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Biomedical subjects

J Toft

Publications and source records attributed to J Toft.

At least 19 recordsLinked to original sources

A novel mutation in the mitochondrial tRNA(Phe) gene associated with mitochondrial myopathy.

We report a novel heteroplasmic T-->C mutation at nt position 582 within the mitochondrial tRNA(Phe) gene of a 70-year-old woman with mitochondrial myopathy. No other family members were affected, suggesting that our patient was a sporadic case. The muscle showed frequent ragged red fibers and 43% cytochrome c oxidase deficient fibers. The mutation alters a conserved base pairing in the aminoacyl acceptor stem. The mutation load was 70% in muscle homogenate and varied from 0 to 95% in individual muscle fiber segments. Cytochrome c oxidase-negative fibers showed significantly higher levels of mutated mtDNA (>75%) than Cytochrome c oxidase-positive fibers (<55%). This mutation adds to the previously described four pathogenic mutations in the tRNA(Phe) gene.

Aged↗

The optimal reference population for cardiac normality in myocardial SPET in the detection of coronary artery stenoses: patients with normal coronary angiography or subjects with low likelihood of coronary artery disease?

Both subjects with a low likelihood for coronary artery disease (CAD) and patients with normal findings on coronary angiography have been used as reference populations in non-invasive stress testing, including myocardial perfusion scintigraphy. Both of these criteria of normality--low likelihood of CAD and normal coronary angiography--have been criticised, and consensus on this issue is lacking. The aim of this study was to compare two different reference populations by testing the performance of artificial neural networks designed to interpret myocardial scintigrams. The networks were trained on myocardial perfusion scintigrams from 87 patients with angiographically documented CAD and on studies from one of two different reference groups: 48 patients with no signs of CAD based on angiography or 128 healthy volunteers with a likelihood for CAD <5%. The performance of the two different networks was then tested using scintigrams from a separate test group of 68 patients. Coronary angiography was used as the gold standard in this group. The network trained on patients with no signs of CAD based on angiography showed an area under the receiver operating characteristic (ROC) curve of 93%. The ROC area for the network trained on healthy volunteers was 72%, and this difference was statistically significant (P=0.03). The results of this study using artificial neural networks suggest that normal angiography should be preferred as the reference standard in myocardial scintigraphy when a patient is examined for CAD prior to possible angiography. Whether the same is true for other indications, e.g. in prognostic evaluation, is unknown.

Adult↗

[Substances other than alcohol found in the blood among Danish road-users during a week in 1996].

INTRODUCTION: This investigation is the Danish contribution to a Nordic comparative study of other drugs than alcohol found in road users. MATERIAL AND METHODS: 255 blood samples received from the police for alcohol and/or drug determination during one week in 1996 were investigated for drugs. RESULTS: 56 (22%) of the 255 blood samples were positive for other drugs than alcohol. Cannabis was detected in 11%, benzodiazepines, mainly diazepam and flunitrazepam, in 9% and amphetamine in 5% of the blood samples. DISCUSSION: The police suspected other drugs than alcohol in 3% of the 255 blood samples, but drugs were detected in 22%. This investigation showed that the frequency of other drugs than alcohol was similar in Denmark and Norway for the blood samples with an alcohol concentration above the statutory limit. This contrasts with the fact that the number of blood samples from road users investigated for substances other than alcohol is about 200/year in Denmark and 4000/year in Norway.

Accidents, Traffic↗

[Fatal intoxications among drug addicts in Denmark in 1997].

INTRODUCTION: The purpose of this study was to investigate fatal poisonings among drug addicts in 1997 and to compare the results to similar investigations from 1985 and 1991. MATERIAL AND METHODS: All fatal intoxications among drug addicts in Denmark in 1997, investigated at the three Institutes of Forensic Medicine in Denmark. RESULTS: The number of fatal intoxications increased by 32% from 1991 to 1997, mainly outside the metropolitan area, The average age increased from 32 to 36 years. The proportion of heroin/morphine intoxications increased from 57% to 71%. The most commonly used drugs were as in 1991 heroin/morphine, diazepam and methadone. The frequency of cocaine increased from one positive case in 1991 to 14% positive cases in 1997. DISCUSSION: This study showed an increasing number of fatal intoxications and changes in drug abuse pattern and place of death since 1991.

