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Biomedical subjects

M Sørensen

Publications and source records attributed to M Sørensen.

At least 19 recordsLinked to original sources

[What are the associations between occupational physical activity and overweight?].

BACKGROUND: The increasing trend for obesity, together with reduced occupational physical activity in Norway, led us to study the association between work activity and body mass index. MATERIAL AND METHODS: We analysed data from population screenings in Norwegian counties 1974-97. Occupational physical activity was measured by a question with four alternative answers. RESULTS: Among women, sedentary or light physical work was associated with the lowest body mass indices and heavy physical work with the highest. Among men, occupational physical activity was associated with a slightly higher body mass index in general, but not in all counties and not in men who were physically inactive in their leisure time. In the survey in Nord-Trøndelag 1995-97 the body mass index in men was lower in those with physical work than in those with sedentary occupations. INTERPRETATION: The inverse association between physical work and overweight does not indicate an important role of physical work in weight control of women. In men, several explanations are possible. One interpretation is that physical work is of importance for weight control in some rural areas and in men with physical activity in their leisure time.

Adult↗

On the formation of radical dications of protonated amino acids in a "microsolution" of water or acetonitrile and their reactivity towards the solvent.

In high-energy collisions (50 keV) between O2 and protonated amino acids AH+, radical dications AH2+* are formed for A = Phe, His, Met, Tyr, and Trp. When solvated by water or acetonitrile (S), AH2+*(S)1,2 are formed for A = Arg, His, Met, Tyr, and Trp. The stability of the hydrogen-deficient AH2+* in the "microsolution" depends on the energetics of the electron transfer reaction AH2+* +S --> AH++S+*, the hydrogen abstraction reaction AH2+*+S --> AH2(2+)+[S-H]*, and the proton transfer reaction AH2+* + S --> A+*+SH+. Using B3LYP/ 6-311+G(2d,p)//B3LYP/6-31+G(d) model chemistry, we describe these three reactions in detail for A=Tyr and find that the first two reactions are unfavorable whereas the third one is favorable. However, energy is required for the formation of Tyr+* and SH+ from TyrH2+*(S) to overcome the Coulomb barrier, which renders the complex observable with a life-time larger than 5 micros. The ionization energy, IE, of TyrH+ is calculated to be 11.1 eV in agreement with an experimental measurement of 10.1+/-2.1 eV ([IE(CH3CN)+IE(Tyr)]/ 2); hydration further lowers the IE by 0.3 eV [IE(TyrH+(H2O) = 10.8 eV, calculated]. We estimate the ionization energies of TrpH+, HisH+, and MetH+ to be 10.1+/-2.1 eV, 12.4+/-0.2 eV, and 12.4+/-0.2 eV, and that of PheH+ to be larger than 12.6 eV.

Acetonitriles↗

Effects of a Brussels sprouts extract on oxidative DNA damage and metabolising enzymes in rat liver.

The apparent anticarcinogenic effect of cruciferous vegetables found in numerous epidemiological and experimental studies has been associated with their influence on phase I and phase II metabolising enzymes as well as on the antioxidant status. In the present study we investigated the effect of administration of a Brussels sprouts extract on the expression at the mRNA level and/or catalytic activity in rat liver of three phase I enzymes [cytochrome P450-1A2 (CYP1A2),-2B1/2 (CYP2B1/2) and-2E1 (CYP2E1)] and two phase II enzyme [NADPH:quinone reductase (QR) and glutathione S-transferase pi 7 (GSTpi)], all previously suggested to be induced by vegetables. We also examined the activity and/or expression of several important antioxidant enzymes: glutathione peroxidase (GPx), catalase and gamma-glutamyl-cysteine synthetase (GCS) and the activity of the repair enzyme 8-oxoguanine DNA glycosylase (OGG1). QR, GPx and catalase activity was also assessed in the kidneys. In order to examine a possible effect of the Brussels sprouts related to oxidative stress, we measured oxidative DNA damage in terms of 7-hydro-8-oxo-2'-deoxyguanosine (8-oxodG) and lipid peroxidation in terms of malondialdehyde (MDA) formation in the liver. Oral administration of an aqueous Brussels sprouts extract for 4 days was found to induce the expression of GST 1.3-fold (P < 0.05) and the activity of QR 2.6-fold in rat liver (P < 0.05). No significant differences were seen in the expression of the phase I enzymes. No differences in antioxidant enzyme activity/expression or OGG1 activity were observed. In a second experiment, administration of the Brussels sprouts extract for 3 or 7 days was found to increase the level of 8-oxodG in rat liver from 0.75 to 0.97 per 10(5) dG and from 0.81 to 0.97 per 10(5) dG, respectively (P < 0.05). No effects on MDA levels were found. The present results support the data obtained in several studies that consumption of cruciferous vegetables is capable of inducing various phase II enzyme systems. However, the observed increase in oxidative DNA damage raises the question of whether greatly increased ingestion of cruciferous vegetables is beneficial.

