Martin Døssing - Academia.edu (original) (raw)

Papers by Martin Døssing

Clinical Pharmacology and Therapeutics, 1984

Physical fitness, as expressed by maximal oxygen uptake (1.702max), was measured in 14 subjects b... more Physical fitness, as expressed by maximal oxygen uptake (1.702max), was measured in 14 subjects before and during physical education consisting of 4 to 8 hr of daily physical training. Mean pulse rate during training was 115 bpm. After 3 mo of physical training, f/02 max increased a mean 6% (range 5% to +23%). Corresponding mean increases in hepatic drug metabolism, as expressed by the metabolism of the model drugs antipyrine and aminopyrine, were 12% (range 12% to +59%) and 13% (range 21% to +47%). Changes in the two groups were still present 6 mo after physical education. There was only a moderately close but nonetheless significant correlation (r = 0.7) between the extent of change inf702max and the corresponding relative change in antipyrine metabolism during the 3-mo period of this investigation. The correlation between oxygen uptake and aminopyrine metabolism (r = 0.6) was slightly less and was not significant. Improved physical fitness associated with enhanced drug metabolism may lead to changes in drug efficacy and drug toxicity that may be clinically important in the case of drugs with low therapeutic indices.

Clinical Pharmacology and Therapeutics, 1981

Human & Experimental Toxicology, 1994

1. We measured the antipyrine clearance in 18 healthy Saudi subjects and determined the urinary e... more 1. We measured the antipyrine clearance in 18 healthy Saudi subjects and determined the urinary excretion of three of its metabolites: 4-hydroxyantipyrine (4-OH AP), norantipyrine (NOR AP) and 3 hydroxymethylantipyrine (3-OHM AP) in 21 subjects. 2. The mean +/- SD of the antipyrine clearance was 2.4 +/- 1.1 h-1 (range 1.0-5.5 l h-1) and the corresponding value per kg body weight was 0.6 +/- 0.2 ml min-1 kg-1. Urinary excretion of antipyrine (AP), 4-OH AP, NOR AP and 3-OHM AP expressed as a percentage of the oral dose of antipyrine given was 2.8 +/- 2.2, 14.5 +/- 6.9, 12.3 +/- 5.6 and 7.6 +/- 3.2 respectively. 3. Compared to Africans, Saudis preferentially metabolize AP to NOR AP and compared to Caucasians to 3-OHM AP, rather than to 4-OH AP. These discrepancies may reflect age differences between the study populations rather than genetic or ethnic variations.

European Journal of Epidemiology, 1995

Lipid pneumonia has been observed in infants exposed by inhalation of oil or butter applied into ... more Lipid pneumonia has been observed in infants exposed by inhalation of oil or butter applied into the nose or throat as part of an old custom. We performed a case-control study to test the hypothesis, that this ancient tradition may be a predisposing factor to bronchiectasis. A case group of 59 patients with bronchiectasis and three control groups -46 patients with COPD, 32 asthmatics, and 71 healthy Saudis -were questioned about possible risk factors of bronchiectasis including nasal or oral application of oil/butter at infancy. The risk of witnessed exposure to this old folk remedy was significantly higher among the cases than the controls (OR = 3.9 (1.7-8.8), (95% confidence interval) p < 0.001). Application of oil or butter into the nasal or oral cavity of infants may be a risk factor for bronchiectasis.

Clinical Pharmacokinetics, 1985

Recent research indicates that physical exercise and fitness are new host factors with impact on ... more Recent research indicates that physical exercise and fitness are new host factors with impact on hepatic drug metabolism, contributing to the intra- and interindividual variation in drug response. Moderate to heavy physical exercise for a few hours reduces liver blood flow as assessed by indocyanine green clearance, leading to a decreased elimination of drugs exhibiting flow-limited metabolism (high clearance drugs) such as lignocaine (lidocaine). However, hepatic elimination of drugs exhibiting capacity-limited metabolism (low clearance drugs) such as antipyrine (phenazone), diazepam and amylobarbitone (amobarbital) is not affected by acute physical exercise. Improved physical fitness as expressed by the maximum oxygen uptake seems to increase the elimination rate of the low clearance drug antipyrine and possibly also aminopyrine, while investigations of the biotransformation of high clearance drugs are contradictory. The sum of research in this recent field is rather limited and the mechanism whereby changes in physical fitness influence hepatic drug metabolism needs to be established. It is not known if other liver functions are changed. If the findings also apply for drugs with a low therapeutic index, there may be a risk of exercise-induced changes in drug efficacy and toxicity. It is suggested that future studies on host factors influencing drug metabolism should include information on physical activity.

