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Biomedical subjects

K Ström

Publications and source records attributed to K Ström.

At least 19 recordsLinked to original sources
PubMed2006

The hormone-sensitive lipase C-60G promoter polymorphism is associated with increased waist circumference in normal-weight subjects.

OBJECTIVE: Hormone-sensitive lipase (HSL) is a key enzyme in the mobilization of fatty acids from triglyceride stores in adipocytes. The aim of the present study was to investigate the role of the HSL gene promoter variant C-60G, a polymorphism which previously has been associated with reduced promoter activity in vitro, in obesity and type 2 diabetes. DESIGN: We genotyped two materials consisting of obese subjects and non-obese controls, one material with offspring-parents trios, where the offspring was abdominally obese and one material with trios, where the offspring had type 2 diabetes or impaired glucose homeostasis. HSL promoter containing the HSL C-60G G-allele was generated and tested against a construct with the C-allele in HeLa cells and primary rat adipocytes. HSL mRNA levels were quantified in subcutaneous and visceral fat from 33 obese subjects. RESULTS: We found that the common C-allele was associated with increased waist circumference and WHR in lean controls, but there was no difference in genotype frequency between obese and non-obese subjects. There was a significant increased transmission of C-alleles to the abdominally obese offspring but no increased transmission of C-alleles was observed to offspring with impaired glucose homeostasis. The G-allele showed reduced transcription in HeLa cells and primary rat adipocytes. HSL mRNA levels were significantly higher in subcutaneous compared to visceral fat from obese subjects. CONCLUSION: The HSL C-60G polymorphism is associated with increased waist circumference in non-obese subjects.

Adult↗
PubMed2005

Improving assessment of postoperative pain in surgical wards by education and training.

PROBLEM: There is a need to improve postoperative pain organisation and management in hospitals. One of the most important factors in achieving this is to improve active assessment of pain in the postoperative phase. DESIGN: Repeated audits on an annual basis over a 3 year period. Ward nurses, appointed as "pain control representatives", performed the data collection. SETTING: Departments of general surgery and orthopaedics in a university hospital with 1200 beds. KEY MEASURE FOR IMPROVEMENT: Assessment of postoperative pain intensity using a numerical rating scale. STRATEGIES FOR CHANGE: On the basis of the first audit in 1999 the team decided to introduce a mandatory training programme in postoperative pain management for all involved staff, including surgeons and ward nurses. Guidelines for postoperative care were upgraded and made accessible through the intranet. Regular staff meetings in the surgical wards with representatives from the acute pain service team were introduced. EFFECTS OF CHANGE: The assessment of pain according to protocols increased from 71% to 91% in the surgical wards and from 60% to 88% in the orthopaedic wards between 1999 and 2001/2. LESSONS LEARNT: To increase the awareness of pain and improve pain assessment, the importance of mandatory training, regular staff meetings and regular audits must be emphasised. It is also imperative to give feedback on the regular audits to the ward and staff members involved.

Clinical Protocols↗
PubMed2002

Effects of formoterol and ipratropium bromide in COPD: a 3-month placebo-controlled study.

The aim of this study was to compare the effects of formoterol, ipratropium bromide and a placebo on walking distance, lung function, symptoms and quality of life (QoL) in chronic obstructive pulmonary disease (COPD) patients. A total of 183 patients (mean age 64 yrs, 86 female) with moderate-to-severe nonreversible COPD participated in this randomised, double-blind, parallel-group study. After a 2-week placebo run-in, patients were randomised to formoterol Turbuhaler 18 microg b.i.d. (delivered dose), ipratropium bromide 80 microg t.i.d. via a pressurised metered dose inhaler, or placebo for 12 weeks. Inhaled short-acting beta2-agonists were allowed as relief medication and inhaled glucocorticosteroids were allowed at a constant dose. The primary variable was walking distance in the shuttle walking test (SWT). Baseline mean SWT distance was 325 m, mean forced expiratory volume in one second (FEV1) was 40% predicted. Clinically significant improvements in SWT (>30 m) were seen in 41, 38 and 30% of formoterol, ipratropium and placebo patients, respectively (not significant). Mean increases from run-in were 19, 17 and 5 m in the formoterol, ipratropium and placebo groups, respectively. Both active treatments significantly improved FEV1, forced vital capacity, peak expiratory flow and daytime dyspnoea score compared with placebo. Formoterol reduced relief medication use compared with placebo. Neither active treatment improved QoL. Formoterol and ipratropium improved airway function and symptoms, without significant improvements in the shuttle walking test.

