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Biomedical subjects

T O Klemsdal

Publications and source records attributed to T O Klemsdal.

18 recordsLinked to original sources
PubMed2006

Comparison of biochemical, functional and structural aspects of arterial wall properties in elderly men.

OBJECTIVE: A variety of methods are available to assess arterial wall properties. The aim of this study was to investigate the relationship between some of the biochemical, functional and structural measurements of arterial wall characteristics. MATERIAL AND METHODS: The study comprised 563 elderly men at high risk of coronary heart disease. Circulating levels of intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), E-selectin, von Willebrand factor (vWF) and tissue-type plasminogen activator antigen (tPAag) were compared with pulse wave velocity (PWV) measured by finger photoplethysmography and intima-media thickness (IMT) and plaque score of the common carotid artery. RESULTS: Levels of ICAM-1 were significantly correlated with plaque score (r = 0.17, p<0.001). Levels of vWF were significantly correlated with plaque score (r = 0.11, p = 0.009) and PWV (r = 0.12, p = 0.007), and levels of tPAag were significantly correlated with PWV (r = 0.16, p<0.001). These associations, although generally weak, remained statistically significant after adjustment for relevant cardiovascular risk factors. PWV did not correlate significantly with IMT or plaque score. CONCLUSIONS: The limited intercorrelation between biochemical, functional and structural measurements of arterial wall properties observed in the present population indicate that the various methods reflect different aspects of the atherosclerotic process.

Aged↗
PubMed1999

Effects of selective angiotensin II type 1 receptor blockade with losartan on arterial compliance in patients with mild essential hypertension.

It has been suggested that antihypertensive drugs should not only decrease blood pressure, but also improve large artery compliance. The aim of the present study was to examine the effect of losartan, a selective angiotensin II type 1 receptor antagonist, on parameters reflecting arterial compliance. In a randomized, double-blind cross-over study, 16 patients with mild essential hypertension were examined after 4 weeks of treatment with placebo/losartan. The effect on finger plethysmographic arterial pulse curves were quantified by computing the relative height of the dicrotic notch, and pulse wave velocity was estimated by measurements of the time delay from the start of the QRS-complex (electrocardiogram) to the foot of the plethysmographic pulse wave. Compared with placebo, losartan reduced the relative height of the dicrotic notch from 55% (SD 12) to 47% [14] (p < 0.01), and pulse wave velocity from 9.3 m/sec to 8.7 m/sec (p < 0.05). The supine blood pressure decreased from 146/89 mmHg to 134/82 mmHg (p < 0.01). There was no correlation between the effects on blood pressure and the effects on the arterial compliance parameters, suggesting that losartan exerted an effect on arterial compliance beyond its effect on blood pressure.

Adult↗
PubMed1997

Transdermal nitroglycerin: clinical and pharmacokinetic consequences of renewing the patch and the application site.

OBJECTIVE: We examined whether nitroglycerin (glyceryl trinitrate, GTN) patch treatment for 24 h could induce local cutaneous changes that impaired drug delivery and clinical efficacy. METHODS: Twenty angina patients were exercise-tested after 2 and 24 h of treatment and then 2 h after patch renewal. The patch was either renewed on a new skin location or on the previous application site in a randomised, double-blind, cross-over protocol. GTN plasma concentrations and finger plethysmography were obtained before and after each exercise test. RESULTS AND CONCLUSIONS: The clinical efficacy, the effect seen on plethysmography and the GTN plasma concentrations tended to increase after patch renewal, regardless of the application site of the renewed patch. Hence, cutaneous changes of clinical importance could not be demonstrated.

Administration, Cutaneous↗
PubMed1996

Intermittent or continuous transdermal nitroglycerin: still an issue, or is the case closed?

