Hemodialysis membrane-related neutrophil dysfunctions and pentoxifylline - a pilot study

Hemodialysis treatment is associated with activation of neutrophil granulocytes. Pentoxifylline has been shown to inhibit neutrophil activation in vitro and in vivo. We investigated the effect of pentoxifylline on leukocyte and platelet counts and on plasma levels of extracellularly released neutrophil elastase and lactoferrin during a four-hour hemodialysis treatment. Eight patients received 400 mg of pentoxifylline or placebo orally twice a day over 14 days and an additional dose of 400 mg of pentoxifylline intravenously during hemodialysis. Each subject served as his own control in a randomized, double-blind, cross-over study. Combined oral and intravenous treatment with pentoxifylline prevented neither leukopenia nor neutrophil degranulation during the time interval studied. Elastase plasma levels paralleled the drop in leucocyte counts and thereafter increased similarly in both groups. Lactoferrin plasma levels exhibited less increase in the treated group; however, this effect was not statistically significant. This may be due to the small number of cases studied and to difficulties in reaching effective plasma levels without side effects

Influence of high-dose aprotinin treatment on blood loss and coagulation patterns in open-heart surgery

Intraoperative administration of the proteinase Inhibitor aprotinin causes reduction in blood loss and homologous blood requirement in patients undergoing cardiac surgery. To ascertain the blood-saving effect of aprotinin and to obtain further information about the mode of action, 40 patients undergoing primary myocardial revascularization were randomly assigned to receive either aprotinin or placebo treatment. Aprotinin was given as a bolus of 2 X 105 kallikrein inactivator units (KIU) before surgery followed by a continuous infusion of 5 X 105 KIU/h during surgery. Additionally, 2 X 105 KIU were added to the pump prime. Strict criteria were used to obtain a homogeneous patient selection. Total blood loss was reduced from 1,431 +/- 760 ml in the control group to 738 +/- 411 ml in the aprotinin group (P < 0.05) and the homologous blood requirement from 838 +/- 963 ml to 163 +/- 308 ml (P < 0.05). In the control group, 2.3 +/- 2.2 U of homologous blood or blood products were given, and in the aprotinin group, 0.63 +/- 0.96 U were given (P < 0.05). Twenty-five percent of patients in the control group and 63% in the aprotinin group did not receive banked blood or homologous blood products. The activated clotting time as an indicator of inhibition of the contact phase of coagulation was significantly Increased before heparinization in the aprotinin group (141 +/- 13 s vs. 122 +/- 25 s) and remained significantly Increased until heparin was neutralized after cardiopulmonary bypass (CPB). The concentration of the thrombin-antithrombin III complex was significantly decreased at the end of CPB in the aprotinin group, indicating less thrombin generation in the aprotinin-treated group. The total concentration of the fibrinogen-fibrin split products (FSP) and the split products of the cross-linked fibrin (D-dimers) were also significantly reduced due to attenuated proteolytic activities of thrombin and plasmin. The results of the fibrin plate assay revealed higher fibrinolytic activity during CPB in the control group. The results demonstrate the beneficial effect of high-dose aprotinin treatment on blood loss and homologous blood requirement. This effect can be attributed to the inhibition of the contact phase of coagulation and the consequently reduced thrombotic and fibrionolytic activity during and after CPB

Sr-isotope analysis of speleothems by LA-MC-ICP-MS: High temporal resolution and fast data acquisition

Speleothems are well established climate archives. A wide array of geochemical proxies, including stable isotopes and trace elements are present within speleothems to reconstruct past climate variability. However, each proxy is influenced by multiple factors, often hampering robust interpretation. Sr isotope ratios (87Sr/86Sr) can provide useful information about water residence time and water mixing in the host rock, as they are not fractionated during calcite precipitation. Laser ablation multi-collector-inductively coupled plasma mass spectrometry (LA-MC-ICP-MS) has rarely been used for determination of Sr isotope signatures in speleothems, as speleothems often do not possess appropriately high concentrations of Sr to facilitate this analysis. Yet the advantages of this approach include rapid data acquisition, higher spatial resolution, larger sample throughput and the absence of chemical treatment prior to analysis. We present LA-MC-ICP-MS Sr isotope data from two speleothems from Morocco (Grotte de Piste) and India (Mawmluh Cave), and we compare linescan and spot analysis ablation techniques along speleothem growth axes. The analytical uncertainty of our LA-MC-ICP-MS Sr data is comparable to studies conducted on other carbonate materials. The results of both ablation techniques are reproducible within analytical error, implying that this technique yields robust results when applied to speleothems. In addition, several comparative measurements of different carbonate reference materials (i.e. MACS-3, JCt-1, JCp-1), including tests with standard bracketing and comparison of the 87Sr/86Sr ratios with a nanosecond laser ablation system and a state-of-the-art femtosecond laser ablation system, highlight the robustness of the method