Adrenergic beta-Agonists↗
PubMed2001

[Oxygen therapy undisputed in severe, but doubtful in moderate, hypoxia. Comment to meta-analysis of home oxygen therapy in chronic obstructive lung disease].

The review included randomized controlled trials on patients with chronic obstructive pulmonary disease (COPD) receiving domiciliary long-term oxygen therapy (LTOT). The authors identified six articles concerning four randomized controlled trials but could not perform any meta-analysis due to the heterogenous patient populations and treatments. From these trials they conclude that LTOT improves survival in patients with severe hypoxemia (arterial PaO2 less than 8 kPa) but has no effect in patients desaturating only at night or in patients with moderate hypoxemia. They also sensibly remark that it is possible that statistically significant improvements in some physiological variables have little measurable impact on subjects perceived quality of life or survival. The conclusion that survival benefit is demonstrated also in patients with hypoxemia in the range 7,4-8 kPa is debatable, with the strongest evidence pointing against benefit. These patients are better classified as moderately hypoxemic. In Sweden, they comprise 20% of new patients starting on LTOT. For them, the effect of LTOT should be evaluated individually in terms other than survival or quality of life. A more recently published trial supports the conclusion that domiciliary nocturnal oxygen therapy has no impact on survival in nocturnal desaturation without severe daytime hypoxemia. There is also new evidence that the type of oxygen equipment might have a decisive impact on the quality of life in mobile patients receiving LTOT--improved quality of life with liquid oxygen and poorer quality of life with concentrator and conventional (heavy) gas cylinder. The importance of optimum equipment selection for each patient has been overlooked but merits further investigation.

Evidence-Based Medicine↗
PubMed2001

Amino acid repetitions in the dihydropteroate synthase of Streptococcus pneumoniae lead to sulfonamide resistance with limited effects on substrate K(m).

Sulfonamide resistance in Streptococcus pneumoniae is due to changes in the chromosomal folP (sulA) gene coding for dihydropteroate synthase (DHPS). The first reported laboratory-selected sulfonamide-resistant S. pneumoniae isolate had a 6-bp repetition, the sul-d mutation, leading to a repetition of the amino acids Ile(66) and Glu(67) in the gene product DHPS. More recently, clinical isolates showing this and other repetitions have been reported. WA-5, a clinical isolate from Washington State, contains a 6-bp repetition in the folP gene, identical to the sul-d mutation. The repetition was deleted by site-directed mutagenesis. Enzyme kinetic measurements showed that the deletion was associated with a 35-fold difference in K(i) for sulfathiazole but changed the K(m) for p-aminobenzoic acid only 2.5-fold and did not significantly change the K(m) for 2-amino-4-hydroxy-6-hydroxymethyl-7,8-dihydropteridine pyrophosphate. The enzyme characteristics of the deletion variant were identical to those of DHPS from a sulfonamide-susceptible strain. DHPS from clinical isolates with repetitions of Ser(61) had very similar enzyme characteristics to the DHPS from WA-5. The results confirm that the repetitions are sufficient for development of a resistant enzyme and suggest that the fitness cost to the organism of developing resistance may be very low.

Adolescent↗
PubMed1998

Oral corticosteroid treatment during long-term oxygen therapy in chronic obstructive pulmonary disease: a risk factor for hospitalization and mortality in women.

Pharmacological therapy can influence morbidity and mortality in severe chronic obstructive pulmonary disease (COPD). Long-term domiciliary oxygen therapy (LTOT) improves survival in COPD with chronic hypoxaemia. Oral steroid medication has been associated with improved survival in men and increased mortality in women, while inhaled steroid medication has been associated with a reduction in the exacerbation rate. We have analysed the relationships between pharmacological therapy including oxygen therapy, sex, performance status and need for hospitalization and mortality in 403 patients with COPD (201 men) after their registration in a national oxygen register for LTOT. The mean value of days spent in hospital per year was 44. An increased need of hospital care was independently predicted by a poor performance status, high age and, in women, orally administered steroid medication. Hospital admissions were significantly longer in the terminal stage of COPD among women receiving oral steroid medication. Increased mortality was predicted by a poor performance status and, in women, oral steroid treatment. Predictors of morbidity and mortality during LTOT were found to coincide. The increased mortality in women receiving oral steroid medication was found to be associated with an increased need of hospital care due to longer hospital stays during the terminal stage of the disease. When analysing effects and side-effects of steroid medication in COPD, the possibility of sex-related differences should be considered.

