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Biomedical subjects

S Gallistl

Publications and source records attributed to S Gallistl.

46 records · Page 3Linked to original sources
PubMed1995

Inherited resistance to activated protein C in a boy with multiple thromboses in early infancy.

Resistance to activated protein C is a recently discovered genetic defect with a high prevalence in adult patients with thromboembolic disease. It is an autosomal dominant disorder and is ten times more common in these patients than antithrombin III-, protein C- and protein S deficiency together. In spite of this high prevalence among adults with thromboembolic disease no clinical manifestation in infancy so far has been reported. We describe a 4-year-old boy with a complex cardiac malformation and inherited resistance to activated protein C, who developed multiple thromboses after cardiac catheterization in early infancy. Conclusion. Resistance to activated protein C can cause thrombosis in infants and children if additional risk factors for the development of thrombosis are present.

Blood Coagulation Tests↗
PubMed1995

Effects of heparin and hirudin on thrombin generation and platelet aggregation after intrinsic activation of platelet rich plasma.

The effects of unfractionated heparin (UH) and recombinant hirudin (rH) on prothrombin activation, free thrombin generation, and platelet aggregation induced by endogenously generated thrombin after intrinsic activation of platelet rich plasma were compared. Free thrombin generation and platelet aggregation were assessed simultaneously by delaying fibrinogen polymerisation with GPRP. UH more effectively inhibited prothrombin activation and free thrombin generation than rH. Increasing concentrations of rH had hardly any effect on the peak amount of free thrombin, while in the presence of 400 nM UH only traces of free thrombin were detected. Comparison of TAT and THC (thrombin-hirudin complex) generated until the onset of platelet aggregation on a molar basis showed that much more thrombin was inactivated in the presence of rH than in plasma containing UH. The explosive generation of free thrombin in hirudinized plasmas was accompanied by a markedly steeper aggregation curve as compared to heparinized plasmas. The generation of thromboxane B2 was markedly delayed in the presence of UH but not influenced in the presence of rH. Our results suggest that UH is more effective than rH in inhibiting prothrombin activation after intrinsic activation of platelet rich plasma, while rH prevents clotting more by direct inactivation of already generated thrombin. The inability of even high concentrations of rH to prevent the explosive generation of free thrombin might contribute to the observed inefficiency of rH to inhibit platelet aggregation.

Blood Platelets↗
PubMed1994

Thrombin-Hirudin complex formation, thrombin-antithrombin III complex formation, and thrombin generation after intrinsic activation of plasma.

To investigate the relative importance of direct inhibition of thrombin by complex formation and of inhibition of thrombin generation to the mechanisms by that unfractionated heparin (UH) and recombinant hirudin (rH) exert their anticoagulant effects, thrombin-antithrombin III complex (TAT) and thrombin-hirudin complex (THC) formation was compared with the generation of thrombin and prothrombin fragments 1 + 2 (F 1 + 2). Clotting was initiated by activation of citrated plasma in the absence or presence of UH or rH using partial thromboplastin, ellagic acid and calcium chloride. THC was determined by means of ELISA using specific antibodies to thrombin and rH. Activation of citrated plasma resulted in a sudden onset of thrombin generation after a lag phase of 2 min. Addition of 50 ng rH/ml plasma or 0.1 UH/ml plasma prolonged the clotting time to 3 min. While the peak of thrombin was only slightly decreased in hirudinized plasma, in heparinized plasma thrombin generation was significantly lower than in not anticoagulated plasma. This difference was more pronounced when the lag phase was prolonged to 5 min using 400 ng rH/ml plasma or 0.35 U UH/ml plasma. Using 1200 ng rH/ml or 0.65 U UH/ml to obtain a clotting time of 9 min only a small amount of thrombin could be detected in heparinized plasma, but hirudinized plasma still showed a high peak of thrombin. F 1 + 2 showed essentially the same pattern as thrombin. Prior to the onset of visible clot formation in all experiments using different concentrations of UH about the same values of TAT were observed.(ABSTRACT TRUNCATED AT 250 WORDS)

Antithrombin III↗
PubMedDate not supplied

Alpha-2-macroglobulin inhibits the anticoagulant action of activated protein C in cord and adult plasma.

Healthy newborns have a very low risk of thrombosis. It has been suggested that this is partly due to the anticoagulant effect of alpha-2-macroglobulin (a2-M). This broad-spectrum protease binding glycoprotein is physiologically elevated in newborns over adult values and has been shown to complex generated alpha-thrombin. In our present study, we point out that a2-M also acts as a procoagulant by inhibiting activated protein C (APC). In all experiments performed in cord and adult plasma the anticoagulant action of APC was diminished in a dose-dependent manner when a2-M levels were successively elevated, reflected in increased thrombin potential (TP), and enhanced at low a2-M levels, reflected in decreased TP.

Adult↗
PubMedDate not supplied

No relationship between leptin and cortisol in obese children and adolescents.

