the possibilities and limitations of the equipment available for examinations were carefully examined and the method was improved in several important aspects. The precision and accuracy of the improved method was tested in-vitro and in-vivo studies. It was shown that the ultrasound Doppler method has now been developed to an acceptable degree of precision and accuracy for use in scientific investigations and daily clinical routine. The method was then used to examine the fetal and the renal allograft hemodynamics. Reference values for quantitative blood flow in the fetal aorta and the umbilical vein, and for vascular resistance in the normal fetus and the renal allograft were provided, and the method was used to describe hemodynamic changes during several pathological conditions. Some hitherto unknown physiological and pathophysiological variations of blood flow and vascular resistance were found. Thus it was demonstrated that fetal hemodynamics are affected during untreated maternal hypertension in pregnancy and changed towards normal during treatment of the mother, and that renal vascular resistance is increased during rejection of the allograft and normalized following treatment. Furthermore, it was demonstrated that the ultrasound Doppler examination is of diagnostic value when dysfunction of the renal allograft is present.

Adult↗
PubMed1992

Methylmalonic acid concentration in serum not affected in hepatic disease.

Accumulation of methylmalonic acid may provide an early clue to deficiency of cobalamin (vitamin B12) in tissue. Metabolic abnormalities involving precursors of methylmalonic acid are frequently observed in patients with hepatic diseases. To establish whether methylmalonic acid accumulates and thereby gives false-positive test results for cobalamin deficiency, we measured the concentration of methylmalonic acid in serum of patients with various hepatic diseases. Many of the patients had increased concentrations of cobalamin in serum. In serum from 70 patients, the mean concentration of methylmalonic acid (252, SE 25 nmol/L) did not differ significantly from that found in healthy subjects (211, SE 12 nmol/L). We conclude that the assay of methylmalonic acid in serum may be useful for evaluating cobalamin status in hepatic disease with functional cobalamin deficiency despite an artificially increased normal or high concentration of cobalamin in serum.

Acute Disease↗
PubMed1991

Cholecystokinin (CCK) and schizophrenia: the selective CCKB antagonist LY262691 decreases midbrain dopamine unit activity.

Chronic administration of antipsychotic drugs has previously been shown to decrease the number of spontaneously active midbrain dopamine cells. In an effort to evaluate CCK antagonists as potential antipsychotic drugs, we have examined the effects of a selective CCK-B antagonist, LY262691, on the number of spontaneously active midbrain dopamine neurons using extracellular, single-unit recordings in anesthetized rats. Acute and chronic administration of LY262691 decreased the number of spontaneously active A9 and A10 dopamine cells. Administration of apomorphine did not reverse the effect of LY262691 on A9 and A10 dopamine neurons. These results suggest that LY262691 may have an antipsychotic effect without delayed onset, and that its effects on dopamine cells may not be mediated through depolarization inactivation.

Animals↗
PubMed1991

The 5-HT3 receptor antagonist zatosetron decreases the number of spontaneously active A10 dopamine neurons.

Acute and chronic administration of low doses (e.g. 0.1, 0.3 mg/kg i.p.) of the selective 5-HT3 antagonist zatosetron decreased the number of spontaneously active A 10 dopamine cells but did not change the number of spontaneously active A9 dopamine cells; higher doses (1.0, 10 mg/kg) were less effective. The decrease in the number of spontaneously active A 10 dopamine cells following zatosetron administration was not reversed by the administration of apomorphine. These data indicate that zatosetron's effects on spontaneously active dopamine neurons: (1) differs from other 5-HT3 antagonists; (2) may not be mediated by depolarization inactivation; and, (3) may be predictive of an atypical antipsychotic action without delayed onset.

Action Potentials↗
PubMed1991

Effects of lymphocyte activation on transfer RNAs.

The influences of mitogen activation on the functional capacity of rat splenic tRNAs were evaluated. The specific amino acid acceptor activity, pmol of a specific amino acid accepted per nmol of tRNA, of isolated splenic tRNAs from in vivo Concanavalin A (37 h)-treated rats were up to 8 times the specific amino acid acceptor activities of splenic tRNAs from control rats. Control splenic tRNAs were treated with purified liver tRNA nucleotidyltransferase in vitro to repair the 3'[CCA] terminus of tRNAs, and subsequently assayed in an aminoacylation reaction. The specific amino acid acceptor activities were slightly increased over those tRNAs not repaired with tRNA nucleotidyltransferase, indicating the presence of a low level of defective but repairable tRNAs in the control rat spleen. Furthermore, our results indicate that cyclosporin A (inhibitor of lymphocyte activation) blocks the Concanavalin A stimulation of tRNA charging ranging from 16 to 93%.

Amino Acyl-tRNA Synthetases↗
PubMed1991

[The significance of brain death as a criterion for renal transplantation. Status after 9 months].

The effect of introduction of the brain-death criterion in Denmark on the course of cadaver kidney transplantation was evaluated by comparing the course of 31 consecutive patients transplanted after introduction of brain-death criterion with the course of a similar consecutive group of patients transplanted just before the new death criterion. The consequences of the new death criterion were significantly earlier onset of graft function, diminished need for posttransplant dialyses, reduced need for immunosuppressive treatment with Minnesota-antilymphocytglobulin and briefer hospital stays. The easier postoperative course had great psychological effects for the patients and the staff, and the cost of each transplantation was estimated to be reduced by at least 50,000 DKr per patient (approximately 5,000 pounds).

Brain Death↗
PubMed1991

[Assessment of the health risk of a residential area contaminated with arsenic and lead. Biological monitoring in Mundelstrup].

Industrial use of toxic substances has resulted in contamination of the outer environment so that polluted area now constitutes a considerable environmental problem. This article describes biological monitoring employed as part of the basis for assessment of the health risk due to contaminated housing soil. As an example was chosen the environmental contamination with lead and arsenic in Mundelstrup Station Town, where a manure factory previously was situated. This area, which was found to be contaminated to a considerable extend with lead and arsenic, was subdivided for living area in 1921. The present material includes 99 residents from a housing area with 30 family houses with gardens in Mundelstrup. At the commencement of the investigation in 1988/1989, blood lead levels and arsenic levels in the urine were measured and the latter were repeated in 1989/1990. For both adults and children, the blood lead levels were the same as in the reference populations. Children below 12 years had in the average higher arsenic contents in the urine compared with women and men: 16.3 mu/l 8.6 mu/l and 11.5 mu/l, respectively. For both children and adults, the arsenic values were similar to those in a limited Danish reference population. In Ruston, an area in USA heavily polluted with arsenic, contamination of the surface was found to correspond to a factor ten times higher than in Mundelstrup where arsenic is measured at a deeper level. Correspondingly, arsenic values in the urine revealed higher average values in children, 30 micrograms/l for females and 65 micrograms/l for males. The average values for the reference group were found to be 11.3-13.0 micrograms/l.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