Animals↗

Electron loss from multiply protonated lysozyme ions in high energy collisions with molecular oxygen.

We report on the electron loss from multiply protonated lysozyme ions Lys-Hn(n)+ (n = 7 - 17) and the concomitant formation of Lys-Hn(n+1)+. in high-energy collisions with molecular oxygen (laboratory kinetic energy = 50 x n keV). The cross section for electron loss increases with the charge state of the precursor from n = 7 to n = 11 and then remains constant when n increases further. The absolute size of the cross section ranges from 100 to 200 A2. The electron loss is modeled as an electron transfer process between lysozyme cations and molecular oxygen.

Algorithms↗

Pharmacoeconomic evaluation of calcipotriol (Daivonex/Dovonex) and UVB phototherapy in the treatment of psoriasis: a Markov model for The Netherlands.

BACKGROUND: The high prevalence and chronic nature of psoriasis leads to high costs in relation to the treatment and control of the disease. A number of clinical trials have shown that a combination therapy of calcipotriol cream (Daivonex/Dovonex), Leo Pharmaceutical Products) and ultraviolet B phototherapy (UVB) decreases the total number of UVB exposures required compared to UVB treatment alone. From a societal point of view, the addition of calcipotriol to UVB therapy could achieve cost savings due to the fewer UVB treatments needed and the reduced travelling and time off work for patients. Fewer UVB exposures may also have other beneficial effects, i.e., shortened waiting lists and less risk to patients of developing cancer or photoaging of the skin. OBJECTIVE: To compare the cost-effectiveness of treating psoriatic patients in the Netherlands with calcipotriol cream used daily combined with twice weekly UVB treatments to emollient used daily combined with UVB given 3 times weekly. METHODS: Based on the clinical results from a Canadian trial, a decision-analytical model was constructed to simulate treatment outcomes and estimate the costs of managing psoriatic patients in the Netherlands over a period of 20 weeks from initiation of therapy. Unit costs and details of standard treatment protocols were collected from Dutch dermatology centres in hospitals and the community for use in the model. Other therapies, such as topical corticosteroids, tar or dithranol were not investigated in this analysis. RESULTS: The total cost of managing psoriatic patients in the Netherlands over a 20-week period is estimated as EUR 1,175.90 for those treated with calcipotriol and UVB and EUR 1,212.14 for patients treated with emollient and UVB. Thus, the former treatment, adding calcipotriol to UVB phototherapy, provides a minor cost saving of EUR 36.24 (3%) compared to the cost of UVB treatment alone. Sensitivity analyses demonstrated that these results are sensitive to changes in the cost of UVB treatment. CONCLUSION: Calcipotriol treatment combined with UVB phototherapy is a cost-neutral alternative to UVB phototherapy used with an emollient. The patients achieve treatment success in the same time on both treatments but the former, with calcipotriol, requires less exposure to UVB radiation. The additional drug costs from using calcipotriol are offset by savings from the fewer UVB sessions required. Essential beneficial effects for patients are less inconvenience, less risk of developing photoaging of the skin and less exposure to potentially carcinogenic radiations.

Calcitriol↗

[Fatal outcome of Strongyloides stercoralis infection in a patient with no previously known immunosuppression].

