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Biomedical subjects

H K Nielsen

Publications and source records attributed to H K Nielsen.

At least 19 recordsLinked to original sources

[Anticoagulant and thrombolytic therapy in deep venous thrombosis and pulmonary embolism].

During the last 10 years anticoagulant (AC) therapy and thrombolytic treatment of venous thromboembolism (VT) have been evaluated in randomized studies. Adjusted subcutaneous (s.c.) heparin and low molecular weight heparin (LMWH) are found at least as effective as intravenous (i.v.) infusion of heparin in deep venous thrombosis (DVT) without an increased bleeding risk. In pulmonary embolism (PE) randomized trials assessing the efficacy of s.c. heparin and LMWH are missing. Oral AC-treatment can be initiated from the first or second day in VT. The recommended duration is three months for medical patients, and 4 weeks seem appropriate for surgical patients that are completely mobilized and without persisting predisposing factors. Long-term efficacy of thrombolytic treatment of DVT has only been assessed in small trials showing a trend towards reduced risk of developing chronic venous insufficiency. Short-term thrombolytic treatment of DVT is evaluated in ongoing trials. In the treatment of PE short-term thrombolysis with either t-PA or urokinase is found to be as effective as long-term thrombolytic treatment with a reduced bleeding risk. Thrombolytic therapy rapidly reduces embolic mass and stabilizes haemodynamics, but mortality and long-term efficacy of thrombolysis and AC-treatment versus AC-treatment alone in PE are being assessed in ongoing studies.

Anticoagulants

[Interaction between thrombocytes and blood vessel wall--significance for acute ischemic coronary syndromes].

Intracoronary thrombus formation is the essential pathogenic substrate for the development of the acute ischaemic coronary syndromes (unstable angina pectoris (UAP), acute myocardial infarction (MI) and sudden cardiac death). Rupture of an atherosclerotic plaque has been shown to be of major importance for initiation of the thrombogenic process, but the reactivity of the circulating platelets and their interaction with the coronary vessel wall are also important for the formation and propagation of the intracoronary thrombus. The evidence favouring the role of platelets is: 1) the aggregability of platelets is increased in the morning where the incidence of MI and sudden cardiac death has been shown to be high, 2) shortened bleeding time and increased mean platelet volume in the acute phase of MI, 3) the synthesis of proaggregatory thromboxane A2 is increased in the acute phase of MI and in UAP, 4) a high platelet count and an increased ADP-induced platelet aggregation predispose to MI and death in healthy males, 5) high mean platelet volume and increased spontaneous platelet aggregation are risk factors for MI and death in patients with a recent MI, 6) the platelet inhibitor, acetylsalicylic acid, has been shown to reduce the incidence of MI and mortality in patients with silent myocardial ischaemia, stable and unstable angina pectoris and in patients with MI.

Angina, Unstable

Irradiation of bone metastases in breast cancer patients: a randomized study with 1 year follow-up.

The results from a prospective randomized trial comparing two different radiation schedules for treatment of painful bone metastases in women with recurrent breast cancer are presented. A total of 217 patients with painful bone metastases were randomized to either 30 Grey (Gy) in ten fractions, five fractions a week (5F/W) or 15 Gy in three fractions 2F/W. The effect of treatment was evaluated by pain assessment, the radiological response and the degree of side-effects. The patients were rated at start of treatment and after 1, 3, 6 and 12 months. No difference between the two radiation regimes was found, neither in achieved pain relief, improvement in level of activity and medication, nor was there any difference in radiological response and side-effects from treatment. Both regimes resulted in a significant improvement in both pain score and level of activity 1 month after treatment, an improvement which persisted during the follow-up period. We conclude that 15 Gy given in three fractions 2F/W is as effective as 30 Gy in ten fractions 5F/W, but more convenient to the patient and of less cost to society.

Adult

Physical examinations and laboratory tests in antenatal care visits in Denmark. Do reported practice and current official guidelines concord with results of literature reviews? A nationwide study of the public scheme of shared antenatal care in general practice, centres of midwifery and hospital outpatients' clinics.

