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Biomedical subjects

K Rasmussen

Publications and source records attributed to K Rasmussen.

At least 73 records · Page 4Linked to original sources

Prevalence of left ventricular hypertrophy in a general population; The Tromsø Study.

AIMS: Left ventricular hypertrophy has been shown to be an independent predictor of cardiovascular morbidity. Acknowledging the skewed distribution of left ventricular mass, we wanted to develop criteria for left ventricular hypertrophy based on percentiles of left ventricular mass, and observe the effect on estimates of left ventricular hypertrophy prevalences in different subgroups and on the relationship to cardiovascular risk factors in a general population. METHODS AND RESULTS: In a population-based sample of 3287 subjects aged 25-85 years, left ventricular mass was estimated using M-mode echocardiography. A 'healthy' subgroup was used as a reference sample to define sex-specific left ventricular hypertrophy criteria. Sex-specific 97.5 percentiles for left ventricular mass by height, based on the reference sample, were 145.5 and 125.4 g.m(-1), for men and women, respectively. The prevalences of left ventricular hypertrophy in the total population were 14.9% for men and 9.1% for women. The main independent predictors of left ventricular hypertrophy were male gender, body mass index, systolic blood pressure, valvular heart disease, cardiovascular disease and antihypertensive medication. Body mass index and systolic blood pressure had a strong synergistic association with left ventricular hypertrophy in men, but not in women. CONCLUSION: An alternative framework for defining left ventricular hypertrophy is provided. Body mass index is the culprit factor for risk of left ventricular hypertrophy. Our study indicates that weight reduction is a relevant measure for treatment and possibly prevention of left ventricular hypertrophy in a substantial part of the general population.

Adult↗

Static magnetic field and the inner ear. A functional study of hearing and vestibular function in man after exposure to a static magnetic field.

The sensory cells of the inner ear are vulnerable to several agents (aminoglycosides, cytostatics, ionizing irradiation). The effect of strong magnetic fields occurring in industries with production based on electrolytic processes and with medical magnetic resonance equipment is unknown. The aim of this study was to clarify the effect of strong static magnetic fields on the inner ear, by exposing 11 healthy men to a magnetic field with flux density of 2-7 mT for 9 h. No damage was found to the acoustic or vestibular system.

Adult↗

Serum cobalamin, homocysteine, and methylmalonic acid concentrations in a multiethnic elderly population: ethnic and sex differences in cobalamin and metabolite abnormalities.

BACKGROUND: Low cobalamin concentrations and mild hyperhomocysteinemia are common in the elderly but ethnic differences have not been defined. OBJECTIVE: Our objective was to determine the demographic characteristics of cobalamin deficiency in the elderly and its role in their hyperhomocysteinemia. DESIGN: We measured serum cobalamin, total homocysteine (Hcys), and methylmalonic acid (MMA) concentrations in 725 subjects >60 y old, and folate concentrations in 520 subjects. RESULTS: After exclusion of subjects taking cobalamin supplements or with renal insufficiency, high prevalences of low cobalamin (11.8%), high MMA (16.6%), and high Hcys (26.1%) concentrations were seen. Most cobalamin concentrations <140 pmol/L appeared to reflect deficiency because 78. 3% of them were accompanied by abnormal metabolites. Subjects with cobalamin concentrations of 140-258 pmol/L had significantly fewer metabolic abnormalities. A low cobalamin concentration and renal insufficiency were the strongest predictors of abnormal Hcys concentrations. Elderly men had higher Hcys concentrations than did women (P = 0.0001). Whites and Latin Americans had lower cobalamin concentrations than did blacks and Asian Americans (P < 0.005). Whites also had higher Hcys concentrations than all the other groups (P < 0.05). When included in the analysis, renal insufficiency in subjects was associated with 23.8% of all high Hcys and 25.5% of all high MMA concentrations; most with renal insufficiency were Asian American and black men. CONCLUSIONS: Mild cobalamin deficiency is most common in elderly white men and least common in black and Asian American women. Hyperhomocysteinemia, which is most strongly associated with low cobalamin concentrations, is also most common in elderly whites, whereas that associated with renal insufficiency is more common in blacks and Asian Americans. Ethnic differences in cobalamin deficiency and the Hcys patterns associated with it or with renal insufficiency warrant consideration in supplementation strategies. Extending suspicion of deficiency to persons with cobalamin concentrations of 140-258 pmol/L appears to provide more disadvantages than advantages.

Aged↗

Thrombophilic predisposition in stroke and venous thromboembolism in Danish patients.

