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Biomedical subjects

M Hørder

Publications and source records attributed to M Hørder.

At least 19 recordsLinked to original sources

Reference intervals for trace elements in blood: significance of risk factors.

A random sample of 100 men and 100 women was examined for whole-blood concentrations of mercury, lead, cadmium and selenium, and the serum concentrations of selenium, nickel, fluoride, aluminium, zinc and copper. Major predictors were sex, hormonal factors (pregnancy, menopause, use of oral contraceptives), age, tobacco smoking and alcohol drinking. Among notable associations, increased blood-mercury was related to the presence of more than four amalgam fillings in the teeth. Blood-mercury correlated with blood-selenium, but a relation to fish intake could only be demonstrated for the former parameter. In women, blood-lead appeared to increase with age, with the highest levels seen after the menopause. Serum-nickel was slightly lower in patients with nickel-related contact eczema. Only the selenium concentrations showed a slight increase in individuals taking mineral supplements. Serum-zinc concentrations decreased considerably during the day. Thus, due to the substantial influence of physiological and environmental factors, individual results must be interpreted in the light of the known predictors for the trace element concentration. However, population-based reference intervals for trace elements in blood are useful to explore geographic and temporal variations.

Adult

Lack of indication of myocardial cell damage after myocardial ischaemia in patients with severe stable angina.

To evaluate myocardial cell damage in relation to spontaneous and exercise-induced ischaemia, release of myoglobin, creatine kinase (CK) and its isoenzyme MB (CK-MB) into the serum was estimated in 10 patients with severe stable angina. All patients had a positive exercise test, significant stenosis of one or more of the main coronary arteries and more than five ischaemic attacks per week. ST-segment monitoring was performed for 36 h. During the last 24 h of that period (period A) serial blood samples were analysed for myoglobin, CK and CK-MB using sensitive assays. Three days later (period B) the patients performed an exercise test at 0815 h, with ST-segment monitoring and blood sampling carried out as described for period A. During period A, 47 ischaemic episodes (100% silent) with a total duration of 599 min were noted in four patients. Forty-seven ischaemic episodes (94% silent) with a total duration of 804 min, were observed in seven patients during period B. Release of myoglobin, CK, and CK-MB did not increase in relation either to spontaneous or exercise-induced ischaemia. Thus even frequent and prolonged episodes of transient myocardial ischaemia (symptomatic or asymptomatic) in patients with severe stable angina pectoris does not seem to cause irreversible myocardial damage.

Adult

Risk stratification in suspected acute myocardial infarction based on a sensitive immunoassay for serum creatine kinase isoenzyme MB. A 2.5-year follow-up study in 156 consecutive patients.

This prospective study was an evolution of a new sensitive creatine kinase (CK) isoenzyme MB immunoassay in 156 patients, admitted consecutively to the coronary care unit, suspected of having acute myocardial infarction (MI), with regard to clinical applicability and clinical outcome. 42% of the patients had MI based on WHO criteria. The remaining 91 patients could be divided into a group with ischemic heart disease (IHD) without MI being present (n = 65) and a group with non-IHD (n = 26). In the former, a subgrouping based on changing CK MB levels (n = 24) or stable CK MB levels (n = 41) as compared to the non-IHD group could be performed. These patients were not diagnosed using the routine diagnostic procedures. Follow-up was carried out for 30 months (median 22). The prognosis as evaluated by cardiac death was significantly better for patients with stable CK MB levels than for those with changing CK MB levels, inasmuch as the cumulative probability not to suffer cardiac death was 95 +/- 3 and 66 +/- 10% after 2.5 years, respectively (p less than 0.003). It was 52 +/- 6% for the patients with MI, similar to patients with changing CK MB levels (p = 0.15). We conclude that this new CK MB assay can detect a subgroup of patients with IHD, which is not diagnosed using routine diagnostic procedures, with a poor clinical outcome.

Adult

Gene dosage and down-regulation of the alpha-interferon receptor.