Adolescent↗

Scandinavian test of artificial neural network for classification of myocardial perfusion images.

Artificial neural networks are systems of elementary computing units capable of learning from examples. They have been applied to automated interpretation of myocardial perfusion images and have been shown to perform even better than experienced physicians. It has been shown that physicians interpreting myocardial perfusion images benefit from the advice of such networks. These networks have been developed and validated in the same hospital. However, widespread use of neural networks will only take place if the networks can maintain a high accuracy in other hospitals, i.e. hospitals using different gamma cameras, different acquisition techniques, different study protocols, etc. The purpose of this study was to develop a neural network in one hospital and test it in another. An artificial neural network was trained to detect coronary artery disease using myocardial perfusion scintigrams from 135 patients at a Swedish hospital. Thereafter, this network was tested using scintigrams from 68 patients at a Danish hospital and compared to six criteria based on expert physician analysis and quantitative analysis by the CEqual program. The sensitivity of the network was significantly higher than that of one of the physician criteria (0. 92 versus 0.71) and two of the CEqual-based criteria (0.94 versus 0. 63 and 0.96 versus 0.65) compared at equal specificities. It was concluded that an artificial neural network can maintain high accuracy in a hospital other than the one where it was developed.

Coronary Disease↗

[Fatal poisonings during a 5-year period in Eastern Denmark].

In the period 1992-1996, both years included, 1079 cases of deaths from poisoning by drugs or poisons were found by forensic-chemical analyses at The Institute of Forensic Medicine, Dept. of Forensic Chemistry, in Copenhagen, covering a population of 2.4 million. Morphine was by far the most frequently occurring compound accounting for 421 deaths, followed by methadone with 185 deaths. Then alcohol, ketobemidone, and carbon monoxide were represented with 80, 74 and 66 deaths, respectively. Drug addicts dominated in the survey with 549 cases. According to Danish law, autopsy with following chemical analyses must be performed on all dead drug addicts, whereas many other deaths by poisoning are defined only from the medicine found in the vicinity of the dead body.

Adolescent↗

[Drug and narcotic use among Danish drivers].

An investigation was made of the presence of drugs and narcotics in samples from Danish drivers having violated the Danish Road Traffic act in 1993. Four hundred and twenty-five cases were received, but only 317 cases were analysed for drugs or narcotics. In 256 cases drugs or narcotics were found present with a total of 531 findings. In 112 of the cases only one compound was found present. Benzodiazepines, morphine, methadone, cannabinoids and amphetamine were the most frequently occurring compounds with 239, 52, 42, 32 and 28 findings, respectively. The study has shown that especially the benzodiazepines together with the illicit drugs seem to constitute a threat to traffic safety. For two countries very much alike, namely Denmark and Norway this study has shown a remarkable difference in the number of samples analysed and the results found.

Adult↗

False-positive defects in technetium-99m sestamibi myocardial single-photon emission tomography in healthy athletes with left ventricular hypertrophy.

Exercise ECG and myocardial single-photon emission tomography (SPET) are fundamental in the non-invasive evaluation of patients suspected of having coronary artery disease (CAD). The purpose of the present study was to investigate the influence of physiological left ventricular hypertrophy (LVH) on myocardial sestamibi SPET in healthy young and old athletes. Eighteen young male elite athletes (ten rowers, five power/weight lifters and three triathletes) and 14 well-trained elderly rowers were studied. All underwent a bicycle test as part of a 2-day sestamibi SPET protocol. Attenuation correction was not performed. The studies were evaluated visually and quantitatively analysed by the CEqual program with its reference files and with a file from a local non-athletic age-matched population. Echocardiographic LVH was an inclusion criterion in the young athletes. Exercise ECG was normal in all subjects. In at least three of the young athletes a reversible defect was observed by visual analysis. On quantitative analysis one-third of the young athletes had "significant" (>10 pixels) defects compared with both the local reference base and the CEqual reference population. Nearly all defects were found in the anterior or inferior wall. The remaining subjects, including all old rowers, had normal SPET findings. Anterior and inferior wall defects are so common in healthy athletes with physiological LVH that the specificity of myocardial SPET, in contrast to exercise ECG, seems to be too low for evaluation of chest pain in this group. The mechanism of anterior and inferior defects may be related to hot spots (papillary muscles?) in the lateral wall. The specificity of SPET is maintained in athletes without LVH.

