| 1. |
- Andersson, C, et al.
(author)
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Cystic fibrosis transmembrane conductance regulator (CFTR) activity in nasal epithelial cells from cystic fibrosis patients with severe genotypes
- 2002
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In: Clinical science (London, England : 1979). - : Portland Press Ltd.. - 0143-5221 .- 1470-8736. ; 103:4, s. 417-424
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Journal article (peer-reviewed)abstract
- Cystic fibrosis is a heterogenic disease, in which the phenotype can also vary for patients with the same genotype. In the present study the function of the cystic fibrosis transmembrane conductance regulator (CFTR) in nasal epithelial cells from 19 adult patients with cystic fibrosis was investigated. All patients had severe mutations, whereby no or little functional CFTR is expected in the plasma membrane. Of the patients, 15 were homozygous for ΔF508-CFTR (i.e. CTFR lacking residue Phe-508). The others were ΔF508-heterozygous with 3659delC, 394delTT or 2183AA→G. Nasal epithelial cells, obtained by nasal brushings, were loaded with the fluorescent probe N-(ethoxycarbonylmethyl)-6-methoxyquinolinium bromide to measure Cl- efflux. In most of the cystic fibrosis patients, forskolin plus isobutylmethylxanthine was unable to elicit any response. Unexpectedly, cells from three cystic fibrosis patients (two ΔF508/ΔF508 patients and one ΔF508/3659delC patient) responded to stimulation in a wild-type manner. It was investigated whether this residual chloride transport function was associated with a milder phenotype. Clinical parameters studied were lung function, number of antibiotic courses, Shwachman score, Bhalla score, age at chronic colonization with Pseudomonas aeruginosa and the pattern of essential fatty acids in serum phospholipids. Unknown factors may affect the presence of functional CFTR in patients with severe CFTR mutations. However, we could not find a correlation between the response to cAMP and any of the phenotype parameters. It appears that functional cAMP transport in the nasal epithelium is no guarantee of a mild phenotype and, conversely, that a patient lacking cAMP-dependent chloride transport can develop a mild phenotype.
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| 2. |
- Andersson, S E, et al.
(author)
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Cutaneous vascular reactivity is reduced in aging and in heart failure: association with inflammation
- 2003
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In: Clinical Science. - 1470-8736. ; 105:6, s. 699-707
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Journal article (peer-reviewed)abstract
- In the present study, we have investigated whether changes in vascular reactivity in congestive heart failure (CHF) patients can be detected in the cutaneous microvessels and whether these changes are due to endothelial dysfunction, are affected by increasing age and related to an ongoing inflammation. The responses to local warming and iontophoretically administered endothelium-dependent and -independent vasodilators were investigated in healthy young adults, healthy elderly adults and elderly adults with CHE The results were correlated with plasma concentrations of vascular risk factors and markers for endothelial dysfunction and inflammation. The vasorelaxant responses were reduced in the elderly groups and were attenuated further in the CHF group. This group also had increases in levels of several markers associated with inflammation, higher blood glucose and homocysteine levels, a lower low-density lipoprotein-cholesterol and a rise in the concentration of von Willebrand factor, indicating a prothrombotic endothelial function. The severity of the heart failure, measured as the plasma level of brain natriuretic peptide, correlated with the intensity of inflammation and to the changes in vascular risk factors and endothelial function. It is concluded that the reactivity of the cutaneous microvessels is reduced with age, and the presence of CHF causes a further impairment. There is endothelial dysfunction in CHF, but it is uncertain to what extent this contributes to the reduced vasodilatory capacity. The inflammatory response appears central for many of the manifestations of the CHF syndrome.
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| 3. |
- Barle, H, et al.
(author)
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Albumin synthesis in humans increases immediately following the administration of endotoxin
- 2002
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In: Clinical science (London, England : 1979). - : Portland Press Ltd.. - 0143-5221 .- 1470-8736. ; 103:5, s. 525-531
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Journal article (peer-reviewed)abstract
- In order to investigate the immediate (i.e. within 3h) response of albumin synthesis to the administration of endotoxin, as a model of a moderate and well controlled catabolic insult, two measurements employing L-[2H5]phenylalanine were performed in 16 volunteers. One group (n = 8) received an intravenous injection of endotoxin (4ng/kg; lot EC-6) immediately after the first measurement of albumin synthesis, whereas the other group received saline. A second measurement was initiated 1h later. In the endotoxin group, the fractional synthesis rate of albumin was 6.9±0.6%/day (mean±S.D.) in the first measurement. In the second measurement, a significant increase was observed (9.6±1.2%/day; P<0.001). The corresponding values in the control group were were 6.6±0.6%/day and 7.0±0.6%/day respectively (not significant compared with first measurement and P<0.001 compared with the second measurement in the endotoxin group). The absolute synthesis rates of albumin were 148±35 and 201±49mg·kg-1·day-1 before and after endotoxin (P<0.01). In the control group, the corresponding values were 131±21 and 132±20mg·kg-1·day-1 (not significant compared with the first measurement and P<0.01 compared with the second measurement in the endotoxin group). In conclusion, these results indicate that albumin synthesis increases in the very early phase after a catabolic insult, as represented by the administration of endotoxin.
