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Biomedical subjects

F Nielsen

Publications and source records attributed to F Nielsen.

At least 19 recordsLinked to original sources
PubMed1999

On clustering fMRI time series.

Analysis of fMRI time series is often performed by extracting one or more parameters for the individual voxels. Methods based, e.g., on various statistical tests are then used to yield parameters corresponding to probability of activation or activation strength. However, these methods do not indicate whether sets of voxels are activated in a similar way or in different ways. Typically, delays between two activated signals are not identified. In this article, we use clustering methods to detect similarities in activation between voxels. We employ a novel metric that measures the similarity between the activation stimulus and the fMRI signal. We present two different clustering algorithms and use them to identify regions of similar activations in an fMRI experiment involving a visual stimulus.

Algorithms↗
PubMed1999

Biomarkers for exposure to ambient air pollution--comparison of carcinogen-DNA adduct levels with other exposure markers and markers for oxidative stress.

Human exposure to genotoxic compounds present in ambient air has been studied using selected biomarkers in nonsmoking Danish bus drivers and postal workers. A large interindividual variation in biomarker levels was observed. Significantly higher levels of bulky carcinogen-DNA adducts (75.42 adducts/10(8) nucleotides) and of 2-amino-apidic semialdehyde (AAS) in plasma proteins (56.7 pmol/mg protein) were observed in bus drivers working in the central part of Copenhagen, Denmark. In contrast, significantly higher levels of AAS in hemoglobin (55.8 pmol/mg protein), malondialdehyde in plasma (0. 96 nmol/ml plasma), and polycyclic aromatic hydrocarbon (PAH)-albumin adduct (3.38 fmol/ microg albumin) were observed in the suburban group. The biomarker levels in postal workers were similar to the levels in suburban bus drivers. In the combined group of bus drivers and postal workers, negative correlations were observed between bulky carcinogen-DNA adduct and PAH-albumin levels (p = 0.005), and between DNA adduct and [gamma]-glutamyl semialdehyde (GGS) in hemoglobin (p = 0.11). Highly significant correlations were found between PAH-albumin adducts and AAS in plasma (p = 0.001) and GGS in hemoglobin (p = 0.001). Significant correlations were also observed between urinary 8-oxo-7, 8-dihydro-2'-deoxyguanosine and AAS in plasma (p = 0.001) and PAH-albumin adducts (p = 0.002). The influence of the glutatione S-transferase (GST) M1 deletion on the correlation between the biomarkers was studied in the combined group. A significant negative correlation was only observed between bulky carcinogen-DNA adducts and PAH-albumin adducts (p = 0.02) and between DNA adduct and urinary mutagenic activity (p = 0.02) in the GSTM1 null group, but not in the workers who were homozygotes or heterozygotes for GSTM1. Our results indicate that some of the selected biomarkers can be used to distinguish between high and low exposure to environmental genotoxins.

Adult↗
PubMed1997

Evaluation of evaporation and concentration distribution models--a test chamber study.

Occupational exposure to airborne volatile organic compounds is governed by the source strength and dispersion of the pollutant into workroom air. The purpose of the present test chamber study was to validate suggested models for the prediction of evaporation rates and concentration distributions. The study design was organized into different scenarios to simulate workplace conditions. Evaporation rates of organic compounds of different volatilities were recorded gravimetrically and the corresponding concentrations in air were measured at various locations equally distributed in the test chamber. The evaporation models generally showed a fair agreement with experiments but tended to underestimate the evaporation rate especially at low air velocity. Based on factorial experiments a new simple evaporation model was suggested. The performances of the concentration distribution models were of different quality. The model developed by Roach (Annals of Occupational Hygiene 24, 105-132, 1981) cannot be used in predicting the concentration distribution in case of a convective air flow. If knowledge of the evaporation rate and pollutant concentration at some distances from the source were available, the model suggested by Scheff et al. (Applied Occupational and Environmental Hygiene 7, 127-134, 1992) generated a concentration distribution in reasonable agreement with the observed data. The box-model (Sinden, Building and Environment 13, 21-28, 1978) generally offered a fair performance but tended to underestimate the pollutant concentration in a region close to the source in the direction of the main air flow.