A case of fatal infection with Strongyloides stercoralis in a previously healthy young African with no known immunosuppression is reported. The patient suffered severe gastrointestinal bleeding and despite intensive treatment died of multiorgan failure. Postmortem, signs of ulcerating T-cell lymphoma were found in a jejunal specimen, and the patient was found to be infected with HTLV-1. Gastrointestinal bleeding in relation to infection with Strongyloides stercoralis is discussed as well as possible relations between the severity of infection, lymphoma and HTLV-1.

Adult↗

Pudendal nerve function in idiopathic fecal incontinence.

PURPOSE: The study was undertaken to determine whether idiopathic fecal incontinence in middle-aged and elderly females is likely to be a result of pudendal nerve damage (neurogenic incontinence) or merely a consequence of aging. METHODS: One hundred seventy-eight females over the age of 50 years with fecal incontinence were studied. The incontinence was classified as idiopathic because none of the patients related the incontinence to trauma (including obstetric trauma) or other events or diseases. All had an anal physiology examination, including determination of nerve conduction velocity of both pudendal nerves (pudendal nerve terminal motor latency). RESULTS: With a cutoff value of 2.4 msec, 79 percent (95 percent confidence limit, 73-85) had normal pudendal nerve terminal motor latency on both sides, 13 bilaterally prolonged latency (7 percent; 4-11), and 25 unilaterally prolonged latency (14 percent; 9-19). With a cutoff value of 2.2 msec, 66 percent (59-73) had normal latency on both sides, 15 percent (9-20) bilaterally prolonged pudendal nerve terminal motor latency, and 20 percent (14-26) unilateral prolongation. No relationship between the groups with normal, bilateral, or unilateral prolongation of pudendal nerve terminal motor latency and anal resting and squeeze pressure was found. Anal resting pressure decreased with increasing age (P < 0.05). CONCLUSION: Our data support the view that idiopathic fecal incontinence in the majority of females is likely to be a result of the aging process and that only a limited number may suffer from anal incontinence of neurogenic origin. Furthermore, unilateral prolongation of pudendal nerve terminal motor latency probably is without clinical significance.

Age Factors↗

No significant paraquat-induced oxidative DNA damage in rats.

The metabolism of paraquat generates oxygen radicals. Paraquat has thus been suggested as a model compound to induce oxidative damage to DNA, lipids and proteins in different cells and tissues, although experimental data are inconsistent. In order to explore the possibilities for an animal model of oxidative DNA damage in vivo, rats were treated with 20 mg/kg paraquat or vehicle i.p. One and five days later we measured DNA oxidation in terms of 7-hydro-8-oxo-2'-deoxyguanosine (8-oxodG) in the liver and lung as well as the urinary excretion of 8-oxodG. No significant effects on the level of 8-oxodG in the liver, the lung or the urinary excretion, could be distinguished following paraquat treatment. We found, however, a significant correlation (r = 0.69; p<0.0002) between the 8-oxodG level in the lung and the urinary excretion, but no significant correlation between the level in the liver and the urinary excretion or between the levels in the liver and the lung. During the experiment the rats were clearly affected by the paraquat as they were very lethargic compared to the controls. Accordingly, even at toxic doses, paraquat did not cause detectable oxidative damage to DNA. The data do not support the use of paraquat as a model compound in experiments investigating effects or prevention of oxidative damage to DNA.

8-Hydroxy-2'-Deoxyguanosine↗

Antioxidants, DNA damage and gene expression.

Reactive oxygen species (ROS) are generated from incomplete reduction in the respiratory chain. On one hand they pose a serious threat of deleterious effects on important macromolecules, among which DNA is considered most important since it carries the genetic information and changes will be carried on to future generations, or will fundamentally change the behaviour of the cells. On the other hand, it is becoming evident that there are important changes in the cells in response to redox changes. This review summarises the genes, the intracellular signalling elements and molecules that presently are known to be regulated by oxidative stress. It is now clear that both oxidants and antioxidants can regulate a multitude of different cellular functions, signal transduction pathways and gene expression. However, the quantitative importance is unknown and as of yet there are no examples of regulation exclusively by oxidative stress. Also the response to oxidative stress is variable, can be up-regulation as well as down-regulation, and different responses to dose or magnitude of the oxidative stress can be demonstrated. The effect from supplementation with an antioxidant is difficult to predict, and ultimately must be assessed in clinical trials.