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| 4. |
- Ekholm, M, et al.
(author)
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Long-term angiotensin-converting enzyme inhibition with ramipril reduces thrombin generation in human hypertension
- 2002
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In: Clinical science (London, England : 1979). - : Portland Press Ltd.. - 0143-5221 .- 1470-8736. ; 103:2, s. 151-155
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Journal article (peer-reviewed)abstract
- Antihypertensive treatment reduces the risk of thromboembolic events in hypertension. The aim of this study was to examine the influence of angiotensin-converting enzyme inhibition on blood coagulation in subjects with mild-to-moderate essential hypertension. Fibrinogen, thrombin–antithrombin complex (TAT) and Factor VII were determined in plasma at rest and after a mental stress test following placebo for 6 weeks, or ramipril for 6 weeks or 6 months. Ramipril reduced resting TAT, and tended to reduce fibrinogen; Factor VII remained unchanged. Mental stress increased fibrinogen, but did not alter TAT or Factor VII activity. The reduced thrombin generation in patients taking ramipril may explain in part why angiotensin-converting enzyme inhibitors reduce thromboembolic complications in patients with cardiovascular disease.
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| 5. |
- Frostegard, J, et al.
(author)
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Circulating oxidized low-density lipoprotein is increased in hypertension
- 2003
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In: Clinical Science. - 1470-8736. ; 105:5, s. 615-620
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Journal article (peer-reviewed)abstract
- Oxidized low-density lipoprotein (OxLDL) and autoantibodies to OxLDL (aOxLDL) are implicated in the development of atherosclerosis. The objective of this study was to determine the importance of these factors in hypertension, a major risk factor for atherosclerosis. Samples were obtained from I I I men with established hypertension (diastolic pressure > 95 mmHg) from the Swedish component of an ongoing hypertension study (European Lacidipine study on Atherosclerosis, ELSA) and from 75 normotensive control men, who were from a Swedish population-screening programme (diastolic pressure < 80 mmHg). The presence of carotid atherosclerosis and the intima-media thicknesses were determined by ultrasonography. A monoclonal antibody to OxLDL, EO6, was used to determine oxidation epitopes in LDL. aOxLDL of IgG and IgM subclass were tested by ELISA against OxLDL. Hypertensive men had increased OxLDL levels compared with normotensives (P = 0.002), whereas autoantibodies tested were largely similar between groups. There was no association between the antibodies tested, or OxLDL and carotid atherosclerosis. Age was not associated with OxLDL or aOxLDL measurements. Taken together, our findings indicate that OxLDL is elevated in hypertensive men, which may predispose to atherosclerosis in hypertension. In contrast, aOxLDL levels were unchanged and the role of aOxLDL may depend on disease stage and/or type.
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| 6. |
- Fugmann, Andreas, et al.
(author)
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Central and peripheral haemodynamic effects of hyperglycaemia, hyperinsulinaemia, hyperlipidaemia or a mixed meal
- 2003
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In: Clinical Science. - 0143-5221 .- 1470-8736. ; 105:6, s. 715-721
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Journal article (peer-reviewed)abstract
- The aim of the present study was to evaluate the haemodynamic changes during hyperinsulinaemia, hyperglycaemia or hypertriglyceridaemia in relation to those following a mixed meal. Ten subjects were subjected to hypertriglyceridaemia (3.9 mmol/l) for 2 h by an infusion of Intralipid and heparin. Nine subjects received a hyperglycaemic clamp (12.5 mmol/l) with octreotide and low-dose insulin infusion to maintain normoinsulinaemia (10 m-units/l). Ten subjects received saline for 2 h as a control and, thereafter, 2 h of normoglycaemic hyperinsulinaemic clamp (80 m-units/l). Finally, ten subjects were evaluated for 2 h following an ordinary mixed meal. Calf blood flow was measured by venous occlusion plethysmography and cardiac index by thoracic bioimpedance. Both the mixed meal and normoglycaemic hyperinsulinaemia lowered total peripheral resistance, and increased calf blood flow and cardiac index, whereas blood pressure decreased (P <0.05-0.001). Both hyperglycaemia and hypertriglyceridaemia increased calf blood flow, but blood pressure was unchanged. Total peripheral resistance was unchanged in hypertriglyceridaemia, whereas hyperglycaemia induced a significant increase. Normoglycaemic hyperinsulinaemia induced a haemodynamic pattern similar, but to a lesser extent, to the pattern seen following a mixed meal. Hyperinsulinaemia seems to be a major mediator of the haemodynamic response, but other factors are obviously also of great importance. Hypertriglyceridaemia and hyperglycaemia induced haemodynamic responses that are not similar to those seen following a mixed meal.
