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Biomedical subjects

S Gallistl

Publications and source records attributed to S Gallistl.

At least 37 records · Page 2Linked to original sources
PubMed2000

Cystatin C, an early indicator for incipient renal disease in rheumatoid arthritis.

Rheumatoid arthritis (RA) is a chronic disease requiring potential nephrotoxic therapy with nonsteroidal antiinflammatory drugs (NSAIDs) and disease modifying antirheumatic drugs (DMARDs). The rationale of our study was to examine the renal status of patients suffering from prolonged RA by means of plasma cystatin C, a new parameter of renal function. Fifty-six patients affected with RA for more than 5 years, and treated with NSAIDs for more than 50 months, were included in the study. Besides conventional markers of renal function (i.e. plasma creatinine, estimated glomerular filtration rate, creatinine clearance), we analysed plasma cystatin C by an automated, nephelometric immunoassay on a Behring nephelometer. Sixty percent of the RA patients exhibited elevated levels of plasma cystatin C, whereas only three out of 56 patients showed an elevated plasma creatinine, even though the creatinine clearance was decreased in 57% of these patients. Cystatin C exhibited a by far better correlation with creatinine clearance than plasma creatinine. In conclusion, patients with prolonged RA for more than 50 months, show a disturbed renal function despite normal plasma creatinine. Elevated cystatin C indicates such incipient renal disease, and is, not least because of a simple, well reproducible technique, more recommendable for screening purposes than tedious clearance determinations.

Aged↗
PubMed2000

Stroke following appendectomy under general anesthesia in a patient with basilar impression.

We report a boy who developed a vertebral stroke immediately after an appendectomy. Basilar impression was diagnosed eight years after this event when skull roentgenograms revealed basilar impression with high standing tip of the odontoid. We speculate that muscle relaxation and cervical hyperextension during intubation in the presence of basilar impression resulted in vertebral artery dissection and stroke. We suggest that patients with vertebral stroke and no obvious risk factors should be evaluated for the presence of malformations of the craniovertebral junction to be able to take precautions against excessive neck movement during intubation.

Anesthesia, General↗
PubMed2000

Determinants of haemostatic risk factors for coronary heart disease in obese children and adolescents.

OBJECTIVE: To investigate the contribution of serum lipids, parameters of glucose metabolism, body composition and cardiovascular fitness to the variance of several haemostatic risk factors for coronary heart disease (CHD) in obese children and adolescents. SUBJECTS AND MEASUREMENTS: Forty-two healthy, obese children and adolescents (20 male, 22 female, age 12.6 +/- 3.2y; body mass index (BMI), 30.4 +/- 5.3 kg/m2), were screened for haemostatic and metabolic risk factors for CHD. Thirty-five of the participants (18 male, age 13.5 +/- 2.9y; BMI, 29.9 +/-4.5kg/m2; 17 female, age 12.8+/-2.1 y, BMI, 31.1 +/- 5.3 kg/m2) were assessed for cardiovascular fitness by means of incremental cycle ergometer exercise. RESULTS: After adjustment for age, fat mass correlated significantly with plasminogen activator inhibitor-1 antigen (PAI-1-Ag) in boys and girls and factor VIIc only in girls. Children with lower power output (< or = 2.77W/kg) showed significantly higher values for factor VIIc, fibrinogen and tissue-type plasminogen activator antigen (tPA-Ag). Neither body composition nor cardiovascular fitness contributed independently to the variance of the determined haemostatic risk factors, except PAI-1-Ag, which has been shown to be determined by fat mass. In multiple linear regression analysis, triglycerides and PAI-1-Ag explained significant independent proportions of the variance of tPA-Ag. Factor VIIc was explained by C-peptide, insulin and fibrinogen. Von Willebrand factor antigen (vWF-Ag) was significantly related to glucose and insulin. CONCLUSION: The results suggest that in obese children and adolescents the haemostatic risk factors factor VIIc, vWF-Ag and tPA-Ag are mainly determinated by plasma insulin and triglyceride concentrations, but are primarily independent of body composition and cardiovascular fitness.