Air Pollution, Indoor↗
PubMed1997

Antioxidative enzyme activities in human erythrocytes.

Reliable and standardized methods are necessary to determine the expression of antioxidative enzymes and their role in maintaining health. In addition, the variability of the enzyme activities within the general population caused by age, gender, and life-style factors must be described. This study describes methodological conditions that are suitable for analyzing copper-zinc superoxide dismutase (CuZn-SOD), glutathione peroxidase (GSH-Px), catalase (CAT), and glutathione reductase (GR) in human erythrocytes with a high degree of reproducibility. Intervals for the enzyme activities have been established in a randomly selected population of 220 individuals between 20 and 89 years of age. An age-related decrease was observed in CuZn-SOD and GR activities, whereas no age-related changes were demonstrated for GSH-Px and CAT. The GSH-Px activity was positively associated with the intake of dietary supplements and negatively correlated with tobacco consumption. These factors probably account for the fact that women tended to have higher GSH-Px activity.

Adult↗
PubMed1997

Plasma malondialdehyde as biomarker for oxidative stress: reference interval and effects of life-style factors.

Malondialdehyde (MDA) is one of the most frequently used indicators of lipid peroxidation. To generate reliable reference intervals for plasma malondialdehyde (P-MDA), a reference sample group was established in Funen, Denmark. The group consisted of 213 individuals (107 men, 106 women), ages 20-79 years. P-MDA was measured in EDTA-treated plasma after derivatization by thiobarbituric acid (TBA) and separation on HPLC. UV detection was performed at 532 nm. A reference interval was calculated as recommended by IFCC with REFVAL 3.42. The estimated reference limits (0.025 and 0.975 fractals) for the group were 0.36 and 1.24 mumol/L. The data were analyzed for gender- and age-related differences. Analysis of variance showed no interaction between gender and age, but separate analyses showed an independent effect of gender (P = 0.03), but not of age (P = 0.11). Daily smokers had a slightly higher average concentration of P-MDA than nonsmokers (P = 0.05), and P-MDA correlated with daily exposure to cigarette smoke (r = 0.162; P = 0.03). A positive correlation was also demonstrated between P-MDA and weekly alcohol consumption (r = 0.153; P = 0.03). Within-subject and day-to-day variations of P-MDA indicated that the potential of P-MDA as a biomarker for individuals is questionable. However, on a group basis, the present data support that P-MDA may be a potential biomarker for oxidative stress.

Adult↗
PubMed1996

Impact of quinidine on plasma and cerebrospinal fluid concentrations of codeine and morphine after codeine intake.

OBJECTIVE: The analgesic effect of codeine depends on its O-demethylation to morphine via sparteine oxygenase (CYP2D6) in the liver and presumably also via this enzyme in the CNS. We studied the ability of quinidine, which is a potent inhibitor of CYP2D6, to penetrate the blood brain barrier and its possible impact on codeine O-demethylation in CNS. METHODS: The study comprised 16 extensive and one poor metaboliser of sparteine, who underwent spinal anaesthesia for urinary tract surgery or examination. Eight patients were given an oral dose of 125 mg codeine and 9 patients (including the poor metaboliser) were given 200 mg quinidine 2 h before the same dose of codeine. Plasma and spinal fluid samples were collected 2 h after codeine intake. RESULTS: Free concentrations of quinidine were 11-times lower in cerebrospinal fluid than in plasma, and ranged from 9-15 nmol.l-1. Morphine concentrations were significantly lower in patients pre-treated with quinidine, both in plasma (median 1.45 nmol.l-1, range 0.74-1.95 nmol.l-1 vs 9.86 nmol.l-1, range 4.59-28.4 nmol.l-1) and in cerebrospinal fluid (0.23, 0.16-0.61 nmol.l-1 vs 3.63, 0.6-8.09 nmol.l-1). The morphine/codeine concentration ratio in plasma (3.07 x 10 (-3), 1.68-3.68 x 10 (-3) vs 19.87 x 10 (-3), 9.87-66.22 x 10 (-3) and in cerebrospinal fluid (0.83 d 10 (-3), 0.58-1.45 x 10 (-3) vs 7.19 x 10 (-3), 2.03-17.7 x 10 (-3) was also lower. The morphine/codeine concentration ratios were significantly lower in cerebrospinal fluid both without and with quinidine, but the difference between the plasma and spinal fluid ratio was significantly smaller with quinidine than without (p = 0.0002). CONCLUSION: Quinidine penetrates the blood brain barrier poorly, but quinidine pre-treatment leads to pronounced lowering of the cerebrospinal fluid concentration of morphine after codeine intake. However, the O-demethylation of codeine in CNS may not be totally blocked by quinidine.

