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Biomedical subjects

W Heller

Publications and source records attributed to W Heller.

At least 19 recordsLinked to original sources
PubMed1995

Alterations of coagulation and fibrinolytic and kallikrein-kinin systems in the acute and postacute phases in patients with unstable angina pectoris.

BACKGROUND: Unstable angina pectoris is frequently associated with intracoronary thrombus formation. In a prospective study, we investigated in 35 patients with unstable angina pectoris markers of coagulation and the kallikrein-kinin and fibrinolytic systems in the acute and postacute phases. METHODS AND RESULTS: We determined serially in the patients up to 10 days after admission factor XII and the beta-factor XIIa inhibition, kallikrein-like activity, prekallikrein, C1-esterase inhibitor, kallikrein inhibition, high molecular weight kininogen as indicators of the contact phase and bradykinin generation, thrombin-antithrombin III (TAT) complex as marker of the activated coagulation cascade, fibrinogen, plasminogen, plasminogen activator inhibitor-1 (PAI-1), tissue-type plasminogen activator (TPA), and D-dimers as indicators of the fibrinolytic system. Data were compared with those from control subjects (n = 25) and from patients with stable angina pectoris (n = 25). In patients with unstable angina pectoris, initially the contact phase and the kallikrein-kinin system were markedly elevated (factor XII, 96 +/- 5% versus 117 +/- 5%; kallikrein-like activity, 35.7 +/- 2.9 versus 27.4 +/- 1.3 U/L; high molecular weight kininogen, 52.7 +/- 5.2% versus 87.7 +/- 3.9%; P < .01 versus control subjects). Contact-phase activation persisted for the following 10 days, whereas the initially enhanced bradykinin generation normalized after 2 days. Furthermore, we had evidence of a hypercoagulative state (TAT, 10.9 +/- 3.1 versus 4.5 +/- 0.7 micrograms/L, P < .05; D-dimer, 474 +/- 81 versus 272 +/- 71 ng/mL) persisting longer than the clinically symptomatic period in association with disturbed fibrinolysis (TPA, 15.9 +/- 1.9 versus 5.1 +/- 0.4 ng/mL; P < .01; PAI-1, 9.9 +/- 2.6 versus 4.6 +/- 1.6 AU/mL; P = NS) in the presence of elevated fibrinogen levels. CONCLUSIONS: Our data indicate that in patients with unstable angina pectoris, intracoronary thrombus formation is associated with a hypercoagulative state, including activation of the contact phase and of the kallikrein system and increased bradykinin generation. The persistence of this hypercoagulative state, together with a disturbed fibrinolysis, might indicate an increased risk for further coronary events.

Acute Disease↗
PubMed1995

Lower cardiac troponin T levels in patients undergoing cardiopulmonary bypass and receiving high-dose aprotinin therapy indicate reduction of perioperative myocardial damage.

Nowadays in many European heart centers the activation of the fibrinolytic system, always occurring during cardiopulmonary bypass, is routinely reduced by high-dose application of the proteinase inhibitor aprotinin (total of > 4 million KIU). In this study parameters of myocardial ischemic injury were investigated with the aim of identifying further benefits of aprotinin, particularly the protection of the myocardium during the ischemic period of aortic crossclamping. Forty patients with coronary artery disease who underwent aorta-coronary bypass grafting were randomly and in a double-blind fashion divided into two groups, one that received high-dose aprotinin therapy and one that received only saline solution. Markers such as troponin T, with high specificity for detection of myocardial ischemia and infarction, and markers with more general specificity such as creatine kinase, its isoenzyme, and lactate dehydrogenase showed significantly increased values after ischemia in both groups. In patients who received high-dose aprotinin therapy 3 days after cardiopulmonary bypass all parameters measured showed significantly lower levels compared with those in the control group. Therefore we can presume that the application of high-dose aprotinin provides myocardial protection from perioperative ischemic injury.

Aprotinin↗
PubMed1995

Patterns of perceptual asymmetry in depression and anxiety: implications for neuropsychological models of emotion and psychopathology.

More than 1,000 university undergraduates were simultaneously classified as either high or low depressed and high or low anxious and given a face-processing task that typically elicits a left hemispatial bias. Depression and anxiety were associated with opposing biases in perceptual asymmetry scores. In particular, high-depressed students had smaller left hemispatial biases than low-depressed students, whereas high-anxious students had larger left hemispatial biases than low-anxious students. The results suggest that depression and anxiety may be associated with different patterns of asymmetric hemispheric function. Because the rate of comorbidity of depression and anxiety in the population is high, these findings confirm the importance of separating anxiety and depression when examining the relationship among patterns of brain activity, emotion, and psychopathology.