Adolescent↗
PubMed2000

Relationship between plasminogen activator inhibitor-1 antigen, leptin, and fat mass in obese children and adolescents.

Hyperleptinemia may be associated with cardiovascular risk and is linked with parameters of fibrinolytic processes in adults. We studied whether body fatness, leptin, and insulin interact with plasminogen activator inhibitor-1 antigen (PAI-1-Ag) and tissue-type plasminogen activator antigen (tPA-Ag) in obese children and adolescents. Twenty-three boys (mean +/- SD: age, 10.7 +/- 3.3 years; body mass index [BMI], 28.7 +/- 5.4 Kg/m2) and 19 girls (age, 11.9 +/- 2.7 years; BMI, 29.4 +/- 4.8 Kg/m2) were investigated. Body fat mass (FM) in the children was calculated by bioelectrical impedance analysis, and blood samples were obtained for leptin, insulin, C-peptide, PAI-1-Ag, and tPA-Ag. The children were divided into 3 subgroups according to maturation. Maturity was associated with greater adiposity and higher levels of leptin and C-peptide, but insulin and PAI-1-Ag were not different between prepubertal, pubertal, and late/postpubertal children. PAI-1-Ag was associated with leptin and insulin, but not after adjustment for fatness. PAI-1-Ag was independently associated with tPA-Ag (r = .36, P < .02). Multiple regression analysis showed that tPA-Ag failed to reach the level of significance (P = .07), but FM contributed to the variation in PAI-1-Ag (adjusted R2 = .29). The BMI was the main determinant for the variation in leptin (adjusted R2 = .386) and in insulin (adjusted R2 = .60, all P < .001). Neither gender, maturation, chronological age, or leptin contributed significantly to the variation in either PAI-1-Ag or tPA-Ag. Our data suggest that adiposity and other variables contribute to higher levels of PAI-1-Ag. Leptin seems not to be independently linked with fibrinolytic parameters, but an unfavorable metabolic and fibrinolytic risk profile might emanate from the obese pubertal stage.

Adipose Tissue↗
PubMed2000

Effects of the glycoprotein IIb/IIIa receptor antagonist c7E3 Fab and anticoagulants on platelet aggregation and thrombin potential under high coagulant challenge in vitro.

The present study was performed to investigate the combined effects of the platelet glycoprotein IIb/IIIa receptor antagonist c7E3 Fab (abciximab) and the anticoagulants unfractionated heparin (UH), low molecular weight heparin (LMWH), and recombinant hirudin (rH) on platelet aggregation and thrombin generation under high coagulant challenge by extrinsic activation of platelet-rich plasma. Platelet aggregation and thrombin generation were assessed simultaneously in the presence of different concentrations of abciximab and anticoagulants. Increasing concentrations of abciximab resulted in a dose-dependent anti-aggregating effect with a maximum at 20 microg/ml. Doses of 5, 10, and 20 microg/ml abciximab prolonged the lag phase until the onset of platelet aggregation, but this effect was independent of the dosage used. Abciximab had no influence on the thrombin potential under our high coagulant challenge. UH, LMWH, and rH showed a dose-dependent prolongation of the lag phase until the onset of platelet aggregation and decreased the thrombin potential. Addition of anticoagulants did not contribute to further inhibition of platelet aggregation in the presence of abciximab, but the combination of abciximab and anticoagulants exhibited an additive effect on prolongation of the lag phase until the onset of platelet aggregation. Addition of abciximab to anticoagulants did not result in further decrease of the thrombin potential. Our study demonstrates the respective specific effects of abciximab and anticoagulants on platelet aggregation and thrombin potential under high coagulant challenge, and also an additive effect of abciximab and the anticoagulants UH, LMWH, and rH on the lag phase until the onset of platelet aggregation.

Abciximab↗
PubMed2000

Correlation between cholesterol, soluble P-selectin, and D-dimer in obese children and adolescents.