Adult↗

Myocardial sestamibi single-photon emission tomography: variations in reference values with gender, age and rest versus stress?

Reference data files support the evaluation of myocardial perfusion single-photon emission tomography (SPET). The aim of this study was to create a large reference data base for technetium-99m sestamibi SPET, age and gender matched to the general patient population. One hundred and twenty-eight healthy volunteers (76 males and 52 females) with a likelihood of coronary artery disease of less than 5% underwent rest and maximal exercise 99mTc-sestamibi SPET with a 2-day protocol and 180 degrees elliptical rotation. The normalized activity values of 99mTc-sestamibi in the inferior wall differed significantly between men and women. Age variations were found for men in the anterior wall. Normalized activity values in all four walls were strikingly similar during rest and stress. Our results suggest that the use of reference files in 99mTc-sestamibi SPET requires a gender- and, for males, possibly an age-matched reference population. Different reference files at rest and during stress might not be necessary.

Adult↗

The occurrence of false-positive technetium-99m sestamibi bull's eye defects in different reference databases. A study of an age- and gender-stratified healthy population.

Myocardial perfusion single-photon emission tomographic (SPET) imaging has been shown to be sensitive in the detection of coronary artery disease (CAD), whereas its specificity has been suboptimal. The aim of the present study was to study the frequency of abnormal bull's eye perfusion defects in a large age-stratified group of healthy subjects undergoing myocardial SPET assessed by comparison with two existing commercially available reference databases. One hundred and twenty-eight healthy volunteers (76 males and 52 females) with a less than 5% likelihood of CAD underwent rest and exercise technetium-99m sestamibi SPET. The false-positive response rate, defined as a significant reversible defect, was 12% when compared to the CEqual database and 29% when compared to the Cedars-Sinai database. With the CEqual program, rest defects occurred in 12% of the subjects. Defects occurred more often in women than in men, but the difference did not attain statistical significance. Significant defects were most frequent in the inferior wall and in women in the anterior wall as well. The distribution of defects was independent of age. Our results suggest that the specificity of 99mTc-sestamibi myocardial SPET using commercially available reference files is suboptimal. The risk of obtaining a false-positive test result in subjects undergoing 99mTc-sestamibi myocardial SPET with a very low likelihood of CAD was higher than anticipated. With both reference files false-positive test results were most frequently observed in the inferior wall. Our data suggest that commercial reference files for myocardial SPET need to be optimised, and should be used with caution. The use of attenuation correction may prove to be a major step forward.

Adult↗

Lymphocyte cAMP and ageing: significance of subset composition, plasma noradrenaline, regular physical training and long-term smoking.

1. We studied 37 healthy men at rest in the supine. position to examine the effect of ageing, smoking and physical training of beta 2-adrenoceptor function, plasma catecholamines and the proportions of various lymphocyte subsets. 2. In 14 young subjects the proportion of natural killer cells was correlated with cAMP production in lymphocytes and inversely correlated with plasma noradrenaline level. 3. In 16 elderly non-smokers plasma noradrenaline was negatively correlated with the natural killer cell subset CD3-CD16+. Lymphocyte cAMP responses did not differ between young and elderly non-smokers, whereas plasma noradrenaline increased slightly but significantly with age. Physical training did not influence either plasma noradrenaline or adrenaline at rest or cAMP in lymphocytes. 4. In seven elderly long-term smokers cAMP production and the viability of lymphocytes were reduced. Plasma noradrenaline attained its highest values in long-term smokers. 5. It is concluded that cAMP production and plasma noradrenaline are related to lymphocyte subset composition. The greater the proportion of natural killer cells and related subsets, the higher is cAMP production and the lower is plasma noradrenaline. Thus, the inverse correlation between lymphocyte cAMP and plasma noradrenaline is indirect and most likely mediated by variability in lymphocyte subset composition. In elderly subjects, reduced cAMP production was observed in long-term smokers, and this abnormality was probably due to a reduced viability of lymphocytes and especially of natural killer cells. The negative correlation between the proportion of natural killer cells and plasma noradrenaline at rest contracts with a well-known mobilizing effect of adrenaline on natural killer cells.