The gene coding for the alpha,beta-interferon (alpha,beta-IFN) receptor is localized to chromosome 21. Cells from patients with Down's syndrome (trisomy 21) contain an extra chromosome 21, which results in a 1.5 times increase of dosage for the genes localized to this chromosome. Trisomy 21 cells express more cell-surface alpha-IFN receptors, consistent with the increased gene dosage. Down-regulation of the alpha-IFN receptors in trisomy 21 and normal cells was studied by incubating the cells with alpha-IFN. The alpha-IFN-induced effects showed 1.6 times more internalized cell-surface alpha-IFN receptors in trisomy 21 cells compared with normal cells, but no statistically significant change in the dissociation constants. A close relationship was found between the alpha-IFN receptor number and the biological response expressed as 2',5'-oligoadenylate synthetase activity.

Down Syndrome

[Costs and prices of laboratory services].

Cost accounting is performed in private and public laboratories. Guidelines for these activities are required and with this objective in mind, the Board of the Danish Society of Clinical Chemistry commissioned a working group to produce a position paper which is presented now in this report. The report discusses the objectives, the principles and the general requirements for cost accounting. The significance of information on costs for the clinicians' rational use of the laboratory is also illustrated. The working group points out that prerequisites for lucid and appropriate costing guidelines are clarification of which purposes information on costs are meant to serve, identification of the relevant cost centers and quality assurance of laboratory services to a defined extent. It is common practice to express laboratory costs as costs per test. The report advocates calculation of the cost per patient contact, i.e. the overall costs for laboratory service in a given investigative situation.

Accounting

[Therapy control of perphenazine in paranoid conditions. 1. Organizational aspects].

A prospective investigation was carried out in the Department of Psychiatry, Odense University Hospital, on therapy control by serum monitoring of the neuroleptic, perphenazine for a period of one year. Newly admitted patients requiring treatment for paranoid symptoms, excluding mania, were offered medication with perphenazine (fixed dosage, oral or parenteral (depot)) which would be serum-monitored. A global record was made of the therapeutic effect and the side-effects by the physicians in the department. In the investigation period, 605 admissions were registered in the department, of them 363 were prospectively registered in the investigation. In all 199 were found to satisfy the inclusion criteria. Either one or two blood tests were carried out on each of 141 patients in the treatment period, i.e. six weeks. The gap in registration is consistent with the result from other investigations. Participation in the investigation varied from ward to ward (33%-87%). The reason for the variation is mainly due to different treatment procedures and traditions. The main conclusion drawn from the investigation is that it is possible to set up a stable treatment/serum-monitored system. In the majority of cases, the team of physicians in the department succeeded in finding the dosage most appropriate on the basis of the serum concentration level. Laboratory recommendations were followed in 93% of the cases.

Adult

[Therapy control of perphenazine. 2. Clinical aspects].

Rational use of serum concentration monitoring of the neuroleptic, perphenazine, was evaluated in a prospective investigation. A total of 141 hospitalized patients with paranoid symptoms (excluding mania) requiring treatment were included during the investigation period (one year). Perphenazine was administered (fixed doses) orally (92 patients) and parenterally (depot, decanoate, 45 patients) in a six-week treatment period. Serum concentrations of perphenazine were monitored after 10-14 days oral treatment, on the 14th and 21st days after the commencement of depot treatment. The patients were steered on to the recommended therapeutic range for perphenazine (1.5-6 nmol), according to the serum level measured. Global clinical assessment was carried out by the departmental physicians. Therapy control of perphenazine by serum monitoring was an important supplement to the clinical evaluation of therapeutic effect. Fifteen (65%) out of 23 patients who were treated orally with insufficient therapeutic effect, showed non-compliance or elevated metabolism. On the basis of a single serum concentration measurements (12 hours values), it proved possible to steer the majority of patients onto the recommended therapeutic level. In this way, the individual patient reached optimal therapeutic effect with a minimum of side-effects.

Adult

[Iron stores, iron deficiency and iron supplementation].

