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Biomedical subjects

K Simonsen

Publications and source records attributed to K Simonsen.

At least 19 recordsLinked to original sources
PubMed2000

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 In a yet unpublished study a much shorter half-life was observed, and the present trial was therefore conducted in order to estimate the half-life after intravenous administration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.

Administration, Oral↗
PubMed1999

Rapid and simple determination of hereditary haemochromatosis mutations by multiplex PCR-SSCP: detection of a new polymorphic mutation.

Hereditary haemochromatosis is a common inherited disorder leading to excessive accumulation of iron in various organs. Two missense substitutions at the HFE-gene have recently been associated with the disease, 187C G and 845G-->A (mutations H63D and C282Y, respectively). We present a simple, rapid PCR-SSCP multiplex screening method allowing the simultaneous detection of both substitutions. Furthermore, testing the method on 420 Danish blood donors revealed the presence of a hitherto undetected third substitution in 13 individuals. The new substitution, a 193A-->T transversion, affects codon 65 changing the code for serine to that of cysteine (S65C). It may thus have functional consequences for the HLA class protein encoded by the HFE-gene. The allele frequencies observed were: H63D 14.8%, C282Y 6.2% and S65C 1.5%, which for the two former alleles are in agreement with frequencies reported for other North European population samples.

Adolescent↗
PubMed1999

Evaluation of pneumonia diagnosis in intensive care patients.

The aims of this study were to investigate the frequency of bronchopneumonia diagnosed by histological criteria among autopsied intensive care unit (ICU) patients and to compare these with rates of pneumonia diagnosed by conventional clinical methods. The study material comprised 141 autopsied ICU patients from 7 ICUs in university hospitals in Copenhagen from a 1-y period. A total of 20 lung tissue specimens were sampled from each patient and the histopathological diagnoses were classified as no, mild, moderate or severe bronchopneumonia. Inter-observer variation was calculated using kappa statistics. Demographic data and diagnoses of pneumonia were registered from the patient files. Twenty-six percent of the patients had pneumonia diagnosed whilst in the ICU. Histological evidence of pneumonia, found for every second patient, was regarded as the gold standard. Diagnosis of pneumonia in the ICU had a sensitivity of 29% and if diagnoses of pneumonia during the month before ICU-admission were included, a sensitivity of 60% was found. Specificity for pneumonia diagnosed in the ICU was 77%. The percentage of all ICU-patients with pneumonia was calculated to be between 36% and 56%, depending on the extent of excess mortality attributable to pneumonia. Pulmonary segments with histologically diagnosed pneumonic lesions were distributed diffusely, although the upper segments tended to be affected less. Nearly all patients had other histopathological findings than bronchopneumonia. The reliability coefficient among the 6 pathologists was found to be moderately good (kappa = 0.45).

Adolescent↗
PubMed1998

Citalopram concentrations in samples from autopsies and living persons.

Concentrations of citalopram in medicolegal samples from 92 autopsies and 27 living persons are described. In autopsy cases in which citalopram alone was the cause of death, concentrations ranged from 2.0 to 6.2 mg/kg whole blood. In autopsy cases in which citalopram together with other substances was considered to be the cause of death, the concentrations of citalopram ranged from 0.6 to 5.2 mg/kg whole blood. In autopsy cases toxic concentrations ranged from 0.4 to 0.9 mg/kg whole blood and therapeutic concentrations from 0.03 to 0.6 mg/kg whole blood. In samples from living persons the concentrations of citalopram in whole blood were 0.02 to 0.3 mg/kg.

Adult↗
PubMed1996

Nerve growth factor receptor expression in heterotransplanted vestibular schwannoma in athymic nude mice.

