Hanne Rolighed Christensen

24-h ambulatory blood pressure in 352 normal Danish subjects, related to age and gender

UNLABELLEDnThe study was conducted to determine age and sex stratified normal values for 24-h ambulatory blood pressure. A sample of 352 healthy subjects (all white) were randomly selected from the community register and stratified by sex and age groups in decades from 20 to 79 years of age. Persons with a history of hypertension, cerebral apoplexy, diabetes, myocardial or renal disease, and who were taking blood pressure-influencing medication were excluded. Ambulatory blood pressure was recorded over 24 h, with measurements taken every 15 min from 07:00 to 22:59, and every 30 min from 23:00 to 6:59. Systolic blood pressure increased only slightly with age and was significantly higher in men than in women. The diastolic blood pressure increased only slightly with age in both sexes until the 50 to 59 years age group and declined thereafter. The diastolic blood pressure was not different for the two sexes. Both systolic and diastolic blood pressure were approximately 15% lower during the night regardless of age or sex. Ambulatory blood pressure during the daytime was on an average of 5 mm Hg lower than office blood pressure, but the mean difference between the two measurements increased with age. The variability of the difference also increased with age.nnnIN CONCLUSIONnNormal values for ambulatory blood pressure are presented in a randomly selected age- and gender-stratified population. Differences between office blood pressure and ambulatory blood pressure increased with age suggesting that the previously observed higher blood pressure seen in the elderly partly might be explained by a greater impact of white coat hypertension in older people.

Homocysteine and Risk of Recurrent Stroke

Background and Purpose— The goals of this work were to investigate whether elevated total homocysteine (tHcy) measured within 24 hours of acute stroke was an independent risk factor for recurrent stroke and to compare levels of tHcy in groups of patients with diagnoses of ischemic and hemorrhagic cerebrovascular events. Methods— We performed a longitudinal study of 1039 stroke patients (mean age, 75 years). Fasting tHcy was measured the morning after primary admission. Patients were followed up for 15 months. Results— Serum homocysteine was significantly higher in the 105 patients who experienced a recurrent stroke during the follow-up period than in patients without recurrence. The geometric mean±SD was 13.4±10.7 versus 11.8±7.1 &mgr;mol/L (P =0.008), and the mean difference was 1.2 &mgr;mol/L [95% confidence interval (CI), 1.05 to 2.3]. In a multiple logistic regression model, tHcy was an independent explanatory variable of recurrent stroke within 15 months (odds ratio, 1.3; 95% CI, 1.1 to 1.5) for each increase in tHcy of 10 &mgr;mol/L. At the index event, serum homocysteine was significantly higher in 909 patients with ischemic cerebrovascular events than in 130 patients with intracerebral hemorrhage (geometric mean, 12.1±7.3 versus 10.4±5.2 &mgr;mol/L;P <0.001). Conclusions— The data in this study indicate that elevated tHcy is an independent risk factor for recurrent stroke.

Smoking Related to 24-h Ambulatory Blood Pressure and Heart Rate A Study in 352 Normotensive Danish Subjects

This study shows the association between smoking and both office and ambulatory blood pressure. By means of stratification, a uniform number of subjects of both sexes and spanning 6 decades (aged 20 to 79 years) were recruited randomly from the local community register. A total of 352 subjects participated, including 161 smokers. Smokers (both sexes and all age groups summed), as compared with nonsmokers had statistically significant lower office blood pressure as follows (mean systolic +/- SED/mean diastolic +/- SED): (systolic and diastolic, -6.8 +/- 2.1/-3.9 +/- 1.3); day ambulatory blood pressure (diastolic, /-2.8 +/- 1.0); and night ambulatory blood pressure (systolic and diastolic, -4.2 +/- 1.8/-3.9 +/- 1.1). The intraperson variability of the day ambulatory blood pressure (as measured every 15 min) was identical for the smokers and the nonsmokers. Smokers were found to have a diminished white coat effect; this diminished white coat effect has not previously been described. The major white coat effect was seen in the older nonsmokers, whereas the diminished white coat effect was most pronounced in the older male smokers and in the younger female smokers. Smokers seem to have a diminished white coat effect, as well as a lower ambulatory blood pressure throughout the day (diastolic) and at night (systolic and diastolic). The similar intraperson variability found in the smokers and nonsmokers blood pressure further speaks for a consistently lower blood pressure in smokers as compared with nonsmokers.

