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Biomedical subjects

C Bode

Publications and source records attributed to C Bode.

At least 37 records · Page 2Linked to original sources
PubMed1998

Management strategies for a better outcome in unstable coronary artery disease.

Unstable coronary artery disease is a term encompassing both unstable angina and non-Q-wave (non-ST-segment elevation) myocardial infarction. Patients with these conditions are at risk of early progression to acute myocardial infarction and death. Thus, management of these conditions must aim to reduce long-term mortality and morbidity. Risk stratification is crucial for the identification of patients whose risk of early progression is high; they may require coronary angiography and (if suitable) either percutaneous transluminal coronary angioplasty or coronary artery bypass surgery. No single variable can accurately predict risk, but considerable data are emerging to show that biochemical markers of myocardial injury, such as troponin-T and troponin-I, are valuable in combination with electrocardiographic findings and clinical features. Routine early invasive procedures (coronary angiography with or without revascularization) have not yet been shown to have any significant advantage over conservative regimens for the majority of patients. Antiplatelet, anticoagulant, and anti-ischemic agents remain the mainstay of treatment in the acute phase. New agents, such as glycoprotein IIb/IIIa receptor inhibitors and low-molecular-weight heparins, as well as antithrombins and Factor Xa inhibitors add to the treatments currently available. Thrombolytic agents are contraindicated in the absence of ST-segment elevation. After clinical stabilization, ongoing assessment should include exercise testing for all patients who are able; other imaging techniques should be used for patients unable to exercise. A profile indicating a high risk of future events is an indication for elective angiography and consideration for revascularization.

Algorithms↗
PubMed1998

Augmentation of arterial endothelial cell expression of the plasminogen activator inhibitor type-1 (PAI-1) gene by proinsulin and insulin in vivo.

Diabetes mellitus is associated with an increased incidence and greater severity of primary atherosclerosis as well as restenosis after angioplasty for reasons not yet clear. We have shown previously that insulin and proinsulin-typically elevated in blood in patients with type II diabetes-increase plasma activity of plasminogen activator inhibitor type 1 (PAI-1)in vivo. Others have demonstrated that increased PAI-1 activity is associated with coronary heart disease. Accordingly, the present study was performed to identify sites of increased expression of the PAI-1 gene within the vessel wall. Equimolar concentrations of insulin, proinsulin, or vehicle alone as a control, were administered intravenously over 1 h to conscious rabbits that were kept euglycemic throughout by the use of glucose clamping. Within 3 h plasma PAI-1 activity increased from 1.15+/-1.34 to 11.33+/-4.30 AU/ml with insulin (mean+/-s.d., P=0.015) and from 2.83+/-0.74 to 15.43+/-4.70 AU/ml with proinsulin (P=0.035). This was found to be in contrast to the controls where the increase in plasma PAI-1 activity was of lesser degree (2.43+/-1.86 to 6.80+/-1.10 AU/ml, P=n.s., n=4 each). As judged from the results of in situ hybridization, the site of prominent aortic expression of the PAI-1 gene was the endothelium. Furthermore, expression increased further in this site after administration of insulin or proinsulin. As judged from results of immunohistochemistry, PAI-1 protein in the aorta was also prominent in endothelium. These results suggest that "hyper(pro)insulinemia", increases PAI-1 not only in blood but also in arterial endothelium. Thus, attenuation of vasculopathy and especially of restenosis after angioplasty in type II diabetes may be possible with somatic gene therapy targeting PAI-1 expression in endothelial cells.

Animals↗
PubMed1998

[Prevention and treatment of restenosis after percutaneous transluminal coronary angioplasty].

Restenosis is a clinical problem after coronary angioplasty associated with major ischemic events or repeat interventions in 20-50% of the patients undergoing this procedure. Major efforts have been undertaken in the past decade to successfully prevent or treat restenosis but no pharmacologic approach to the problem has as yet been identified to be effective enough in clinical conditions. New strategies to cope with restenosis are targeted by local application of ionizing radiation which markedly reduces cell proliferation after angioplasty in animal experiments. Preliminary clinical trials indicate that endovascular radiation therapy is a safe and effective means to treat restenosis. Randomized, multicenter studies with long follow-up periods are needed to support these early results.

Angioplasty, Balloon, Coronary↗
PubMed1998

[Catheter-assisted techniques for decreasing the rate of restenosis after coronary angioplasty: an overview of radiotherapy].