After a decade of controversy and debate, many experts have now concluded that continuous nitroglycerin patch treatment leads to complete tolerance development and therefore cannot be recommended for any angina patient. This conclusion is largely based on the disappointing results of the large Transdermal Nitroglycerin Cooperative Study, in which continuous patch treatment in doses of 15-105 mg daily failed to increase exercise duration more than placebo after 2 and 8 weeks of treatment. However, other well-designed studies recently reported maintained efficacy during continuous treatment, and the differences in results has remained unexplained. The disagreeing data may be better understood if certain facts are considered: (1) The cooperative study tested a patient population with a very low first-dose treatment response--only 34 seconds (or 10-12%) improvement compared with placebo. At the end of the study, 25% of the patients terminated exercise for reasons other than angina, and a reduced nitrate responsiveness had developed, even in the placebo group. (2) Patients who demonstrate a large first-dose nitrate responsiveness tend to be less susceptible to tolerance development. (3) Even during continuous therapy, maintained efficacy is often observed in exercise tests done 2-5 hours after patch renewal, while typically no effect is seen at the end of the application period. Attenuation of the initial effects is seen with all long-acting nitrate treatment regimens, but the degree of tolerance varies with the patient population, the efficacy parameter (exercise test vs. attack counts), the timing of the efficacy test, the patch dose, and whether or not nitrate-free (-low) intervals are used. In general, intermittent patch therapy is superior to continuous therapy in improving exercise duration, but even continuous therapy may retain some effect. Rebound phenomena do occur but are clinically relevant only in a minority of the patients. Rebound phenomena are not a problem during continuous therapy, which therefore may be of value in patients with frequent and/or nocturnal angina attacks. Patients experiencing angina during exercise only and with low first-dose effects are likely to benefit more from intermittent therapy. Doses of 0.6-0.8 mg/hr (15-20 mg/24 hr) are usually optimal, and the efficacy is comparable with that observed after oral nitrates.

Administration, Cutaneous↗
PubMed1996

Effects of carvedilol and atenolol on arterial pulse curves (plethysmography) and finger temperature after hand cooling.

OBJECTIVE: In a double-blind, parallel study, the effects of 25 mg carvedilol and 50 mg atenolol on peripheral finger circulation and arterial pulse curve configuration were compared. METHODS: Healthy volunteers (n = 17) were examined at baseline and for 15 min after 60 s of hand cooling in ice-water. Finger temperature and digital plethysmography were recorded each minute from the cooled and the control hands. Measurements were also made before and 2 h after drug administration. RESULTS: Blood pressure declined from 120/86 to 108/74 mm Hg after atenolol (n = 9), and from 122/88 to 108/73 mm Hg after carvedilol (n = 8). In both groups, baseline finger temperature increased slightly after drug, and a more rapid rise in finger temperature was observed after cooling. There was no group difference in the drug effect on finger temperature, except in the first few minutes after cooling, when temperature recovery was greater after carvedilol. Carvedilol reduced the vasoconstrictor response to local cooling (digital plethysmography), compared both to the value before drug and after atenolol. At rest, carvedilol changed the pulse curves (control hand) towards vasodilatation and high compliance, expressed as a mean change in the relative height of the dicrotic notch of -10.3% versus 0.0% after atenolol. CONCLUSION: Future studies should clarify whether the vasoactive profile of carvedilol may translate into reduced occurrence of cold hands and feet amongst patients treated for hypertension.

Adrenergic beta-Antagonists↗
PubMed1996

Mechanisms of tolerance during treatment with nitroglycerin patches for 24 h.

OBJECTIVE: We examined the relationship between tolerance development, counterregulatory responses and arterial vasodilating effects evaluated by digital pulse plethysmography. METHODS: Twenty patients with stable angina pectoris were exercise tested before, after 2 and after 24 h of open nitrate patch treatment. RESULTS: The effects observed after 2 h of treatment on exercise duration, ST-segment depression, blood pressure and heart rate were lost in most individuals after 24 h. In contrast, the effects on the arterial pulse curves persisted after 24 h, with a mean change from baseline of 29%, compared to 33% at 2 h. After 24 h, a significant decrease in haematocrit and an increase in body weight were observed. The haematocrit changes correlated with the loss of clinical efficacy (r = 0.57 for ST-segment depression, and r = 0.54 for exercise duration). CONCLUSION: Clinical nitrate tolerance may be observed despite maintenance of the arterial vasodilating effects, and tolerance is more related to plasma volume expansion as a counterregulatory mechanism.