Animals↗

[Individual registration of children in the national health service. New possibilities for epidemiological research in primary health care].

Since January 1st 1996 all Danish citizens, children included, have been recorded individually in The National Health Service Register (SSR). Services rendered to children are no longer registered with an adult person. This article describes the implementation of this new arrangement. The part of health services to children recorded under an adult personal identification number is getting asymptotically closer to a minimum of about four percent, which is determined by the average time of naming of children. After the introduction of individual registration of children the SSR has improved considerably as a basis for epidemiological studies in Danish primary care.

Adult↗

The effect of exercise and diet on mental health and quality of life in middle-aged individuals with elevated risk factors for cardiovascular disease.

Mental health and quality of life were assessed before and after a one-year exercise and diet intervention among 219 healthy individuals, aged 41-50 years, with elevated risk factors for cardiovascular disease. The participants were randomized to four groups: diet (n = 55), diet and exercise (n = 67), exercise (n = 54) and no active intervention (n = 43). Quality of life was measured with one eight-item scale and two one-item scales. Mental health was measured by the General Health Questionnaire (30-item version). Depression, anxiety, feelings of competence and self-esteem, coping and social dysfunction were measured using subscales of the General Health Questionnaire. Somatic anxiety was measured by the anxiety subscale of the Symptom Check List-90. Exercise improved the total GHQ scores, perceived competence/self-esteem, and coping as measured by the GHQ subscales. There were no significant effects of diet or exercise on quality of life, depression or anxiety. A high rate of participation in the exercise programme (>70%) was associated with greater improvements in total GHQ scores, anxiety, perceived competence/self-esteem and coping.

Adult↗

Inhibitors of topoisomerase II as pH-dependent modulators of etoposide-mediated cytotoxicity.

Chloroquine intercalates into DNA and protects cells against topoisomerase II (topo II) poisons such as etoposide by hindering the DNA cleavage reaction of this target enzyme. Chloroquine, in contrast to etoposide, is a weak base and therefore barely enters the cell when the extracellular fluid is acidic, as is the case in most solid tumors. Such a pH-dependent drug interaction could be useful in targeting the cytotoxicity of topo II poisons toward solid tumors. Unfortunately, antagonistic chloroquine concentrations cannot be reached in vivo because of its unacceptable toxicity. Thus, antagonists with a higher therapeutic index are needed. We report here on the structure-activity relationship of several chloroquine and acridine analogues in a clonogenic assay. There were major differences in the cytotoxicity of the different compounds, with acridines being 50-fold more toxic than the chloroquine analogues. Several compounds were, however, able to antagonize etoposide-mediated cytotoxicity in a pH-dependent manner as chloroquine. Dependency on pH was lost if the aminoalkyl side arm of chloroquine was removed or lengthened by one CH2 whereas pH dependency was strong with hydroxychloroquine. In contrast, the aminoalkyl side arm was clearly dispensable in the acridines because both quinacrine and 9-aminoacridine demonstrated profound pH dependency. The results from clonogenic assay were compared with cellular transport measurements and topo II enzyme inhibition. Compounds with the most marked pH-dependent intracellular accumulation were also the best pH-dependent protectors of etoposide cytotoxicity, clearly supporting the hypothesis that extracellular pH can be used to regulate topo II poisoning.

Antineoplastic Agents, Phytogenic↗

[Anal and urinary incontinence after obstetric anal sphincter rupture].

The aim of the study was to assess the long term impact of obstetric anal sphincter rupture on the frequency of anal and urinary incontinence, and identify factors to predict patients at risk. In 94 consecutive women who had sustained an obstetric anal sphincter rupture, anal manometry, anal sphincter electromyography and pudendal nerve terminal motor latency at three months post partum was performed. A questionnaire regarding incontinence was sent between two to four years post partum. Forty-two percent of responders had anal incontinence, 32% had urinary and anal incontinence. Overall, 56% of the women had incontinence symptoms. The occurrence of anal incontinence was associated with pudendal nerve terminal motor latencies > 2.0 milliseconds and the occurrence of urinary incontinence was associated with the degree of rupture, the use of vacuum extraction and previous presence of urinary incontinence. Thirty-eight percent of the women with incontinence wanted treatment, but only a few had sought medical advice.

