Birgit Fischer Hansen

Interobserver variation in diagnosing coeliac disease. a joint study by Danish and Swedish pathologists

There is an almost 40‐fold difference in incidence rates of symptomatic coeliac disease between Denmark and Sweden. In an attempt to explain this difference, the present study focused on the interobserver agreement when pathologists were assessing small intestinal biopsy specimens from children suspected of suffering from coeliac disease. The study was performed on 90 biopsy specimens from 73 children. Most of the biopsies came from children who turned out not to suffer from coeliac disease after a clinical evaluation including small intestinal biopsy. Using the kappa methodology, the interobserver agreement between two Danish pathologists and one Swedish pathologist, all of whom were experienced, was “moderate” to “substantial” or 0.57–0.75. Kappa indices when the pathologists evaluated selected histological elements were in the interval from 0.24 to 0.67. A comparison of a previous routine diagnostic assessment of the 90 biopsies (14 pathologists) with the results of the experienced pathologists in the present study gave kappa indices of from 0.53 to 0.57. The study could prove no major differences in the histopathological assessment of small intestinal biopsy specimens made by Danish and Swedish pathologists. The difference in clinical presentation of coeliac disease in Denmark and Sweden does not relate to differences in the histopathological assessment of small intestinal biopsies.

The value of the Nitro-BT method in fresh myocardial infarction: Frequency and location of fresh myocardial infarction in a consecutive series of autopsies

Abstract With the object of getting an impression of the frequency with which fresh myocardial infarctions escape recognition at autopsy, the dehydrogenase activity in the myocardium was examined and assessed on the basis of the Nitro-BT method (the formazan test) during 100 consecutive autopsies. Forty fresh myocardial infarctions were demonstrated but in 23 of them it was not until after the Nitro-BT test had been made. In 15 of these cases ordinary macroscopic evaluation did not give rise to any suspicion of fresh infarction. In seven of the cases the infarction was more extensive than had been expected. In cases where a fresh myocardial infarction was found unexpectedly, the microscopic examination revealed early infarction changes because the method employed made it possible to remove tissue sections in a correct way. It cannot be expected that definite macroscopic changes will be revealed by the test until clinical symptoms of myocardial infarction have been present for about eight hours before death. If this latent period is disregarded, no false-negative reactions will be seen. No false-positive reactions were demonstrated. Our patients are mostly elderly people suffering mainly from severe coronary sclerosis, and in only five cases was there coronary thrombosis. Many of them were in shock (hemorrhage, infection, operation, cancer in the terminal stages) which, together with the coronary sclerosis, must be presumed to cause a relative myocardial ischemia. Therefore, the percentage of appearance of subendocardial infarctions is very high. The method is expeditious and inexpensive, and the autolysis does not seem to exert any influence on the human myocardium within a reasonable period of time (72 hours).

Acute myocardial infarct size estimated by serum CK-MB determinations: Clinical accuracy and prognostic relevance utilizing a practical modification of the isoenzyme approach☆

The clinical reliability and relevance of a practical enzymatic method to estimate infarct size (IS) were evaluated in patients with acute myocardial infarction (AMI). The technique utilized was that of relatively few sequential determinations of serum heart specific isoenzyme CK-MB, as corroborated by studies of numerous CK-MB measurements. Isoenzyme IS was determined in 321 consecutively admitted patients with AMI. Autopsies were performed in 22 of the 43 decedents for quantification of myocardial necrosis by histochemical and histologic techniques. A highly significant correlation (r = 0.83 p less than 0.001, SEE = 28%) was observed between IS values calculated from serum CK-MB and IS defined by necropsy examination. The CK-MB median IS was significantly increased in decedents compared to survivors (p less than 0.005), with IS ranges having substantial overlap between the two groups. The present study demonstrates that a practical and reliable estimation of IS in vivo is obtainable by serum CK-MB. While such estimated IS is of relatively moderate value for predicting in-hospital prognosis in single patients, the isoenzyme method appears particularly well suited for clinical evaluation of potentially beneficial interventions anticipated to limit myocardial necrosis in groups of AMI patients.