Nerve growth factor (NGF) has the potential to induce cellular differentiation in various neoplastic and non-neoplastic cell lines. The purpose of the present study was to determine by immunohistochemistry: the presence/distribution of nerve growth factor receptor (NGFr), cellular proliferation expressed by Ki-67, and intratumoral vascularization visualized by the endothelial marker CD 31, in a series of 61 human vestibular schwannoma heterotransplants in athymic nude mice. The immunohistochemical results were correlated to the observed macroscopic growth in 22 heterotransplants (36%) with obvious macroscopic growth, versus 39 heterotransplants (64%), that were stationary or regressed. The positive immunoreactivity to NGFr, number of Ki-67 positive nuclei and number of intratumoral vessels were significantly higher in the 22 (36%) growing heterotransplants than in the 39 heterotransplants (64%), which were stationary or regressed (p < 0.00005, p = 0.046, p < 0.00001). NGFr was statistically related to the vascularity of the heterotransplants expressed by CD 31 (p<0.00001). No significant relation was observed between NGFr and the proliferation, as estimated by Ki-67. The results revealed that the macroscopic growth of VS in athymic nude mice was associated with strong positive expression of NGFr, high cellular proliferation expressed by Ki-67 and vivid neovascularization expressed by CD 31. The possible clinical applicability of the achieved results is discussed.

Animals↗
PubMed1995

Priming and treatment with molgramostim (rhGM-CSF) in adult high-risk acute myeloid leukemia during induction chemotherapy: a prospective, randomized pilot study.

In a randomized study of 18 adult patients with high-risk or advanced acute myeloid leukemia (AML) we investigated the effect of supplementing conventional induction chemotherapy with recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF). For comparison, a historical control group of 90 patients treated for de novo AML with conventional chemotherapy during the previous period, 1984-1990, was also analyzed. Before induction chemotherapy, 10 patients were randomized to receiving rhGM-CSF, starting on day 1 to 3 before chemotherapy and continued for a maximum of 21 days after the start of induction treatment. Fatal complications and treatment outcome did not differ between the study groups and historical controls. Nor were there any differences between the groups in terms of hematological toxicity, e.g. time to three-lineage regeneration and need for supportive therapy. However, sequential weekly bone marrow examinations revealed a prolonged reduction of the relative number of myeloid (CD33-positive) marrow cells in the rhGM-CSF treated group. Although the small number of patients studied may not permit a definite conclusion, this randomized study did not demonstrate major beneficial effects of combining rhGM-CSF with standard induction chemotherapy in high-risk patients with AML.

Adolescent↗
PubMed1995

Iatrogenic radiant heat burns in severely asphyxic newborns.

We report two cases of newborns who developed second-degree burns following resuscitation under infra-red heating lamps. Both infants were asphyxic and suffered from insufficient peripheral circulation which, combined with the long duration of the exposure to the light, contributed to the development of the lesions. Both infants died shortly after birth for reasons other than the burns.

Abdominal Injuries↗
PubMed1994

[Malignant lymphoma of the heart].

A case of malignant lymphoma in the heart is presented. A 75-year-old man was admitted to hospital for dyspnea. Echocardiography revealed a right atrial tumour and enlargement of the right ventricular wall. Myxoma was suspected clinically. The patient died from rapidly progressing congestive heart failure. Autopsy revealed massive infiltration of the myocardium in the right atrium, right ventricle and the tricuspid valves by a high grade malignant non-Hodgkin lymphoma of B-cell type. Malignant lymphoma was found at no other sites except for a five mm tumour in the thyroid gland and a larger six by five by four cm mediastinal tumour.

Aged↗
PubMed1993

Recycling with nicotine patches in smoking cessation.

The aim was to evaluate if recycling of failures from a smoking cessation study may be of value. The study comprised 126 smokers (50%) of 252 failures, from a double-blind smoking cessation trial with nicotine patch, who accepted recycling after 1 year. Subjects were allocated nicotine patches delivering 15, 20 or 25 mg of nicotine (over 16 hours) according to their base-line saliva cotinine concentrations in an open trial. The treatment period was 12 weeks followed by tapering over 6 weeks. The percentage of quitters after 3, 12, 26, and 52 weeks was 44, 20, 7 and 6%, respectively. After 26 weeks, all subjects had relapsed in the group previously treated with active nicotine patch compared with 12% abstainers in the previous placebo subjects. The sustained abstinence rate without slips after one year was 2%. Recycling does not seem to be of long-term clinical relevance in our set-up for subjects initially treated with nicotine, but of some value in subjects quitting without nicotine therapy initially.

Administration, Cutaneous↗
PubMed1993

Pharmacokinetics and dynamic response of plain and slow release isradipine formulations in moderately hypertensive patients.