In order to assess the prevalence of iron deficiency in the Danish population, a randomised cross sectional investigation was carried out one year after repealing of the order from 1939 concerning supplementing of corn products with iron. A randomised group of 198 persons divided into ten groups of 20 persons with equal numbers of men and women in the age group 20-69 years was submitted to determinations of serum-iron, serum-transferrin and serum-ferritin. The prevalence of iron deficiency as determined by serum-ferritin values of below 15 micrograms/l was 18% and 12% respectively, for women under and over 45 years while iron deficiency determined by transferrin saturation under 16% was 18% for both groups. 6% of the women under 45 years had severe iron deficiency as determined by low transferrin saturation and low ferritin. The prevalence among men was 1% and 3% as assessed by serum-ferritin levels and transferritin saturation. These results were compared with corresponding population investigations from Sweden where iron enrichment is the highest in the world and the sale of iron tablets is the greatest in the world. No significant differences in the frequency of latent iron deficiency could be demonstrated but the number of persons with severe iron depletion appears to be less in Sweden. Differences in the methodological procedures, however, cannot be excluded.

Adult

Elevated serum levels of creatine kinase BB in autosomal dominant osteopetrosis type II.

Serum levels of creatine kinase isoenzyme BB (CK-BB) were measured spectrophotometrically and by electrophoresis in 17 patients with autosomal dominant osteopetrosis (ADO) and compared with those of age- and sex-matched controls. Eight patients had ADO type 1 and nine patients had ADO type II. CK-BB was significantly increased (p less than 0.002) in type II but normal in type I compared with controls. This finding supports heterogeneity of ADO, and it may indicate a potential role for CK-BB as a marker of immature osteoclasts.

Adult

Screening for haemochromatosis: influence of analytical imprecision, diagnostic limit and prevalence on test validity.

Serum ferritin (S-ferritin) and the saturation of transferrin iron-binding capacity (TIBC-sat) were evaluated as screening procedures for idiopathic haemochromatosis in a non-diseased population. Special attention was paid to the influence of the analytical quality, but the effects of prevalence and discrimination limits were also considered. Changes in the analytical quality for S-ferritin and TIBC-sat used as single tests highly influenced the number of false test-positives. Increasing the coefficient of variation from 0.0 to 0.2 resulted in nearly a doubling of the number of false test-positives to be further investigated. Using even a high, yet achievable analytic quality with a low coefficient of variation of 0.056 and 0.059 for S-ferritin and TIBC-sat respectively, screening procedures had unacceptably high fractions of false test-positives and false test-negatives associated with any discrimination limit. If the prevalence of haemochromatosis is 0.003, the predictive value of a positive test result did not exceed 0.05, accepting a fraction of false test-negatives of 0.025. This was found to be too low for a screening test to be used in the general population. The combined use of S-ferritin and TIBC-sat resulted in higher performance with a sensitivity of 0.90, a specificity of 0.99 and a predictive value of a positive test result of 0.29 if a fraction of misclassification of 0.01 is accepted for each.

False Positive Reactions

Screening for haemochromatosis: prevalence among Danish blood donors.

Hereditary haemochromatosis is an autosomal recessive disease that is genetically expressed by excessive accumulation of iron in the tissues, resulting in cirrhosis, diabetes mellitus, cardiomyopathy and hypogonadism. As the disease may be diagnosed before the appearance of symptoms, and prevented by repeated phlebotomies, there are strong implications for adoption of a screening procedure. Determinations of transferrin saturation (TS) and serum ferritin concentration (SF) were used to screen 4302 blood donors, who were selected for follow-up studies if they fulfilled any of the following three criteria: (i) TS greater than or equal to 0.7; (ii) TS greater than or equal to 0.5 together with SF greater than or equal to 150 micrograms l-1; (iii) SF greater than or equal to 300 micrograms l-1. A total of 58 subjects who fulfilled at least one of these criteria were reinvestigated, after which 18 individuals still fulfilled at least one criterion. Fifteen subjects having SF greater than or equal to 300 micrograms l-1 were offered liver biopsy and thirteen of these accepted. In one individual, no stainable iron was detected, and two subjects did not fulfil the previously established diagnostic criteria for the diagnosis of hereditary haemochromatosis. Ten subjects who had a high TS and liver iron grade 2-4 according to Bassett were classified accordingly as homozygotes. On the basis of these results, the prevalence of haemochromatosis in Denmark was estimated to be 0.0037-0.0046.

