Heparin-level-based anticoagulation management during cardiopulmonary bypass: a pilot investigation on the effects of a half-dose aprotinin protocol on postoperative blood loss and hemostatic activation and inflammatory response

Cardiac surgery involving cardiopulmonary bypass (CPB) leads to activation of the hemostatic/inflammatory system. We compared the influence of a half-dose aprotinin regimen on postoperative blood loss and the activation of the hemostatic/inflammatory system during CPB, when used during a heparin-level-based heparin management for cardiac surgery. Two-hundred patients (n = 100 in each group) were enrolled in this randomized prospective study. In Group I only heparin was given according to the results of the Hepcon HMS Plus. In Group II aprotinin was added with a bolus of 1 x 10(6) kallikrein inhibiting units (KIU) for the patient immediately before initiation of CPB, 1 x 10(6) KIU in the priming solution of the CPB, and a continuous infusion of 250,000 KIU/h during CPB. Postoperative blood loss was determined after 12 h. Heparin and antithrombin activity were evaluated by an anti-Xa assay and measurement of antithrombin III activity. Hemostatic activation was evaluated by adenosine diphosphate-stimulated platelet aggregometry and by measurements of the generation/release of beta-thromboglobulin (beta-TG), soluble P-selectin (sPS), thrombin (TAT), prothrombin 1 and 2 fragments (PTF1+2), factor XIIa (FXIIa), plasmin (PAP), and D-dimers. Inflammatory response was evaluated by measuring complement factors 5b-9 (C5b-9), interleukin (IL)-6, and neutrophil elastase (NE). There were no differences in the pre-CPB values or duration of CPB between the two groups. There were no differences in the post-CPB values for platelet count, platelet aggregation, beta-TG, sPS, TAT, PTF1+2, C5b-9, NE, or IL-6. The additional use of aprotinin resulted in a significant decrease of PAP, D-dimers, and 12 h postoperative blood loss, whereas generation of the contact factor XIIa was increased. The administration of aprotinin significantly reduced postoperative blood loss after cardiac surgery and CPB. This most likely has to be attributed to the antifibrinolytic effects of aprotinin. No effects on thrombin generation, platelet activation, inflammatory response, or clinical outcome were noted. IMPLICATIONS: The use of half-dose aprotinin and heparin-level-based anticoagulation management during cardiopulmonary bypass leads to a significant reduction of postoperative blood loss after cardiac surgery. This effect can most likely be attributed to the antifibrinolytic effects of aprotinin, as we did not observe effects on other variables of activation of the hemostatic/inflammatory system.     

Implicit alcohol-related cognitions in a clinical sample of heavy drinkers

Patients undergoing treatment in an alcohol-rehabilitation clinic performed an Extrinsic Affective Simon Task (EAST) and two Implicit Association Tests (IATs) that were designed to measure implicit attitudes toward alcohol or implicit alcohol-arousal associations. The EAST and IAT data indicated that patients had a more negative implicit attitude toward alcohol than toward softdrinks and possessed strong implicit alcohol-arousal associations. Our results replicate and extend those of Wiers et al. (J. Abnormal Psychol 111 (2002) 648).     

Dexamethasone-induced growth inhibition of porcine growth plate chondrocytes is accompanied by changes in levels of IGF axis components

High (pharmacological) doses of glucocorticoids inhibit the proliferation of growth plate chondrocytes, which leads to one of the side-effects of these steroids, namely suppression of longitudinal growth. Growth inhibition by glucocorticoids is thought to be mediated in part by impaired action of components of the IGF axis, which are important for chondrocyte regulation and hence for longitudinal growth. The aim of the present study was to determine whether glucocorticoid-induced growth retardation involves changes in IGF axis components. Chondrocytes were isolated from epiphyseal growth plates of neonatal piglets and treated with pharmacological doses of dexamethasone (DXM) for 24 h to study glucocorticoid-induced growth retardation. Under IGF-I-supplemented (10 nM) culture conditions, IGF-binding proteins (IGFBPs)-2, -4 and -5 were secreted by the growth plate chondrocytes and IGFBP-2 protein and mRNA levels were decreased by the DXM treatment, whereas IGFBP-4 and -5 were not affected. Proliferation of the chondrocytes, as measured by [(3)H]thymidine incorporation, was 3.5-fold higher in serum-supplemented medium in contrast to IGF-I-supplemented (10 nM) medium. In the presence of serum, DNA synthesis was significantly inhibited by 50-63% when treated with 100 nM DXM, which was prevented by the glucocorticoid-receptor antagonist Org34116. mRNA levels of IGF axis components were determined using Northern blot analysis. IGFBP-2 to -6 were expressed in the chondrocytes, IGFBP-1 was absent and both IGF-I and IGF-II, and the type I and type II IGF receptors were expressed. Treatment with DXM (100 nM) resulted in a 2-fold increase in mRNA levels of both IGFBP-5 and the type I IGF receptor, whereas IGFBP-2 mRNA levels decreased by 55%, in concert with the decrease in protein level observed under IGF-I-supplemented culture conditions. The changes in mRNA levels due to the DXM treatment were prevented by the glucocorticoid receptor antagonist. Our data show that exposure to pharmacological doses of DXM results in inhibition of proliferation and changes in components of the IGF axis, IGFBP-2 and -5 and the type I IGF receptor, suggesting a role for these components in glucocorticoid-induced growth retardation at the local level of the growth plate.     

