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Biomedical subjects

C Bode

Publications and source records attributed to C Bode.

At least 91 records · Page 5Linked to original sources
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↗
PubMed1997

Histones: genetic diversity and tissue-specific gene expression.

Histones are the major protein constituents of the chromatin of eukaryotic cell nuclei. This group of basic proteins is extremely conserved throughout evolution and includes five classes termed H1, H2A, H2B, H3 and H4. In mammals, each of these classes except H4 is subdivided into several subtypes. The most divergent class of histones is the H1 protein family, which consists of seven different subtypes, termed H1.1-H1.5, H1 degree, and H1t. The subtypes H1.2 and H1.4 are found in most somatic cell nuclei, whereas H1 degree is found in several differentiated tissues, and H1t is restricted to mammalian testicular cells. Similarly, core histone subtypes replacing the major forms of H2A, H2B or H3 have been described. Biochemical analysis of protein and RNA from different tissues and cell lines demonstrates varied patterns of expression of individual histone subtype genes. Moreover, antibodies against specific histone subtypes and in situ hybridization with subtype-specific probes indicate that the expression of histone subtype genes is in several cases modulated in a tissue-specific manner. This is particularly evident at the different stages of spermatogenesis when chromatin undergoes substantial reorganization, which finally results in the highly condensed state of chromatin of the mature sperm head.

Animals↗
PubMed1997

Decreased endotoxin-binding capacity of whole blood in patients with alcoholic liver disease.

BACKGROUND/AIMS: The proinflammatory effects of endotoxemia, which is often observed in alcohol-abusing patients with various degrees of liver disease, may be modulated by changes in the concentration of endotoxin binding factors. Therefore, the plasma endotoxin concentration and the overall endotoxin binding capacity of whole blood were measured in these patients. METHODS: Patients with minor (A1; n=27), more pronounced (A2; n=13), cirrhotic alcoholic liver disease (A3; n=18), and non-alcoholic cirrhosis (NC; n=6), and 15 healthy control persons (HC) were included in the study. Endotoxin plasma levels were determined using a standardized limulus assay. A modified assay was applied to additionally detect tightly bound endotoxin. To measure the endotoxin-binding capacity, aliquots of whole blood were incubated with serial dilutions of endotoxin, supernatants were obtained, and endotoxin retrieval was estimated by addition of limulus lysate, followed by photometric measurement of the maximal reaction velocity (dODmax). Endotoxin binding capacity equals the endotoxin concentration at which dODmax reaches a predefined threshold. RESULTS: All groups of alcohol abusers had significantly elevated endotoxin plasma levels with a considerable portion of 'bound' endotoxin. Conversely, the endotoxin binding capacity was markedly diminished, mainly in patients with more advanced liver disease (A1: 85.8% of the control value [non-significant vs. controls]; A2: 25.4% [p<0.05]; A3: 43.6% [p<0.02], NC: 43.2%). CONCLUSIONS: The endotoxin-binding capacity is diminished in patients with alcoholic and non-alcoholic cirrhosis, as well as in less advanced alcoholic liver disease. Reduced endotoxin binding may contribute to the adverse effects of endotoxemia.

Adult↗
PubMed1997

Clinical trial results with a new plasminogen activator.

Thrombolysis has become an accepted form of therapy for acute myocardial infarction. As demonstrated in the Global Utilization of Streptokinase and t-PA for Occluded Arteries trial, early, complete and sustained patency of the infarct-related coronary artery is correlated with reduced mortality. However, current thrombolytic regimens are able to achieve such patency within 90 min in only 81% of cases. To improve the risk/benefit ratio of thrombolytic therapy, newer agents such as reteplase have been developed to establish more rapid, more complete and more stable coronary artery patency, thus reducing mortality. This report summarizes the pharmacological properties of reteplase. It also summarizes the findings from various animal and clinical studies in which reteplase was compared with alteplase and streptokinase and the findings from animal and clinical studies evaluating infusion, single-bolus, double-bolus, doses of reteplase.

Amino Acid Sequence↗
PubMed1997

A diet rich in fat and poor in dietary fiber increases the in vitro formation of reactive oxygen species in human feces.