OBJECTIVE: To analyse physical examinations and laboratory tests reported in antenatal care visits in relation to official guidelines and reviews of appropriateness. DESIGN: A nationwide cross sectional study based on questionnaires completed by general practitioners (GPs), midwives, and hospital doctors. Physical examinations and laboratory tests in connection with one specific visit were reported. SUBJECTS: The questionnaires were completed by 722 GPs (61% of eligible from a random sample), 584 midwives (86% of eligible), 250 hospital doctors who made health examinations in pregnancy, week 16-18 (63% of eligible), and 181 hospital doctors who saw women with at-risk pregnancies (55% of eligible). RESULTS: General practice: weight, blood pressure (BP) measurement, and test for proteinuria were reported in more than 90% of visits. Urine culture was reported in 46%, and cervical smear in 41% of first visits. Rubella antibody test at the first visit was only reported in 23% of nulliparae. Vaginal examination was reported in 95% of first visits. Fewer were reported in second (27%) and third (48%) routine visits during pregnancy. Midwives: checks of BP, oedema, and proteinuria were reported in more than 95% of visits irrespective of week of gestation. Vaginal examination was reported in about a third of checkups. Hospitals: vaginal examination was reported in 66% of checkups in at-risk pregnancies. CONCLUSIONS: A surplus of resources were spent on (repeat) examinations and tests with little or no documented benefit. Cervical cytology was grossly overused. Urine culture and rubella serology were not sufficiently applied.

Clinical Laboratory Techniques

[Preventive check-ups of pregnant women in Denmark. Common ailments in pregnancy].

The study was conducted in order to describe the extent and content of advice on common ailments in pregnancy given by doctor or midwife during prenatal visits and to describe the frequency of ailments in the period before the visits. The design was a nationwide cross-sectional study based on questionnaires completed by pregnant women who had seen a general practitioner (GP), midwife or hospital doctor for prenatal care. Ailments and advice in connection with one specific visit were reported. The questionnaires were completed by 517 women after a prenatal visit to their GP (92% of eligible), by 514 women after a prenatal visit to the midwife (91% of eligible), and by 203 women after a prenatal visit to a doctor in the maternity department in pregnancy week 16-18 (84% of eligible). The results showed that nausea, pollakisuria, tiredness and heartburn had been present during the period before the visit in about half the women. Between a third and a fourth of the women had been discomforted by back pain, discharge or cramps. From 15 to 58 percent had been given advice, depending on the symptom. The advice was of many different kinds. To a large extent the women wanted to talk to the health professionals about the ailments, and most often they wanted to talk to a midwife about the ailments. We conclude that common ailments of pregnancy are frequent and they should be investigated more. Nearly all pregnant women want to talk about the subject during prenatal visits. The objectives of giving advice should be clearer, and clinical studies of the effectiveness of the advice are needed.

Cross-Sectional Studies

[The optimal administration time for neostigmine following atracurium blockade. Kinetics of antagonists].

UNLABELLED: The aims of the study were: (1) to predict reversal time from intensive atracurium blockade; and (2) to determine the optimal time of neostigmine administration during recovery from atracurium blockade, i.e., the time at which the administration of neostigmine results in the shortest total recovery time (time from administration of last supplemental dose of atracurium to train-of-four [TOF] ratio 0.70), and at the same time results in the shortest time from administration of neostigmine to TOF ratio 0.70. METHOD: The spontaneous and neostigmine-facilitated recovery in 52 healthy women anaesthetised with thiopentone, fentanyl, droperidol, and nitrous oxide was followed. Post-tetanic count (PTC) of TOF stimulation of the ulnar nerve and mechanomyography were used for monitoring neuromuscular transmission. The neuromuscular blockade was induced with atracurium 0.6 mg/kg and supplemental doses of 0.15 mg/kg were given when the first twitch response in the TOF (TH1) had recovered to 20%. Neostigmine 0.036 mg/kg body weight was given at different levels of neuromuscular blockade to 37 of the patients. RESULTS: Multiple regression analyses including pre-reversal time (time from administration of the last atracurium dose to neostigmine administration), PTC, weight, and age of the patients suggest that pre-reversal time is the best predictor of reversal time: reversal time = 27.3 min - (0.89 x pre-reversal time [min]; (SEE = 6.0 min). If pre-reversal time is unknown, PTC can be used: reversal time = 24 min - (4.5 x ln PTC) at time of reversal); (SEE = 6.8 min). Total recovery time was 47 min (SEM = 2.0 min, n = 15) in the patients allowed to recover spontaneously, and 29 min (SEM = 1.2 min, n = 29) in the patients reversed by neostigmine; the difference of 18 min (SE diff 2.0 min) was significant (P < 0.0005). The level of blockade indicated by PTC (1-24) at the time of reversal had no influence on the total recovery time. The spontaneous recovery times from reappearance of TH1 and TH1 = 10% to TOF ratio 0.70 were 29.2 min (SEM = 1.7 min) and 24.4 min (SEM = 2.6 min), respectively. DISCUSSION: The results suggest that pre-reversal time is the strongest predictor of reversal time when neostigmine is administered during intense atracurium blockade. To achieve the optimal time-saving effect, neostigmine must be given 18 min (the time saved by giving neostigmine) plus 7 to 11 min (needed for neostigmine to reach its peak effect), giving a total of 25 to 29 min before TOF ratio 0.70. As TH1 is between 1% and 10% 25 to 29 min before TOF ratio 0.70 is reached during spontaneous recovery, the optimal level of neuromuscular blockade for neostigmine administration in atracurium blockade is when TH1 is between 1% and 10%. CONCLUSION: Reversal time can be predicted as 27.3 min - (0.89 x prereversal time (min), and the optimal time of neostigmine administration in atracurium blockade appears to be when TH1 is 1%-10%.