The present study describes 403 patients with thrombosis, from a uniform ethnic and geographical background. Two-hundred-and-seven individuals had suffered mild or moderate stroke and 196 individuals suffered venous thromboembolism. We recorded levels of antithrombin, protein C and protein S, plasminogen and plasma homocysteine, and the presence of the factor V Leiden mutation, the prothrombin 20210G-->A variant, and the methylenetetrahydrofolate reductase (MTHFR) 677C-->T polymorphism. Controls for the mutation frequencies consisted of Guthrie card blood spots from a cohort of new-born babies. The cumulative prevalence of deficiencies in antithrombin, protein C, protein S or plasminogen was 2.4% in patients with stroke and 11.2% in patients with venous thrombosis. The factor V Leiden mutation was present in 11.1% of patients with stroke and 26.5% of patients with venous thrombosis, compared with 6.6% of controls (n = 4188; P < 0.05 and P < 0.0001, respectively). The prevalence of the prothrombin 20210A variant was 3.1% in patients with venous thrombosis, 1.9% in patients with stroke and 2.0% in controls (n = 500; P > 0.05). Hyperhomocysteinemia was present in 16.0% of patients with stroke and 17.6% of patients with venous thrombosis. The prevalence of the MTHFR 677T/T genotype was no different in patients with stroke (10.6%) and venous thrombosis (8.7%) than in controls (8.3%; n = 1084; P > 0.05); thus, it apparently contributed to thrombosis only via its influence on total plasma homocysteine, which was significantly increased in patients with the T/T genotype (P < 0.001). The MTHFR T/T genotype did not further increase the risk for thrombosis in carriers of the factor V Leiden mutation. Overall, thrombotic events were associated with a known risk factor in 27% of patients with stroke and 55% of patients with venous thrombosis.

Adolescent↗

Can single-lead computerized electrocardiography predict myocardial infarction in young and middle-aged men? The Tromsø study.

BACKGROUND: In epidemiological studies, the electrocardiogram has often been interpreted by means of a categorical classification. Computerized recording offers the possibility of analysing electrocardiographic measurements as continuous variables. OBJECTIVE: To test the hypothesis that duration of QRS complex and T-wave inversion would be independent predictors of myocardial infarction. METHODS: In a population-based study, we prospectively investigated the risk of developing myocardial infarction according to duration of ORS complex and peak-to-peak T-wave amplitude measured from lead I of the 12-lead electrocardiogram by computerized electrocardiography. In total 6628 men aged 25-61 years who had not previously suffered a myocardial infarction were followed up for 3.9 years. RESULTS: Eighty-two first myocardial infarctions (55 non-fatal and 24 fatal myocardial infarctions and three sudden deaths) were identified. The risk of myocardial infarction increased with duration of ORS complex and with decreasing T-wave amplitude. A proportional hazards model with adjustment for possible confounders yielded a relative risk of myocardial infarction of 3.74 (P for linear trend 0.015) for duration of QRS complex > or = 120 ms compared with duration of QRS complex <80 ms. The multivariate relative risk for T-wave amplitude > or = 0.35 mV compared with T-wave amplitude < 0.20 mV was 0.55 (P for linear trend 0.036). When both duration of ORS complex and T-wave amplitude were included in the multivariate model, T-wave amplitude retained its predictive power, whereas duration of ORS complex became marginally no longer significant (P=0.067). CONCLUSIONS: Peak-to-peak T-wave amplitude from lead I is an independent predictor of myocardial infarction in men who have not previously suffered a myocardial infarction. Greater duration of ORS complex clearly indicates a higher risk of myocardial infarction. However, when T-wave amplitude is included as a covariate, the predictive power of duration of QRS complex does not remain significant. Single-lead electrocardiography is a feasible method for improving the assessment of the relative risk of myocardial infarction.

Adult↗

Olanzapine: a basic science update.

Olanzapine, an atypical antipsychotic, has a broad receptor binding profile, which may account for its pharmacological effects in schizophrenia. In vitro receptor binding studies showed a high affinity for dopamine D2, D3, and D4 receptors; all 5-HT2 receptor subtypes and the 5-HT6 receptor; muscarinic receptors, especially the M1 subtype: and alpha 1-adrenergic receptors. In vivo studies showed that olanzapine had potent activity at D2 and 5-HT2A receptors, but much less activity at D1 and muscarinic receptors, and that it inhibited dopaminergic neurons in the A10 but not the A9 tract, suggesting that this agent will not cause extrapyramidal side-effects (EPS). Microdialysis studies showed that olanzapine increased the extracellular levels of norepinephrine and dopamine, but not 5-HT, in the prefrontal cortex, and increased extracellular dopamine levels in the neostriatum and nucleus accumbens, areas of the brain associated with schizophrenia. Studies of gene expression showed that olanzapine 10 mg/kg also increased Fos expression in the prefrontal cortex, the dorsolateral striatum, and the nucleus accumbens. These findings are consistent with the effectiveness of olanzapine on both negative and positive symptoms and suggest that, with careful dosing, olanzapine should not cause EPS.

