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Biomedical subjects

H O Andersen

Publications and source records attributed to H O Andersen.

At least 19 recordsLinked to original sources
PubMed2001

Ageing is associated with a prolonged fever response in human endotoxemia.

The purpose of this study was to investigate whether an age-associated impaired acute-phase response exists. Nine healthy elderly volunteers (median, 66 years; range, 61 to 69 years) and eight young controls (median, 24 years; range, 20 to 27 years) were given an intravenous bolus of endotoxin (2 ng/kg). The rectal temperature was monitored continuously, and blood samples for cytokine measurements were obtained before endotoxin administration as well as 0.5, 1, 1.5, 2, 3, 4, 8, 12, and 24 h after the injection. The elderly subjects showed a more prolonged fever response compared to the young controls. Levels of tumor necrosis factor alpha (TNF-alpha), soluble TNF receptors (sTNFR-I), interleukin-6 (IL-6), IL-8, IL-10, and IL-1 receptor antagonist (IL-1ra) in plasma increased markedly following endotoxin administration in both groups. The elderly group showed larger initial increases in TNF-alpha and sTNFR-I levels and prolonged increased levels of sTNFR-I. Monocyte concentrations decreased in both groups, with the elderly group showing a more rapid decrease and a slower subsequent increase than did the young group. Furthermore, the elderly group had a more rapid increase in C-reactive protein levels than did the young group. In conclusion, ageing is associated with an altered acute-phase response including initial hyperreactivity, prolonged inflammatory activity, and prolonged fever response.

Acute-Phase Reaction↗
PubMed1999

Effect of cyclosporine on arterial balloon injury lesions in cholesterol-clamped rabbits: T lymphocyte-mediated immune responses not involved in balloon injury-induced neointimal proliferation.

Restenosis after balloon dilatation of stenosed coronary arteries is a major clinical problem. Because T lymphocytes occur in neointima and because cyclosporine inhibits T-lymphocyte proliferation, we tested the hypothesis that cyclosporine would attenuate neointimal proliferation after balloon dilation injury. Rabbits with a balloon-injured aorta, randomized to cyclosporine in the human therapeutic range (n=13) or vehicle (n=14) were followed up for 5 weeks; as a control for the effect of cyclosporine, half the rabbits received in addition an aorta allograft. Rabbits were clamped at a human plasma cholesterol level of 5 to 7 mmol/L. Cyclosporine did not affect aorta cholesterol accumulation or neointimal proliferation in balloon-injured aortas; however, it attenuated both in transplanted aortas. Likewise, cyclosporine had no effect on endothelial cells at balloon-injured sites, but protected these cells in the transplanted aortas. Infiltration of smooth muscle cells, T lymphocytes, and macrophages were unaffected by cyclosporine in balloon-injured aortas; however, in transplanted aortas, cyclosporine reduced the relative number of T lymphocytes and macrophages but increased the relative number of smooth muscle cells. Finally, in balloon-injured aortas, cyclosporine did not affect expression of vascular adhesion molecule-1, intercellular adhesion molecule-1, or major histocompatibility complex II, but all these cellular activation markers were attenuated by cyclosporine in transplanted aortas. These results suggest that cyclosporine does not attenuate neointimal proliferation after balloon dilatation, and that T lymphocyte--mediated immune responses are not involved in neointimal proliferation after balloon dilatation.

Animals↗
PubMed1997

Effect of cyclosporine during initiation of transplant arteriosclerosis. An ultrastructural study in the aorta-transplanted rabbit.

The immunosuppressant cyclosporine protects against the development of experimental transplant arteriosclerosis. To investigate the mechanism underlying this effect, aorta-allografted rabbits were randomly assigned to cyclosporine (n = 6) in the human therapeutic range or to its vehicle (n = 5). Perfusion fixation was performed 2 weeks after the transplantation, followed by light, scanning and transmission electron microscopy examination. Intimal proliferation was absent in native aortas, present in all grafts from vehicle-treated animals, and either absent or sparse in grafts from cyclosporine-treated rabbits. The endothelium of native aortas from both vehicle- and cyclosporine-treated rabbits was normal. Aortic allografts from cyclosporine-treated rabbits exhibited a normal endothelium with only a few adhering mononuclear cells, whereas aortic allografts from vehicle-treated rabbits exhibited an endothelial surface ranging from near-normal with only few adhering platelets and mononuclear cells, to an almost destroyed endothelium, lined with lymphocyte-like cells, monocytes/macrophages, platelets, erythrocytes and fibrin; in the subendothelial layer, mononuclear cells and smooth muscle cells were abundant. These results suggest that damage to the endothelial cells as well as invasion of lymphocytes, monocytes/macrophages and smooth muscle cells into the subendothelial space are important events during initiation of transplant arteriosclerosis, and that cyclosporine largely attenuates these early pathological changes.

