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Biomedical subjects

K Simonsen

Publications and source records attributed to K Simonsen.

At least 19 recordsLinked to original sources

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

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

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

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

[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

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

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

[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

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

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

[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

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

[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

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

PEEP-masks in patients with severe obstructive pulmonary disease: a negative report.

Positive pressure during expiration by face masks applied by the patient has gained wide acceptance in the treatment of chronic bronchitis, but the efficacy is still unproven. The effect of 6 months of treatment with PEEP-masks (positive end-expiratory pressure) was therefore studied in 47 patients with severe irreversible obstructive pulmonary disease (forced expiratory volume in one second (FEV1) about 1 l), and mucus hypersecretion. Patients were double-blindly randomized to at least 45 min daily treatment with PEEP-masks with either 10 or 0 cm water pressure. After 6 months of treatment, no statistical difference was found between the two groups in change of median values (month 6 - month 0) of FEV1, forced vital capacity (FVC), arterial oxygen tension (PaO2), amount of sputum or dyspnoea. Median values of arterial carbon dioxide tension (PaCO2) decreased significantly (0.03 kPa) in the placebo group. Cough intensity and dyspnoea during walking on staircases improved significantly in the placebo group. No difference among groups was found in number of days bedridden, hospitalized, number of exacerbations or antibiotic consumption. We conclude, that the use of PEEP-masks in these patients is without clinical documentation and cannot be recommended.

Adult

Dose-response relationship and incidence of adverse drug reactions with isradipine in patients with essential hypertension.

Based on pooled data from three randomized placebo-controlled dose-finding studies in a total of 489 patients, the dose-response relationship for efficacy and adverse events was estimated, using the Michaelis-Menten equation: Effect = maximal effect multiplied by dose/constant plus dose. Three conclusions were derived from the pooled data: (1) A marked increase in efficacy is seen when the reduction in diastolic blood pressure after one week of treatment is compared with that seen after five weeks of treatment, with both placebo and active treatment. Thus, dose increases should preferably be made at intervals of at least four weeks to avoid unnecessarily high doses. (2) Isradipine 2.5 mg twice daily offers an efficacy of approximately 80 percent of the maximum with an incidence of adverse events which, statistically, is not significantly different from the incidence seen in the placebo groups. (3) With continued treatment, a marked decrease in the incidence of adverse drug reactions is seen between the first and fifth weeks, especially with doses at 1.25 and 2.5 mg twice daily. However, with doses above 10 mg per day, this effect is no longer evident.

Antihypertensive Agents