Administration, Cutaneous↗
PubMed1995

Physical exercise increases plasma concentrations of nicotine during treatment with a nicotine patch.

The effect of physical exercise on plasma nicotine concentrations was studied in eight healthy subjects treated with a nicotine patch releasing 14 mg 24 h-1. After 11 h of patch application, plasma nicotine concentrations were measured before and after 20 min of moderate bicycle exercise, or 20 min of rest. Mean plasma nicotine concentration increased from 9.8 to 11.0 ng ml-1 (P = 0.015) during physical exercise, and fell non-significantly from 10.5 to 10.2 ng ml-1 during rest. The increase in plasma nicotine concentration during exercise is similar to that observed for transdermal nitroglycerin, and may be related to an exercise-induced increase in blood flow in the patch area.

Administration, Cutaneous↗
PubMed1994

[Heart failure in Norwegian hospital departments. Prevalence, diagnostic and therapeutic aspects].

The prevalence of congestive heart failure was studied in the medical departments of eight Norwegian hospitals for two days. A mean of 179 patients with heart failure was identified, representing 20% of the total number of in-patients in the participating hospital departments. About 60% of the patients studied were over 70 years of age. There were equal numbers of men and women, but men dominated below 70 years. Ischemic heart disease (59%), valvular heart disease (15%) and hypertension (14%) were the most common primary heart diseases. The drugs used most frequently were diuretics (91%), digitalis (60%), nitrates (40%), and ACE-inhibitors (38%); the last were used more often among patients with severe heart failure (56%).

Aged↗
PubMed1994

A new isosorbide dinitrate extended-release formulation: pharmacokinetic and clinical parameters in patients with stable angina pectoris.

In a double-blind, cross-over study the acute clinical efficacy and pharmacokinetic profile of a newly developed isosorbide dinitrate extended-release (ISDN-ER) formulation (10 mg immediate release and 60 mg slow release) were examined in eight angina patients. Exercise tests were done 1 h before and 1, 6 and 10 h after acute ISDN or placebo; similar testing was repeated after 14 days of open-labelled treatment. At 1, 6 and 10 h after administration, ISDN-ER significantly reduced the mean ST depression at highest comparable workload (HCWL) by 0.8, 0.6, and 0.6 mm, respectively. Total exercise duration increased significantly by 46, 42 and 72 s. The rate-pressure product at HCWL was not reduced significantly at any time, while digital plethysmography demonstrated a significant effect on arterial pulse curves throughout the 10 h. After 14 days of once-daily treatment, similar or somewhat attenuated clinical effects were observed. Pharmacokinetic measurements showed a first peak of ISDN at 1-2 h and a second peak at 4-5 h. The 5-isosorbide mononitrate (5-ISMN) metabolite peaked at 5-8 h and remained high at 10 h. After 14 days of treatment, the mean plasma concentrations of ISDN and 5-ISMN before drug were 0 and 69 ng.ml-1, respectively. Thus, satisfactory acute clinical efficacy and low nitrate levels during the night were observed. However, long-term clinical efficacy needs to be established in larger, placebo-controlled trials.

Aged↗
PubMed1994

Vitamin E restores endothelium dependent vasodilatation in cholesterol fed rabbits: in vivo measurements by photoplethysmography.

