Biomedical subjects
Publications and source records attributed to Peter Riis Hansen.
Polycythaemia vera is a myeloproliferative syndrome with thromboembolic and haemorrhagic complications. We describe a patient with polycythaemia vera and acute coronary syndrome in whom two-vessel intracoronary stent thrombosis occurred a few hours after percutaneous coronary intervention. The case was successfully treated by repeated stenting and abciximab infusion.
Bivalirudin is a direct thrombin inhibitor that has biological and pharmacokinetic advantages over heparin, e.g., by inhibiting both fibrin-bound and -unbound thrombin. In patients undergoing subacute or elective percutaneous coronary intervention, bivalirudin + provisional glycoprotein IIb/IIIa inhibition is as effective as unfractionated heparin + glycoprotein IIb/IIIa inhibition and is associated with a reduced risk of bleeding. The results of ongoing trials will further define the promising role of bivalirudin in the treatment of patients with acute coronary syndromes.
Patients with acute coronary syndromes can display widespread coronary instability. We report a case presenting with ST segment elevation myocardial infarction and rapid progression to thrombosis of all major epicardial coronary arteries documented by angiography and at autopsy.
A low level of high-density lipoprotein (HDL) cholesterol is an important cardiovascular risk factor. The protective effects of HDL have been attributed to its promotion of reverse cholesterol transport, antioxidant activity and anti-inflammatory actions on endothelial cells. Several treatment strategies aimed at exploiting the favourable effects of HDL are currently undergoing clinical trials and hold considerable promise as a novel approach to atheroprotection.
BACKGROUND: In early studies, a median survival time of 5 to 7 years from onset of diabetic nephropathy was observed. Furthermore, end-stage renal disease (ESRD) was the main cause of death. We prospectively assessed the impact of reno- and cardiovascular protective treatment on prognosis in type 1 diabetic patients with diabetic nephropathy. METHODS: We prospectively followed 199 type 1 diabetic patients with diabetic nephropathy and 192 patients with normoalbuminuria for 10 years. Aggressive antihypertensive treatment was initiated in patients with diabetic nephropathy in mid 1980s, whereas statins and aspirin were not prescribed routinely until April 2002. The primary end point was cardiovascular mortality and morbidity. Secondary end points were all-cause mortality and ESRD. RESULTS: During follow-up, 79 patients (40%) with nephropathy reached the primary end point versus 19 (10%) of normoalbuminuric patients, log rank test P < 0.0001. Predictors of the primary end point were: nephropathy (hazard ratio 3.26; 95% confidence interval 1.89 to 5.62), previous event (3.19; 2.04 to 4.97), age (1.27; 1.04 to 1.55), and systolic blood pressure (1.13; 1.03 to 1.24). In the nephropathy group, 60 patients (30%) died; hereof, 25 deaths (42%) were ascribed to cardiovascular causes while 30 patients (50%) with nephropathy died with ESRD. The estimate of median survival time from onset of diabetic nephropathy was 21.7 years, SE 3.3 years. CONCLUSION: The survival of patients with diabetic nephropathy has improved most likely due to aggressive antihypertensive treatment and improved glycaemic control.
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BACKGROUND: The mineralocorticoid receptor antagonist spironolactone (SPIR) reduces the mortality and morbidity in patients with congestive heart failure (CHF). Overexpression of proinflammatory cytokines contribute to the development and progression of CHF. MATERIAL AND METHODS: We examined the effect of SPIR on in vitro cytokine production by human peripheral blood mononuclear cells (PBMC). PBMC were cultured with 10-1000 microM SPIR and stimulated with lipopolysaccharide or phytohaemagglutinin-P. Tumour necrosis factor-alpha (TNF-alpha), interleukin (IL)-6, IL-1beta, and interferon (IFN)-gamma were measured in culture supernatants by enzyme-linked immunosorbent assay and mRNA expression of the cytokines was determined by real-time reverse transcriptase polymerase chain reaction (PCR). RESULTS: SPIR inhibited the stimulated production of TNF-alpha, IL-6, and IFN-gamma, whereas the release of IL-1beta was not significantly affected. The SPIR-induced cytokine inhibition occurred at the transcriptional level and was independent of antimineralocorticoid and antiandrogen activities. CONCLUSION: The findings suggest that inhibited production of proinflammatory cytokines may be an extrarenal mechanism that contributes to the beneficial effect of SPIR in patients with CHF.
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Vulnerable atherosclerotic plaques are characterised by a large lipid core and a thin fibrous cap infiltrated with activated inflammatory cells. Heat is a cardinal sign of local inflammation, and atherosclerotic lesions display thermal heterogeneity, with increased temperature being correlated with inflammatory cell density, unstable clinical presentation, and unfavourable outcome after percutaneous interventions. Thermography is a promising new technique for assessment of atheroclerotic plaque composition.
Optical coherence tomography (OCT) is a novel technique for two and three-dimensional imaging of tissues at a histological level. The technique is based on optical technology and commercially available fiber-optic components that may be adapted for use in conventional endoscopes or intravascular catheters. OCT is a non-invasive technique, which does not utilize ionizing radiation, and it may within a few seconds provide in vivo images ("optical biopsies") of tissues in cases where excisional biopsy is hazardous or impossible, or when repeated examinations are required. OCT has numerous potential clinical applications, and the technique is currently used in ophthalmology, where it may improve diagnosis and therapeutic control of various eye diseases. Detection and characterization of skin tumors and other dermatological diseases is another area where OCT has tremendous clinical potential. In the field of cardiology, intravascular OCT may be capable to contribute to early diagnosis of vulnerable atherosclerotic lesions. The OCT technique is also being developed in other clinical areas and is expected to become integrated in a range of clinical situations in the future.
Inflammation is present in all stages of atherosclerosis, from fatty streaks to rupture of mature plaques. Tumour necrosis factor (TNF)-alpha is expressed in atherosclerotic lesions but its role in atherogenesis has not been defined. To clarify the role of this cytokine, we administered thalidomide, a compound known to inhibit TNF-alpha production, to homozygous apolipoprotein E-deficient (apoE-/-) mice in order to examine the effect of thalidomide on the development of early atherosclerotic lesions. Twelve apoE-/- mice were randomized to receive either sustained-release thalidomide or placebo pellets implanted subcutaneously, and the amount of atherosclerosis was quantified six weeks later. Thalidomide was well tolerated and did not result in any changes in body weight. Mice treated with thalidomide had significantly smaller mean (7986 +/- 5189 vs 19607 +/- 10353 microns 2, p = 0.05) and maximum (15800 [12777-23675] vs 37169 [28000-41351] microns 2, p = 0.03) lesion sizes than those treated with placebo. Thus, thalidomide is capable of inhibiting the early development of atherosclerosis, presumably by inhibition of TNF-alpha secretion.
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