Production of reactive oxygen species in the lumen of the colon, a process that is influenced by nutritional factors, may be important in the etiology of colorectal cancer. Because research on humans in support of this hypothesis is lacking, the objective of this study was to measure the effect of different dietary compositions on the in vitro oxygen radical production in human feces. Over a period of 12 d, seven healthy subjects received a diet rich in fat (50%) and meat and poor in dietary fiber. After a period of 1 wk, they received a vegetarian diet poor in fat (20%) and rich in dietary fiber. At the end of each study period, feces were collected and analyzed for in vitro oxygen radical production with dimethylsulfoxide as the free radical scavenger. The mean hydroxyl radical production was 13 times greater in feces of subjects when they consumed the diet rich in fat and poor in dietary fiber [52.7 +/- 29.5 micromol/(g feces x h)] than when they consumed the diet poor in fat and rich in dietary fiber [3.9 +/- 3.9 micromol/(g feces x h); P < 0.05]. This difference was associated with a 42% higher fecal iron concentration when they consumed the first diet (7.0 +/- 19.2 micromol/g feces) than when they consumed the second (4.9 +/- 1.9 micromol/g feces; P < 0.05). The results of this study confirm that diets high in fat and meat and low in fiber markedly increase the potential for hydroxyl radical formation in the feces, which in turn may contribute to an enhanced risk of colorectal cancer.

Adult↗
PubMed1997

Inhaled nitric oxide inhibits platelet aggregation after pulmonary embolism in pigs.

BACKGROUND: Inhaled nitric oxide (NO) is reported to prolong bleeding time in animals and humans and to inhibit platelet aggregation in persons with acute respiratory distress syndrome. In pulmonary embolism (PE), inhibition of platelet aggregation appears useful because further thrombus formation may lead to right ventricular dysfunction that results in circulatory failure. In the present study, the effect of inhaled NO on platelet aggregation after acute massive PE was investigated. METHODS: After acute massive PE was induced in 25 anesthetized pigs by injecting microspheres, 5, 20, 40, and 80 parts per million inhaled NO were administered stepwise for 10 min each in 11 animals (NO group). In the control group (n = 14). NO was not administered. Adenosine diphosphate-induced initial and maximal platelet aggregation were measured before PE (10), immediately after induction of PE (PE), at the end of each 10-min NO inhalation interval (t10-t40), and 15 min after cessation of NO inhalation (t55) in the NO group, and at corresponding times in the control group, respectively. RESULTS: Two animals in the control group and one in the NO group died within 10 min after PE induction and were excluded from analysis. Peaking at t40 and t55, respectively, initial (-13 +/- 6%; P < 0.05) and maximal (+44 +/- 17%; P < 0.05) platelet aggregation increased significantly after PE in the control group. In contrast, NO administration after PE led to a significant decrease in initial (maximum decrease, -9 +/- 3% at t40; P < 0.05) and maximal (maximum decrease, -15 +/- 7% at t30; P < 0.05) platelet aggregation. In the NO group, platelet aggregation had returned to baseline levels again at t55. In addition, NO administration significantly decreased mean pulmonary artery pressure and significantly increased end-tidal carbon dioxide concentration and mean systemic blood pressure. CONCLUSIONS: Inhaled NO has a systemic and rapidly reversible inhibitory effect on platelet aggregation after acute massive PE in pigs. This may be beneficial in treating acute massive PE.

Administration, Inhalation↗
PubMed1997

Circulating vascular cell adhesion molecule-1 correlates with the extent of human atherosclerosis in contrast to circulating intercellular adhesion molecule-1, E-selectin, P-selectin, and thrombomodulin.

Secondary prevention of atherosclerosis, especially before the onset of symptoms, appears desirable and could be possible with a serum marker detecting atherosclerosis. Circulating, shedded forms of adhesion molecules may serve as such because their expression is upregulated in atherosclerotic plaques. In 52 patients with peripheral arterial vascular disease (Fontaine class IIa, 7 patients; class IIb, 29 patients; and class III, 16 patients), the extent of atherosclerosis was evaluated on the basis of angiograms of a large portion of the arterial system. The area diseased by atherosclerosis was determined by the percentage of vessel wall irregularities of the following calculated segments: aorta (distal from the kidney arteries), common iliac artery, external iliac artery, common femoral artery, lateral circumflex femoral artery, and popliteal artery. The maximal surface area that could exhibit atherosclerotic changes was 250 cm2. The serum concentration of circulating vascular cell adhesion molecule-1 (VCAM-1) correlated with the extent of atherosclerosis (r = .8, P < .001). In contrast, circulating intercellular adhesion molecule-1, E-selectin, P-selectin, and thrombomodulin (as markers for endothelial cell damage) did not correlate with the extent of atherosclerosis. Furthermore, circulating VCAM-1 could be used to indicate stages of atherosclerosis with a high degree of statistical significance. The potential bias of factors such as age, diabetes mellitus, hypercholesterolemia, arterial hypertension, renal failure, and history of myocardial infarction on the correlation of circulating VCAM-1 with the extent of atherosclerosis could be excluded by multivariate analysis. These findings suggest an important role of VCAM-1 in atherosclerosis and may serve as the basis for further evaluation of circulating VCAM-1 as a potential serum marker for atherosclerosis.