The pharmacokinetic variables and antihypertensive effect of the calcium antagonist isradipine, were investigated in 30 hypertensive patients. Isradipine was given orally in parallel group design in plain and slow release formulations in doses of 2.5 mg twice daily and 5.0 mg once daily, respectively. Isradipine concentration in serum was measured by a sensitive RIA method after the first dose and after 6 weeks of treatment. The pharmacokinetics and concentration/effect relationship after the first dose and after 6 weeks of treatment were compared. No differences in pharmacokinetics were observed between single and multiple dosing. Data were in accordance with results from studies in healthy volunteers. Rate, but not extent of bioavailability differs between the two isradipine formulations. Antihypertensive efficacy of the two formulations was similar (16/11 and 19/15 mmHg), and a significant time dependent increase in Emax from 10/3 mmHg to 23/14 mmHg after 6 weeks of treatment was observed.

Blood Pressure↗
PubMed1992

[A double-blind trial of nicotine patches in smoking cessation].

The use of nicotine chewing gum combined with psychological support improves the success rate in stopping smoking. We studied the safety and efficacy of a transdermal nicotine patch in stopping smoking. We conducted a double-blind randomized study comparing the effect of a 16-hour nicotine patch (15 +/- 3.5 mg of nicotine in 16 hours) with those of a placebo patch. Of the 289 smokers (207 women and 82 men) enrolled in the study, 145 were treated with nicotine patches and 144 with placebo patches for 16 weeks. The rates of sustained abstinence were significantly better with active treatment than with the placebo: 53, 41, 24 and 17% of those in the nicotine-patch group were abstinent after 6, 12, 26, and 52 weeks, respectively, as compared with 17, 10, 5 and 4% of those in the placebo-patch group (p less than 0.0001). Only two subjects with the nicotine patch and one with the placebo patch withdrew from the study because of side effects. The nicotine skin patch proved to be safe and effective, as demonstrated by a higher rate of abstinence than with the placebo.

Administration, Cutaneous↗
PubMed1992

Long-term nicotine substitution after application of a 16-hour nicotine patch in smoking cessation.

The purpose of the study was to examine long-term nicotine substitution and its variability during use of a nicotine patch. In two smoking cessation studies a 16-h nicotine patch, releasing 15 mg nicotine, was applied daily for 16 h over 12 weeks, to 167 smokers. Salivary cotinine was highly correlated with plasma cotinine (r = 0.93), and the concentration of cotinine in a single sample in the afternoon was well correlated with the AUCcontinine over 24 h (r = 0.94). The salivary cotinine concentration after 1 week in 60 abstainers was 183 ng.ml-1. After 3,6 and 12 weeks the cotinine concentrations were 86%, 79% and 59% of the 1-week value. The degree of nicotine compensation attained by the patch after 1 week was 52% (SD 24%) in subjects who succeeded in stopping smoking for at least 3 weeks. A quarter of the subjects achieved a compensation of less than 35% of their usual nicotine intake. Nicotine substitution with this 16-h nicotine patch was stable and the risk of overcompensation was small in this group of smokers.

Administration, Cutaneous↗
PubMed1992

Smoking habits in relapsed subjects from a smoking cessation trial after one year.

Reports of smoking cessation studies often claim that many relapsed subjects reduce their smoking. We investigated the smoking habits of relapsers 1 year after quitting in a smoking cessation trial using nicotine or placebo patches. All 289 participants in that study were summoned to a 1-year follow-up visit--148 (57%) of 259 relapsers attended, as did all 30 sustained abstainers. Fewer than 1% of the subjects had quit spontaneously after the primary relapse. Daily cigarette consumption, standard nicotine yield per cigarette, saliva cotinine concentration, expired carbon monoxide level and two nicotine dependency scales were assessed at entry and at the 1-year follow-up. In five of these six smoking-related characteristics, there was a small but significant mean reduction of 7%-27%. A significant weight gain of 0.5 +/- 2.9 kg (mean +/- SD) was recorded in the relapsers compared with 4.8 +/- 4.2 kg for abstainers (p less than 0.001). It is concluded that smoking habits in relapsers are relatively unchanged, and thus the most important outcome measure in smoking cessation trials is abstinent subjects.

Administration, Cutaneous↗
PubMed1991

[Histiocytic necrotizing lymphadenitis (Kikuchi's disease)].