Restenosis after percutaneous transluminal coronary angioplasty (PTCA) is a clinical problem associated with major ischemic events or repeat interventions in 20-50% of the treated patients. Systemic drug therapy has not yet been shown to prevent restenosis in clinical conditions. However, local therapeutic strategies are evolving, such as the catheter-based delivery of drugs, of antiproliferative genes, or of ionizing radiation. Experimental studies show that radiation therapy reduces restenosis rates, and preliminary clinical trials investigating a small number of patients indicate that, in particular, catheter-based radiation may be safe and effective. Randomized multicenter studies with long follow-up periods are needed to support these early results.

Angioplasty, Balloon, Coronary↗
PubMed1998

Expression of the mouse histone gene H1t begins at premeiotic stages of spermatogenesis.

The gene encoding H1t, a testicular variant of histone H1, is expressed in mammals during spermatogenesis. Northern blot and in situ hybridization has detected H1t mRNA only at the stage of pachytene spermatocytes. We have extended this analysis to more sensitive approaches and demonstrate, by RNase protection and electron-microscopic in situ hybridization, that H1t mRNA is detectable even in spermatogonia. Just a faint H1t band is seen in Western blots of nuclear protein from 9-day-old mice. This indicates that the H1t gene is expressed at premeiotic stages, albeit at a low level. In contrast to H1t mRNA, the H1t protein has not been detected in spermatogonia by electron microscopy after immunogold staining.

Animals↗
PubMed1998

Prospective use of glycoprotein IIb/IIIa receptor blockers in the emergency department setting.

Platelets play a pivotal role in the pathophysiology of acute coronary syndromes (ACS) and thus are logical therapeutic targets for treatment of this disease process. Platelet glycoprotein (GP) IIb/IIIa receptor antagonists, which interrupt the final common pathway of platelet aggregation, have been proved to reduce the 30-day incidence of death, acute myocardial infarction (MI), and urgent revascularization in both high-risk and low-risk patients undergoing percutaneous intervention procedures. Three-year follow-up has indicated that these benefits appear durable. Recent large-scale randomized trials have demonstrated the value of GP IIb/IIIa receptor inhibitors in reducing the risk of death and MI in patients with unstable angina or those with MI with non-Q-wave abnormalities who are receiving pharmacologic management. In addition, emerging evidence suggests a future role for GP IIb/IIIa receptor inhibitors as an adjunct to low-dose fibrinolytic therapy in patients with acute MI. As the list of indications for GP IIb/IIIa receptor antagonists expands to encompass the full spectrum of ACS, there is increasing interest in the potential use of these agents in the emergency department setting. The integration of GP IIb/IIIa receptor inhibitors into ED protocols will ultimately depend largely on whether these drugs prove to be safe and effective regardless of the direction of ST-segment deviation, and irrespective of whether definitive therapy will be invasive or conservative.

Acute Disease↗
PubMed1998

Validation and comparison of two computerized methods of obtaining a diet history.

The aim of this study was to validate two computerized methods of obtaining a diet history (DH and EBIS). The food consumption of 12 men and eight women was calculated by weighing each food item over a period of 8 days. Thereafter the diet history was taken over this period by using both programs alternatively. The intake of energy, protein, fat and carbohydrates, and 10 further nutrients was evaluated and the percentage difference calculated. In general, the intake of nutrients calculated from the diet history tended to be underestimated by most of the people interviewed. The mean daily intake of the nutrients calculated from the DH program deviates from -34% to +20% (mean SD = 48.1) and -35% to +15% for EBIS (mean SD = 28.1). In conclusion, both computerized methods proved useful for epidemiological studies, but not for the determination of deficiencies in individuals.

Aged↗
PubMed1998

Light and electron microscopic in-situ hybridization of collagen type I and type II mRNA in the fibrocartilaginous tissue of late-stage osteoarthritis.

OBJECTIVE: Biochemical analysis indicates the presence of collagen type I in fibrocartilaginous tissue of osteoarthritic cartilage, whereas normal hyaline cartilage contains only collagen type II produced by normal chondrocytes. Fibrocartilaginous tissue of late-stage osteoarthritis also exhibits irregularly shaped type 2b secretory chondrocytes as described in the literature. We have attempted to elucidate the type of cell which produces each type of collagen in late-stage osteoarthritis. DESIGN: We carried out in-situ hybridization at the light and electron microscopic level on the same tissue embedded in LR-Gold applying silver enhancement for gold-coupled anti-DIG antibodies. We correlated the types of cells with the expression of transcripts for type I and type II collagen. RESULTS: We found that cells resembling type 2b secretory chondrocytes of deep zones of fibrocartilaginous tissue expressed collagen type I mRNA and almost no collagen type II mRNA. The amount of collagen type I mRNA was as high as the amount produced in normal human skin fibroblasts. CONCLUSION: Some of the collagen type I in osteoarthritic human cartilage of late-stage disease is produced by cells resembling type 2b secretory chondrocytes of the deep zone.