Hormone replacement therapy prevents coronary artery disease in ovariectomized cholesterol-fed rabbits

The prevention of coronary artery disease in women is of considerable importance. We have therefore investigated the influence of oestrogen monotherapy and oestrogen‐progestogen replacement therapy on coronary artery disease using a simple morphometric method. We studied sixty‐three cholesterol‐fed rabbits for nineteen weeks. They were randomized to either ovariectomy (51 rabbits) or a sham operation (12 rabbits). The ovariectomized rabbits were randomized to receive either 17 β‐estradiol, 17 β‐estradiol plus norethisterone acetate, 17 β‐estradiol plus levonorgestrel, or placebo. The rabbits with the sham operation received placebo. The hormone therapies reduced the development of coronary artery disease compared to placebo (p<0.0001). Furthermore, the coronary artery disease was attended by atherosclerosis in the more distal parts of the coronary arteries (p< 0.0001), the thoracic aorta (p<0.0001) and the abdominal aorta (p<0.0001), and by a reduced relative heart weight (p<0.05). We conclude that coronary atherosclerosis can be determined quantitatively by morphometry in rabbit arteries. Estradiol monotherapy reduces coronary atherosclerosis in cholesterol‐fed rabbits and the addition of norethisterone acetate or levonorgestrel does not attenuate this beneficial effect.

Effect of oestrogen replacement therapy on development of experimental arteriosclerosis: A study in transplanted and balloon-injured rabbit aortas

The mechanism underlying possible protection of oestrogen replacement therapy against cardiovascular disease appears to go beyond beneficial changes in plasma lipoproteins. A direct action of oestrogen on the metabolism of lipoproteins after entering the arterial wall may occur. The present study evaluated whether oestrogen replacement therapy affects the development of experimental arteriosclerosis in immunologically injured (experiment A + B) and balloon-injured (experiment B) aortas in ovariectomized rabbits maintained at a human level of plasma cholesterol; both models involve severe damage to the endothelium with resulting rapid accumulation of lipoproteins in the arterial intima and therefore appear suitable for studying factors directly affecting subendothelial lipoprotein metabolism. In experiment A, dietary cholesterol required to maintain a human level of plasma cholesterol was significantly higher for the oestrogen group than for the placebo group. Similarly, cholesterol accumulation in the aortic grafts was borderline higher for the oestrogen than the placebo group, whilst intimal hyperplasia was without difference between the groups. Due to a modified schedule of cholesterol feeding in experiment B, oestrogen and placebo groups received the same amount of dietary cholesterol, and cholesterol accumulation and intimal hyperplasia were similar in immunologically injured and balloon-injured parts of the aorta in both groups. These results suggest that in the female rabbit maintained at a human level of plasma cholesterol, oestrogen replacement therapy has no direct action on the development of experimental arteriosclerosis when induced by immunological or mechanical injury to the endothelium.

Aspergillus fumigatus fungaemia and myocarditis in a patient with acquired immunodeficiency syndrome

Necrotizing myocarditis due to Aspergillus fumigatus was a contributory cause of death in a patient with acquired immunodeficiency syndrome and non‐Hodgkin lymphoblastic malignant lymphoma of the Burkitt type. A transient remission of the lymphoma had been obtained by cytostatic treatment. A. fumigatus was isolated from blood two weeks before death, but myocarditis was not diagnosed until autopsy.

Intermediate density lipoprotein cholesterol as the best lipoprotein predictor of atherosclerosis severity in the Watanabe Heritable Hyperlipidemic rabbit.

a Department of Clinical Biochemistry, Rigshospitalet, Uni6ersity of Copenhagen, Copenhagen, Denmark b Department of Clinical Biochemistry, Herle6 Hospital, Uni6ersity of Copenhagen, Herle6 Ring6ej 75, DK-2730 Herle6, Denmark c Department of Pathology, H6ido6re Hospital, Uni6ersity of Copenhagen, Copenhagen, Denmark d Department of Cardiology, H6ido6re Hospital, Uni6ersity of Copenhagen, Copenhagen, Denmark e Institute of Toxicology, National Food Agency of Denmark, Denmark

Thrombosis of epicardial coronary veins in acute myocardial infarction.

Thrombosis of epicardial coronary veins was demonstrated in 16 of 50 cases of left ventricular acute myocardial infarction and/or recent coronary arterial thrombosis. All patients with valvular heart disease had venous thrombosis. In cases without valvular heart disease, venous thrombosis was seen in infarctions involving more than 30% of the left ventricular myocardial mass with a post-attack survival time of at least 24 hours. The veins thrombosed were in all cases those draining the infarcted myocardium. Coronary vein thrombosis seems not to be prevented by anticoagulant medication.