Administration, Oral↗
PubMed1998

Domiciliary liquid oxygen versus concentrator treatment in chronic hypoxaemia: a cost-utility analysis.

Whether long-term oxygen therapy (LTOT) improves quality of life in chronic hypoxaemia has been questioned. LTOT with an oxygen concentrator (C/C) and gas cylinders for ambulation is considered cumbersome compared to mobile liquid oxygen equipment (L). The hypothesis for this study was that LTOT with liquid oxygen treatment (L) improves patients' health-related quality of life, but that it is also more expensive compared to concentrator (C/C) treatment. A prospective, randomized multicentre trial comparing C/C with L for LTOT was conducted during a six-month period. Fifty-one patients (29 on L and 22 on C/C) with chronic hypoxaemia, regularly active outside the home, participated in the study initially. Costs for oxygen were obtained from the pharmacies. Patient diaries and telephone contacts with members of the healthcare sector were used to estimate costs. Health-related quality of life was measured by the Sickness Impact Profile (SIP) and the EuroQol, instruments at the start and after 6 months. The average total cost per patient for group C/C for the six-month period was US$1,310, and for group L it was US$4,950. Health-related quality of life measured by the SIP instrument showed significant differences in favour of group L in the categories/dimensions of physical function, body care, ambulation, social interaction and total SIP score. In conclusion, liquid-oxygen treatment was more expensive compared to concentrator treatment. However, treatment effects showed that liquid oxygen had a better impact on quality of life.

Chronic Disease↗
PubMed1997

Long-term oxygen therapy: how can maximum benefit be achieved?

Domicillary long-term oxygen therapy (LTOT) is an established procedure, with demonstrable survival benefit. It is a complicated treatment modality and, for optimum cost-benefit to be attained, it must be performed well. This calls for careful patient selection and the selection of a suitable form of treatment for each individual patient. Follow-up, preferably with home care as an option, is also essential. No full cost-benefit analysis in economic terms has, so far, been presented. Even so, some suggestions can be made concerning the factors which need to be considered to obtain the best possible results.

Humans↗
PubMed1996

Inverse relation between the concentration of low-density-lipoprotein vitamin E and severity of coronary artery disease.

Oxidation of low-density lipoprotein (LDL) is believed to play an important role in atherogenesis, and antioxidant vitamins are thought to protect against coronary artery disease (CAD). We investigated whether the vitamin E concentrations in serum and LDL were associated with the severity of CAD as assessed by a semiquantitative scoring system in which coronary angiograms are analyzed for the number and size of distinct stenotic lesions (global stenosis score). The study group consisted of 64 consecutive male survivors of myocardial infarction aged < 45 y. Lipid-adjusted serum and LDL vitamin E concentrations were significantly lower in the patients than in 35 age-matched male control subjects, whereas the absolute serum and LDL vitamin E concentrations did not differ significantly. No associations were found between the serum concentration or lipid-adjusted serum values of vitamin E and the stenosis score. In contrast, significant inverse correlation was found between the LDL vitamin E concentration, whether adjusted to the lipid (r=-0.477,P<0.001) or protein (r=-0.375, P<0.01) content of LDL, and the global coronary stenosis score. We conclude that a low LDL vitamin E concentration might play a role in the development of stenoses in coronary arteries and may contribute to clinically manifest CAD.

Adult↗
PubMed1996

Alcohol consumption modifies the total lung capacity in smokers.

Smoking-related airflow obstruction can develop with or without emphysema. Moderate alcohol consumption has been suggested to diminish the risk of centrilobular emphysema caused by smoking. Our aim was to study the influence of total energy and nutrient (protein, fat, carbohydrate and alcohol) intake on smoking-related emphysema. Lung function and nutrient intake including alcohol consumption were recorded at age of 68 years in 478 men as part of the population study 'Men Born in 1914' in Malmö, Sweden. In nonsmokers (n = 88) and ex-smokers (n = 223), there were no significant relationships between energy and nutrient intake and lung function. In smokers (n = 167), men in the highest and lowest quintile of total lung capacity (TLC) differed in alcohol intake (p = 0.004) but not in intake of total energy or other nutrients. In smokers with a forced expiratory volume in 1 s/vital capacity ratio of below 70% (n = 81), alcohol intake was positively correlated with TLC (r = 0.31; p = 0.006) after adjustment for smoking and body mass index. We conclude that in men with smoking-related airway obstruction, emphysema defined as large TLC was associated with high alcohol consumption but not with the intake of total energy or other nutrients.