Anxiety Disorders↗
PubMed1994

Activation of leukocytes and of the kallikrein-kinin system in patients with unstable angina pectoris.

We investigated the leucocyte-elastase and the activity of the kallikrein system including kinin precursors and plasma inhibition levels in 14 patients with unstable angina pectoris (normal or only slightly elevated creatinine kinase levels; no transmural myocardial infarction) and compared them with 10 controls. Leucocyte-elastase levels and activity of the kallikrein system were significantly elevated in unstable angina pectoris. The bradykinin precursor high-molecular-weight kininogen was markedly decreased to 79 +/- 16% indicating kinin generation. Except for a slight decrease in the beta factor XIIa inhibition, we observed no abnormalities in the plasma kallikrein inhibition or in the antithrombin III levels in patients with unstable angina pectoris. The findings indicate a significant activation of the plasma kallikrein-kinin system, which is not associated with a considerable reduction in the plasma inhibitor levels. Kinin generation might influence vascular tone and leucocyte function and thus be involved in the pathophysiologic alterations occurring in patients with recurrent angina at rest.

Aged↗
PubMed1994

Heparin-coated oxygenators significantly reduce contact system activation in an in vitro cardiopulmonary bypass model.

Over the past decade our group has shown that the contact system of blood is activated in cardiopulmonary bypass (CPB), that heparins enhance this activation and that aprotinin reduces both this activation and blood loss in CPB. We have developed an in vitro CPB model to assess the effects of added components to blood and new components in the artificial devices of CPB. In the present study we have compared membrane oxygenators with or without heparin-coated surfaces under identical conditions in the CPB model. Recalcified ACD blood was circulated in a closed system for 90 min at 28 degrees C. Blood samples were taken at various times during circulation. 4 IU/ml heparin was used with the non-coated oxygenators; no heparin was used in the coated system. Heparin levels were measured in the plasma together with various contact system components. Haemolysis, platelet count, platelet factor 4 and alpha 1-proteinase inhibitor-PMN elastase complexes, were also determined. No heparin was detected during the period of recirculation in samples from the coated oxygenators, showing the excellent adhesive quality of the heparin coating. In keeping with a significant greater fall in the platelet count in non-coated vs coated oxygenators (mean [+/- SD] final counts of 170 +/- 50 x 10(9)/l and 97 +/- 34.2 x 10(9)/l respectively after 90 min circulation), platelet factor 4 levels were significantly higher (682.9 +/- 187.3% and 95.8 +/- 46.5% of the initial value respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Coagulation↗
PubMed1993

The prolonged activated clotting time (ACT) with aprotinin depends on the type of activator used for measurement.

In cardiopulmonary bypass (CPB) surgery high dose heparin is necessary to inhibit the clotting cascade which is activated through damage to the vessels (extrinsic pathway) as well as contact activation of the blood with the various artificial surfaces of the CPB machine (intrinsic pathway). In most European heart surgery centres, the fibrinolytic activation that always occurs in CPB due to contact activation is reduced by the proteinase inhibitor aprotinin. Monitoring of anticoagulation during CPB is performed with the activated whole blood clotting time (ACT). The two machines commonly used for this purpose, Hemotec and Hemochron, use different contact system activators, kaolin and celite. These activators displayed highly significant differences, in both in vitro tests (modified APTT with whole blood in a neutral coagulometer), and ACT in both machines where aprotinin and heparin were used, as well as with parallel measurements with the two machines with blood from patients undergoing CPB with high dose aprotinin therapy (P < 0.001). The Hemotec machine with kaolin as activator was not affected by aprotinin throughout surgery, while the Hemochron clotting times almost doubled as soon as aprotinin and heparin were combined. Our studies show that for the determination of ACT in CPB were high dose aprotinin therapy is used only ACT determinations with machines using kaolin as activator yield accurate results.

Aprotinin↗
PubMed1992

Aprotinin in cardiopulmonary bypass--effects on the Hageman factor (FXII)--Kallikrein system and blood loss.