Thirty-eight obese children and adolescents were investigated for a possible relation between cholesterol and markers of platelet activation, endothelial cell dysfunction, and activation of the coagulation system. Soluble P-selectin, von Willebrand factor antigen (vWf-Ag), D-dimer, and prothrombin fragment 1 + 2 (F1 + 2) were determined by enzyme-linked immunosorbent assays, and factor VIII coagulant activity (VIIIc) was measured by means of one-stage clotting assay. Cholesterol correlated significantly with log P-selectin (r = 0.43, P = 0.003) and log D-dimer (r = 0.33, P = 0.02). Cholesterol did not correlate with vWf-Ag, factor VIIIc, and F1 + 2. Log P-selectin correlated significantly with log D-dimer (r = 0.42, P = 0.003), which remained significant after adjustment for cholesterol (P = 0.02). Log D-dimer correlated significantly with F1 + 2 (r = 0.38, P = 0.01). Our study demonstrates that, in obese children and adolescents, cholesterol is significantly associated with P-selectin and D-dimer, and suggests an unfavorable intercorrelation between metabolic and hemostatic risk factors for coronary heart disease in childhood obesity.

Adolescent↗
PubMed2000

The relationship between different subcutaneous adipose tissue layers, fat mass and leptin in obese children and adolescents.

We studied the relationships of subcutaneous adipose tissue layers (SAT-layers), body fat mass (FM) and waist-to-hip ratio (WHR) with leptin in obese children and adolescents. Twenty-nine obese children and adolescents (12 boys: age: 11.3 +/- 3.7 yr; body mass index [BMI]: 28.5 +/- 4) and 17 girls (age: 12.2 +/- 2.2 yr; BMI: 29.8 +/- 4.7) (mean +/- SD) were studied. FM was estimated by bioelectrical impedance. SAT-layers were determined at 15 different body sites from 1-neck to 15-calf by the Lipometer optical device. Leptin and insulin were determined by RIA. Maturity was associated with a greater thickness of certain SAT-layers from the upper body and with a lower thickness of SAT-layers from the abdominal region and lower extremities. Significant correlations were found for all estimates of adiposity and leptin (all p<0.001). Waist and hip circumferences were not correlated to leptin after adjustment for FM. SAT-layers from the upper body were significantly and positively correlated to leptin. Multiple regression analysis revealed FM as a main contributor to the variation in leptin (R2=0.53, p<0.0001). FM together with SAT-layers 5-front chest and 13-rear thigh explained 72% of the variation in leptin (p<0.0001). In a body fat distribution model, hip circumference together with SAT-layers 4-upper back and 2-triceps explained 75% of the variation in leptin (p< 0.0001). The results suggest that SAT-layers and their topography are main determinants for leptin in obese children and adolescents. Maturity in obese children is associated with higher values of upper body SAT-layers and lower values of abdominal and lower extremities SAT-layers. Whether leptin is under the control of certain subcutaneous adipose tissue depots from the upper body remains to be elucidated by longitudinal studies.

Adipose Tissue↗
PubMed2000

No evidence for leptin as an independent associate of blood pressure in childhood and juvenile obesity.

We studied whether leptin is an independent associate of blood pressure in obese children and adolescence. 102 obese children (48 girls, age: 11.6 +/- 2.22 yr; body mass index [BMI]: 27.45 +/- 4.4; blood pressure: 122.5 +/- 11.1/64.7 +/- 10.6 mm Hg and 54 boys, age: 11.5 +/- 2.4 yr; BMI: 27.6 +/- 4.4; blood pressure: 122.5 +/- 13.2/60.9 +/- 8.1 mm Hg [mean +/- SD]) were investigated. Serum leptin and insulin were measured by RIA; glucose was determined enzymatically. Fat mass (FM) was calculated by bioelectrical impedance. Leptin was higher in girls than in boys (p=0.018) but no significant gender differences were found with respect to indices of adiposity and systolic blood pressure (SBP). Children were divided into three groups, according to pubertal stage (Group 1: prepubertal, 32 boys/13 girls; Group 2: pubertal, 17 boys/25 girls; Group 3: late/postpubertal, 5 boys/10 girls). SBP and DBP correlated with body weight in the whole group (r=0.49, p<0.0001, and r=0.27, p=0.004). In Group 1, BMI showed the highest correlation to SBP; in Group 3 no indices of adiposity were related to SBP. In no case was leptin significantly associated with SBP after adjustment for adiposity. In Group 2, glucose was significantly associated with SBP after adjustment for body weight. In Group 3, however, no correlations were found between SBP, DBP and metabolic characteristics, perhaps due to small sample size. Stepwise multiple regression revealed that body weight and glucose contributed to the variation in SBP in the whole group (R2=0.31, p<0.0001). Insulin accounted for almost 8% of the variation in DBP (R2=0.08, p=0.0034). Body weight contributed significantly to SBP in boys (R2=0.39, p<0.0001) and girls (R2=0.24, p< 0.001). The results imply that body weight contributes independently to the variation in blood pressure. Glucose and insulin contribute to mean blood pressure to some extent, but our data do not support the assumption that leptin per se serves as an independent predictor of blood pressure in obese children and adolescents.