Animals↗
PubMed1997

Dose-dependent suppression of transplant arteriosclerosis in aorta-allografted, cholesterol-clamped rabbits. Suppression not eliminated by the cholesterol-raising effect of cyclosporine.

Cyclosporine may suppress transplant arteriosclerosis; however, it also raises plasma cholesterol, which could promote the disease. Our aim was to test these hypotheses experimentally. In experiment 1 (n = 34), cholesterol was clamped at a human level of 5 to 7 mmol/L, and rabbits were given either saline or cyclosporine in a low, medium or high dose. In experiment 2 (n = 15), in which dietary cholesterol was fixed at 0.05 g.kg-1.d-1, and experiment 3 (n = 16), in which no dietary cholesterol was added to the chow, rabbits were given either medium-dose cyclosporine, saline, or vehicle. The duration of each experiment was 5 weeks. In experiment 1, cyclosporine attenuated the development of transplant arteriosclerosis dose dependently (trend test: P < .0001). Cyclosporine also suppressed, in a dose-dependent manner, the activation of the immune system (trend test: P < .05) and the presence of T lymphocytes (trend test: P < .0001) and macrophages in the intima (trend test: P < .01). Despite a higher plasma cholesterol level in cyclosporine-treated rabbits compared with saline-treated rabbits in both experiment 2 (4.9 versus 2.9 mmol/L) and experiment 3 (1.6 versus 0.8 mmol/L), transplant arteriosclerosis was significantly reduced by cyclosporine (Mann-Whitney U test; P < .05 and P < .05). These results suggest that cyclosporine suppresses experimental transplant arteriosclerosis dose dependently. Accordingly, in the assessment of the optimal cyclosporine dose to heart-transplanted patients, it should be taken into account that a dose reduction may promote transplant arteriosclerosis.

Animals↗
PubMed1997

Antiatherogenic effect of estrogen abolished by balloon catheter injury in cholesterol-clamped rabbits.

The purpose of this study was to investigate the importance of an intact endothelial cell layer for the direct antiatherogenic effect of estrogen on the arterial wall. Thirty rabbits were bilaterally ovariectomized and subjected to mechanical injury of the endothelium by balloon catheterization of the upper thoracic aorta. Immediately after the operation, treatment was initiated with either 17 beta-estradiol or placebo given intramuscularly. All rabbits were clamped at a similar plasma cholesterol level from 1 week before the operation until the experiment was terminated 13 weeks later. In the undamaged aorta, ie, the aortic arch, the lower thoracic aorta, and the upper abdominal aorta, the estrogen-treated rabbits had one third (P = .06), one sixth (P = .002), and one seventh (P = .001), respectively, the accumulation of cholesterol of the placebo-treated rabbits. In the upper thoracic aorta that had been subjected to mechanical injury of the endothelium, however, aortic cholesterol accumulation was not significantly different between the two groups. Similar results were obtained by histological evaluation of the aortic tissues. Immunohistochemical staining with antibodies against macrophages, smooth muscle cells, and T lymphocytes revealed no significant differences in the intimal distribution of cells between estrogen- and placebo-treated rabbits, except for a higher number of T lymphocytes per unit intimal area of the undamaged aortic arch (P < .0005) in the estrogen-treated-rabbits than the placebo-treated rabbits. This is the first study to demonstrate that the antiatherogenic effect of estrogen is abolished by balloon catheter injury in cholesterol-clamped rabbits. These results may indicate that an intact endothelial cell layer is crucial for the direct antiatherogenic effect of estrogen on the arterial wall.

Animals↗
PubMed1996

Pancreas autotransplantation in pig with systemic or portal venous drainage. Effect on the endocrine pancreatic function after transplantation.