Management of heparin resistance during cardiopulmonary bypass: the effect of five different anticoagulation strategies on hemostatic activation

OBJECTIVE: Attenuation of hemostatic activation is a central goal during CPB. However, this poses a problem in patients insensitive to heparin. The present investigation was performed to assess different strategies of managing patients with heparin resistance during CPB. DESIGN: A randomized, prospective clinical investigation. SETTING: A major European heart center. PARTICIPANTS: Five groups with 20 patients each were investigated. INTERVENTIONS: The groups were handled as follows: (1). maintenance of a target ACT, (2). maintenance of the target unfractionated heparin (UFH) level and supplementation of a UFH level-based strategy with (3). AT III, (4). the direct thrombin inhibitor r-hirudin, or (5). the short-acting platelet glycoprotein (GP) IIb/IIIa antagonist tirofiban. Platelet count and generation of contact factor XIIa, thrombin, and soluble fibrin were assessed. Samples were obtained before CPB and after CPB before protamine infusion. MEASUREMENTS AND MAIN RESULTS: There were no differences observed in the generation of factor XIIa. The UFH-based strategy and supplementation with AT III, r-hirudin, and tirofiban resulted in significantly reduced (p < 0.05) thrombin generation compared with ACT management. A significant reduction of fibrin formation was seen only in patients who received AT III, r-hirudin, or tirofiban supplementation to the UFH. The administration of tirofiban resulted in a significant preservation of the platelet count compared with the other groups. There were no significant differences in the postoperative blood loss. CONCLUSIONS: Activation of hemostasis during CPB in heparin-resistant patients most likely has to be attributed to stimulation of the tissue factor pathway. Even the sole use of high concentrations of UFH does not effectively inhibit this activation. Therefore, in these patients anticoagulation during CPB with UFH should be supplemented with either AT III, a short-acting direct thrombin inhibitor, or a short-acting platelet glycoprotein IIb/IIIa antagonist.     

Magnetic resonance cholangiopancreatography: sensitive and specific diagnostic method for suspected choledolithiasis

OBJECTIVE: To evaluate the role of magnetic resonance pancreaticography (MRCP) in the diagnostic process of common bile duct stones. DESIGN: Retrospective. METHOD: All 27 MRCPs performed in the period December 1997-December 1998 in the Deventer Hospital, the Netherlands, were evaluated using chart examination. The group comprised 11 males and 16 females with an average age of 57 years (SD 3.2) with anamnestic or biochemical cholestasis. If at MRCP stones were diagnosed, endoscopic retrograde cholangiopancreaticography (ERCP) was performed. If MRCP was without abnormalities, no further diagnostic procedures were performed. The findings at MRCP were compared with those at ERCP and with the clinical course. The MRCP examinations were performed on a 1.5 Tesla MR unit. RESULTS: In 16 patients MRCP was performed before laparoscopic cholecystectomy and in 5 there after. In 5 MRCP was performed to rule out a biliary cause of acute pancreatitis and in 1 patient because of an elevated alkaline phophatase after laparotomy for an abdominal stab injury. There was one false-positive MRCP result and no false-negative ones. Accordingly, the sensitivity of MRCP for choledocholithiasis was 100% and the specificity 95%.     

How come I've got it? (A review of Helicobacter pylori transmission)

Numerous epidemiological studies have shown the two main risk factors for Helicobacter pylori acquisition: childhood and low socio-economic level both in developing and developed countries. Nevertheless, in the absence of ubiquitous extra-human reservoir(s), the route(s) for person-to-person transmission remains undetermined. Very recent data favour the oro-oral route: besides gastric mucosa, mouth might be a sanctuary site and the oro-oral transmission hypothesis seems applicable worldwide. Nevertheless, the gastro-oral route (vomiting, gastro-oesophageal reflux) is still possible and deserves further research. In developing countries, feco-oral transmission (perhaps through the water supply) might be a significant mechanism of human contamination both for primary infection in children and perhaps, reinfection in adults.     

Sporovexins A-C and a new preussomerin analog: antibacterial and antifungal metabolites from the coprophilous fungus Sporormiella vexans

Sporovexins A-C (1-3) and 3'-O-desmethyl-1-epipreussomerin C (4) have been isolated from liquid cultures of the coprophilous fungus Sporormiella vexans (JS 306). The structures of these new metabolites were elucidated on the basis of MS and NMR analysis. Compounds 1 and 4 show antifungal activity against competitor fungi, as well as antibacterial effects.     

Mixed connective tissue disease in childhood: A clinical and serologic survey

Mixed connective tissue disease is a syndrome with overlapping clinical features of SLE, scleroderma, and polymyositis. Only one other child with MCTD has been described in detail. In this study 14 children with MCTD are described. Each had overlapping clinical findings that evolved over an extended period of observation, and all 14 had high serum titers of speckled ANA and antibodies to RNP. A serologic survey of 127 children with various rheumatic diseases confirmed the specificity of high titer of speckled ANA and antibodies to RNP for MCTD in children. Significant cardiac and renal involvement, and thrombocytopenia, may be more common in affected children than in adults with MCTD, may lead to longer therapy with higher doses of a corticosteroid, and may contribute to a more serious prognosis than in adults.