Adult↗
PubMed1998

Free methionine supplementation limits alcohol-induced liver damage in rats.

Alcohol feeding to rats that were submitted to a jejunoileal bypass operation has been shown to result in liver damage being comparable with alcohol-induced liver disease in man. In the present study, a striking effect of free methionine consumption on histological liver injury, triglyceride accumulation, and energy-rich nucleoside content in the liver of rats with a jejunoileal bypass is demonstrated. The animals obtained 0, 30, and 120 mg of methionine in the control group and 0, 30, 120, and 240 mg in the alcohol-fed group per day and per kilogram of body weight for 12 weeks. Methionine was found to strongly improve the alcohol-induced histological changes in the liver. Triglyceride content of the liver was found to decrease in a dose-dependent manner with increasing methionine ingestion (from 255 +/- 20.7 to 49.7 +/- 6.1 micromol/g of protein in the control group and from 233 +/- 17.3 to 42.1 +/- 7.2 micromol/g of protein in the alcohol group). Hepatic adenosine triphosphate content increased significantly with higher methionine consumption (13.5 +/- 0.8 vs. 26.9 +/- 2.8 micromol/g of protein in the control group and 11.9 +/- 1.4 vs. 20.5 +/- 2.5 micromol/g of protein in the alcohol group), whereas no differences were found in the protein and DNA content of the liver. These results underscore the impairment of the transmethylation/transsulfuration pathway in the development of alcohol-induced liver diseases.

Adenine Nucleotides↗
PubMed1998

A low concentration of ethanol reduces the chemiluminescence of human granulocytes and monocytes but not the tumor necrosis factor alpha production by monocytes after endotoxin stimulation.

The ability of polymorphonuclear neutrophils (PMNs) and monocytes (Mphi) to produce reactive oxygen species (ROS) has been related closely to their potential in the killing of microorganisms. Ethanol has been shown to impair the generation of ROS in these phagocytes after stimulation with some immunogens and to increase the susceptibility of alcohol abusers to infectious diseases. As endotoxemia is common in alcohol abusers, we investigated the effect of ethanol (21.7 mmol/liter) on the luminol-amplified chemiluminescence of PMNs and Mphi after endotoxin stimulation and the release of tumor necrosis factor alpha (TNF-alpha) from Mphi. Further, the efficiency of ethanol to inactivate chemically generated ROS was tested. Significant stimulation of ROS release occurred at endotoxin concentrations of 1 ng/ml or higher in both PMNs and Mphi. Ethanol significantly suppressed the formation of ROS in both cell types, the decrease being more pronounced in Mphi (-73. 8%) than in PMNs (-45.7%). The correlations between endotoxin concentration and the amount of released ROS showed a dose-dependent, sigmoidal course. Concentrations of endotoxin necessary for half-maximum stimulation were nearly identical (6 to 8 ng/ml) in both PMNs and Mphi, independent of the presence of ethanol. In contrast to ROS formation, ethanol had no effect on the amount of TNF-alpha produced by endotoxin-stimulated Mphi. Ethanol was shown to be unable to decrease the levels of chemically generated ROS under physiological conditions. Therefore, ethanol cannot be assumed to be an "antioxidative" compound but rather seems to modify processes of endotoxin recognition, intracellular signal transduction, or metabolism.

Adult↗
PubMed1998

[Pregnancy in corrected transposition of great arteries and therapy with ACE inhibitors].

A pregnancy after Mustard repair for transposition of the great arteries and ventricular septal defect with pulmonary stenosis is reported. The 23-year-old gravida 1 was treated with ACE inhibitors up to 26 weeks of gestation until cardiac medication was changed to dihydralazine. At 28 weeks of gestation the patient developed cardiac decompensation leading to caesarean section for maternal indication at 29 weeks of gestation. The neonate did not show any congenital malformation nor anuria. The patient was moved to a normal ward six days after delivery. A cardiac follow-up examination showed no difference to the condition before pregnancy.

Adult↗
PubMed1998

Effect of the type of beverage and meat consumed by alcoholics with alcoholic liver disease.