We report a typical case of histiocytic necrotizing lymphadenitis (Kikuchi's disease). To our knowledge this is the first reported case in Denmark. Histiocytic necrotizing lymphadenitis is a benign self-limiting disorder, which mainly involves the cervical lymph nodes. The disease commonly affects young women of Asian origin, but it is seen more and more often in other populations. Clinically and histologically it can be misdiagnosed as malignant lymphoma. The etiology is unknown.

Adult↗
PubMed1991

A double-blind trial of a 16-hour transdermal nicotine patch in smoking cessation.

BACKGROUND: The use of nicotine chewing gum combined with psychological support improves the success rate in quitting smoking. We studied the safety and efficacy of a transdermal nicotine patch in smoking cessation. METHODS: We conducted a double-blind randomized study comparing the effects of a 16-hour nicotine patch (15 +/- 3.5 mg of nicotine in 16 hours) with those of a placebo patch. Of the 289 smokers (207 women and 82 men) enrolled in the study, 145 were treated with nicotine patches and 144 with placebo patches for 16 weeks. RESULTS: Rates of sustained abstinence were significantly better with active treatment than with placebo: 53, 41, 24, and 17 percent of those in the nicotine-patch group were abstinent after 6, 12, 26, and 52 weeks, respectively, as compared with 17, 10, 5, and 4 percent of those in the placebo-patch group (P less than 0.0001). Only two subjects with the nicotine patch and one with the placebo patch had to withdraw from the study because of side effects. CONCLUSIONS: The nicotine skin patch proved to be safe and effective, as demonstrated by a higher rate of abstinence than with placebo. However, the absolute rate of abstinence after one year was only 17 percent, which is lower than the rate in studies that have combined the use of nicotine chewing gum with behavioral therapy.

Administration, Cutaneous↗
PubMed1991

[Registration of postoperative wound complications at a department of vascular surgery].

During the period 1 March 1987 to 31 December 1988, current registration of all vascular surgical operations in the Department of Vascular Surgery RK, Rigshospitalet, was undertaken employing a PC-based programme (DANOP-DATA). A total of 1,898 primary vascular surgical operations were performed on 1,335 patients. During the entire period, 48 (2.5%) patients with wound infection were registered. In half of these, the infection was superficial and in the remainder the infection was deep. Comparison between 1987 and 1988 revealed a non-significant tendency towards a lower incidence of infection in 1988. Significantly more wound infections were found after non-sterile operations (p = 0.005). Significantly more deep infections were found on employing synthetic vascular prostheses (p less than 0.00001) and with inguinal incisions (less than 0.05). No significant connection could be found with age, duration of preoperative hospitalization, duration of operation and the degree of planning of the operation. The authors find that computer-based monitoring of the surgical activity is a good which renders current assessment and analysis of the pattern of complications possible. The authors did not find that DANOP-DATA was sufficient for registration in a special department for vascular surgery and a programmel (KARBASE) has been developed which is more suitable for this purpose.

Adolescent↗
PubMed1991

A randomized comparison of isradipine slow release given once daily with isradipine twice daily on 24 hour blood pressure in hypertensive patients.

Isradipine, a new calcium channel blocker, was given to 32 patients with mild to moderate essential hypertension. After a run-in period of three weeks, 32 patients were randomized double-blindly to six weeks' treatment with either isradipine 2.5 mg twice daily or isradipine 5.0 mg once daily in a modified release formulation. Based on conventional 'clinic' BP measurements 12 or 24 hours postdose, the two treatments resulted in clinically relevant BP reduction (16/11 and 19/15 mmHg) without reflex tachycardia. No differences were seen between the groups. Efficacy increased throughout the study period. By determination of the 24 hour BP profile with a noninvasive method, the two groups were comparable during the placebo period, and no differences were seen between the two treatments. Both treatments resulted in satisfactory BP reduction during 24 hours (daily reduction of 4/6 and 12/9 mmHg twice daily and once daily dosing respectively). One third of the patients had 'white-coat' hypertension based on ambulatory daytime mean BPs, compared with conventional measurements. No relationship was found between the initial BP lowering effect and the effect after long-term treatment with isradipine in either dose.

Adult↗