Adult

Circadian and circatrigintan changes in osteoblastic activity assessed by serum osteocalcin. Physiological and methodological aspects.

The author has shown the existence of reproducible circadian changes and significant variation during the circatrigintan rhythm in the osteoblastic marker, serum osteocalcin. The author find that appropriate exploratory data analyses are important and often imperative tools in the demonstration of these low frequent rhythms, and the effects of intervention. The metabolism of osteocalcin needs further investigation since it is essential to consider the kinetic of serum osteocalcin in the interpretation of data. However, based on current knowledge of the kinetics of serum osteocalcin, and the variation in other osteoblastic markers, the author conclude that the results are indicative of the existence of biological rhythms in osteoblastic activity rather than changes in metabolic clearance. The physiological aspects on the circadian rhythm are that osteoblastic activity peaks during the early night and decrease in the morning in both men and women. The circadian osteoblastic activity is relatively stable during seasons and apparantly not acutely related to sleep. Modest doses of alcohol decrease serum osteocalcin within few hours but the circadian rhythm is not different in smokers compared with non-smokers. There are evidences for endogeneous cortisol as regulator of the osteocalcin rhythm especially by mediating the morning decrease in osteocalcin. Osteocalcin synthesis is not completely blocked by glucocorticoids since the effect is blunted by administration of 1,25-(OH)2D3. Although serum osteocalcin may respond to acute doses of several other osteotrophic hormones, it is doubtfull whether endogeneous PTH, 1,25-(OH)2D3, sex hormones, or growth hormone play any role as acute regulators of the circadian osteocalcin rhythm. The circatrigintan rhythm is characterized by highest levels of serum osteocalcin during the luteal phase. There is a significant cross correlation with the follicular increase in serum estradiol but the regulation of serum osteocalcin during the ovulatory cycle remains to be settled. The results, however, support the interaction between sex hormones and bone metabolism. The practical implications are that blood sampling for determination of serum osteocalcin should be strictly standardized with regard to the time of the day and the time since last medication or intervention with factors that may affect osteoblastic activity.

Circadian Rhythm

Intravenous acetylsalicylic acid--dose-related effects on platelet function and fibrinolysis in healthy males.

Low-dose acetylsalicylic acid (ASA) has been shown to be beneficial in patients with acute myocardial infarction and unstable angina pectoris. Oral administration of ASA is difficult in the acute phase of these syndromes. In this study we evaluated the effect of 25 mg, 50 mg or 100 mg of ASA given as an intravenous bolus injection on platelet function and fibrinolysis in healthy males and related this to plasma concentrations of ASA. No adverse effects were found. A complete inhibition of serum thromboxane B2 synthesis was demonstrated 5 min after injection of 100 mg ASA intravenously. ASA disappeared from the circulation within 60 min after bolus injection and at this time thromboxane B2 synthesis was inhibited dose-dependently by 71%, 90% and 100% for doses of 25 mg, 50 mg and 100 mg, respectively. Inhibition of thromboxane B2 synthesis after 100 mg of intravenous ASA was still 96.5% at 24 h and 93.4% at 48 h after the injection. The bleeding time measured at 30 min after ASA administration was significantly prolonged on the average by 70 s, 144 s and 211 s after 25 mg, 50 mg and 100 mg of ASA, respectively. Minor, but significant changes were found in tissue plasminogen activator antigen and in plasminogen activator inhibitor within the first hour after injection of low dose ASA, but similar changes were found after injection of saline. No change in tissue plasminogen activator activity was found.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

[The reliability of serum potassium levels measured in blood from a central venous catheter].

A clinical investigation was undertaken to assess the agreement between serum potassium (S-K) (1) in the peripheral venous blood and S-K in ten samples of 2 ml blood taken via a central venous catheter (2) where fluid containing potassium had been infused prior to taking the blood-samples (3). The results revealed that in order that S-K in 95% (twice the SD) of the samples taken from the central venous catheter is to fall within +/- 0.5 mmol/l as compared with S-K in the peripheral blood, it is necessary to discard the first 12 ml of blood withdrawn.