Administration, Oral↗
PubMed1996

Sodium cromoglycate as a replacement for inhaled corticosteroids in mild-to-moderate childhood asthma.

We investigated whether sodium cromoglycate 10 mg three times daily, delivered as an aerosol via Nebuhaler (in addition to terbutaline 0.5 mg three times daily), could replace inhaled steroid in children with mild-to-moderate asthma. Children (mean age 10.3 years) were randomly allocated to 12-week treatment with sodium cromoglycate 10 mg plus terbutaline 0.5 mg (group A; n = 30) or placebo plus terbutaline 0.5 mg (group B; n = 32), both taken three times a day. The daily steroid dose was reduced by 50 microg/week for 4 weeks from a starting dose of 200 microg. Fewer patients withdrew owing to worsening asthma from group A (n = 1) than group B (n = 11). Symptom scores, morning and evening peak flows, and additional beta2-agonist usage, recorded on diary cards, were better in group A than group B. Lung function measured at clinic visits was unchanged in either group. Overall opinions of efficacy favoured Group A. Adverse events were similar in the groups. Sodium cromoglycate plus terbutaline substituted effectively for inhaled steroid therapy.

Administration, Inhalation↗
PubMed1995

Lack of relationship between quinidine pharmacokinetics and the sparteine oxidation polymorphism.

Quinidine is a very potent inhibitor of CYP2D6, but the role of the enzyme in the biotransformation of quinidine has only been investigated in a single in vitro study and in two small in vivo experiments, with contradictory results. The present investigation was designed to present definite evaluation of whether quinidine is metabolised by CYP2D6. Eight poor metabolizers (PM) and 8 extensive metabolizers (EM) of sparteine each took one oral dose of 200 mg quinidine. In the EM, the total clearance, the clearance via 3-hydroxylation and the clearance via N-oxidation, were 33, 3.7 and 0.23 l.h-1, respectively. In the PM, the corresponding values were 29, 3.1 and 0.18 l.h-1, respectively. There were no statistically significant differences between EM and PM in any of these pharmacokinetic parameters. It is concluded that CYP2D6 is not an important enzyme for the oxidation of quinidine.

Adult↗
PubMed1995

Impact of immediate and delayed myocardial scintigraphy on therapeutic decisions in suspected acute myocardial infarction.

Early myocardial scintigraphic imaging has become technically feasible in patients admitted to hospital with suspected acute myocardial infarction. After prompt injection of 99mTc-sestamibi, subsequent scintigraphic imaging of perfused myocardium can be performed. During a 5-month period, 237 patients were admitted to the coronary care unit of a district hospital on suspicion of acute ischaemic syndrome, and injection of 99mTc-sestamibi for the performance of myocardial scintigraphy was carried out in 134 patients, on average 2 h after onset of symptoms. The investigation was repeated in 126 patients, on average 18 h after the injection. Three planar views were taken in the coronary care unit with a mobile gamma camera. The prevalence of acute myocardial infarction was 53%. The predictive value at the first scintigraphic imaging for a positive or negative test for myocardial infarction 54% and 56%, respectively. Even exclusion of patients with a previous infarction did not increase the diagnostic validity. The predictive value of a negative test, 77%, at the second scintigraphy was still insufficient to make immediate therapeutic decisions. Myocardial scintigraphy performed early, on suspicion of acute myocardial infarction, cannot therefore be used routinely as a diagnostic test prior to intervention in unselected patients because some 90% of this patient group have myocardial perfusion defects.