Animals↗

External quality assessment of methylmalonic acid and total homocysteine.

BACKGROUND: The use of analyses for methylmalonic acid (MMA) and total homocysteine (HCY) in plasma has become widespread. Realizing the need for external quality assessment for these measurements, we started a program in 1997. The results for 1998 are reviewed in this report. METHODS: Fourteen laboratories participated with 15 sets of results for MMA, and 28 laboratories participated with 34 sets of results for HCY. Results for four identical samples, made up from the same unmodified serum (MMA) or EDTA-plasma (HCY) pool, sent out under different identifications, were used for assessing the imprecision. Samples made up from the same pools supplemented with MMA or L-HCY to three concentrations were used for assessing the recovery. By using literature data for the biological variation, quality goals for both analytes were calculated. RESULTS: The overall within-laboratory CV was 12% for MMA and 7.5% for HCY. Gas chromatography-mass spectrometric HCY results had lower imprecision than the HPLC or immunoassay results. For MMA, no significant between-laboratory component of variance was found. Only results for HCY obtained with HPLC methods showed significant between-laboratory variance. CONCLUSIONS: Eight of the 15 participants achieved the minimum imprecision goal for MMA vs 9 of the 34 participants for HCY. The minimum quality goals for bias as approximated by the recovery were achieved by 13 participants for MMA and 26 for HCY.

Chromatography, High Pressure Liquid↗

Within-person variation of plasma homocysteine and effects of posture and tourniquet application.

BACKGROUND: Frequently, the result of only a single determination of total homocysteine in plasma (P-Hcy) is used to distinguish between the probability of the presence or absence of risk for vascular disease. A prerequisite for the interpretation of a single P-Hcy test is knowledge of the magnitude of within-person variation and the possible effects of preanalytical variables. However, data on within-person variation are still sparse and inconsistent, and data for the effect on P-Hcy of posture and tourniquet application during venipuncture are not available. METHODS: The within-person variation of P-Hcy and the effects of posture and tourniquet application during venipuncture were studied in 24 healthy subjects. The analytical imprecision of our stable-isotope dilution assay was 3.1%. RESULTS: The within-person variation (CV) was 8.1%. Daily supplementation with 0.4 mg of folic acid for 2 weeks produced a small but significant decrease in P-Hcy, but there were no significant changes in within-person variation before and after supplementation. After 30 min in the horizontal posture, P-Hcy declined by 6.3%. A 3-min tourniquet application caused a 2.8% increase of P-Hcy. CONCLUSIONS: Our value for within-person variation is consistent with results from studies reported recently in the literature. A 3-min tourniquet application does not add appreciable variation to the measurement of P-Hcy, but the posture of the subject during venipuncture contributes considerably to the within-person variation. We recommend that blood collection when the patient is in a supine position be avoided.

Adult↗

[Percutaneous transluminal coronary angioplasty in acute myocardial infarction. A prospective controlled study].

In the present study we compared the outcome of primary percutaneous coronary angioplasty (PTCA) (PTCA without prior or concomitant administration of thrombolytic drugs) in 82 consecutive patients with acute myocardial infarction (AMI) with the outcome of 82 AMI patients, who were treated with intravenous thrombolysis. The thrombolysis patients were prospectively matched to the angioplasty patients regarding age, sex, duration of symptoms and infarct localisation. The in-hospital mortality was 3.7% in the PTCA group versus 4.9% in the thrombolysis group. Thrombolysis-treated patients had increased use of diuretics and ACE-inhibitors as compared to PTCA-treated patients. The mean ejection fraction was 52 +/- 11% in the PTCA group versus 47 +/- 10% (p = 0.01) in the thrombolysis group. We conclude that initial Danish experience with primary PTCA is promising, and that this treatment may favourably affect the outcome of acute myocardial infarction.

Aged↗

Unexpected antipsychotic-like activity with the muscarinic receptor ligand (5R,6R)6-(3-propylthio-1,2,5-thiadiazol-4-yl)-1-azabicyclo[3.2.1]octane .