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| 7. |
- Jensen, J., et al.
(author)
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Deterioration in peak systolic velocity is closely related to ischaemia during angioplasty : a vectorcardiographic and tissue Doppler imaging study
- 2001
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In: Clinical Science. - : Portland Press Ltd.. - 0143-5221 .- 1470-8736. ; 100:2, s. 137-143
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Journal article (peer-reviewed)abstract
- We tested the hypothesis that the extent of signs of ischaemia detected by vectorcardiography (VCG) during elective coronary angioplasty (percutaneous transluminal coronary angioplasty: PTCA) is related to systolic and diastolic myocardial velocities, as determined by tissue Doppler echocardiography. A total of 15 patients undergoing PTCA (12 men/three women; age 61 +/- 9 years), without prior myocardial infarction and with an election fraction of > 50%, were included. The balloon inflation was repeated three times, with minimum intervals of 2 min between inflations. Tissue Doppler echocardiography was performed. in an apical two- or four-chamber view, before and at the end of each inflation. Peak systolic velocity, time-to-peak systolic velocity (TTP), peak early (E-m) and late (A(m)) diastolic velocities, the E-m/A(m) ratio and jsovolumic relaxation time were measured in the basal segments of the left ventricle. VCG recordings were carried out during the whole procedure. ST vector magnitude (ST-VM) and ST change vector magnitude (STC-VM) were monitored. The total duration and area of each VCG change during inflation were calculated for each patient. Isovolumic relaxation time, peak E-m and A(m) values and the E-m/A(m) ratio did not change significantly during inflation. Peak systolic velocity decreased (6.7+/-2.0 to 5.3 +/- 1.9 cm/s; P < 0.001) and TTP increased (157 +/- 60 to 192 +/- 60 ms; P<0.01) during inflation. Both STC-VM rime (r = -0.68, P<0.01) and STC-VM area (r = -0.68, P < 0.01) were related to peak systolic velocity during inflation. STC-VM time was also related (r = 0.55, P < 0.05) to the difference in peak systolic velocity during compared with before inflation. ST-VM was less closely related to peak systolic velocity. Thus the duration and degree of ischaemia, as measured by VCG, are related to peak systolic velocity in the basal segments of the left ventricle.
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| 8. |
- Jorfeldt, L., et al.
(author)
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Influence of leg position and environmental temperature on segmental volume expansion during venous occlusion plethysmography
- 2003
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In: Clinical Science. - 0143-5221 .- 1470-8736. ; 104:6, s. 599-605
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Journal article (peer-reviewed)abstract
- Blood flow determinations by venous occlusion plethysmography applying the strain-gauge technique are frequently used. A problem with the strain-gauge technique is that the relationship between venous volume and transmural pressure is not linear and, furthermore, changes with the sympathetic tone. The present study tests the hypothesis that these factors lead to a redistribution of venous blood, which may impair the accuracy of the technique. The relative volume expansion rates of four leg segments were studied with the leg in different positions and at disparate temperatures, thereby inducing varying venous pressures and sympathetic tone (n = 6). With elevated leg and relaxed veins (at 50°C), the distal thigh showed a relatively low expansion rate (25.8 ± 4.5 ml·min-1, l-1), whereas values in the calf segments were higher (34.5-39.0ml·min-1·l-1). With lower initial transmural pressure, calf segments can increase their volume much more during occlusion compared with the distal thigh. In a higher transmural pressure region (lowered leg), the difference in compliance between limb segments is less. In this case, compliance and volume expansion rate was higher in the distal thigh (14.2, 13.5 and 22.2ml·min-1·l-1 at 10, 20 and 50°C respectively) than in the calf segments (for the distal calf: 6.4, 7.7 and 16.2 ml·min-1=1-1 respectively). There was a significant interaction (P < 0.001) between temperature and leg position, indicating a higher degree of sympathetic vasoactivity in the calf. It is concluded that blood flow determination by strain-gauge plethysmography is less accurate, due to a potential redistribution of the venous blood. Therefore possible influences of variations in sympathetic tone and venous pressure must be considered even in intra-individual comparisons, especially in interventional studies.