Adult↗
PubMed1997

Effect of treatment with paromomycin on endotoxemia in patients with alcoholic liver disease--a double-blind, placebo-controlled trial.

The results of experimental and clinical studies support the hypothesis that gut-derived endotoxins might be of relevance for the development and course of alcoholic liver disease. The aim of this study was to test the effect of a nonabsorbable, broad-spectrum antibiotic on endotoxemia in patients with alcoholic liver disease. Fifty patients with alcoholic liver disease (27 with cirrhosis, 23 without cirrhosis) were randomly assigned to receive either paromomycin sulfate (3 x 1 g/day) or placebo in a double-blind fashion for at least 3 weeks, and if possible 4 weeks. Endotoxin concentration, liver function tests, and other laboratory parameters were determined in weekly intervals. Endotoxin concentration was also determined in 15 healthy controls. Groups receiving paromomycin or placebo were similar for clinical and biological items collected initially. Mean initial endotoxin concentrations were significantly elevated in both groups (mean +/- SEM; paromomycin, 16.7 +/- 5.3 pg/ml; placebo, 17.5 +/- 6.9 pg/ml; healthy controls, 2.3 +/- 0.4 pg/ml). Although the mean endotoxin concentration was lower in the verum group after 1 week (paromomycin, 8.0 +/- 1.9 pg/ml; placebo, 14.6 +/- 3.5 pg/ml; p > 0.05), paromomycin treatment had no significant effect on endotoxin concentration or liver function tests during the 4-week period. The beneficial effect of paromomycin treatment on endotoxemia in cirrhotics reported in earlier studies could not be reproduced under the conditions of this trial in patients with alcoholic liver disease.

Adult↗
PubMed1996

Patency trials with reteplase (r-PA): what do they tell us?

Thrombolytic therapy has been shown to reduce mortality and morbidity after acute myocardial infarction. Therapeutic benefit seems to be directly correlated with completeness of reperfusion (Thrombolysis in Myocardial Infarction [TIMI] grade 3 flow) of the infarct-related coronary artery, as well as the timeliness of reperfusion. To determine which regimen of reteplase (r-PA), a deletion mutant of wild-type tissue plasminogen activator (t-PA), is most effective for clinical thrombolysis, several reteplase regimens were compared with the most successful standard regimens of recombinant t-PA (alteplase) in 2 large-scale, randomized studies. All patients received aspirin and intravenous heparin. In the Reteplase Angiographic Phase II International Dose Finding Trial (RAPID-1), results in 606 randomized patients showed that a 10 + 10 U double bolus of reteplase was more effective than a 15 U single bolus, a 10 + 5 double bolus, or conventional alteplase (100 mg over 3 hours). In the Reteplase versus Alteplase Patency Investigation During Acute Myocardial Infarction (RAPID-2) trial, results in 324 patients showed that significantly more patients achieved patency of the infarct-related artery (TIMI grade 2 or 3 flow) at 90 minutes with reteplase (10 + 10 U double bolus) than with accelerated alteplase (100 mg over 90 minutes): 83.4% versus 73.3%, respectively (p = 0.03). The incidence of complete patency (TIMI grade 3 flow) at 90 minutes was likewise greater with reteplase than with accelerated alteplase (59.9% vs 45.2%, respectively; p = 0.01). At 60 minutes, the incidence of TIMI grade 2 or 3 flow was also significantly higher with reteplase than with alteplase (81.8% vs 66.1%, respectively; p = 0.01), as was the incidence of TIMI grade 3 flow (51.2% vs 37.4%, respectively; p < 0.031). The 35-day mortality rate was 4.1% for reteplase and 8.4% for alteplase (p = not significant). Reteplase and alteplase did not differ significantly with regard to the occurrence of severe bleeding (12.4% vs 9.7%, respectively) or hemorrhagic stroke (1.2% vs 1.9%, respectively). The results of these trials show that reteplase, given as a 10 + 10 U double bolus, achieves significantly higher rates of early reperfusion of the infarct-related coronary artery and is associated with significantly fewer acute coronary interventions when compared with front-loaded alteplase. The benefits of reteplase are achieved without any apparent increased risk of complications.

Cerebral Hemorrhage↗