The effect of the type of venous drainage of the graft on its endocrine function was studied in two groups of pigs after segmental pancrease autotransplantation. Group 1 comprised 10 pigs with portal venous drainage (PVD) and group 2 comprised 10 pigs with systemic venous drainage (SVD). The graft consisted of body and tail of the pancreas. The pigs were totally pancreatectomized. The pancreatic duct was occluded by neoprene injected into the duct. One week before and 1 and 3 months after transplantation, intravenous glucose tolerance (IVGTT) and meal stimulation tests (MST) were performed. Plasma glucose (PG), insulin (INS), C-peptide, glucagon (GLU),and pancreatic polypeptide (PP) were measured during the tests. All pigs had normal fasting PG, 1 and 3 months after PanTx, although MST disclosed significantly higher PG (P<0.05) during the test after transplantation. In the PVD group, a decrease in INS level during both test was recorded after PanTx (P<0.05), while in the SVD group a nonsignificant rise in INS level was recorded compared with before transplant. A significant difference (P<0.05) in INS levels were present both 1 and 3 mon. after PanTx between the two groups. Pigs with PVD showed a higher (P<0.05) C-peptide level than pigs with SVD during IVGTT. The initial significant rise in PP during MST and the initial fall in PP during IVGTT recorded in all pigs before transplantation were totally lost after transplantation in both groups. During the tests, PP remained steady and significantly lower than the pretransplantation levels in both groups. A significantly higher GLU level during both IVGTT and MST was observed in SVD compared with PVD 1 month after PanTx (P<0.05), being more pronounced during MST. This accentuated GLU concentration decreased by 3 months after transplantation, although it was still significantly greater than pretransplantation levels. We concluded that the unnatural mode of delivery of pancreas endocrine secretion to systemic rather than to portal circulation leads to derangements in pancreatic endocrine function in order to maintain glucose homeostasis. This may cause earlier exhaustion of islet cells. Segmental rather than whole organ and duct occlusion rather than exocrine drainage may further contribute to this, shortening the effective life of the graft.

Animals↗
PubMed1995

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↗
PubMed1995

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↗
PubMed1995

Effect of the antioxidant probucol on transplant arteriosclerosis in aorta-allografted rabbits.

The attenuation of atherogenesis by oral probucol treatment, demonstrated in several animal studies, has been attributed to the antioxidative property of probucol. It is thought that probucol, by inhibiting oxidation of low density lipoproteins (LDL) decreases the uptake of LDL into monocytes, and thereby reduces the development of foam cells and fatty streaks. Also, the neointimal proliferation seen after balloon injury has been attenuated by treatment with probucol. Since foam cells and neointimal proliferation are both important elements of transplant arteriosclerosis, we have investigated whether probucol might also retard the development of experimental transplant arteriosclerosis. The thoracic aorta from one rabbit was transplanted as a bypass graft onto the abdominal aorta of another rabbit. Nine rabbits were treated with 1 g probucol per day and seven animals were treated with vehicle. After a recovery period of 2 weeks, all rabbits were clamped at a human level of plasma cholesterol (6 to 7 mmol/l) for a period of 3 weeks. The amount of dietary cholesterol necessary for this clamping tended to be higher in probucol treated than in vehicle-treated rabbits. The distribution of plasma cholesterol between lipoprotein classes was similar in the two groups, except for the concentration of high density lipoproteins (HDL), which was significantly lowered by probucol. Probucol markedly decreased the susceptibility of LDL and intermediate density lipoprotein plus very low density lipoprotein (IDL + VLDL) particles to oxidation, as measured by the production of conjugated dienes when adding Cu2+. Despite this, the development of transplant arteriosclerosis as well as the number of macrophages in the neointima were not significantly different in the aortic allografts from the two groups. These results suggest that antioxidative agents do not retard the development of experimental transplant arteriosclerosis.

Animals↗
PubMed1994

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↗
PubMed1993

[Tetracycline pleurodesis in the treatment of spontaneous pneumothorax].

From 1979 to 1988 483 patients were admitted with primary spontaneous pneumothorax. All patients underwent thoracoscopy to identify the cause of pneumothorax. Chemical pleurodesis with tetracycline was performed if cysts less than 2 cm in diameter were found. If larger cysts were found the patient underwent thoractomy. In 93 patients with cysts larger than 2 cm the recurrence rate after thoracotomy was 4%. In 390 patients treated with intrapleural instillation of tetracycline, the recurrence rate was 16% (61 patients). The cause of recurrence in 42 patients was cysts missed at the initial thoracoscopy. This study has demonstrated that thoracoscopy is a reliable and safe method for selection of patients for chemical pleurodesis.

Adolescent↗
PubMed1992

Long-term results after tetracycline pleurodesis in spontaneous pneumothorax.