Adult

Gradation of unstable angina based on a sensitive immunoassay for serum creatine kinase MB.

A newly developed, highly sensitive immunoassay for creatine kinase MB isoenzyme was evaluated in 68 patients with or without different types of ischaemic heart disease. Patients were classified on the basis of clinical criteria in four groups: no ischaemic heart disease, stable angina, unstable angina, and acute myocardial infarction. Enzyme concentration in patients with stable angina was the same (even during exercise) as seen in the patients without ischaemic heart disease. Patients with unstable angina, however, could be divided into two groups. One group showed clear evidence of severe myocardial ischaemia by serial changes and higher mean values of creatine kinase MB up to 40 hours after the onset of symptoms, whereas in the remainder values were stable and resembled those seen in the patients without ischaemic heart disease. The changes in concentration correlated with signs of repetitive ischaemic episodes deduced from continuous ST segment monitoring during the first 24 hours after admission. These findings indicate that patients with unstable angina are a heterogenous group. In some, severe and prolonged ischaemia can be detected by a serological assay with high sensitivity.

Angina Pectoris

Creatine kinase determination: a European evaluation of the creatine kinase determination in serum, plasma and whole blood with the Reflotron system.

We evaluated a new dry-reagent carrier system for the determination of creatine kinase (EC 2.7.3.2) activity, Reflotron CK, with special attention to analytical performance with whole blood. We found a good within series imprecision. The median coefficient of variation was 3.1% for Reflotron CK (blood, serum and plasma) and 0.9% for the automatic analysers (serum and plasma only). The between-days imprecision with Reflotron CK (median CV: less than or equal to 3%) was similar to that for the comparison method on different analysers. Fresh samples of human blood, plasma and serum were examined by Reflotron CK and by a N-acetylcysteine activated creatine kinase method in six different clinical laboratories and in the Evaluation Department of Boehringer Mannheim GmbH. The correlation between these methods was excellent (r greater than or equal to 0.99), the median systematic deviation (bias) for all samples being smaller than -5%. Haematocrits between 0.25 and 0.50, haemolysis up to 6 g/l haemoglobin, and icteric samples with bilirubin concentrations up to 0.2 g/l showed no interference. No drug in therapeutic concentration was found to affect the Reflotron CK results; ascorbic acid, calcium dobesilate and sulphamethoxazole lowered the values only when present in high concentrations. Reflotron CK may be considered as a suitable alternative for decentralized testing sites, especially in situations where creatine kinase results are needed quickly.

Autoanalysis

The influence of extracellular magnesium on cell damage induced by ATP depletion in human fibroblasts.

Magnesium is an essential ion for the structural and functional integrity of cells. We have examined whether a low extracellular magnesium concentration contributes to cell damage induced by ATP depletion in a model system of quiescent fibroblasts. Cell damage assessed by the release of lactate dehydrogenase was slightly, but significantly increased in the absence of Mg2+. The increased cell damage may be caused by an increased Mg2+ loss during ATP depletion, by an altered cell membrane permeability for potassium and sodium, or by a disturbed balance between Mg2+ and Ca2+.

Adenosine Triphosphate

Effect of long-term monitoring of glycosylated hemoglobin levels in insulin-dependent diabetes mellitus.