Blood Specimen Collection

Meniscal repair by fibrocartilage? An experimental study in the dog.

Longitudinal lesions in the avascular part of the dog's meniscus were repaired by implantation of a porous polyurethane. Ingrowing repair tissue was characterized by biochemical and immunological analysis. Histologically, repair tissue initially was composed of fibrous tissue containing type I collagen. After 3 months, fibrocartilaginous tissue developed inside the implants, whereas control defects only showed fibrous repair tissue. Both type I and II collagen, the major collagen types of normal meniscal fibrocartilage, could be detected in this newly formed fibrocartilage. It is concluded that fibrocartilage resembling normal meniscal tissue is formed and that longitudinal lesions can be healed after meniscal repair by implantation of a porous polymer.

Animals

Effects of a short course of oral phosphate treatment on serum parathyroid hormone(1-84) and biochemical markers of bone turnover: a dose-response study.

To investigate the possible use of oral phosphate as an activator of bone remodeling in coherence treatment of osteoporosis, 82 postmenopausal females, aged 50-75 years, were randomized to treatment with oral phosphate (750, 1500, or 2550 mg/day) or placebo for 7 days and followed for 4 months thereafter. All patients had sustained at least one previous fracture of the distal forearm and had a bone mineral content of the contralateral forearm or bone mineral density of the lumbar spine lower than normal mean for age. Urinary phosphate/creatinine ratio increased in a dose-dependent fashion during treatment (P less than 0.001), whereas no significant changes were seen in serum phosphate or serum calcium. Serum parathyroid hormone (PTH) rose significantly (P less than 0.05) during treatment to a maximum of 36 and 33% in the groups receiving 1500 and 2250 mg/day, respectively, whereas serum 1,25-dihydroxycholecalciferol remained unchanged. In the group receiving 1500 mg/day, mean serum osteocalcin was increased in the period from day 1 to day 28 (P less than 0.05), but no significant changes were observed in urinary hydroxyproline/creatinine ratio, or serum bone alkaline phosphatase. We conclude that a short course of oral phosphate treatment increases serum PTH considerably. Furthermore, 1500 mg/day but not 2250 mg/day increases serum osteocalcin. No clear biochemical evidence, however, of increased activation of bone remodeling could be demonstrated in either group.

Administration, Oral

Porous polymer implants for repair of full-thickness defects of articular cartilage: an experimental study in rabbit and dog.

Full-thickness defects of articular cartilage were repaired by implantation of porous polymer implants in rabbits and dogs. The quality of the repair tissue was determined by collagen typing with antibodies. Implants with varying pore sizes and chemical composition were used. The effect of loading and motion was determined by inserting implants higher than, level with and lower than the surrounding cartilage. It appeared that healing took place by formation of fibrocartilaginous repair tissue containing both type I and type II collagen. Hyaline cartilage was observed in a minority of the rabbits used but not in the dog. Fibrocartilage formation in the dog was simulated by implantation of a porous polymer. Chemical composition of the polymer did not alter the results, neither did loading of the implant. It is concluded that the formation of fibrocartilaginous repair cartilage is stimulated by implantation of a porous polymer. This tissue seemed to function adequately in the dog but did show signs of degeneration in the rabbit.

Animals

The accuracy of train-of-four monitoring at varying stimulating currents.

Train-of-four (TOF) monitoring of neuromuscular block at submaximal current stimulation has been recommended because it is less painful than monitoring at supramaximal stimulation. The measurement error, however, when using submaximal stimulation has not as yet been fully elucidated. The authors therefore quantified the measurement error of TOF monitoring at low currents near the initial threshold for stimulation (ITS) by assessing precision (the difference between duplicated TOF ratios measured at the same current) and accuracy (the difference between TOF ratios at lesser currents and the TOF ratio at 58 mA, which served as the reference standard method). A stable neuromuscular block at a TOF ratio of 0.40 and subsequently 0.70 was established in 20 patients using a continuous infusion of atracurium. The ulnar nerve was stimulated at the wrist using TOF stimulation, and the evoked twitch response of the adductor pollicis muscle was measured with a force-displacement transducer. The stimulating current was varied in 5-mA steps between ITS and 55 mA. Whereas there were no statistical significant differences between the mean TOF ratios at the different currents, the standard deviation increased with decreasing currents (P less than 0.01 at currents less than 40 mA). The precision was acceptable except at ITS, where the limits of precision (mean intracurrent difference in TOF ratio +/- two standard deviations) exceeded 0.05, which was the chosen acceptable difference. The standard deviation of the accuracy was significantly increased at currents less than or equal to ITS + 25 mA (P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Electric Stimulation

Inhibition of the morning cortisol peak abolishes the expected morning decrease in serum osteocalcin in normal males: evidence of a controlling effect of serum cortisol on the circadian rhythm in serum osteocalcin.