We analyzed meat products and alcoholic beverage preference in patients with the three stages of alcoholic liver disease (ALD) compared with controls using diet history data. Daily consumption of total alcohol, types of alcoholic beverages, and types of meat and meat products in grams was obtained by dietary history taken from patients with biopsy proven stage of ALD. A strong association was found between the ALD subjects and total alcohol and beer consumption. There was a significant increase in the consumption of total pig products, pork, and offal in the ALD groups compared with controls. There was a significant positive correlation between beer consumption and pork in alcoholic hepatitis, total pork products in alcoholic hepatitis, and cirrhosis and offal in alcoholic hepatitis and cirrhosis. There was no correlation with the fatty liver stage of ALD. The strongest correlation was between beer and total pig products in the alcoholic hepatitis group. Wine consumption was negatively correlated with the consumption of pig products and beer in the alcoholic cirrhosis group. In conclusion, the association of total pig product consumption with cirrhosis mortality in various countries was validated by personal diet history data obtained from ALD patients in a tested clinical microcosm. The results suggest that this association may be modified by the type of alcoholic beverage that is preferentially consumed.

Adult↗
PubMed1998

Augmented platelet aggregation as predictor of reocclusion after thrombolysis in acute myocardial infarction.

RATIONALE: Reocclusion after thrombolysis diminishes the benefits of early reperfusion after acute myocardial infarction (AMI). No clinical or laboratory variables have been identified as predictors for reocclusion yet. METHODS AND RESULTS: To evaluate hemostatic variables as potential risk determinants platelet aggregation (PA, representing platelet activity), thrombin/antithrombin complexes (TAT, representing thrombin generation), and plasminogen activator inhibitor type 1 (PAI-1, representing endogenous fibrinolysis) were determined in 31 patients with AMI at 0, 1, 2. and 12 h after the start of thrombolysis as well as at hospital discharge. Reocclusion (defined as reinfarction or angiographically confirmed, clinically silent coronary reocclusion) occurred in 5 patients within 5-14 days and in 8 patients within 1 year. TAT plasma concentrations were lower in patients with reocclusion than in those without (9.9+/-5.7 vs. 22.9+/-22.2 ng/ml at 2 h, 6.5+/-3.1 vs. 1 1.2+/-6.4 ng/ml at 12 h, means+/-SD, p <0.05 each). Neither concentration nor activity of PAI-1 in plasma differed between both patient groups. However, both slope and maximum of PA (induced by 2 micromol/l ADP) were augmented in patients with reocclusion (slope: 39.4+/-1.7 vs. 32.5+/-7.4 at 2 h, p <0.001; 42.6+/-2.6 vs. 36.6+/-8.9 at 12 h, p <0.01). Results were independent of the thrombolytic agent used (alteplase or reteplase). A PA slope at 2 h higher than the average slope before thrombolysis (37.2+/-5.7) could be identified as best predictor for early (within 5-14 d, p=0.017, sensitivity 1.00, specificity 0.69) and late reocclusion (within 1 y, p=0.009, 0.88 and 0.74, respectively). CONCLUSIONS: Increased PA following coronary thrombolysis appears to be associated with early and late reocclusion. This marker could be useful in identifying patients who may benefit from more aggressive antiplatelet (such as GP IIb/IIIa receptor antagonists), interventional, or both strategies.

Adenosine Diphosphate↗
PubMed1998

Prospective use of platelet glycoprotein IIb/IIIa receptor blockers in the emergency department setting.

Platelets play a pivotal role in the pathophysiology of acute coronary syndromes (ACS) and thus are logical therapeutic targets for treatment of this disease process. Platelet glycoprotein (GP IIb/IIIa receptor antagonists, which interrupt the final common pathway of platelet aggregation, have been proven to reduce the 30-day incidence of death, acute myocardial infarction (MI), and urgent revascularization in both high-risk and low-risk patients undergoing percutaneous intervention procedures. Three-year follow-up has indicated that these benefits appear durable. Recent large-scale randomized trials have demonstrated the value of GP IIb/IIIa receptor inhibitors in reducing the risk of death and MI in unstable angina/non-Q-wave MI patients receiving pharmacologic management. And, emerging evidence suggests a future role for GP IIb/IIIa receptor inhibitors as an adjunct to low-dose fibrinolytic therapy in patients with acute MI. As the list of indications for GP IIb/IIIa receptor antagonists expands to encompass the full spectrum of ACS, there is increasing interest in the potential use of these agents in the emergency department setting. The integration of GP IIb/IIIa receptor inhibitors into emergency department protocols will ultimately depend largely on whether these drugs prove to be safe and effective regardless of the direction of ST-segment deviation, and irrespective of whether definitive therapy will be invasive or conservative.

