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Biomedical subjects

B F Hansen

Publications and source records attributed to B F Hansen.

At least 19 recordsLinked to original sources

Relative importance of ischemic injury and immunological injury on the development of transplant arteriosclerosis in rabbit aortic allografts.

The development of transplant arteriosclerosis has emerged as a major problem to long-term survival after heart transplantation. The accelerated development of arteriosclerosis in the transplanted arteries, including the aorta, could result either from an ischemic injury in connection with the transplantation, or from an immunological reaction against the transplant, or both. We evaluated histologically and biochemically whether extension of the ischemic period from 1 to 24 hr has any influence on the development of transplant arteriosclerosis, in aorta-allografted rabbits clamped at human levels of plasma cholesterol. One set of rabbits was without immunosuppressive treatment (n = 10 + 9) and another otherwise identical set of rabbits received cyclosporine to achieve blood cyclosporine levels in the human therapeutic range (n = 10 + 12). The number of T lymphocytes in intima suggested that, in the grafts from untreated animals, an immunological injury had arisen, which cyclosporine reduced. A clear trend toward a worsening of the transplant arteriosclerosis was demonstrated as a function of the severity of the ischemic injury, both with and without immunosuppressive treatment. However, the worsening effect of maximal ischemic injury was less than that due to maximal immunological injury. In grafts from cyclosporine-treated animals, the development of transplant arteriosclerosis was significantly less than in grafts from untreated animals exposed to identical periods of ischemia. These results suggest that compared with immunological injury, ischemic injury is of minor importance for the development of experimental transplant arteriosclerosis.

Animals

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.

Animals

Tetracycline-resistant micro-organisms recovered from patients with refractory periodontal disease.

Tetracycline in combination with scaling and root planing is frequently used to treat refractory periodontal disease. This study examined tetracycline resistance in bacteria recovered from periodontal pockets of patients with refractory periodontitis. Bacterial isolates resistant to 10 micrograms/ml of tetracycline were isolated from plaque samples of 17 patients, of whom 6 had received tetracycline within 8 weeks prior to sampling. Minimal inhibitory concentrations (MICs) of tetracycline and minocycline were determined by agar dilution. In the 6 patients who had received tetracycline, a mean of 22.9% (+/- 38.2) of the total cultivable subgingival flora were resistant to tetracycline, compared with a mean of 7.2% (+/- 8.5) in the untreated group. Although various organisms were isolated, in most patients, the tetracycline-resistant organisms were dominated by Streptococcus spp. Overgrowth of Candida was found in one patient, and of Enterobacteriaceae in another patient, while small numbers of yeast or Staphylococcus spp. were isolated from the plaque samples of 9 others. 3 out of 4 patients who did not respond to tetracycline treatment had a variety of tetracycline-resistant anaerobic Gram-negative rods present. No correlation was found between increased proportions of tetracycline resistance in the whole bacterial sample and the presence of resistant periodontal pathogens.

Adult

Prevalence of radiographic alveolar bone loss in young adults, a multinational study.

In a multinational study of alveolar bone loss, bite-wing radiographs of 8,703, 15-17-year-old adolescents from 18 centres in 16 countries were examined. Of these, 13 per cent were excluded as non-informative because of bad quality radiographs or missing first molars. Bone loss was a common finding globally (mean prevalence rate of subjects with bone loss 10.2 per cent), although there were great geographical variations. The bone loss was mostly horizontal, infrabony lesions were rare. The most frequently affected sites were the mesial aspects of the first maxillary molars followed by the distal aspects of the same teeth. Twenty-three subjects from the Finnish bite-wing study were examined for clinical conditions. When subjects with and without radiographic bone loss were compared, no statistically significant differences in the mean Gingival Index were found. The subjects were re-examined 5 years later. The gingival condition and the oral hygiene tended to be better at the end of the period than they had been at the start, but it was only in males that the differences were statistically significant. Periodontal destruction cannot be predicted from the gingival condition, but bite-wing radiographs of adolescents seem to be a valuable diagnostic tool for early detection of periodontal bone loss.

Adolescent

[AIDS and heart disease].