Aged↗
PubMed1994

Determination of quinidine, dihydroquinidine, (3S)-3-hydroxyquinidine and quinidine N-oxide in plasma and urine by high-performance liquid chromatography.

A specific and sensitive method for the quantitation of quinidine, (3S)-3-hydroxyquinidine, quinidine N-oxide, and dihydroquinidine in plasma and urine has been developed. The method is based on a single-step, liquid-liquid extraction procedure, followed by isocratic reversed-phase high-performance liquid chromatography, with fluorescence detection. After extraction from 250 microliters plasma and 100 microliters urine, the limit of determination is 10 nM and 25 nM, respectively. For the use as standards, commercially available quinidine was purified from dihydroquinidine; quinidine N-oxide was synthesized.

Chromatography, High Pressure Liquid↗
PubMed1994

Characterisation of a trisulphide derivative of biosynthetic human growth hormone produced in Escherichia coli.

A novel protein derivative has been found during process development of biosynthetic human growth hormone; it has been characterised as human growth hormone with a Cys182-Cys189 trisulphide bridge. We have not been able to find a previous report in the literature about this kind of derivative. The characterisation was obtained partly on the full-length derivative and partly on a tryptic fragment of the derivative. The full-length derivative was characterised by reduction with 1,4-dithiothreitol followed by electrospray mass spectrometry, treatment with cysteine and measurement of hydrogen sulphide liberation upon cysteine treatment. The tryptic fragment from peptide mapping was characterised by amino acid analysis, amino acid sequencing and mass spectrometry. All data indicated an extra sulphur atom in the Cys182-Cys189 cystine bridge.

Amino Acid Sequence↗
PubMed1994

Myocardial infarction 1979-1988 in Denmark: secular trends in age-related incidence, in-hospital mortality and complications.

All admissions to a coronary care unit (CCU) in Copenhagen County were prospectively registered over a 10-year period, from 1979 to 1988, i.e. after the introduction of CCUs but before the era of intervention with thrombolytic or prophylactic medical treatment. The catchment area remained nearly constant throughout the study period; all patients with MI were admitted to the CCU regardless of age and concomitant diseases, and treatment and discharge policy of the department was unchanged. A total of 4176 MI admissions were registered. During the study period, the age-specific incidence of MI decreased in males above 50 years of age, but was virtually unchanged in females, increasing the proportion of women in the MI population from 26 to 33%. In-hospital and 30-day mortality was unchanged. The occurrence of atrial fibrillation during the admission increased significantly (from 11 to 18%), while the incidence of ventricular fibrillation, heart failure and pulmonary oedema was unchanged.

Adult↗
PubMed1993

Effective antihypertensive treatment postpones renal insufficiency in diabetic nephropathy.

The effect of long-term, aggressive, antihypertensive treatment on kidney function in diabetic nephropathy was studied prospectively in 11 insulin-dependent diabetic patients (mean age, 30 years). Renal function was assessed every 4 months by measurement of glomerular filtration rate (GFR) (single-bolus 51Cr-EDTA technique) and by albuminuria (radial immunodiffusion). During the median pretreatment period of 2.4 years (range, 1.9 to 5.5 years), the GFR decreased significantly and albuminuria and the arterial blood pressure increased significantly. During the 9.7-year (range, 2.8 to 10.4 year) period of antihypertensive treatment with metoprolol, hydralazine, and furosemide, the arterial blood pressure decreased from 143/96 mm Hg to 130/84 mm Hg and albuminuria decreased from 1,038 micrograms/min to 547 micrograms/min. The rate of decline in GFR decreased from 10.7 mL/min/yr (range, 5.3 to 17.5 mL/min/yr) before treatment to 2.5 mL/min/yr (range, 0.5 to 4.8 mL/min/yr) during treatment. The rate of decline in GFR is significantly smaller during the last 6 years compared with the first 3 years in patients who received long-term antihypertensive treatment (> or = 9 years). One patient died from acute myocardial infarction (GFR, 46 mL/min/1.73 m2). Effective antihypertensive treatment postpones renal insufficiency in diabetic nephropathy.

Adult↗
PubMed1992

Plasma lipoproteins and renal function during simvastatin treatment in diabetic nephropathy.