Aged↗
PubMed1996

Asthma but not smoking-related airflow limitation is associated with a high fat diet in men: results from the population study "Men born in 1914", Malmö, Sweden.

The purpose of this study was to investigate whether there is an association between asthma and the intake of food with pro-oxidant or antioxidant activity (fat, alcohol, iron, zinc, and vitamins A and C), and to analyse whether any such association is specific to asthma or is found in airflow limitation in general. This study deals with 478 men, who were randomly selected from all the men born in Malmö in 1914. They were investigated using spirometry and their medical, occupational and dietary history was recorded in 1982-1983, at the age of 68 yrs, as part of the cohort study "Men born in 1914". Asthma was defined as a past or present physician's or nurse's diagnosis of asthma and airflow limitation was defined as a forced expiratory volume in one second/vital capacity ratio (FEV1/VC) of less than 70%. The relative risk of having asthma or airflow limitation as related to dietary intake at the age of 68 yrs was analysed after adjustments for smoking history and body mass index. Asthma was reported in 21 men and was not related to smoking history. Asthma was more common in men with a high fat intake (relative risk of asthma 1.74 for a 10% increase in fat intake, 95% confidence interval for the relative risk 1.13-2.68). The consumption of alcohol was higher for current smokers than ex-smokers and nonsmokers, and the intake of carbohydrates, vitamin C and iron was lower. Airflow limitation without asthma was present in 156 men and was related to smoking but not to dietary intake. Men with asthma had a significantly higher intake of fat than men without asthma. This difference appeared to be specific to asthma and was not found in airflow limitation in general.

Aged↗
PubMed1995

The uptake of ascorbic acid into human umbilical vein endothelial cells and its effect on oxidant insult.

Intracellular reduced ascorbate (AA) levels in confluent cultures of human umbilical vein endothelial (HUVE) cells, grown under conventional conditions, were shown to be very low, ranging between undetectable, < 0.1 nmol/mg protein, and 0.3 nmol/mg protein. Reduced ascorbate was accumulated into the endothelial cells from M199 culture medium in time- and concentration-dependent manners, and was saturated at medium concentrations related to the normal plasma concentrations of the antioxidant (i.e. between 50 microM and 100 microM). Cells derived from different individuals demonstrated considerable inter-individual variation in these AA uptake parameters. The uptake of AA was sensitive to temperature and the presence of the structural analogue isoascorbate in the medium, indicating the involvement of an active transport mechanism. A role for the glucose transporter is, however, not indicated, as AA uptake was not sensitive to phloretin, an inhibitor of the cellular glucose transporter, nor greatly enhanced by depletion of glucose from the medium. Incubation of HUVE cells with dehydroascorbate (DHAA) caused a dose-dependent, but transient increase in intracellular AA. This indicates that HUVE cells are both competent in the uptake and intracellular reduction of oxidised ascorbate, and may resecrete AA into the medium. Indeed, reduced ascorbate in the medium was shown to be preferentially maintained in the presence of cells. The uptake of AA was not sensitive to the presence of DHAA in the medium, perhaps indicating different transporters for reduced and oxidised forms of ascorbate in these human cells. Pre-loading HUVE cells with AA was shown to protect control cells only weakly from the acute, sub-lethal toxicity of H2O2 generated by xanthine oxidase (1 U/mL or 10 U/mL). Protection was optimal at intracellular levels of 3-4 nmol AA/mg protein, with higher concentrations lacking a protective effect. Additionally, the presence of the iron chelator, desferoxamine, significantly protected GSH-depleted HUVE cells only in response to the peroxide, but did not potentiate the protective action of intracellular AA in either control or GSH-depleted cells. This indicates that ascorbate-driven redox-cycling of the Fe2+/Fe3+ does not hamper the intracellular protective function of ascorbate during hydrogen peroxide-derived oxidative stress. These results are discussed in terms of the central role of endothelial cells in the distribution of AA to the tissues of the body, the use of the HUVE cell system for model studies of the toxicity of oxidants in the human endothelium, and the balance between the antioxidant and pro-oxidant actions of AA.

