Ulrike Krämer

Justus-Liebig-Universität Gießen, Gieben, Hesse, Germany

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Publications (7)19.92 Total impact

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    ABSTRACT: With an increasing number of heart transplantations (HTx) performed in children and an extended long-term survival of these patients, the importance of transplant coronary artery disease (TCAD) rises in this group of transplant recipients. Reliable serum markers for diagnosis or non-invasive monitoring of this disease in pediatric transplant recipients are still missing. We studied the systemic expression of adhesion molecules as well as plasma coagulation markers and the occurrence of TCAD and/or rejection in pediatric heart transplant recipients. The systemic plasma levels of soluble forms of sVCAM-1 and sICAM-1, d-dimer, tissue factor (TF), prothombin fragments F(1+2), and tissue factor pathway inhibitor (TFPI) were assessed in serial venous blood samples (2-4 per patient) in 50 pediatric transplant recipients children and 63 age- and sex-matched non-transplanted controls. TCAD and rejection were diagnosed angiographically or by combined histological, echocardiographic, or clinical signs, respectively. Plasma levels of sICAM-1 and sVCAM-1, d-dimers and prothrombin fragment F(1+2) but not TF and TFPI were significantly increased in children following HTx compared with non-transplanted controls (p<0.001). Among the transplanted patients, sICAM-1 levels were significantly higher in patients with angiographically detectable TCAD than in patients without evidence of TCAD (p<0.005). Plasma sICAM-1 levels above a cutoff value of 1500 ng/mL (95.5 percentile of control values) were indicative of the presence of TCAD (odds ratio 2.7; 95% confidence interval, 1.34-5.56, p = 0.022; Fisher's exact test). Only d-dimers were found to be significantly elevated in children with signs of myocardial rejection compared with those without rejection. Our results suggest that plasma sICAM-1 and d-dimer levels may be potentially useful to non-invasively assess TCAD and rejection, respectively, in pediatric heart transplant recipients.
    Pediatric Transplantation 06/2006; 10(4):434-40. · 1.63 Impact Factor
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    ABSTRACT: Children undergoing heart transplantation in the first year of life appear in clinical observation to develop atopic eczema at an above-chance frequency despite immunosuppressive therapy with cyclosporine A. A clinical study was undertaken to clarify the extent to which those children develop atopic eczema with above-chance frequency. In this cross-sectional study, we examined 41 consecutive children after heart transplantation. Twenty-seven underwent heart transplantation in the first year of life, seven after the first birthday, and seven had cardiac surgery other than heart transplantation in the first year of life and served as a control group. Atopic eczema was diagnosed in 11 out of 27 children with heart transplant in the first year of life. No atopic eczema was diagnosed in the other two groups. Children undergoing heart transplant prior to the first birthday apparently develop atopic eczema more frequently than children whose surgery was performed after the first birthday, and also more frequently than children undergoing organ-preserving procedures, despite immunotherapy. It remains an open question whether a surgical procedure within the first months of life with subsequent immunosuppression causes an alteration in the reactivity of the immune system in these children compared to older children which promotes the occurrence of atopic eczema despite immunosuppression.
    Pediatric Dermatology 06/2005; 22(2):102-8. · 1.52 Impact Factor
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    ABSTRACT: Ouabain, an inhibitor of the sodium pump, has been identified as a constituent of bovine adrenal glands. We were interested whether the release of this cardiotonic steroid is stimulated by physical exercise. Hence, athletes and healthy dogs were subjected to ergometry. Ouabain-like compound (OLC) was measured in venous blood by enzyme-linked immunosorbent assay as well as by (86)Rb+ uptake inhibition (as ouabain equivalents). OLC increased in venous blood of athletes after 15 minutes of ergometry from 2.5+/-0.5 to 86.0+/-27.2 nmol/L (n=51; P<0.001), as did the concentration of a circulating inhibitor of the sodium pump from 7.3+/-1.7 to 129.8+/-51 nmol/L (ouabain equivalents, P<0.05). Half-maximal increase in heart rate and systolic blood pressure occurred at 5.1+/-1.2 nmol/L and at 30+/-1 nmol/L OLC, respectively. On rest, OLC decreased in humans and dogs with a half-life of 3 to 5 minutes. In beagles exposed to moderate exercise on a treadmill for 13 minutes, levels of OLC increased 46-fold (from 3.7+/-0.8 to 166.9+/-91.8 nmol/L; n=6; P<0.005). This effect was suppressed when the dogs had been treated for 3 weeks with the beta1-adrenergic receptor blocker atenolol or the angiotensin-converting enzyme inhibitor benazepril. We conclude that OLC changes rapidly during exercise and is under the control of norepinephrine and angiotensin II.