This article reviews cardiac manifestations of AIDS in terms of etiology, pathogenesis, pathoanatomic lesions and heart function. Hypothetically the prevalence of myocarditis and disperse fibrosis of the myocardium are correlated to increasing rates of dilated cardiomyopathy and cardiac insufficiency. Echocardiography has proved to be of value in detecting early abnormalities and should be recommended on broad indications, though aggressive therapy of cardiac abnormalities is of importance to ensure quality of life and surveillance for the patients.

Acquired Immunodeficiency Syndrome

Gastrin and somatostatin in Helicobacter pylori infected antral mucosa.

Helicobacter pylori infection is associated with increased meal stimulated gastrin secretion, but the reason for this is unknown. Sequence specific radioimmunoassays were used to measure the concentration of alpha-amidated gastrin, the total progastrin product, and somatostatin in biopsy specimens of human antral mucosa. The antral concentrations of alpha-amidated gastrin and of total progastrin products were significantly higher in H pylori infected patients than in those not infected by this organism. In contrast, the antral somatostatin concentration was significantly decreased in infected patients. Progastrin processing, determined by gel chromatography, seemed unaffected by H pylori infection. The results suggest that the finding of increased gastrin secretion from the antral G cells in H pylori infected patients may be a result of reduced inhibition of G-cell secretion by somatostatin.

Adult

Cyclosporin suppresses transplant arteriosclerosis in the aorta-allografted, cholesterol-clamped rabbit. Suppression preceded by decrease in arterial lipoprotein permeability.

The immunosuppressant cyclosporin has been suggested to aggravate as well as retard the development of transplant arteriosclerosis, the major long-term problem for patients with heart transplants. We examined the effect of human therapeutic levels of blood cyclosporin on the development of experimental transplant arteriosclerosis. The thoracic aorta from one rabbit was transplanted as an end-to-side bypass on the abdominal aorta of another rabbit, and plasma cholesterol was clamped at 5 to 7 mmol/L. Cyclosporin markedly suppressed the severity of transplant arteriosclerosis, judged both biochemically and histologically: cholesterol content in aortic transplants was reduced by 70% and 80% after 10 days and 20 days of cholesterol feeding, respectively (both comparisons, P < .01), and after 20 days of cholesterol feeding myointimal proliferation was totally inhibited in grafts from cyclosporin-treated animals, judged from maximal intimal thickness and intimal area on cross sections of grafts (both comparisons, P < .05). In another group of non-cholesterol-fed, aorta-transplanted rabbits, cyclosporin reduced by 90% (P < .01) an otherwise markedly increased permeability to low-density lipoprotein in transplanted aortas. These results suggest that cyclosporin causes a substantial decrease in the severity of transplant arteriosclerosis and that this effect is mediated at least partly via a large decrease in aortic lipoprotein permeability.

Animals

Atherosclerosis in Watanabe heritable hyperlipidaemic rabbits. Evaluation by macroscopic, microscopic and biochemical methods and comparison of atherosclerosis variables.

The spontaneous development of atherosclerotic disease in 38 homozygous and 34 heterozygous Watanabe heritable hyperlipidaemic rabbits was evaluated by qualitative and quantitative light microscopy in aorta, coronary, pulmonary and renal arteries, by naked eye and macroscopic morphometric estimation of aortic atherosclerosis extent and by biochemical analysis of aortic cholesterol content. No noteworthy atherosclerosis was demonstrated within 19 months in heterozygous rabbits. In homozygous rabbits, atherosclerotic lesions were seen from the age of 4 months and progressed with age. All 19-month-old rabbits had severe atherosclerotic disease. As much as 64% of the variation in atherosclerosis extent/severity could be explained by serum cholesterol and age. A highly significant correlation between the various methods for quantitation of atherosclerosis extent and/or severity was demonstrated, suggesting that quantitative microscopy, macroscopic morphometry and determination of aortic cholesterol content may be equally valid as a measure of atherosclerosis in WHHL rabbits and are therefore interchangeable.

Animals

The influence of dietary olive oil and margarine on aortic cholesterol accumulation in cholesterol-fed rabbits maintained at similar plasma cholesterol level.