OBJECTIVE: Pulse curve plethysmography was used to examine the effect of vitamin E on endothelium dependent and independent vasodilatation in unanaesthetised cholesterol fed rabbits in vivo. The height of the dicrotic notch was used as an index of general arterial vasodilatation. METHODS: Twenty eight rabbits were divided into three study groups; a control group (group 1, n = 8), a group fed 1% cholesterol (group 2, n = 10), and a group fed 1% cholesterol with the addition of 0.2% vitamin E after four weeks (group 3, n = 10). After six weeks on diet the vasodilator responses to acetylcholine and glyceryl trinitrate were measured by photoplethysmography of the rabbit ear. Recordings were made during light sedation at baseline and during infusion of acetylcholine (1.5, 3.0, 6.0, and 12 micrograms.min-1) and glyceryl trinitrate (3.75, 7.5, and 15.0 micrograms.min-1). In a second set of experiments with control fed rabbits (n = 5), acetylcholine infusions were given before and after infusion of L-nitro-arginine (15 mg). RESULTS: The relative height of the dicrotic notch (which predominantly indicates arterial tone in the larger vessels) was reduced by acetylcholine in a dose dependent manner, but in cholesterol fed rabbits (group 2) this response was significantly decreased. Rabbits receiving concomitant dietary vitamin E responded in a similar manner to controls. The difference was most prominent using acetylcholine at a dose of 3.0 micrograms.min-1, where the mean change from baseline was 11(SEM 4)% in group 2, compared to 31(6)% in group 1 (p = 0.01), and to 26(5)% in group 3 (p = 0.02). Similar differences between the groups were observed for the increase in heart rate during acetylcholine infusions. In contrast, the responses to glyceryl trinitrate were similar in all groups. After infusions of L-nitro-arginine, the responses to acetylcholine were blunted. CONCLUSIONS: Supplementation with vitamin E restored the otherwise reduced vascular response to acetylcholine in cholesterol fed rabbits. Analysis of photoplethysmographic pulse curves is a simple non-invasive method of evaluating arterial vasodilator effects. However, the nature of the measured dilator response needs to be characterised further.

Acetylcholine↗
PubMed1994

Quality of life on enalapril after acute myocardial infarction.

Quality of life was assessed 4-6 months after an acute myocardial infarction in a randomized double-blind study of enalapril versus placebo. Quality of life was evaluated using the Nottingham Health Profile (NHP), the Physical Symptoms Distress Index (PSDI), the Work Performance Scale (WPS) and the Life Satisfaction Index (LSI). The study comprised 36 women (aged 46-85 years, mean 68) and 96 males (aged 39-81 years, mean 62). Quality of life did not differ significantly between patients treated with enalapril versus placebo. The scores were (enalapril vs placebo, mean +/- SE): average NHP 15.4 +/- 2.3 vs 17.1 +/- 2.3; PSDI 9.5 +/- 1.0 vs 10.8 +/- 0.9; WPS 19.8 +/- 2.0 vs 19.4 +/- 1.4; LSI 24.1 +/- 1.0 vs 22.5 +/- 1.4. Men reported a better quality of life than women on most assessments, and non-smokers and ex-smokers better than smokers. Patients with moderate or severe angina pectoris had a worse quality of life measured by PSDI and NHP than patients with minimal or no angina pectoris. Patients with congestive heart failure had a higher PSDI than those without (13.6 +/- 1.7 vs 9.4 +/- 0.7, P < 0.05), while no significant differences were observed in the NHP scores. In conclusion, quality of life was similar in enalapril and placebo-treated patients after an acute myocardial infarction. However, it was reduced in patients with angina pectoris or heart failure and in those who continued smoking.

Activities of Daily Living↗
PubMed1992

[Treatment of heart failure. A questionnaire among Norwegian hospital physicians].

A questionnaire on the treatment of congestive heart failure was distributed to physicians in the medical departments of five hospitals in the Oslo area. The 117 (81%) respondents selected first, second and third line therapy in the treatment of mild, moderate and severe heart failure. Diuretics and restrictions on sodium/water dominated as first line therapy for mild heart failure; less than 5% suggested ACE-inhibitors or digitalis. Some differences in priorities were revealed for moderate and severe heart failure. The majority again suggested diuretics and restrictions on sodium/water, but 20% preferred ACE-inhibitors, which were also stated as second or third line therapy by 60% of the physicians. Less than 50% chose digitalis or nitrates as one of the three first therapies.