(5R,6R)6-(3-propylthio-1,2,5-thiadiazol-4-yl)-1-azabicyclo[3 .2.1]octane (PTAC) is a potent muscarinic receptor ligand with high affinity for central muscarinic receptors and no or substantially less affinity for a large number of other receptors or binding sites including dopamine receptors. The ligand exhibits partial agonist effects at muscarinic M2 and M4 receptors and antagonist effects at muscarinic M1, M3 and M5 receptors. PTAC inhibited conditioned avoidance responding, dopamine receptor agonist-induced behavior and D-amphetamine-induced FOS protein M5 expression in the nucleus accumbens without inducing catalepsy, tremor or salivation at pharmacologically relevant doses. The effect of PTAC on conditioned avoidance responding and dopamine receptor agonist-induced behavior was antagonized by the acetylcholine receptor antagonist scopolamine. The compound selectively inhibited dopamine cell firing (acute administration) as well as the number of spontaneously active dopamine cells (chronic administration) in the limbic ventral tegmental area (A10) relative to the non-limbic substantia nigra, pars compacta (A9). The results demonstrate that PTAC exhibits functional dopamine receptor antagonism despite its lack of affinity for the dopamine receptors and indicate that muscarinic receptor partial agonists may be an important new approach in the medical treatment of schizophrenia.

Animals↗

[Occupational medicine in general practice. A study of the extent and nature of occupational injuries in the county of Ringkjøbing].

The purpose of this investigation was to estimate the occurrence and type of work-related incidents in primary health care in the county of Ringkoebing, Denmark, with 270,000 inhabitants. Symptom-related general practitioner (GP)-consultations among 17-66 year-old residents were registered among 114 GP's during four days over one year. In each occasion the GP evaluated the question of work-relatedness versus none-work-relatedness. Of 3017 registered consultations, 479 were work-related (15.9%). There were 376 disease cases and 103 injury cases. Musculoskeletal diseases constituted the dominating diagnostic category, as well as being the category with the highest proportion of work-relatedness, corresponding to 35% of all musculoskeletal consultations. Notification as a work injury case was performed for 19% of all work-related cases. This investigation represents the hitherto most extensive Danish material of the distribution of work-related incidents within the broad spectrum of the GP's practice.

Adolescent↗

Microelectrode measurements of local mass transport rates in heterogeneous biofilms.

Microelectrodes were used to measure oxygen profiles and local mass transfer coefficient profiles in biofilm clusters and interstitial voids. Both profiles were measured at the same location in the biofilm. From the oxygen profile, the effective diffusive boundary layer thickness (DBL) was determined. The local mass transfer coefficient profiles provided information about the nature of mass transport near and within the biofilm. All profiles were measured at three different average flow velocities, 0.62, 1.53, and 2.60 cm sec-1, to determine the influence of flow velocity on mass transport. Convective mass transport was active near the biofilm/liquid interface and in the upper layers of the biofilm, independent of biofilm thickness and flow velocity. The DBL varied strongly between locations for the same flow velocities. Oxygen and local mass transfer coefficient profiles collected through a 70 micrometer thick cluster revealed that a cluster of that thickness did not present any significant mass transport resistance. In a 350 micrometer thick biofilm cluster, however, the local mass transfer coefficient decreased gradually to very low values near the substratum. This was hypothetically attributed to the decreasing effective diffusivity in deeper layers of biofilms. Interstitial voids between clusters did not seem to influence the local mass transfer coefficients significantly for flow velocities of 1.53 and 2.60 cm sec-1. At a flow velocity of 0.62 cm sec-1, interstitial voids visibly decreased the local mass transfer coefficient near the bottom.

Biofilms↗

Detection of a novel deletion in the cystathionine beta-synthase (CBS) gene using an improved genomic DNA based method.

We elucidated the intron-exon boundaries of the 15 coding exons of the human cystathionine beta-synthase (CBS) gene in order to establish an improved method based on PCR and direct sequencing for detection of CBS mutations. Using this method we identified the pathogenic mutations in two Danish siblings with CBS deficiency. Patients were compound heterozygotes: we detected the 833T-->C mutation and a novel 22 bp deletion of exon 4 (493-514del) that introduces a frameshift and a stop codon immediately after the deletion. The deletion resulted in no detectable mRNA from this allele, as assessed by sequencing of cDNA. The established method represents an improvement of the existing method based on sequencing of cDNA because it permits the detection of mutations within the entire coding region of the CBS gene from a peripheral blood sample, including splice mutations and mutations resulting in the lack or a reduced amount of transcript.