The present study compares the atherogenicity of a standard diet and diets with 10% olive oil or 10% margarine added, in rabbits maintained at a mean plasma cholesterol level of about 20 mM for 13 weeks. Each group consisted of 15 animals. The distribution of cholesterol in plasma between VLDL, IDL, LDL and HDL was similar in the 3 groups. The thoracic aortic cholesterol accumulation was 16.6 +/- 1.6, 11.4 +/- 1.0 (P < 0.05) and 12.6 +/- 1.7 (P > 0.05) nmol/mg wet weight for the group receiving standard diet, diet with 10% olive oil added and diet with 10% margarine added, respectively. There was no significant difference between groups in the occurrence of the atherosclerotic changes in the proximal and distal parts of coronary arteries, abdominal aorta and renal arteries. The occurrence of atherosclerotic changes in the pulmonary arteries was equal in the groups receiving standard diet and diet with 10% margarine added while it was significantly lower (P < 0.05) in the group receiving diet with 10% olive oil added. The atherosclerotic changes at the aortic orifice of coronary arteries were quanticated morphometrically and were most severe in the group on the standard diet. The results indicate a comparable atherogenic effect of 10% olive oil or margarine addition to standard diet on development of atherosclerosis in rabbits maintained at a similar plasma cholesterol level. The study also suggests that supplementation of olive oil or margarine to standard rabbit diet leads to lower cholesterol accumulation in the thoracic aorta compared with standard diet, an effect not modulated by changes in plasma cholesterol concentrations.

Animals

Clinical responses to subgingival application of a metronidazole 25% gel compared to the effect of subgingival scaling in adult periodontitis.

A newly developed metronidazole 25% dental gel was compared with subgingival scaling in the treatment of adult periodontitis. 206 patients in 9 centres participated in the study. Probing pocket depth (PPD) and bleeding on probing (BOP) were recorded before treatment and 2, 6, 12, 18, and 24 weeks after the treatment. All patients had at least 1 tooth in each quadrant with a PPD of 5 mm or more. The treatments consisted of 2 applications of dental gel (days 0 and 7) in 2 randomly selected quadrants (split mouth design) and 2 sessions of subgingival scaling (1 quadrant on day 0, and 1 quadrant on day 7). Instruction in oral hygiene was given 2 weeks after completed treatment. The average PPD and the average frequency of BOP were calculated over all sites with initial PPD of 5 mm or more. PPD and BOP were thus, at each examination, calculated from the same sites. The mean PPD was 5.9 mm before gel application and 5.8 mm before scaling (p = 0.31). BOP was 88% in both treatment groups. 24 weeks after the treatment, PPD and BOP were significantly reduced in both groups and for both parameters (p < 0.01). PPD was reduced by 1.3 mm after gel application and 1.5 mm after scaling; BOP was reduced by 32% and 39%, respectively. The difference between the treatments was statistically significantly, but considered as clinically unimportant.

Adult

Pathology of the heart in AIDS. A study of 60 consecutive autopsies.

Cardiac disease and cardiac death in AIDS patients is seldom reported. In recent years minor cardiac abnormalities have been demonstrated, especially by echocardiography. Cardiac pathology in AIDS patients is here reported from 60 consecutive autopsies where the heart was investigated either using single samples of ventricular myocardium (the first 21 cases) or by an examination of the whole heart (the last 39 cases). Myocarditis according to the Dallas criteria was seen in 25 of 60 cases (42%), and in seven of these cases a probable pathogen (Toxoplasma gondii, cytomegalovirus, fungi) was demonstrated. Diffuse myocardial fibrosis was seen in 40 of 60 cases (67%) and is considered to be partly due to repair after myocyte necrosis/myocarditis. A myocardium thus weakened might not be able to meet an increase in functional demand, and in 15 of the 39 cases (38%) where an examination of the whole heart was performed, there was dilation and/or hypertrophy of the right ventricle. This is in agreement with our knowledge that the main diseases and main causes of death in AIDS patients are pulmonary. Survival time in AIDS is increasing due to ever improving symptomatic treatment, and the results of this study indicate that the prevalence of especially right-sided heart failure will increase.

Acquired Immunodeficiency Syndrome

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.

Acquired Immunodeficiency Syndrome

Effects of glucose and insulin on development of impaired insulin action in muscle.