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| 9. |
- Lind, Lars, et al.
(author)
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Insulin-mediated vasodilatation, but not glucose uptake or endothelium-mediated vasodilatation, is enhanced in young females compared with males
- 2002
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In: Clinical Science. - 0143-5221 .- 1470-8736. ; 102:2, s. 241-246
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Journal article (peer-reviewed)abstract
- In order to evaluate possible differences between men and women with regard to the ability of insulin to induce vasodilatation, promote glucose uptake and enhance endothelium-dependent vasodilatation, 12 young (22-28 years), non-obese women and 15 corresponding males were subjected to 2 h of euglycaemic hyperinsulinaemia (insulin infusion rate of 56 m-units x min(-1) x m(-2)). Forearm blood flow was measured by venous occlusion plethysmography. Endothelium-dependent vasodilatation was evaluated by the local intra-arterial infusion of methacholine into the brachial artery (2-4 microg/min). The cardiac index was measured by thoracic bioimpedance. A 2 h period of hyperinsulinaemia increased the plasma insulin concentration to a similar degree in both sexes (females, 84 +/- 8.8 m-units/l; males, 87 +/- 7.5 m-units/l), but induced a more marked increase in forearm blood flow in females than in males (+104 +/- 67% and +52 +/- 30% respectively; P<0.01; 95% confidence interval for difference 11-94%). Furthermore, a significant decrease in total peripheral resistance (-20 +/- 6.9%; P<0.01) and an increase in cardiac index (+23 +/- 13%; P<0.01) were seen in women only (P<0.05 compared with men). Blood pressure and heart rate were not altered in either sex. Whole-body insulin-mediated glucose uptake and forearm glucose uptake did not differ between the sexes, and the ability of insulin to enhance endothelium-dependent vasodilatation (+19%; P<0.01) was similar in men and women. In conclusion, the present study shows that the ability of insulin to cause vasodilatation was greater in non-obese young women compared with men. However, no differences between the sexes were seen with regard to insulin-mediated glucose uptake and the ability of insulin to enhance endothelium-dependent vasodilatation.
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| 10. |
- Lind, Lars, et al.
(author)
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The impairment in endothelial function induced by non-esterified fattyacids can be reversed by insulin
- 2000
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In: Clinical Science. - 0143-5221 .- 1470-8736. ; 99:3, s. 169-174
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Journal article (peer-reviewed)abstract
- Dyslipidaemia, with elevations of circulating triacylglycerols (triglycerides) and non-esterified (free) fatty acids, and hyperinsulinaemia are often found in the same subjects, the so-called 'insulin resistance syndrome'. The present study aims to investigate how elevated levels of non-esterified fatty acids, hyperinsulinaemia and the combination of these factors affects endothelium-dependent vasodilatation (EDV). Ten volunteers were examined on two occasions. Intralipid (plus heparin) or saline (0.9% NaCl) was infused for 4 h. During the final 2 h, euglycaemic hyperinsulinaemia (80+/-4 m-units/l) was imposed. EDV and endothelium-independent vasodilatation were evaluated in the forearm by local intra-arterial infusion of methacholine or sodium nitroprusside at baseline and after 2 and 4 h. Forearm blood flow was measured by venous occlusion plethysmography. Lipid oxidation was determined by measuring plasma malondialdehyde levels. Infusion of Intralipid plus heparin increased the concentration of non-esterified fatty acids to 2.6+/-1.2 mmol/l and decreased EDV from 27.6+/-8.7 to 21.0+/-5.7 ml x min(-1) x 100 ml(-1) tissue (P < 0.01). This effect was completely reversed by hyperinsulinaemia (P < 0.01). Hyperinsulinaemia alone increased EDV (to 30.4+/-9.5 ml x min(-1) x 100 ml(-1) tissue; P < 0.01), while endothelium-independent vasodilatation was unaltered by the interventions. Infusion of Intralipid plus heparin increased malondialdehyde levels from 0.67+/-0.22 to 1.2+/-0.37 micromol/l (P < 0.001), while hyperinsulinaemiadid not change the malondialdehyde level. In conclusion, an acute increase in serum levels of non-esterified fatty acids increased lipid oxidation and decreased EDV. The effect on EDV of non-esterified fatty acids could be reversed by hyperinsulinaemia.
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