Neonatologie/Pädiatrie – Leitlinie Parenterale Ernährung, Kapitel 13

There are special challenges in implementing parenteral nutrition (PN) in paediatric patients, which arises from the wide range of patients, ranging from extremely premature infants up to teenagers weighing up to and over 100 kg, and their varying substrate requirements. Age and maturity-related changes of the metabolism and fluid and nutrient requirements must be taken into consideration along with the clinical situation during which PN is applied. The indication, the procedure as well as the intake of fluid and substrates are very different to that known in PN-practice in adult patients, e.g. the fluid, nutrient and energy needs of premature infants and newborns per kg body weight are markedly higher than of older paediatric and adult patients. Premature infants <35 weeks of pregnancy and most sick term infants usually require full or partial PN. In neonates the actual amount of PN administered must be calculated (not estimated). Enteral nutrition should be gradually introduced and should replace PN as quickly as possible in order to minimise any side-effects from exposure to PN. Inadequate substrate intake in early infancy can cause long-term detrimental effects in terms of metabolic programming of the risk of illness in later life. If energy and nutrient demands in children and adolescents cannot be met through enteral nutrition, partial or total PN should be considered within 7 days or less depending on the nutritional state and clinical conditions.Eine besondere Herausforderung bei der Durchführung parenteraler Ernährung (PE) bei pädiatrischen Patienten ergibt sich aus der großen Spannbreite zwischen den Patienten, die von extrem unreifen Frühgeborenen bis hin zu Jugendlichen mit einem Körpergewicht von mehr als 100 kg reicht, und ihrem unterschiedlichen Substratbedarf. Dabei sind alters- und reifeabhängige Veränderungen des Stoffwechsels sowie des Flüssigkeits- und Nährstoffbedarfs zu berücksichtigen sowie auch die klinische Situation, in der eine PE eingesetzt wird. Das Vorgehen unterscheidet sich deshalb ganz erheblich von der PE-Praxis bei erwachsenen Patienten, z.B. ist der Flüssigkeits-, Nährstoff- und Energiebedarf von Früh- und Neugeborenen pro kg Körpergewicht höher als bei älteren pädiatrischen und bei erwachsenen Patienten. In der Regel benötigen alle Frühgeborenen <35. SSW und alle kranken Reifgeborenen während der Phase des allmählichen Aufbaus der enteralen Nahrungszufuhr eine vollständige oder partielle PE. Die Zufuhrmengen der PE bei Neonaten müssen berechnet (nicht geschätzt) werden. Der Anteil der PE sollte zur Minimierung von Nebenwirkungen sobald wie möglich durch Einführung einer enteralen Ernährung vermindert (teilparenterale Ernährung) und schließlich komplett durch enterale Ernährung abgelöst werden. Eine unangemessene Substratzufuhr im frühen Säuglingsalter kann langfristig nachteilige Auswirkungen im Sinne einer metabolischen Programmierung des Krankheitsrisikos im späteren Lebensalter haben. Wenn bei älteren Kindern und Jugendlichen dagegen der Energie- und Nährstoffbedarf eines Patienten im Vorschul- oder Schulalter durch eine enterale Nährstoffzufuhr nicht gedeckt werden kann, ist abhängig von Ernährungszustand und klinischen Umständen spätestens innerhalb von 7 Tagen eine partielle oder totale PE zu erwägen

Dextran sulfate activates contact system and mediates arterial hypotension via B2 kinin receptors

To define some of the mechanisms underlying dextran sulfate (DXS)-induced hypotension, we investigated the effects of either the plasma kallikrein inhibitor des-Pro2-[Arg15] aprotinin (BAY x 4620) or the specific bradykinin B2-receptor antagonist Hoe-140 on the hypotensive response to DXS. In the first study, anesthetized miniature pigs were given DXS alone, DXS plus BAY x 4620 in various doses, or saline. As expected, DXS alone produced a profound but transient systemic arterial hypotension with a concomitant reduction in kininogen. Circulating kinin levels, complement fragment des-Arg-C3a, and fibrin monomer were all increased. Treatment with BAY x 4620 produced a dose-dependent attenuation of these effects with complete blockade of the hypotension as well as the observed biochemical changes at the highest dose (360 mg). In a second study, two groups of pigs were given either DXS alone or DXS plus Hoe-140. DXS-induced hypotension was completely blocked by Hoe-140 pretreatment; however, kininogen was again depleted. We conclude, therefore, that DXS-induced hypotension is produced by activation of plasma kallikrein that results in the production of bradykinin and that liberation of bradykinin and its action on B2 receptors in the vasculature are both necessary and sufficient to produce the observed effects on circulatory pressure

Inhibition of Plasma Kallikrein with Aprotinin in porcine endotoxin Shock

Activation of the contact phase of coagulation has been implicated in the pathogenesis of septic shock. We wanted to determine if inhibition of plasma kallikrein can prevent arterial hypotension and liberation of kinins from kininogen, induced by an infusion of bacterial lipopolysaccharide (LPS) in anesthetized, ventilated 20-kg pigs. The LPS was given IV in a dose of 5 [mu]g/kg/h for 8 hours. The plasma kallikrein inhibitor aprotinin, 537 [mu]mol, was given IV during 8 hours, resulting in plasma levels above 10 [mu]mol/L. Ten animals (SA) received LPS and aprotinin and ten randomized controls (SC) received LPS and saline. Kinin-containing kininogen was determined on the basis of the amount of kinin releasable in plasma samples by incubation with trypsin. Kininogen decreased to 58% +/- 4% of the baseline value without any difference between groups. This may indicate participation of other processes than degradation by plasma kallikrein in the decrease of kininogen. Arterial blood pressure was higher at 7 hours in the SA animals than in the SC group (101% +/- 11% vs. 68% +/- 8%; mean +/- SEM; p = 0.026). Fibrin monomer and C3adesArg plasma levels were attenuated by aprotinin treatment. These findings underscore the important role of the contact system in LPS shock