Ascorbic Acid↗
PubMed1995

Effect of protriptyline, 10 mg daily, on chronic hypoxaemia in chronic obstructive pulmonary disease.

A daily dose of 20 mg of protriptyline can improve daytime arterial blood gas tensions in chronic obstructive pulmonary disease (COPD). Its usefulness is limited by anticholinergic side-effects. This study examined whether a daily dose of 10 mg of protriptyline improved daytime arterial oxygen tension (PaO2) and quality of life in patients with stable mild or moderate hypoxaemia caused by COPD. Twenty six patients were randomized to receive protriptyline or placebo in a double-blind parallel-group trial for 12 weeks, following a run-in period of 4 weeks, in order to assess the stability of hypoxaemia. Patients with a change in PaO2 of > 0.7 kPa during the run-in were excluded. Spirometry, quality of life and dyspnoea score were measured at randomization and after 12 weeks, whilst arterial blood gas tensions were also measured 2 and 6 weeks after randomization. No improvement in arterial blood gas tensions, spirometry values, dyspnoea score, or quality of life was found in either the protriptyline or the placebo group. The majority of patients receiving protriptyline experienced anticholinergic side-effects, which necessitated the withdrawal of the drug in one patient. We conclude that there was no evidence that a daily dose of 10 mg of protriptyline had a significant effect on daytime arterial oxygen tension in stable mild and moderate hypoxaemia caused by COPD. Despite the low dose, anticholinergic side-effects occurred in most patients.

Aged↗
PubMed1994

Different prooxidant levels stimulate growth, trigger apoptosis, or produce necrosis of insulin-secreting RINm5F cells. The role of intracellular polyamines.

Increasing concentrations (1-100 microM) of the redox cycling quinone, 2,3-dimethoxy-1,4-naphthoquinone (DMNQ), stimulated growth, triggered apoptosis, or caused necrosis of pancreatic RINm5F cells, depending on the dose and duration of the exposure. Following the exposure of RINm5F cells to 10 microM DMNQ, ornithine decarboxylase activity and polyamine biosynthesis increased. This was accompanied by enhanced cell proliferation. Conversely, exposure to 30 microM DMNQ for 3 h resulted in the inhibition of ornithine decarboxylase, intracellular polyamine depletion, and apoptotic cell killing. Pretreatment of the cultures with the phorbol ester, 12-O-tetradecanoylphorbol-13-acetate, restored polyamine levels and prevented apoptosis. Exposure to the same DMNQ concentration for only 1 h, with subsequent re-incubation in growth medium, neither caused polyamine depletion nor resulted in apoptosis. Finally, exposure to an even higher DMNQ concentration (100 microM) for either 1 or 3 h caused rapid intracellular Ca2+ overload, ATP, NAD+, and glutathione depletion, and extensive DNA single strand breakage, which resulted in necrotic cell death. Our results show that a disturbance of polyamine biosynthesis occurred prior to cell growth or apoptosis elicited by oxidative stress. In addition, we show that effects as opposite as cell proliferation and deletion, by either apoptosis or necrosis, can be induced, in the same system, by varying the exposure to a prooxidant.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed1993

Survival of patients with chronic obstructive pulmonary disease receiving long-term domiciliary oxygen therapy.

Previous trials, in which 76 to 100% of the patients were men, have shown a varied survival time in chronic obstructive pulmonary disease treated with long-term domiciliary oxygen therapy. We have analyzed predictors of survival in chronic obstructive pulmonary disease, including sex-related differences in survival in 403 patients (201 men) registered in a national register when starting long-term oxygen therapy between January 1, 1987 and June 30, 1989. This register covers the whole of Sweden with a population of 8.4 million. Some 90% of all the patients receiving long-term oxygen therapy are included. Lung function and performance status predicted survival during oxygen therapy in men, whereas a poor performance status and the presence of orally administered steroid medication predicted poor survival in women. Oral steroid medication use was correlated with an increased mortality rate in women (relative risk of death, 2.13; 95% confidence interval, 1.38 to 3.29; p < 0.001) and showed no tendency to improve survival in men. In patients not receiving oral steroids, women had a lower mortality rate than did men (relative risk of death, 0.58; 95% confidence interval, 0.39 to 0.97; p < 0.05). Our data indicate that in patients not receiving oral steroid medication, women have a better survival than do men. An increased mortality was found in women receiving oral steroid medication which might be caused by an increased susceptibility to the side effects of oral steroids.

Age Factors↗