Rat hindquarters were perfused for 2 h with either 0, 5, or 25 mM glucose in combination with either 0, 50, or 20,000 microU insulin/ml, whereupon responsiveness of glucose uptake to 20,000 microU insulin/ml and 25 mM glucose was measured. Perfusion with 25 mM glucose and 20,000 microU insulin/ml resulted in an initial glucose uptake of 43.6 +/- 3.9 mumol.g-1.h-1, which decreased to 18.7 +/- 1.6 mumol.g-1.h-1 after 2 h (P less than 0.001). Omission of glucose from the perfusate prevented the decrease in responsiveness, whereas 5 mM glucose caused a lesser decrease (to 28.3 +/- 2.2 mumol.g-1.h-1). At 0 and 50 microU insulin/ml the effects of glucose were present but were less pronounced. The decrease in insulin responsiveness of glucose uptake (55%) was accompanied by a lesser decrease (29%) in muscle glucose transport, whereas glucose transport in muscle membrane vesicles, muscle insulin binding, and insulin receptor tyrosine kinase activity were unchanged. Muscle glycogen synthase activity decreased (P less than 0.005) during perfusion with 25 mM glucose and 20,000 microU insulin/ml but did not decrease during perfusion with no glucose and 20,000 microU insulin/ml. It is concluded that insulin responsiveness of glucose uptake in muscle is decreased by exposure to glucose in a dose-dependent manner and the inhibitory effect of glucose is enhanced by simultaneous insulin exposure. The mechanism behind this insulin resistance could partly be explained by a decrease in muscle membrane glucose transport, possibly caused by changes in intracellular milieu.

Animals

Factors of importance for changes in dental caries among adults. A follow-up study of Oslo citizens from the age of 35 to 50 years.

Eighty-one 35-year-old Oslo citizens examined in 1973 were reexamined after 15 years, to monitor changes in their caries situation expressed as carious surfaces (DS + DFS). Factors considered to be of importance for a change in the number of carious surfaces over this 15-year period were arranged under four items: environment, behavior, human biology, and health care organization. The results showed a slight but not statistically significant increase in the overall caries experience expressed as DMFS. A statistically significant reduction in DS + DFS from the age of 35 to 50 years was demonstrated. Despite this reduction 23% of the 50-year-olds had more carious surfaces than at age 35. The results indicate that the improvement in the number of untreated carious surfaces reported from many Western societies is also valid for adult Norwegians. However, this improvement is not shared by all. Multivariate analyses showed that behavioral factors had the greatest impact on the observed changes in dental health.

Adult

Observer homogeneity in the histologic diagnosis of Helicobacter pylori. Latent class analysis, kappa coefficient, and repeat frequency.

Four pathologists independently examined 82 antral mucosal biopsy specimens for the presence of Helicobacter pylori and indicated whether their assessments were certain. The pathologists made a positive diagnosis in from 56% to 84% of the specimens (significant heterogeneity, p < 0.01). The frequency of uncertain diagnoses was from 4% to 20% (p < 0.01). Uncertain statements occurred more frequently among negative than among positive diagnoses. For the six pairs of observers the kappa coefficients were between 0.39 and 0.82. By a latent class analysis measures of diagnostic accuracy were calculated comparing the observers' assessments with an estimated consensus diagnosis. The predictive values of a positive diagnosis ranged from 0.70 to 1.00. By calculation of repeat frequencies--that is, the probability that an observer's statement was confirmed by another observer--it became evident that uncertain statements were less frequently (61%) confirmed than were certain ones (85%). It is concluded that observer homogeneity is only moderate with regard to the histologic diagnosis of H. pylori, which should be considered both in daily clinical routine and in scientific studies. Disagreement between observers was associated with negative diagnoses, presumably because the pathologists felt more uncertain in these cases.

Adult

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 beta-estradiol, 17 beta-estradiol plus norethisterone acetate, 17 beta-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 less than 0.0001). Furthermore, the coronary artery disease was attended by atherosclerosis in the more distal parts of the coronary arteries (p less than 0.0001), the thoracic aorta (p less than 0.0001) and the abdominal aorta (p less than 0.0001), and by a reduced relative heart weight (p less than 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.

Animals