Aprotinin has been used in our hospital in open heart surgery for almost 20 years and recently published studies have revealed a reduction in postoperative blood loss under this therapy. In the present study patients undergoing aorto-coronary bypass operations received either 20,000 KIU aprotinin/kg body weight (group 2) or 60,000 KIU aprotinin/kg body weight (group 3). Another group of patients without aprotinin served as a control (group 1) and postoperative bleeding was more pronounced in these patients compared with the other groups. In parallel, slight reductions in kallikrein-like activity were observed in patients treated with aprotinin. Furthermore, we have shown that the main inhibitor of the contact phase, C1-esterase-inhibitor, loses some of its activity against beta-FXIIa in the presence of heparin. Aprotinin was able to partly antagonize this phenomenon. All studies dealing with the effect of aprotinin in extracorporeal circulation demonstrate hyperfibrinolysis in untreated patients. Aprotinin is known to inhibit plasmin at low concentrations and thus reduced the postoperative bleeding tendency (group 2). In addition, plasma kallikrein is inhibited by high aprotinin concentrations and is responsible for a reduced activation of the contact phase system. This effect led to a further reduction in blood loss (group 3).

Aprotinin↗
PubMed1992

Influence of oral hygiene on elastase concentration of gingival crevicular fluid.

PMN elastase concentration of gingival crevicular fluid (GCF) was investigated in 11 healthy volunteers before professional tooth cleaning and after a 5-week period of intensive oral hygiene. GCF was collected using filter paper strips and the enzyme concentration was evaluated by the ELISA-technique. Intensive daily oral hygiene led to a considerable improvement in the clinical indices and to a reduction in the concentration of elastase in GCF. Despite the changes in the oral hygiene status, functional elastase was still present in the samples at the end of the experiment. This could mean that even at clinically healthy sites there is a lack of alpha-1-proteinase inhibitor, the major serum protein inactivating PMN elastase.

Adult↗
PubMed1992

The effects of fractionated and unfractionated heparins with and without aprotinin on plasma inhibition of alpha and beta FX11a.

Chromogenic peptide substrate assays were used to compare the effects of fractionated and unfractionated heparins on plasma inhibition of alpha and beta FX11a, with and without various concentrations of aprotinin. All of the heparins reduced beta FX11a inhibition at 1 or 2U/ml. Four heparins increased alpha FX11a inhibition. Aprotinin counteracted the reduction in beta FX11a inhibition and augmented the heparin potentiation of alpha FX11a inhibition.

Aprotinin↗
PubMed1992

Studies on components of the plasma kallikrein system as a risk factor in diabetics undergoing cardiopulmonary bypass.

Components of the FX11-kallikrein systems were determined in blood samples from non diabetics and diabetics undergoing cardiopulmonary bypass (CPB). FX11 and prekallikrein levels fell in both groups with the largest falls in the diabetic group. Kallikrein inhibition was also lower in the diabetic group. Alpha-2-macroglobulin levels were lower in the diabetic group before operation and were markedly lower throughout CPB. Kallikrein like activities were also lower in the diabetic group. Beta FX11a inhibition values were higher in the diabetic group and fell in both groups during CPB. From the results obtained we concluded that the lower levels of FX11, prekallikrein, kallikrein inhibition and alpha-2-macroglobulin in the diabetic patients during CPB reflect enhanced activation of the FX11-plasma kallikrein systems. Blood loss in the diabetic group was higher than the for non diabetic group.

Biomarkers↗
PubMed1991

'La douce indifférence' and mood in anorexia nervosa: neuropsychological correlates.

1. Denial of illness, mood, eating attitudes, and the responses to visual-constructive tasks were assessed in eight right-handed female patients with restricting anorexia nervosa during the acute phase and following weight gain. 2. A lower body weight and more pronounced anorectic symptomatology were associated with increased left hemispheric activation. 3. Weight gain, greater awareness of negative affect, and overestimation of body parts were correlated with an increase in right hemispheric activation. 4. The results suggest a relationship between anorectic symptomatology and asymmetric brain activation.

Adolescent↗
PubMed1990

FXII.

The plasma protein FXII (Hageman factor) has been shown to be linked with the plasma defence systems of coagulation, fibrinolysis, kallikrein-kinin and complement. It can be activated by surface contact activation and in solution. Surface contact activation is a complex phenomenon involving negatively charged surfaces, FXII, high molecular weight kininogen and plasma kallikrein. Fluid-phase activation can be effected by a variety of serine proteases. In both types of activation the FXII zymogen is converted to active enzymes. FXII levels in plasma are low or undetectable in both inherited deficiencies and in a variety of clinical conditions. FXII levels can also be elevated in some clinical conditions. Although discovered as a clotting protein FXII appears to play an important role in the kallikrein-kinin and fibrinolytic systems and also has effects on cells. Recent studies suggest that therapeutic blockade of activation of FXII can be of benefit in certain clinical conditions.

Animals↗