Recent findings have shown that leptin downregulates the steroid producing system in the adrenal. We studied the interactions of leptin, insulin and cortisol in obese children and adolescents at different stages of maturation. In 44 boys (age 11+/-3.1 yr, body mass index [BMI] 29+/-5.3 [mean +/- SD]) and 35 girls (age 11.4+/-2.6 yr, BMI 29+/-4.3), blood levels of leptin, insulin, cortisol, and glucose were determined. Fat mass (FM) was calculated by bioelectrical impedance. No significant differences were found between boys and girls with respect to humoral and anthropometric characteristics. When children were divided according to maturation stage (prepubertal, pubertal, and late/postpubertal) insulin was higher in the more mature groups (p<0.01) and leptin was higher in the pubertal group (p=0.03). In the prepubertal and pubertal groups, the expected positive relationship between adiposity and leptin was found although the magnitude of this association decreased with maturity. In none of the groups studied was cortisol significantly correlated to leptin. Insulin (p=0.03) and glucose (p=0.01) were positively associated with cortisol in the prepubertal group after adjustment for adiposity. However, in the pubertal group an inverse correlation was found between insulin and cortisol (p=0.03), and between insulin and glucose after control for adiposity. In the late/ postpubertal group, no significant correlations were found between estimates of adiposity and humoral parameters even after adjustment for gender. Stepwise multiple regression failed to detect a significant influence of cortisol to explain the variation in leptin, and vice versa. BMI contributed to the variation in leptin (adj. R2 =0.275, p<0.0001), and glucose added 5% to the variation in cortisol (p=0.03). The results do not confirm the inverse association between leptin and cortisol found in adults. Although BMI reflects levels of leptin, it is likely that several other factors in conjunction with fatness modulate the relationship with leptin. Whether leptin per se exerts an influence on the hypothalamic-adrenal-adipo axis remains to be investigated in longitudinal studies.

Adolescent↗
PubMedDate not supplied

Insulin and insulin resistance index are not independent determinants for the variation in leptin in obese children and adolescents.

Recent findings have questioned the independent influence of insulin on leptin. We studied whether insulin contributes to leptin in obese children, independent of confounding parameters, such as total adiposity, fasting insulin resistance index, and fat free mass. In 100 obese boys and 103 obese girls, blood levels of leptin, insulin, glucose, and triglycerides were determined. The fasting insulin resistance index (FIRI) was calculated, and body composition was assessed by means of impedance. Leptin and glucose were higher in girls, and all estimates of adiposity were significantly associated with leptin. However, when adjusted for adiposity, the relationship between insulin and leptin, and also between FIRI and leptin, remained significant in boys and girls (p<0.05). Although several regression models were tested, neither insulin nor FIRI were found to contribute significantly and independently to leptin. BMI together with triglycerides and FFM were the main determinants for the variation in leptin in boys (adj. R2=0.46, p<0.0001). In girls, BMI explained a great magnitude of the variation in leptin (adj. R2=0.60, p<0.0001). These findings indicate that in the state of childhood and adolescent obesity, total adiposity but not insulin or insulin resistance index is the main determinant for leptin. In contrast to obese girls, the fat free mass and triglycerides contribute significantly to the variation in leptin in obese boys. The biological significance for these findings should be elucidated in longitudinal studies.

Adolescent↗
PubMedDate not supplied

Inverse correlation between thyroid function and hemostatic markers for coronary heart disease in obese children and adolescents.

BACKGROUND: Childhood obesity may be associated with thyroid dysfunction. Both obesity and hypothyroidism are related to increased risk of coronary heart disease (CHD) in adults through high levels of serum lipids and/or hemostatic abnormalities. OBJECTIVE: To investigate a possible relationship between thyroid function and hemostatic markers for CHD in obese children and adolescents. STUDY DESIGN: Thirty-nine obese children and adolescents were investigated for thyroid function and markers for CHD after overnight fast. Thyroid hormones were measured by radioimmunoassay. Factor VII coagulant activity (VIIc) and factor VIII coagulant activity (VIIIc) were determined using one stage clotting assays; fibrinogen was measured according to the method of Clauss; von Willebrand factor antigen (vWF-Ag), tissue type plasminogen activator antigen (tPA-Ag), and plasminogen activator inhibitor-1 antigen (PAI-1-Ag) were determined by ELISA. RESULTS: We found a significant inverse correlation between fT4 and factor VIIc (r = -0.33, p = 0.03) and fibrinogen (r = -0.35, p = 0.02), which remained significant after adjustment for body fat mass. Factor VIIIc (r = -0.26, p = 0.066) and vWF-Ag (r = -0.28, p = 0.053) tended to be correlated negatively to fT4. fT4 did not correlate with tPA-Ag and PAI-1-Ag. fT3 was inversely related to factor VIIc (r = -0.3, p = 0.039), which was not independent of body fat mass, and showed a less impressive negative correlation with fibrinogen (r = -0.27, p = 0.058). fT3 did not correlate with vWF-Ag, tPA-Ag, or PAI-1-Ag. There was no relationship between TSH and the determined hemostatic markers. CONCLUSION: Our study demonstrates a close relationship between thyroid function and hemostatic markers for CHD in obese children and adolescents and suggests that thyroid dysfunction is associated with an unfavorable hemostatic state even in pediatric patients.

Adolescent↗
PubMedDate not supplied

The role of inherited thrombotic disorders in the etiology of Legg-Calvé-Perthes disease.

Inherited thrombophilia has been suggested as a cause of Legg-Calvé-Perthes disease in up to 75% of patients. This prevalence seems high compared to the prevalence of inherited thrombophilia in other thrombotic disorders (average, 30%). Therefore, we investigated 44 patients with Legg-Calvé-Perthes disease for antithrombin-III, protein-C, and protein-S deficiency and activated protein C (APC) resistance. Three (6.8%) of our patients were positive for APC resistance, and one patient (2.2%) showed deficiency of protein-C activity. Our results suggest that inherited thrombophilia is not associated with avascular necrosis of the femoral head (Legg-Calvé-Perthes disease).

Activated Protein C Resistance↗