American Journal of Industrial Medicine, 1994

Asbestos has been used extensively in a variety of occupations. In the jewelry industry, inadequa... more Asbestos has been used extensively in a variety of occupations. In the jewelry industry, inadequate hygiene practices may often go unrecognized with resultant exposure to hazardous amounts of asbestos. We report on four retired jewelers. Two of these had both pleural and parenchymal changes. One had isolated pleural plaques and the final patient showed only parenchymal infiltrates. Their work involved hand cutting asbestos plates used for protection during soldering. In the soldering process asbestos fibers were then blown into the workroom air as the plates broke down. In addition, at the end of each work day the workroom floor was swept, with subsequent airborne asbestos dust distribution. Any patient with pleural plaques or interstitial lung disease should be questioned about potential sources of asbestos exposure in the past, regardless of present employment status.

European Journal of Clinical Pharmacology, 1988

Six healthy volunteers received oxazepam 15 mg i.v. and orally at an interval of at least one wee... more Six healthy volunteers received oxazepam 15 mg i.v. and orally at an interval of at least one week. The kinetic variables of i.v. oxazepam were: elimination half-life (t1/2ß) 6.7 h, total clearance (CL) 1.07 ml·min-1·kg-1, volume of distribution (Vc) 0.27 l·kg-1 (0.21–0.49) and volume of distribution at steady-state (Vss) 0.59 l·kg-1. The intravenous disposition of unbound oxazepam was characterized by

Clinical pharmacology and therapeutics, 1981

Nine patients with compensated alcoholic and nonalcoholic cirrhosis of the liver and 11 patients ... more Nine patients with compensated alcoholic and nonalcoholic cirrhosis of the liver and 11 patients with peptic ulcer received 200 mg of cimetidine orally and intravenously. No differences were observed in cimetidine clearance between the group with peptic ulcer (556 +/- 44 ml/min, mean +/- SEM) and the group with cirrhosis (606 +/- 64 ml/min). The bioavailability of cimetidine was unchanged (84 +/- 4% and 97 +/- 7%). In the patients with cirrhosis, cimetidine clearance did not correlate with galactose elimination capacity or antipyrine clearance. Cimetidine clearance was related to creatinine clearance only when both groups were considered. A reduction of cimetidine dose in patients with compensated cirrhosis appears unwarranted.

Clinical pharmacology and therapeutics, 1982

Antipyrine clearance (Cl(AP)) is widely used for assessment of microsomal liver function. The usu... more Antipyrine clearance (Cl(AP)) is widely used for assessment of microsomal liver function. The usual procedure involves collection of 4 to 7 samples of plasma or saliva obtained during 24 to 48 hr. To determine whether this procedure could be simplified it was compared with one based on a single sample (sCl(AP)) and an estimated volume of distribution (V(D)) in 142 persons. VD was estimated from body weight, in kilograms (BW), height, in centimeters (BH), age in years, and sex, or assumed to be 40 l. The agreement between values of Cl(AP and sCl(AP) increased with the time of the single sample and the two clearance estimates were nearly identical in all cases when the sample was taken after 18 hr. The method used for assessment of V(D) had only a small influence on the agreement. It is suggested that antipyrine clearance (in ml/min) is estimated as (formula: see text) where D is the dose of antipyrine (in mg), c(t) the concentration of antipyrine (in mg/t) at sampling time t (in min)...

Preventive Medicine, 2014

Objective: To provide a systematic review of the existing literature on health consequences of va... more Objective: To provide a systematic review of the existing literature on health consequences of vaporing of electronic cigarettes (ECs).

Acta Medica Scandinavica, 1978

A 21-year old man died of an extensive anteroseptal myocardial infarction 16 months after receivi... more A 21-year old man died of an extensive anteroseptal myocardial infarction 16 months after receiving megavoltage radiotherapy to a mantle field for Hodgkin's disease stage PS IA confined to the midcervical lymph nodes on the left side of the neck. Post mortem findings revealed severe atherosclerotic changes in the coronary arteries. This case and a review of the literature suggest that irradiation to the heart may induce or accelerate atherosclerosis of the epicardial vessels. This should be taken into consideration when starting prophylactic irradiation to the mantle field in patients with Hodgkin's disease stage IA without obvious involvement of the mediastinun. Histologic examination of the heart and coronary vessels should be performed in any fatal case after megavoltage therapy involving the heart.

Thorax, 2014

We present the final results of the effect of lung cancer screening with low-dose CT on the smoki... more We present the final results of the effect of lung cancer screening with low-dose CT on the smoking habits of participants in a 5-year screening trial. The Danish Lung Cancer Screening Trial (DLCST) was a 5-year screening trial that enrolled 4104 subjects; 2052 were randomised to annual low-dose CT (CT group) and 2052 received no intervention (control group). Participants were current and ex-smokers (≥4 weeks abstinence from smoking) with a tobacco consumption of ≥20 pack years. Smoking habits were determined annually. Missing values for smoking status at the final screening round were handled using two different models. There were no statistically significant differences in annual smoking status between the CT group and control group. Overall the ex-smoker rates (CT + control group) significantly increased from 24% (baseline) to 37% at year 5 of screening (p&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.001). The annual point prevalence quit rate increased from 11% to 24% during the five screening rounds; the ex-smokers&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; relapse rate remained stable, around 11%, across the same period. Screening with low-dose CT had no extra effect on smoking status compared with the control group, but overall the screening programme probably promoted smoking cessation. The DLCST is registered in Clinical Trials.gov Protocol Registration System (identification no. NCT00496977).