BACKGROUND: The value of routine measurements of glycosylated hemoglobin (hemoglobin A1c) in the care of patients with diabetes mellitus is uncertain. We undertook this study to determine whether knowledge of hemoglobin A1c values would result in improved metabolic control in a group of patients with insulin-dependent diabetes mellitus (IDDM). METHODS: We randomly assigned 240 patients with IDDM to one of two groups that were comparable in age, sex, duration of diabetes, and initial hemoglobin A1c levels. The patients were followed for a year, and the hemoglobin A1c concentration was measured at three-month intervals. The hemoglobin A1c values were used in assessing glycemic control and modifying therapy in one of the two groups. In the other, care givers were not aware of the hemoglobin A1c levels and relied on blood or urine glucose measurements to monitor treatment. RESULTS: Among the 222 patients still being followed after one year, the mean hemoglobin A1c value decreased significantly--from 10.1 to 9.5 percent (P less than 0.005)--in the group whose hemoglobin A1c level was monitored (n = 115), whereas the initial and one-year values in the control group (n = 107) were 10.0 and 10.1 percent, respectively. The proportion of patients with poor control, defined as those having a hemoglobin A1c value above 10.0 percent, decreased from 46 to 30 percent (P less than 0.01) in the group whose hemoglobin A1c level was monitored but did not change significantly (45 to 50 percent) in the control group. The patients in the group whose hemoglobin A1c level was monitored were seen and their insulin regimens changed more often, but they were hospitalized for acute care of their diabetes less often than those in the control group. A similar decrease in hemoglobin A1c values occurred in the control group in the following year, when their care givers knew their hemoglobin A1c values. CONCLUSIONS: Regular measurements of hemoglobin A1c lead to changes in diabetes treatment and improvement of metabolic control, indicated by a lowering of hemoglobin A1c values.

Diabetes Mellitus, Type 1

31P-NMR measurements of ATP, ADP, 2,3-diphosphoglycerate and Mg2+ in human erythrocytes.

Absolute 31P-NMR measurements of ATP, ADP and 2,3-diphosphoglycerate (2,3-DPG) in oxygenated and partly deoxygenated human erythrocytes, compared to measurements by standard assays after acid extraction, show that ATP is only 65% NMR visible, ADP measured by NMR is unexpectedly 400% higher than the enzymatic measurement and 2,3-DPG is fully NMR visible, regardless of the degree of oxygenation. These results show that binding to hemoglobin is unlikely to cause the decreased visibility of ATP in human erythrocytes as deoxyhemoglobin binds the phosphorylated metabolites more tightly than oxyhemoglobin. The high ADP visibility is unexplained. The levels of free Mg2+ [( Mg2+]free) in human erythrocytes are 225 mumol/l at an oxygen saturation of 98.6% and instead of the expected increase, the level decreased to 196 mumol/l at an oxygen saturation of 38.1% based on the separation between the alpha- and beta-ATP peaks. [Mg2+]free in the erythrocytes decreased to 104 mumol/l at a high 2,3-DPG concentration of 25.4 mmol/l red blood cells (RBC) and a normal ATP concentration of 2.05 mmol/l RBC. By increasing the ATP concentration to 3.57 mmol/l RBC, and with a high 2,3-DPG concentration of 24.7 mmol/l RBC, the 31P-NMR measured [Mg2+]free decreased to 61 mumol/l. These results indicate, that the 31P-NMR determined [Mg2+]free in human erythrocytes, based solely on the separation of the alpha- and beta-ATP peaks, does not give a true measure of intracellular free Mg2+ changes with different oxygen saturation levels. Furthermore the measurement is influenced by the concentration of the Mg2+ binding metabolites ATP and 2,3-DPG. Failure to take these factors into account when interpreting 31P-NMR data from human erythrocytes may explain some discrepancies in the literature regarding [Mg2+]free.

2,3-Diphosphoglycerate

[Clinical-chemical testing on admission to Odense Hospital].

The use of laboratory screening on admission (i.e. laboratory tests which are always requested on admission of all of the patients to the department) was investigated at Odense University Hospital. Nursing sisters were interviewed about the current practices at their departments and consultants replied to a questionnaire about their attitudes to laboratory screening on admission. Screening on admission consisted of from 0 to 24 analyses. 90% of the consultants considered that screening on admission saved time, 60% that it might reveal other diseases, 52% that it could be used as a status on control admissions and 79% that it was suitable in the preparation for operation and invasive diagnostic procedures. On the basis of a survey of the literature, it is concluded that routine use of laboratory screening on admission is not justified.

Denmark