Adult↗

Dobutamine-atropine stress echocardiography in asymptomatic healthy individuals. The relativity of stress-induced hyperkinesia.

BACKGROUND: Interpretation of dobutamine-atropine stress echocardiography (DASE) is based on the assumption that the normal response to dobutamine-atropine infusion is characterized by increased systolic thickening and motion of the left ventricular (LV) walls, whereas a reduction or no change is considered indicative of coronary artery disease. The aim of this study was to quantitatively assess changes in LV dimension and wall motion patterns during DASE in a healthy population. METHODS AND RESULTS: Forty-two asymptomatic voluntary subjects (22 men) with a mean age of 59 years (range, 31 to 79 years) and a likelihood of < 5% for coronary artery disease underwent DASE with digital recording of two-dimensional and M-mode echocardiography at baseline and low-dose and peak infusion rates. Mean end-diastolic and end-systolic LV diameters and areas decreased and wall thicknesses increased progressively throughout the test. Wall motion and thickening increased from baseline to low-dose infusion in nearly all subjects. However, from low-dose to peak infusion, the mean absolute wall motion and relative wall thickening decreased by 13.1% (95% CI, 2.7 to 23.5) and 21.4% (95% CI, 6.4 to 36.4) regardless of age, sex, or use of atropine. Changes in fractional shortening and absolute wall thickening varied considerably, with a decrease observed in 15 and 13 individuals (36% and 31%), respectively. CONCLUSIONS: In healthy subjects, measures of wall motion and wall thickening increased from baseline to low-dose infusion but decreased from low-dose to peak infusion. These findings call for revision of the assumptions on which the common analysis of DASE is based.

Age Factors↗

Food odor thresholds in relation to age, nutritional, and health status.

Odor perception plays an important role in nutrition. In the present study, the effect of aging and health status on detection of food odors is shown and interrelations with nutritional status are explored. We have tested 26 healthy young (20-25 yrs) and 23 elderly (61-74 yrs) subjects who were screened according to the SENIEUR protocol. Anthropometric measures and blood samples provided 20 parameters of nutritional status. A validated measurement procedure under forced choice conditions was used to quantify the detection thresholds of two food odors of which one had a trigeminal effect and the other mainly had an olfactory effect. There is a significant declining sensitivity for both odors. Our observations indicate that a relation between nutrition and odor perception in the elderly population exists. Whether olfactory deficits cause or are caused by increased nutritional risk deserves further study.

Adult↗

[Deaths among drug addicts in Denmark. A forensic medical study of deaths among drug addicts during the period 1991-1992 related to the period 1984-1985].

This study includes all deaths among drug addicts in the years 1991 (n = 219) and 1992 (n = 214) investigated at the three institutes of forensic medicine in Denmark. The results are compared with deaths among drug addicts in 1984-1985. The number of deaths among drug addicts increased by approximately 50% in 1991-1992 compared with 1984-1985. The increase was most significant among drug addicts over 35 years of age. The cause of death was intoxication in three-quarters of the cases in 1991-1992. In half of these cases heroin/morphine had caused death, while intoxications caused by methadone accounted for approximately 30% of the cases. In the metropolitan area the frequency of methadone intoxications increased significantly compared with 1984-1985, whereas the number of heroin/morphine intoxications did not change. Outside the metropolitan area, however, a significant increase in heroin/morphine intoxications was noticed. In all parts of the country the number of propoxyphene intoxications decreased to a few annual cases. The most commonly used drugs of abuse were heroin/morphine, diazepam and methadone, often in combination with alcohol.

Adolescent↗