Thorax, 2009

The effect of low-dose CT screening for lung cancer on smoking habits has not been reported in la... more The effect of low-dose CT screening for lung cancer on smoking habits has not been reported in large randomised controlled trials. This study evaluated the effect on smoking habits of screening with low-dose CT at 1-year follow up in the Danish Lung Cancer Screening Trial (DLCST), a 5-year randomised controlled trial comprising 4104 subjects; 2052 subjects received annual low-dose CT scan (CT group) and 2052 received no intervention (control group). Participants were healthy current and former smokers (>4 weeks since smoking cessation) with a tobacco consumption of >20 pack years. Smoking habits were determined at baseline and at annual screening. Smoking status was verified using exhaled carbon monoxide levels. Lung function tests, nicotine dependency and motivation to quit smoking were assessed. Quit rates and relapse rates were determined at 1-year follow-up for all subjects. At 1 year the quit rates among smokers were 11.9% in the CT group and 11.8% in the control group (p = 0.95). Relapse rates for former smokers were 10.0% and 10.5% in the CT and control groups, respectively (p = 0.81). Significant predictors (p<0.05) for smoking cessation were: high motivation to quit, low dependency, low ratio of forced expiratory volume in 1 s to forced vital capacity, low pack years, higher age, longer period of abstinence and CT findings necessitating 3-month repeat CT scans. Overall, quit rates were similar in the CT and control group at 1-year follow-up, with a net quit rate of 6.0%. Quit rates were higher and relapse rate lower among subjects with initial CT findings that necessitated a repeat scan 3 months later.

Scandinavian Journal of Gastroenterology, 1987

Sex-related differences were prospectively studied in patients with the first presentation of alc... more Sex-related differences were prospectively studied in patients with the first presentation of alcoholic liver disease. Among 42 patients the diagnosis was cirrhosis in 8 women and 15 men, alcoholic hepatitis in 4 women and 1 man, steatosis in 6 women and 6 men, and no histologic changes were found in the liver biopsy specimens from 2 men (p greater than 0.1). The median (range) antipyrine clearance was 14.6 (1.0-64) versus 17.2 (3.0-83) ml/min and the clinical score in accordance with the Pugh modification of the Child-Turcotte classification was 8 (5-13) versus 8 (5-11) in the women and men, respectively (p greater than 0.05). In 5 women and only 1 man the antipyrine clearance was less than 5 ml/min, indicating an almost total loss of functional liver mass (p less than 0.05), whereas the Pugh score was above 11 in 6 women, but not in any of the men (p less than 0.05). On an average, the men estimated their total lifetime consumption of alcohol to be 2.1 times greater and the number of days they had consumed more than 5 drinks 2.9 times higher than the women (p less than 0.05). These ratios are reduced to 1.4 and 1.7, respectively (p greater than 0.05), if the female alcohol intake is adjusted to the average male volume of distribution. The results support the concept that women may develop similar, and sometimes even more severe, liver disease after consumption of less alcohol than men. The apparent difference in susceptibility to alcohol may be partly explained by differences in volume of distribution.

Respiratory Medicine, 1994

Based on the clinical impression of a relatively high number of non smoking women with COPD at a ... more Based on the clinical impression of a relatively high number of non smoking women with COPD at a tertiary care facility in Saudi Arabia, we performed a case-control study to reveal possible risk factors. Our hypothesis was that the extensive use of incense burners among Saudis was a risk factor of COPD. Fifty consecutive patients with COPD and 71 healthy controls were questioned about risk factors of COPD. As expected more COPD-men than control men were smokers. Very few women smoked. We found no difference in the use of incense burners between cases and controls. On the other hand, two-thirds of the COPD-women and only 1/20 of the control women had been exposed to indoor open fire for more than 20 yr (P<0.05). Accordingly, indoor exposure to open fire of wood or biomass seems to be a risk factor of COPD among Saudi women.