The aim of this study was to assess the effect of simvastatin on plasma lipoproteins and renal function in hypercholesterolaemic Type 1 (insulin-dependent) diabetic patients with diabetic nephropathy. Twenty-six hypercholesterolaemic (total cholesterol greater than or equal to 5.5 mmol/l) Type 1 diabetic patients with nephropathy were enrolled in a double-blind randomized placebo-controlled study for 12 weeks. The active treatment group (n = 14) received simvastatin (10-20 mg/day) for 12 weeks while the remaining 12 patients received treatment with placebo. The results during simvastatin treatment (baseline vs 12 weeks): total cholesterol 6.6 vs 4.8 mmol/l (p less than 0.01), LDL-cholesterol 4.25 vs 2.57 mmol/l (p less than 0.01) and apolipoprotein B 1.37 vs 1.06 mmol/l (p less than 0.01). HDL-cholesterol, and apolipoprotein A-I remained unchanged. Total cholesterol, LDL-cholesterol, HDL-cholesterol, apolipoprotein A-I, apolipoprotein B remained unchanged during placebo treatment. Albuminuria measured during the simvastatin and the placebo treatment (baseline vs 12 weeks) (the data are logarithmically transformed before analysis because of their positively skewed transformation; geometric mean (x/divided by antilog SE) is indicated) was 458 (x/divided by 1.58) vs 393 (x/divided by 1.61) and 481 (x/divided by 1.62) vs 368 (x/divided by 1.78 micrograms/min (NS). Glomerular filtration rate during simvastatin and placebo treatment (baseline vs 12 weeks) was 64 vs 63 and 72 vs 74 ml.min-1.1.73 m-2, respectively. Two patients receiving simvastatin treatment were withdrawn, one due to gastrointestinal side effects and one due to myalgia.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Myocardial perfusion at fatal infarction: location and size of scintigraphic defects.

In a consecutive study of myocardial scintigraphy in acute ischemic syndrome, four patients had 99mTc-hexamibi injected intravenously before they developed fatal cardiogenic shock. Planar scintigraphy was performed after death. Slices of the hearts after autopsy were analyzed for scintigraphic and pathoanatomic abnormalities. Location of perfusion defects in planar views of the heart was in good agreement with the scintigraphied, sliced sections. The extent of infarction judged from inspection and formasan staining was much smaller (7%-40% and 6%-43% of the total slice area) than found at scintigraphy, where 83%-92% of the myocardium showed ischemia as defined by a 99mTc-hexamibi uptake below an arbitrary limit on half maximum uptake. Myocardial hypoperfusion might thus aggravate the functional impairment at myocardial infarction and lead to cardiogenic shock.

Aged↗
PubMed1989

[A study of cardiac vagal function in chronic alcoholics].

Reduced cardiac vagal tonus is correlated to sudden cardiac death and occurrence of arrhythmia, particularly in patients with ischemic heart disease. In patients with diabetic neuropathy increased frequencies of silent myocardial ischaemia and silent myocardial infarctions have been found, in addition. The object of the present investigation was to assess whether chronic alcoholics have lowered cardiac vagal tonus. The cardiac vagal tonus was assessed by means of a sensitive non-invasive method in which the variations in the pulse rate during six deep respirations were registered on the basis of the R to R interval in the ECG. Fourteen alcoholics and fourteen healthy controlled individuals participated in the investigation. The medians of the variations in the two groups were 15 and 25 beats per minute, respectively. The difference was statistically significant. No significant differences were observed in alcoholics with or without clinical evidence of polyneuropathy. This investigation thus suggests that ethanol has a toxic effect on the cardiac vagal function.

Adult↗
PubMed1989

Transient neonatal diabetes mellitus in a pair of twins.

The occurrence of transient neonatal diabetes mellitus in male twins with almost identical courses of illness is reported. A trial with chlorpropamide treatment of twin A had no obvious influence on the insulin consumption or on duration of treatment. Very low values of plasma C-peptide and serum proinsulin with no detectable insulin antibodies supports the theory of delayed maturation of the beta-cell.

Chlorpropamide↗