Heart Failure↗
PubMed1992

The effect of transdermal nitroglycerin on exercise tolerance in relation to patch application time--a meta-analysis.

Disagreeing results have been reported in the many studies on continuous treatment with nitroglycerin patches. The effects on exercise tolerance are partly studied at the end of a 24-hour application period, and partly examined only a few hours after patch renewal. The present meta-analysis estimates the overall efficacy of nitroglycerin patches in trials with and without concomitant antianginal therapy, and investigates if the treatment effect depends on the patch application time. A computed search (MEDLINE) identified 110 publications, of which 17 trials on nitrate patch monotherapy and six trials on combined therapy satisfied the inclusion criteria. Data on "exercise duration" and "ST-segment depression" were converted to a standardized treatment effect size d, and pooled to an overall treatment effect size d+. In tests 2-5 hours after patch renewal, moderate but significant effects of nitrate monotherapy were observed; d+ was 1.20 with regard to "ST-segment depression" and 0.39 with regard to "exercise duration" (both p < 0.0001). In contrast, 24 hours after patch application, the values for d+ were 0.09 (not significant) and 0.36 (p < 0.01), respectively. When adding the results from the six trials on combined therapy, d+ with regard to "exercise duration" was reduced to 0.28 (p < 0.0001) 2-5 hours after renewal and to 0.17 (p = 0.04) after 24 hours. Thus, the efficacy of continuous nitroglycerin patch treatment is moderate but evident during exercise tests 2-5 hours after patch renewal; however, it is reduced after 24 hours of patch application.

Administration, Cutaneous↗
PubMed1992

Heating and cooling of the nitroglycerin patch application area modify the plasma level of nitroglycerin.

19 healthy volunteers wore a nitroglycerin patch releasing 10 mg per 24 h for 2 h. Subsequently, the skin area surrounding the patch was exposed to 15 min of local heating with an infrared bulb (Group A, n = 10), or local cooling with an ice-pack (Group B, n = 9). The patch was protected by an insulating shield (Styrofoam). After 10 min of heating, the median (Walsh) plasma nitroglycerin level increased from 3.1 to 7.6 nmol.l-1. Body temperature remained constant. After 15 min of cooling the median plasma level had dropped from 2.1 to 1.4 nmol.l-1. The results demonstrate that changes in skin temperature may cause extensive short-term changes in the bioavailability of nitroglycerin. Presumably, a subcutaneous or cutaneous reservoir builds up during transdermal treatment, and changes in regional cutaneous blood flow affect the rate of drainage from the reservoir into the systemic circulation.

Administration, Cutaneous↗
PubMed1991

[Temporal arteritis without elevated erythrocyte sedimentation rate].

Giant cell arteritis is a common disease in the elderly, and may cause serious loss of vision if treatment is delayed. A marked elevation of the erythrocyte sedimentation rate (ESR) is a typical feature of the disease, and diagnosis can usually be confirmed by a biopsy of the arteria temporalis. The article describes a patient who presented typical symptoms, but had a normal ESR. The diagnosis was later confirmed by biopsy. Several similar cases have been reported in the last 15 years, and it is therefore advocated that patients with symptoms indicating giant cell arteritis should be biopsied and treated with steroids without hesitation, even if the ESR is normal.

Aged↗
PubMed1991

Transdermal nitrate therapy: bioavailability during exercise increases transiently after the daily change of patch.

Ten volunteers carried a 10 mg 24 h -1 transdermal glyceryl trinitrate (GTN) patch for 24 h before moderate exercise. Plasma GTN-concentration increased significantly (P less than 0.05) by 19% to peak value at 15 min. Two hours after patch renewal repeat exercise increased GTN concentration by 56% (P less than 0.001). The two nitrate-concentration curves differed significantly (P less than 0.0001). Thus, change of patch augmented nitrate availability during exercise.

Administration, Cutaneous↗