Algorithms↗
PubMed1997

Antithrombotic potency of hirudin is increased in nonhuman primates by fibrin targeting.

BACKGROUND: Inhibition of thrombin by either the indirect thrombin inhibitor heparin or by more potent direct thrombin inhibitors such as hirudin reduces thrombus formation after arterial injury. The present study was designed to determine if a fibrin-specific thrombin inhibitor could, by local thrombin inhibition, prevent thrombosis more effectively. METHODS AND RESULTS: We first studied antithrombotic potency in vitro, comparing fibrin-targeted hirudin (recombinant hirudin covalently linked to the Fab' fragment of the anti-fibrin monoclonal antibody 59D8) to recombinant hirudin in baboon plasma. Fibrin-targeted hirudin was nine times more effective than recombinant hirudin in inhibiting fibrin deposition on experimental clot surfaces in baboon plasma (P < .01). The potency of fibrin-targeted hirudin was then compared with that of recombinant hirudin in a baboon model of thrombus formation. 111In-labeled platelet deposition was measured in a synthetic graft segment of an extracorporeal arteriovenous shunt in control animals and in animals receiving either fibrin-targeted hirudin or hirudin. In these experiments, fibrin-targeted hirudin was 10-fold more potent than hirudin in inhibiting platelet deposition and thrombus formation (P < .05). CONCLUSIONS: These data indicate that targeting a thrombin inhibitors such as hirudin to an epitope present in thrombi results in increased antithrombotic potency.

Animals↗
PubMed1997

Attenuation by gemfibrozil of expression of plasminogen activator inhibitor type 1 induced by insulin and its precursors.

BACKGROUND: Insulin and its precursors found in increased plasma concentrations in non-insulin-dependent diabetes mellitus (NIDDM) augment synthesis of plasminogen activator inhibitor type 1 (PAI-1) in Hep G2 cells in vitro and in rabbit liver in vivo. Reduced endogenous fibrinolysis secondary to increased PAI-1 activity may exacerbate atherogenesis. Recently, the reduction of the coronary heart disease incidence in the Helsinki Heart Study has implicated favorable modulation of endogenous fibrinolysis by gemfibrozil. METHODS AND RESULTS: In Hep G2 cells, 500 (700) mumol/L gemfibrozil decreased basal secretion of PAI-1 by 26% (43%) (P = .012 and P = .021, respectively) and attenuated insulin-induced (10 nmol/L) augmentation of PAI-1 in conditioned media by 61% (109%) (P = .010) within 24 hours. Inhibition was dependent on the duration of exposure (0 to 48 hours) and on the concentration of gemfibrozil (0 to 700 mumol/L) but not on the concentration of insulin (0.1 to 100 nmol/L). Gemfibrozil attenuated the augmentation of PAI-1 secretion induced by proinsulin (> 100%), by des(31,32)proinsulin (75%), and by des(64,65) proinsulin (77%) as well (10 nmol/L each). The specificity of these effects was confirmed by the unaltered levels of newly synthesized protein (metabolic labeling) and of total protein (both in conditioned media and cell lysates). Secretion of fibrinogen by Hep G2 cells was not affected by gemfibrozil. Changes in PAI-1 protein levels reflected modulation of PAI-1 gene expression as manifested by changes in levels of 3.2-kb PAI-1 mRNA (Northern blots). CONCLUSIONS: Gemfibrozil attenuated the augmentation of synthesis and secretion of PAI-1 induced by insulin and its precursors directly and specifically. Accordingly, gemfibrozil may exert favorable therapeutic effects normalizing impaired fibrinolysis in patients with hyperinsulinemia such as NIDDM.

Fibrinogen↗
PubMed1997

Histone gene expression and chromatin structure during spermatogenesis.

The chromatin of male germ cells is restructured throughout spermatogenesis. Analysis of differential histone protein patterns at specific stages of spermatogenesis may contribute towards an understanding of the changes in chromatin structure and function during this differentiation process. The most striking changes in histone patterns occur at the stage of pachytene spermatocytes when most of the linker H1 histones are replaced by the testis specific subtype H1t. In addition, replacement of core histone subtypes is observed at this stage. These structural changes precede the reorganization of chromatin at haploid stages when histones are replaced first by transition proteins and then by protamines.

Animals↗