Adult↗

[Clinics for counseling on cancer genetics. Experiences with genetic studies and counseling on familial breast cancer and colorectal cancer].

Five to ten percent of cases of breast cancer and colorectal cancer are familial. These families can be divided into high-risk families and moderate-risk families. Cancer in high-risk families can often be explained by dominant inheritance of a gene causing increased susceptibility to cancer. There is a great demand for genetic counseling in these families, and the structure of and experiences from a familial cancer clinic at Odense University Hospital is described. The establishment of a familial cancer clinic involves three steps: 1) Identification of families with increased cancer susceptibility; 2) Molecular tests to identify gene carriers; 3) Clinical examinations for early detection of tumors. Achievement of these three steps requires the involvement of several medical specialties to ensure patient care. Experience with familial cancer clinics is still limited and the involvement of genetic testing and clinical examination programs at risk individuals are insufficiently examined. The rapidly improving techniques for genetic testing make it urgent that it is implemented as part of already established clinical programs.

Adult↗

[Traumatic rhabdomyolysis. Physiopathology and treatment].

Crush syndrome or traumatic rhabdomyolysis constitutes the systemic changes seen after crush injury, i.e. the damages seen after a prolonged period of pressure on a muscle group. The pressure causes necrosis of muscle, and during revascularisation diffusion of calcium, sodium and water into the damaged muscle cells is seen, together with loss of potassium, phosphate, lactic acid, myoglobin and creatinine kinase. Untreated these changes can lead to: hyperkalaemia, acidosis, acute renal failure and hypovolaemic shock. Treatment of the systemic changes should be initiated immediately, aiming at a rapid correction of the extracellular volume and forced mannitol-alkaline diuresis. If renal failure develops, haemodialysis is started. The crush injuries are treated conservatively without fasciotomy, despite high or increasing intracompartmental pressure. The only indications for fasciotomy are lack of a distal pulse or open lesions. If fasciotomy is performed, radical removal of all necrotic muscle is essential.

Crush Syndrome↗

Activation of midbrain presumed dopaminergic neurones by muscarinic cholinergic receptors: an in vivo electrophysiological study in the rat.

1. Extracellular single-unit recording and iontophoresis were used to examine the effects of different cholinoceptor agonists and antagonists on the firing rate and firing pattern of A9 and A10 presumed dopaminergic neurones in the anaesthetized rat. 2. Administration of low currents (1-5 nA) of the selective muscarinic agonists oxotremorine M (Oxo M) and muscarine and of the non-selective muscarinic/nicotinic agonist carbamylcholine (CCh) produced a dose-dependent increase in firing rate in most of the A9 and A10 presumed dopaminergic neurones tested. Oxo M-induced activation could be completely blocked by iontophoretic application of the muscarinic antagonist butyl-scopolamine or systemic administration of the muscarinic antagonist scopolamine (300 microg kg(-1), i.v.). 3. Iontophoretic application of the selective nicotinic agonist methylcarbamylcholine (MCCh), but not nicotine, induced a consistent increase in firing rate. Surprisingly, the excitatory effect of MCCh was significantly reduced by the selective muscarinic antagonist scopolamine (300 microg kg(-1), i.v.), but not by the selective nicotinic antagonist mecamylamine (2.2 mg kg(-1), i.v.). Mecamylamine (3 mg kg(-1), i.v.) was also ineffective in reducing the CCh-induced activation of presumed dopamine neurones, suggesting that both CCh and MCCh increased the activity of dopamine neurones via an interaction with muscarinic receptors. 4. Iontophoretic application of the endogenous agonist acetylcholine (ACh) had no or little effect on the firing activity of A10 presumed dopaminergic neurones. However, concomitant application of neostigmine, a potent cholinesterase inhibitor, with acetylcholine induced a substantial activation of these neurones. This activation consisted of two components; one, which was prevalent, was scopolamine (300 microg kg(-1), i.v.)-sensitive, and the other was mecamylamine (2 mg kg(-1), i.v.)-sensitive. 5. In addition to their effect on firing activity, Oxo M, muscarine and concomitant neostigmine/ACh caused a significant increase in burst firing of A10 neurones, but not of A9 neurones. 6. These data suggest that dopamine cells, both in the A9 and A10 regions, possess functional muscarinic receptors, the activation of which can increase their firing rate and, for A10 neurones, their amount of burst activity. These cholinoceptors would be able to influence the activity of the midbrain dopamine system greatly and may play a role in, and/or be a therapeutic target for, brain disorders in which dopamine is involved (e.g., Parkinson's disease, drug addiction and schizophrenia).

Action Potentials↗