Adolescent↗
PubMed2000

Insulin is an independent correlate of plasma homocysteine levels in obese children and adolescents.

OBJECTIVE: The aim of the study was to investigate whether anthropometric and metabolic risk factors for coronary heart disease (CHD) contribute to the variation in homocysteine levels in obese children and adolescents. RESEARCH DESIGN AND METHODS: A total of 84 children and adolescents were assessed for fasting total homocysteine, methylenetetrahydrofolate reductase polymorphism (C677T mutation), folate and vitamin B12 status, and anthropometric and metabolic risk factors for CHD. RESULTS: No significant sex differences were found for all available anthropometric and metabolic characteristics except for homocysteine, which was significantly higher in boys than in girls (7.1 vs. 6.3 micromol/l; P<0.05). After adjustment for age and sex, homocysteine correlated significantly with BMI, fat mass, percentage of fat mass, and insulin and showed an inverse correlation with folate levels. Homocysteine did not correlate with vitamin B12; total cholesterol; LDL, HDL, and VLDL; triglycerides; and glucose. BMI and fat mass correlated significantly with insulin and showed a significant inverse correlation with folate. We found no association between homocysteine and the C677T mutation. In multiple regression analyses, insulin was found to be the main correlate of homocysteine. CONCLUSIONS: Our study demonstrates for the first time that insulin is a main correlate of homocysteine in obese children and adolescents and suggests that fat mass-associated hyper-insulinism may contribute to impairment of homocysteine metabolism in childhood obesity

Adolescent↗
PubMed1999

Effects of antithrombin and protein C on thrombin generation in newborn and adult plasma.

It has been suggested that antithrombin (AT) and protein C (PC) might be less important in newborn plasma than in adult plasma for the inhibition of clotting activation. To assess the importance of AT and PC for the regulation of thrombin generation in newborn as compared with adult plasma, thrombin generation was determined in the presence of different concentrations of AT and PC. In both, newborn and adult plasmas, reduction of AT and PC resulted in an increase of thrombin generation after intrinsic activation. On the other hand, supplementation of AT and PC decreased thrombin generation in a dose-dependent manner. Clotting times were influenced by different PC concentrations, whereas clotting times were almost not affected by different amounts of AT. Our study suggests that the significance of AT and PC in the regulation of thrombin generation is the same in newborn and adult plasma. Our experimental results also support the notion that administration of AT or protein C concentrates may be beneficial in some clinical situations leading to an increased clotting activation in newborns.

Adult↗
PubMed1999

Long-term follow-up of cytokines and soluble cytokine receptors in peripheral blood of patients with juvenile rheumatoid arthritis.