Occupational and Environmental Medicine, 1983

Exposure to toluene vapour enhances hepatic microsomal enzyme function in animals as assessed by ... more Exposure to toluene vapour enhances hepatic microsomal enzyme function in animals as assessed by the metabolism of the test drug antipyrine. Thirty six printing trade workers with long term occupational exposure to a mixture of organic solvents and 39 matched controls were randomly allocated into four groups. Eighteen printers and 21 controls were exposed to 100 ppm of toluene during 6-5 hours in an exposure chamber. The remaining 18 printers and 18 controls were exposed to 0 ppm of toluene under similar conditions. The salivary clearance of antipyrine was measured immediately after the stay in the exposure chamber to investigate a possible acute change in liver function and was repeated two weeks later, shortly before the summer vacation. Antipyrine clearaDce was measured again at the end of the summer vacation-four weeks after exposure. To study a possible effect of chronic exposure on antipyrine clearance 12 printing trade workers with 17 years (median) of occupational exposure to toluene vapour at concentrations of about 100 ppm were investigated before and four weeks after cessation of exposure. No difference in antipyrine clearance was found either within the groups or between the groups at any of the measurements.

Journal of Thoracic Oncology, 2007

Close Window. Close Window. Thank you for choosing to subscribe to the eTOC for Journal of Thorac... more Close Window. Close Window. Thank you for choosing to subscribe to the eTOC for Journal of Thoracic Oncology. Enter your Email address: Wolters Kluwer Health may email you for journal alerts and information, but is committed ...

Journal of Occupational and Environmental Medicine, 1981

The cheletable part of lead body burden was measured in 32 workers and seven office workers after... more The cheletable part of lead body burden was measured in 32 workers and seven office workers after an infusion test with CaNa2EDTA. The workers had been exposed to lead at a lead and zinc processing unit for one to three years (mean one year). There was good correlation (r = 0.87) between blood lead and chelatable urinary lead excretion described by the equation y = 0.07 . 10(0.46.x). From this equation it can be predicted that the generally accepted limit value for chelatable urinary lead excretion, 0.42 mumol/mmol CaNa2EDTA administered per 24 hours (3.1 mumol/24 hours or 650 micrograms/24 hours), corresponds to a blood lead concentration (PbB) of 1.7 mumol/l (or 35 micrograms/100 ml), which is lower than the commonly accepted limit value of 2.9 mumol/l (or 60 micrograms/100 ml) for occupationally lead-exposed persons. There was a better correlation between the cheletable lead excretion and the urinary ALA-excretion (r = 0.45; p less than 0.001) than between PbB and the urinary ALA-excretion (r = 0.26; p greater than 0.05).

Journal of Hepatology, 1995

Our aim was to study whether chronic hepatitis C affects the three metabolic pathways of the mode... more Our aim was to study whether chronic hepatitis C affects the three metabolic pathways of the model drug antipyrine differently. We measured antipyrine clearance from saliva as well as urinary excretion of its main metabolites 4-hydroxy-antipyrine, 3-hydroxy-methyl-antipyrine, and nor-antipyrine in 24 patients with chronic hepatitis C and in 21 healthy control subjects. Due to incomplete urine collection, 12 liver patients and three controls were excluded. Antipyrine clearance (mean +/- SD) was significantly lower in patients with chronic hepatitis C, 1.2 +/- 0.7 l.h-1 (n = 12), than in controls (n = 18), 2.2 +/- 1.0 l.h-1 (p = 0.006). The urinary excretion of each of the metabolites was depressed to an equal extent in liver patients. The severity of the liver disease, as assessed by Child Pugh score, serum albumin and bilirubin, correlated significantly with antipyrine clearance and urinary excretion of the metabolite 3-hydroxy-methyl-antipyrine. The hepatitis activity index (Knodell) correlated with 3-hydroxy-methyl-antipyrine and 4-hydroxy-antipyrine, only. Moderate-severe chronic hepatitis C does not seem to depress the three main metabolic pathways of antipyrine differently.

Journal of Antimicrobial Chemotherapy, 1984

The pharmacokinetics and metabolism of intravenous metronidazole were studied in six patients wit... more The pharmacokinetics and metabolism of intravenous metronidazole were studied in six patients with acute renal failure. In two of the patients a single dose (500 mg) of metronidazole was administered, whereas in four patients the steady-state pharmacokinetics were studied after four days therapy of 500 mg twice daily. Plasma concentrations of metronidazole and its hydroxy and acetic acid metabolites were measured by a specific and sensitive HPLC method. The volume of distribution was 0-65 ±0-13 I/kg (mean ±S.D.), elimination half-life was 9-9 ±2-5 h and total plasma clearance was 55-5 ± 17-7 ml/min. Renal clearance was almost non-existent (1-4± 1-4 ml/min), whereas non-renal clearance was 54-0 ± 18-2 ml/min. Steady-state plasma concentrations of metronidazole were 15-3 ±3-8 mg/1, the hydroxy metabolite were 17-4 ±2-0 mg/1 and the acetic acid metabolite were 1-2 ±0-8 mg/1. In the patients studied, a dosing regimen of 500 mg twice daily resulted in therapeutically adequate blood levels of metronidazole.