Adult↗

Experimental study of oxidative DNA damage.

Animal experiments allow the study of oxidative DNA damage in target organs and the elucidation of dose-response relationships of carcinogenic and other harmful chemicals and conditions as well as the study of interactions of several factors. So far the effects of more than 50 different chemical compounds have been studied in animal experiments mainly in rats and mice, and generally with measurement of 8-oxodG with HPLC-EC. A large number of well-known carcinogens induce 8-oxodG formation in liver and/or kidneys. Moreover several animal studies have shown a close relationship between induction of dative DNA damage and tumour formation. In principle the level of oxidative DNA damage in an organ or cell may be studied by measurement of modified bases in extracted DNA by immunohistochemical visualisation, and from assays of strand breakage before and after treatment with repair enzymes. However, this level is a balance between the rates of damage and repair. Until the repair rates and capacity can be adequately assessed the rate of damage can only be estimated from the urinary excretion of repair products albeit only as an average of the entire body. A number of model compounds have been used to induce oxidative DNA damage in experimental animals. The hepatocarcinogen 2-nitropropane induces up to 10-fold increases in 8-oxodG levels in rat liver DNA. The level of 8-oxodG is also increased in kidneys and bone marrow but not in the testis. By means of 2-nitropropane we have shown correspondence between the increases in 8-oxodG in target organs and the urinary excretion of 8-oxodG and between 8-oxodG formation and the comet assay in bone marrow as well potent preventive effects of extracts of Brussels sprouts. Others have shown similar effects of green tea extracts and its components. Drawbacks of the use of 2-nitropropane as a model for oxidative DNA damage relate particularly to formation of 8-aminoguanine derivatives that may interfere with HPLC-EC assays and have unknown consequences. Other model compounds for induction of oxidative DNA damage, such as ferric nitriloacetate, iron dextran, potassium bromate and paraquat, are less potent and/or more organ specific. Inflammation and activation of an inflammatory response by phorbol esters or E. coli lipopolysaccharide (LPS) induce oxidative DNA damage in many target cells and enhance benzene-induced DNA damage in mouse bone marrow. Experimental studies provide powerful tools to investigate agents inducing and preventing oxidative damage to DNA and its role in carcinogenesis. So far, most animal experiments have concerned 8-oxodG and determination of additional damaged bases should be employed. An ideal animal model for prevention of oxidative DNA damage has yet to he developed.

Animals↗

Viscous fluid expulsion in the evaluation of the constipated patient.

PURPOSE: The aim of this study was to evaluate a viscous fluid expulsion test as a method for quantifying rectal outlet obstruction. METHODS: We examined the ability of 30 severely constipated patients and 40 healthy control subjects to expel a viscous fluid simulating feces. RESULTS: Constipated patients with defecographic rectal retention expelled a significant lower viscous fluid volume compared with controls (P < 0.0001). Considering the viscous fluid expulsion test to be positive if the patient expelled less than 160 ml of fluid (lower 95 percent confidence value in healthy controls) and using the presence of defecographic rectal outlet obstruction as a reference, the predictive value of a negative viscous fluid expulsion test was 100 percent, the predictive value of a positive test was 67 percent, and sensitivity and specificity was 100 percent and 82 percent, respectively. The viscous fluid test identified symptomatic outlet obstruction in almost twice as many patients as did defecography. Some patients, however are-despite their obstructive symptoms-able to evacuate their rectum when examined in the laboratory. CONCLUSION: The viscous fluid expulsion test is a simple, reproducible, nonionizing, and low-cost method of quantifying rectal outlet obstruction. A positive test result should lead to a defecography, whereas a negative test result renders defecography dispensable and spares the patient from pelvic radiation.

Adolescent↗

Pudendal nerve function during pregnancy and after delivery.

The aim of the study was to assess pudendal nerve function serially during pregnancy and after delivery. Twenty-eight women participated at 14, 30 and 36 weeks of pregnancy and 12 weeks postpartum. A prospective study of pudendal nerve terminal motor latency during pregnancy and after delivery was carried out. Results showed that pudendal nerve terminal motor latency did not increase significantly during pregnancy but increased significantly after delivery.

Adult↗