    Hypertension 05/2005; 45(5):1024-8. · 7.63 Impact Factor
  • Pathology - Research and Practice 01/2004; 200(4):297-297. · 1.56 Impact Factor
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    ABSTRACT: Endogenous ouabain changes rapidly in humans and dogs upon physical exercise and is under the control of epinephrine and angiotensin II. Hence, the steroid acts as a rapidly acting hormone. A search for a specific binding globulin for cardiac glycosides in bovine plasma resulted in the identification of the d allotype of the micro chain of IgM whose hydrophobic surfaces interact with cardiotonic steroids and cholesterol. Such IgM complexes might be involved in the hepatic elimination of cardiotonic steroids. Thus, differences in the signaling cascade starting at Na(+),K(+)-ATPase must explain any differences in the action of ouabain and digoxin in the genesis of arterial hypertension.
    Annals of the New York Academy of Sciences 05/2003; 986:678-84. · 4.31 Impact Factor
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    ABSTRACT: Acute rejection of the donor heart is a major cause of mortality in infant heart transplant recipients. The early diagnosis of acute cardiac rejection (ACR) is crucial. Non-invasive methods have shown poor sensitivity in detecting rejection when compared to endomyocardial biopsies (EMB). We assessed troponin I as a new marker to diagnose cardiac rejection. Serum cardiac troponin I (cTNI) levels were retrospectively analysed in 25 heart transplant patients (ages, 2 wk to 13 yr; mean age, 3 months) presenting 36 acute rejections. In early post-operative rejection and initially elevated cTNI levels, rejection was associated with a second increase of serum cTNI concentrations in 21% of the patients (p = 0.15). If cTNI levels were in normal range before ACR an elevation was monitored in 59% of the rejection periods (p < 0.05). In 25% of the cases (n = 9) cTNI levels remained in normal range during the rejection episode (<0.6 ng/mL), in 22% (n = 8) cTNI levels did not exceed pathological values from 0.6 to 1.5 ng/mL and in 53% (n = 19) the measured levels went beyond 1.5 ng/mL. Maximum concentrations of cTNI were measured mostly 12 d from the moment rejection was suspected (day 1) in patients (median day 3). However, cTNI levels were elevated for 2-43 d after ACR was diagnosed (median 10 d). Twenty per cent of the patients with grade 3 rejection (ISHLT) and 75% of the patients with grade 4 rejection had a corresponding elevated cTNI level (p = 0.013). No false-positive elevations of cTNI were documented. The present data demonstrate that cTNI is a not a sensitive but a specific marker of ACR in children.
    Pediatric Transplantation 03/2003; 7(1):43-5. · 1.63 Impact Factor
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    ABSTRACT: Since 1988, 82 heart transplants have been performed in 80 infants and children. Diagnoses pretransplant were: hypoplastic left heart syndrome (HLHS) (n = 43); cardiomyopathy (n = 19); endocardial fibroelastosis (n = 6); and other complex congenital heart diseases (n = 12). Age at transplantation was < 1 yr in 61 patients. Overall survival rate was 79% at 1 yr and 73% at 5 and 10 yr. To date, 20 patients have died after transplantation. Causes of death were: rejection (eight patients); right ventricular failure (four patients); transplant coronary artery disease (TCAD) (two patients); and other causes (six patients). In the majority of patients somatic growth is not impaired, and renal function is reduced (but stable) in all patients. Two patients developed post-transplant lymphoproliferative disease, which was treated successfully. Major long-term morbidity is neurologic deficit - severe in three patients and minor in six. TCAD was present or suspected in six surviving patients. We conclude that heart transplantation in infants and children can be performed with good early and late results. Quality of life is excellent in most patients. TCAD, however, will become an increasing problem in the long term.
    Pediatric Transplantation 12/2001; 5(6):457-62. · 1.63 Impact Factor