Osteocalcin (OC) in serum varies in a remarkably constant circadian rhythm with zenith at night and nadir in the morning. The factors controlling this rhythm are unknown, but several studies indicate that serum cortisol could be of major importance. We tested this hypothesis in a double-blind, placebo-controlled, cross-over study comprising 10 normal male volunteers (aged 23-31 yr) by measuring the response in serum OC and cortisol rhythms to a single dose of metyrapone (30 mg/kg body weight) administered at midnight. During placebo, serum cortisol consistently peaked early in the morning before 0730 h. Ingestion of metyrapone at 2400 h significantly postponed and flattened this peak (P less than 0.01). On both occasions, serum OC increased towards peak levels around 0300 h (P less than 0.01) with no overall differences in the OC profiles. However, when the serum OC time series were synchronized according to the individual cortisol nadirs, we found a significant (P less than 0.01) decrease in serum OC on the placebo day approximately 4 h after the cortisol nadir, whereas no significant changes (P greater than 0.50) were seen on the metyrapone day. Moreover, the mean serum OC level tended to be higher (P less than 0.10 in the interval 0-12 h, and P = 0.06 in the interval 4-8 h) on the metyrapone day compared with the placebo day. On the placebo day, the mean level of serum cortisol during the interval 0-4 h correlated inversely with the mean level of serum OC in the interval 4-8 h (r = 0.77, P less than 0.05). This relation was not found on the metyrapone day. In conclusion, administration of metyrapone, which reduced and postponed the early morning cortisol peak, abolished the normal morning decrease in serum OC. This strongly supports that changes in endogenous serum cortisol are of major importance for the circadian rhythm in serum OC.

Adult

Effects of short-term growth hormone treatment on PTH, calcitriol, thyroid hormones, insulin and glucagon.

We measured changes in serum insulin-like growth factor-1 (IGF-1), calcitriol, parathyroid hormone (PTH), thyroid hormones, insulin, and plasma glucagon in response to seven days of treatment with a pharmacological dosage of recombinant human growth hormone (r-hGH) (0.1 IU/kg sc twice daily) or placebo in 20 normal male volunteers to evaluate whether the effect of r-hGH on biochemical bone markers could be attributed to changes in these hormones. Serum IGF-1 (p < 0.001) and vitamin D-binding protein (p < 0.001) increased steadily during treatment returning to baseline at day 14. Total calcitriol (p < 0.01) and free calcitriol index (p < 0.001) increased transiently at day 4. Furthermore, serum insulin (p < 0.001) and both total (p < 0.001) and free triiodothyronine (p < 0.02) increased during treatment, while serum PTH and plasma glucagon remained unchanged. In conclusion, pharmacological doses of r-hGH increased not only IGF-1 but also free-calcitriol index, insulin, and free T3. The increase in these hormones may be co-responsible for some of the observed effects of r-hGH on bone turnover and calcium homeostasis.

Adult

Homologous radioimmunoassay of human osteocalcin.

Osteocalcin or bone gamma-glutamic acid-containing protein (GLA protein) was isolated from human bone and used to develop a homologous radioimmunoassay of human osteocalcin. The effect of age on serum osteocalcin was studied in 380 normal children and adolescents and 330 normal adults. The mean (+/- SD) values in adults were higher in men [25 +/- 5 micrograms/L (4.3 +/- 0.8 nmol/L)] than in premenopausal women [20 +/- 6 micrograms/L (3.4 +/- 1.0 nmol/L); P < 0.01], but both were lower than in postmenopausal women [29 +/- 2 micrograms/L (5.0 nmol/L)]. The highest concentrations were seen in girls [ages 10-12 years: 99 +/- 38 micrograms/L (17.0 nmol/L)] and boys [ages 14-16 years: 107 +/- 57 micrograms/L (18.4 nmol/L)]. These mean values were substantially higher than those previously reported for results of heterologous osteocalcin radioimmunoassays but the correlation (r = 0.87, n = 77, P < 0.001) between both sets of results was excellent. In patients with metabolic bone diseases characterized by high or low bone turnover, the increase or decrease in serum osteocalcin observed was as expected. This homologous radioimmunoassay of human osteocalcin thus reflects bone turnover but reports serum concentrations higher than previously suspected.

Adolescent