From 1979 to 1988 483 patients were admitted with primary spontaneous pneumothorax. All patients underwent thoracoscopy to identify the cause of pneumothorax. Chemical pleurodesis with instillation of tetracycline was performed if cysts less than 2 cm in diameter were found. If larger cysts were identified the patient underwent thoracotomy. In 93 patients with cysts larger than 2 cm the recurrence rate after thoracotomy was 4%. In 390 patients treated with intrapleural instillation of tetracycline, the recurrence rate was 16%. Fifty percent of the recurrences occurred within 30 days. The cause of recurrence in 42 patients (69%) was cysts missed at the initial thoracoscopy. This study has demonstrated that thoracoscopy is a reliable and safe method for selection of patients for chemical pleurodesis. It is, however, necessary that the thoracoscopy is meticulous to avoid recurrence from missed cysts.

Adolescent↗
PubMed1991

Surgical treatment of large pericardial effusions. Etiology and long-term survival.

From 1977 to 1988 60 patients were treated for large pericardial effusion. The operation consisted of a small left anterior thoracotomy with formation of a pericardial window. In 28 patients (47%) the etiology was a malignant disease. Eight patients (29%) had malignant cells in the pericardial fluid and 23 patients (82%) had metastases to the pericardium. Seven patients (12%) had purulent pericarditis; in 4 cases Staphylococcus was found. Of the remaining 25 patients, the etiology remained unknown in 13. The 5-year survival rate was 60% among patients with nonmalignant effusions. In patients with malignant effusions only 20% were alive after 2 years. There were no deaths related to the operation. We conclude that large pericardial effusions of unknown etiology can be safely treated with a small left anterior thoracotomy. This access gives optimal possibilities for rapid diagnosis and treatment.

Bacterial Infections↗
PubMed1990

[Multiple endocrine neoplasms type I].

The patient had been treated ten years previously for acromegaly. At present he was in hypercalcaemic crisis owing to multiple hyperparathyroid adenomas. He had multiple small pancreatic glucagonomas and a malignant duodenal gastrinoma which led to recurrent episodes of duodenal and gastric ulcers with perforations and hemorrhages. The hypercalcaemia increased the hypergastrinaemia significantly and probably accelerated the ulcer diathesis. This patient illustrates well how severe and complicated the clinical situation can be in patients with MEN-1 and emphasizes the importance of being aware of the syndrome.

Adult↗
PubMed1990

The age-related incidence of meconium ileus equivalent in a cystic fibrosis population: the impact of high-energy intake.

During the decade from 1976 to 1986, the age-related incidence of meconium ileus equivalent (MIE) was calculated on the basis of 240 Danish cystic fibrosis (CF) patients. In the first 5 years, the patients were given enteric-coated granules of pancreatic enzymes (Pancreatin, Rosco, Denmark), and a low fat diet was recommended. In the last 5 years, the Center recommended supplementation with acid-resistant, enteric-coated, encapsulated microspheres (Pancrease, Cilag, Birkerød, Denmark), and high-energy intake with a 40% fat content and no dietary restrictions. There was no difference in the incidence of MIE when these two 5-year periods were compared, and the overall incidence of MIE was low (5.4 MIEs/1,000 patient years). This may, at least in part, be due to the rather high intake of exocrine pancreas enzyme supplementation (EPES) (a mean intake of 0.9 capsules/kg/day). MIE occurred almost exclusively among patients greater than 15 years old and peaked in young adults aged 20-25 years (35.5 MIEs/1,000 patient years). The daily intake of EPES/kg of body weight declined significantly with age, and the patients who developed MIE received even less than average per day. Both of these points strengthen the view that a low enzyme dosage is likely to have an effect on the incidence of MIE.

Acetylcysteine↗
PubMed1990

Screening for multiple endocrine neoplasia type 1 in patients with recognized pituitary adenoma.

A total of 79 consecutive patients with pituitary tumours were screened for multiple endocrine neoplasia type 1 (MEN-1). The 79 patients included 21 patients with acromegaly, nine with Cushing's disease, 18 with prolactinomas, three with mixed pituitary adenomas (GH and PRL), and 28 patients with no detectable hypersecretion of hormones. The screening consisted of: (1) a family history, (2) a uniform medical history of the patient using a standard questionnaire, and (3) hormonal evaluation including measurements of the serum levels of insulin, gastrin, glucagon, somatostatin, vasoactive intestinal polypeptide and pancreatic polypeptide. Ionized calcium and glucose concentration in serum were also measured. We found no patients with the MEN-1 syndrome. In one patient, we found a transient elevation of serum concentrations of pancreatic polypeptide for which we have no explanation. In another patient, the serum gastrin concentration was elevated secondary to achlorhydria. No other endocrine disorders were found, and no patients had relatives with recognized endocrine pancreatic tumours, primary hyperparathyroidism (HPT), or pituitary adenomas.

Adenoma↗