Plasma levels of interleukin-1beta (IL-1beta), IL-2, soluble IL-2 receptor (sIL-2R), IL-6, IL-8, tumor necrosis factor-alpha (TNF-alpha), and the p60 soluble TNF receptor (sTNFR) were repeatedly determined by enzyme-linked immunosorbent assays (ELISA) in 35 patients with different subtypes of juvenile rheumatoid arthritis (JRA) during an observation period of up to 36 months. The data were related to conventional inflammatory parameters and disease activity. Patients with systemic disease showed the most pronounced elevations of plasma cytokines, followed by polyarticular and pauciarticular JRA. Soluble receptors sIL-2R and sTNFR were consistently elevated in patients of all JRA subtypes and indicated disease activity even in patients with normal C-reactive protein (CRP). In contrast, the determination of IL-1beta, IL-2, IL-8, and TNF-alpha revealed strikingly different individual profiles in patients of the same clinical subtype of JRA and irrespective of disease activity. It is concluded that the determination of sIL-2R and sTNFR may be relevant for monitoring JRA, as they indicate disease activity also in cases with unaltered conventional inflammatory parameters. The different individual cytokine profiles of patients within identical subtypes of disease suggest JRA to be even more heterogeneous than hitherto assumed. The data should be considered in attempts to develop anticytokine strategies in the therapy of JRA.

Adolescent↗
PubMed1999

Recombinant factor VIIa does not induce hypercoagulability in vitro.

Recombinant factor VIIa (rVIIa) has been reported to be clinically effective and safe in haemophilic patients with inhibitor antibodies. Compared to activated prothrombin complex concentrates the risk of thrombotic complications seems to be very low after rVIIa administration. Determination of free thrombin generation has been shown to identify hypercoagulability. Therefore, free thrombin and prothrombinase activity (Xa generation) were assessed after extrinsic activation of rVIIa supplemented factor VIII and factor IX deficient plasma. Free thrombin generation was also determined after supplementation of (activated) prothrombin complex concentrates. Addition of 150 U rVIIa/ml shortened the clotting times markedly in control, factor VIII, and factor IX deficient plasma. In contrast, free thrombin and Xa generation were not different in the absence or presence of 150 U rVIIa/ml. Addition of (activated) prothrombin complex concentrates resulted in a marked increase of free thrombin generation in all investigated plasmas. Although in vitro studies cannot reflect specific clinical circumstances our results support the notion that rVIIa does not induce a hypercoagulable state as sporadically observed after administration of (activated) prothrombin complex concentrates.

Blood Coagulation↗
PubMed1998

Activation of the haemostatic system in children with juvenile rheumatoid arthritis correlates with disease activity.

Twenty-four children with juvenile rheumatoid arthritis (JRA) and 10 children with postinfectious arthropathies were investigated for markers of blood coagulation and fibrinolytic activity: Prothrombin fragment 1+2 (F1+2), thrombin-antithrombin complex (TAT), and D-Dimer were measured using solid phase enzyme linked immunosorbent assays (ELISA). Results were compared with clinical and conventional laboratory signs of disease activity. F1+2, TAT, D-Dimer, and fibrinogen were significantly elevated in children with JRA as compared with healthy children and children with postinfectious arthropathies. F1+2, TAT, and D-Dimer correlated significantly with disease activity, assessed by determination of the joint index score and C-reactive protein (CRP). The study demonstrates a subclinical activation of the haemostatic system in children with JRA correlating with disease activity, which might be caused by the action of several immunomediators on cells (monocytes, endothelial cells) playing a role in the regulation of blood coagulation activity.

Adolescent↗
PubMed1998

"Emergency hepatectomy" in a 16-month-old boy with a hepatoblastoma, severe cytomegalovirus-induced pancytopenia, and intractable diarrhea.

A 16-month-old boy presented with massive abdominal enlargement. Magnetic resonance imaging (MRI) revealed a liver tumor measuring 11 x 11 x 10 cm. Pulmonary metastases were detected by chest computed tomography. The diagnosis of a hepatoblastoma was made from the patient's age, the location of the tumor, and marked elevation of alpha1-fetoprotein (AFP). Chemotherapy according to the German Cooperative Pediatric Liver Tumor Study HB-94 was started, leading to a rapid and dramatic decrease in AFP levels. Despite an excellent response to chemotherapy, however, the abdominal distension increased. On a second MRI scan the tumor was unchanged in size, showing large areas of necrosis and cystic transformation. In addition, the patient acquired a cytomegalovirus infection with intractable diarrhea and severe pancytopenia. Since the patient's clinical course had worsened, the decision was made to alleviate the life-threatening tumor compression by an extended right hepatic lobectomy despite platelet-transfusion dependence and a white blood cell (WBC) count of only 300/microliter. Postoperative necrosis of the common bile duct necessitated a secondary resection with Roux-en-Y hepaticojejunostomy. The boy recovered quickly, and the white blood and platelet counts increased to normal values immediately after the first surgery so that chemotherapy could be finished after the postoperative recovery period. He is now in good condition without evidence of local or metastatic disease 1 year after the primary diagnosis.