Relationship Between Baseline Blood Pressure Parameters (Including Mean Pressure, Pulse Pressure, and Variability) and Early Outcome After Stroke Data From the Tinzaparin in Acute Ischaemic Stroke Trial (TAIST)

Background and Purpose— High blood pressure (BP) in acute stroke is associated independently with a poor outcome. Recent evidence suggests that other hemodynamic parameters may also be associated with outcomes following stroke. Methods— The relationship between baseline BP, heart rate, and other hemodynamic parameters, and early outcomes were assessed using data from TAIST trial. Results— Death or neurological deterioration at day 10 was associated, both in unadjusted and adjusted analyses, with systolic BP (adjusted OR, 1.02; 95% CI, 1.01–1.03), mean arterial pressure (OR, 1.02; 95% CI, 1.01–1.04), pulse pressure (OR, 1.02; 95% CI, 1.01–1.03), and BP variability (OR, 1.03; 95% CI, 1.01–1.05). Similar relationships were noted for deterioration alone, and recurrent stroke. Conclusions— Early death or neurologic deterioration, deterioration, and recurrent stroke are associated independently with high systolic BP, mean arterial pressure, pulse pressure, and BP variability. These measures offer potential therapeutic targets for improving early outcome after acute ischemic stroke.

Acute hypoxia and cytochrome P450–mediated hepatic drug metabolism in humans

Our objective was to investigate the effect of acute hypoxia on the activity of hepatic cytochrome P450 (CYP) enzymes.

Effect of growth hormone on hepatic cytochrome P450 activity in healthy elderly men

Our objective was to study the effect of recombinant human growth hormone (rhGH) on hepatic cytochrome P450 (CYP) activity in 30 healthy elderly men.

Intravenous tranexamic acid for hyperacute primary intracerebral hemorrhage: Protocol for a randomized, placebo-controlled trial:

Rationale Outcome after intracerebral hemorrhage remains poor. Tranexamic acid is easy to administer, readily available, inexpensive, and effective in other hemorrhagic conditions. Aim This randomized trial aims to test the hypothesis that intravenous tranexamic acid given within 8u2009h of spontaneous intracerebral hemorrhage reduces death or dependency. Design Phase III prospective double-blind randomized placebo-controlled trial. Participants within 8u2009h of spontaneous intracerebral hemorrhage are randomized to receive either intravenous tranexamic acid 1u2009g 10u2009min bolus followed by 1u2009g 8u2009h infusion, or placebo. Sample size estimates A trial of 2000 participants (300 from start-up phase and 1700 from main phase) will have 90% power to detect an ordinal shift of the modified Rankin Scale with odds ratio 0.79. Study outcomes The primary outcome is death or dependency measured by ordinal shift analysis of the 7 level mRS at day 90. Secondary outcomes are neurological impairment at day 7 and disability, quality of life, cognition, and mood at day 90. Safety outcomes are death, serious adverse events, thromboembolic events, and seizures. Cost outcomes are length of stay in hospital, readmission, and institutionalization. Discussion This pragmatic trial is assessing efficacy of tranexamic acid after spontaneous intracerebral hemorrhage. Recruitment started in 2013; as of 15th January 2016 1355 participants have been enrolled, from 95 centers in seven countries. Recruitment is due to end in 2017. TICH-2 Trial is registered as ISRCTN93732214.

Effect of ethanol and pH on the adsorption of acetaminophen (paracetamol) to high surface activated charcoal, in vitro studies.