Cytomegalovirus Infections↗
PubMed1997

Longer aPTT values in healthy children than in adults: no single cause.

We have shown that activated partial thromboplastin time values in children are considerably longer than in adults, but the causes for this observation remained unclear. Therefore, we investigated the correlation between activated partial thromboplastin time values and concentrations of clotting factors, quotients and titers of the tissue thromboplastin inhibition test, and antiphospholipid antibodies in healthy children, children with recurrent infections, and adults. Concentrations of factors VIII, IX, and HMWK were significantly lower in children than in adults. Simple linear regression analysis failed to show a correlation between the concentration of a single clotting factor and the activated partial thromboplastin time values. No significant correlation was found between activated partial thromboplastin time and elevation of the tissue thromboplastin inhibition test quotients or titers, or antiphospholipid antibodies values. The determined activated partial thromboplastin time was best described by a function including all measured coagulation factors. Our study suggests, that no single clotting factor or lupus anticoagulants are responsible for the longer activated partial thromboplastin time in healthy children, but that activated partial thromboplastin prolongation is caused by the combination of several slightly lower clotting factors.

Adolescent↗
PubMed1995

Serum cytokines in juvenile rheumatoid arthritis. Correlation with conventional inflammation parameters and clinical subtypes.

OBJECTIVE: To examine the usefulness of determining extended serum cytokine profiles in patients with juvenile rheumatoid arthritis (JRA), for the purpose of improving differential diagnosis and monitoring disease activity. METHODS: In a 2-year prospective study, serum levels of interleukin-1 beta (IL-1 beta), soluble IL-2 receptor (sIL-2R), IL-6, IL-8, tumor necrosis factor alpha (TNF alpha), and the p55 soluble TNF receptor (sTNFR) were repeatedly determined by enzyme-linked immunosorbent assay in 40 patients with JRA, 13 patients with postinfectious arthropathies, and 30 healthy controls. The data were compared with conventional parameters of inflammation, such as C-reactive protein (CRP), iron and hemoglobin levels, erythrocyte sedimentation rate (ESR), white blood cell (WBC) counts, and platelet counts. WBC subsets were analyzed by flow cytofluorometry. RESULTS: At the first visit and at the peak of inflammatory activity according to CRP levels and/or ESR, serum levels of sIL-2R, IL-6, and sTNFR in JRA patients correlated significantly with conventional inflammation indicators, whereas IL-1 beta, IL-8, and TNF alpha did not. No changes in leukocyte subset distribution were noted. Among the different clinical subtypes of JRA, sIL-2R, IL-6, and sTNFR values at the time of the initial visit showed a pattern similar to CRP, whereby patients with systemic disease exhibited by far the highest values. TNF alpha and IL-1 beta were variably elevated in certain JRA subtypes. Patients with postinfectious arthropathies showed elevated levels of CRP, sIL-2R, TNF alpha, and sTNFR, which did not differ significantly from levels in the various JRA subtypes with the exception of systemic disease. Detailed analysis of types I and II pauciarticular JRA revealed that levels of CRP, IL-1 beta, and TNF alpha were elevated in patients with type I disease. While these parameters were invariably normal in patients with type II disease, sTNFR and sIL-2R were still found to be significantly elevated. Followup studies suggested that persistently high sTNFR values are a better indicator of JRA activity than are measurements of other cytokines or CRP. CONCLUSION: JRA is associated with significant and consistent changes in serum levels of inflammatory cytokines and soluble receptors. For the clinical monitoring of JRA, determination of levels of sTNFR, and to some extent sIL-2R, may be particularly useful, since these determinations yield information about subtype and/or activity of disease that is not available from conventional parameters of inflammation.

Adolescent↗