Background: Paracetamol (acetaminophen) intoxication often in combination with ethanol, is seen commonly in overdose cases. Doses of several grams might be close to the maximum adsorption capacity of the standard treatment dose (50 g) of activated charcoal. The aim of this study was to determine the maximum adsorption capacity for paracetamol for two types of high surface-activated charcoal [Carbomix® and Norit Ready-To-Use (not yet registered trademark in Denmark) both from Norit Cosmara, Amersfoort, The Netherlands] in simulated in vivo environments: At pH 1.2 (gastric environment), at pH 7.2 (intestinal environment), and with and without 10% ethanol. Methods: Activated charcoal, at both gastric or intestinal pHs, and paracetamol were mixed, resulting in activated charcoal–paracetamol ratios from 10:1 to 1:1. In trials with ethanol, some of the gastric or intestinal fluid was replaced with an equivalent volume of ethanol, resulting in an ethanol concentration of 10% v/v. After incubation, the concentration of unabsorbed paracetamol was analyzed by high-performance liquid chromatography. The maximum adsorption capacity of paracetamol to activated charcoal was calculated as mg paracetamol adsorbed/g activated charcoal, using Langmuirs isotherm. Results: Carbomix [95% confidence limits are shown in square brackets]: 623.7 [612.8;634.5] mg paracetamol adsorbed/g activated charcoal (pH 1.2), 626.2 [611.6;640.9] mg paracetamol adsorbed/g activated charcoal (pH 7.2); Norit Ready-To-Use: 693.6 [676.8;710.5] mg paracetamol adsorbed/g activated charcoal (pH 1.2), 722.6 [687.4;757.9] mg paracetamol adsorbed/g activated charcoal (pH 7.2). For experiments with ethanol (10% v/v) the results with Carbomix were 465.7 [449.2;482.2] mg paracetamol adsorbed/g activated charcoal (pH 1.2), 498.6 [481.8;515.6] mg paracetamol adsorbed/g activated charcoal (pH 7.2); with Norit Ready-To-Use: 617.2 [606.6;627.7] mg paracetamol adsorbed/g activated charcoal (pH 1.2), 640.6 [624.9;656.4] mg paracetamol adsorbed/g activated charcoal (pH 7.2). Conclusion: Under conditions simulating immediate treatment with charcoal, a standard dose of 50 g of either of the two tested activated charcoals adsorbed a sufficient amount of paracetamol to be beneficial in the treatment of the majority of overdoses of this drug. For both types of activated charcoal, with or without ethanol, there was no significant difference in the adsorption of paracetamol at pH 1.2 and 7.2. Norit Ready-To-Use had a larger maximum adsorption capacity than Carbomix, and was not as sensitive as Carbomix to environmental changes (pH and ethanol). The presence of 10% ethanol lowered the adsorption capacity of the two tested activated charcoal preparations by an amount that might be clinically relevant in cases of intoxications by high-gram doses.

Enantioselective determination of isradipine in human serum using chiral stationary phase liquid chromatography and gas chromatography with nitrogen selective detection.

rac-Isradipine is a dihydropyridine type calcium antagonist. Its calcium entry blocking effect is due primarily to the (+)-(S)-enantiomer. This study describes a sensitive enantioselective method for the determination of isradipine in human serum. Following alkaline extraction into hexane, the enantiomers of isradipine are separated quantitatively by high-performance liquid chromatography on a Chiralcel OJ column at 39 degrees C. The collected fractions were evaporated and assayed using capillary gas chromatography on a HP 50+ column with nitrogen selective detection. Using 2.0 ml of serum, 0.7 nmol/1 (0.26 ng/ml) of each enantiomer could be determined with acceptable precision. The method has successfully been used to measure (+)-(S)- and (-)-(R)-isradipine concentrations in samples from volunteers after intravenous and oral administration of isradipine.

Bioavailability and Pharmacokinetics of Isradipine after Oral and Intravenous Administration: Half‐Life Shorter than Expected?

Isradipine is a calcium channel-blocking agent of the dihydropyridine type, used in the treatment of hypertension. A terminal half-life of 8-9 hr has been reported, in several pharmacokinetic studies after oral administration of isradipine. In a yet unpublished study a much shorter half-life was observed, and the present trial was therefore conducted in order to estimate the half-life after intravenous administration of isradipine. The bioavailability was estimated as well. In a randomised cross-over design ten healthy young volunteers were given either isradipine orally or an intravenous infusion. The two study periods were separated by at least 3 days. Blood samples for measurement of isradipine concentration were collected for 10-12 hr after administration and half-life and bioavailability were estimated. Mean terminal half-life after intravenous administration was calculated to be 2.8 hr, and the bioavailability to be 0.28. None of the 10 subjects suffered from side effects. In the present intravenous study the half-life of isradipine seems to be of much shorter than demonstrated in previous oral studies.