Dopamine,dopexamine and dobutamine in liver transplant recipients: a comparison of their effects on hemodynamics,oxygen transport and hepatic venous oxygen saturation

The purpose of this study was to determine the effects of vasoactive treatment with dopamine (DO), dopexamine (DX), and dobutamine (DOB) on hemodynamics, oxygen transport and hepatic venous oxygen saturation (SvhO₂) after orthotopic liver transplantation (OLT). A pulmonary artery catheter was inserted into the right hepatic vein of 17 OLT patients. Timed infusion of DO, DX, and DOB was performed at the following rates: DO at 4 and 8 g/kg per minute, and DOB at 5 and 10 g/kg per minute. Hemodynamics, oxygen transport variables, and SvhO₂ were assessed. Each catecholamine induced a significant increase in cardiac index, oxygen delivery, and SvhO₂. Mean arterial pressure was increased during DO and DOB, but significantly reduced during DX. Each inotrope increased oxygen delivery in parallel with SvhO₂, suggesting a corresponding increase in hepatic oxygen supply. Therefore, it appears that each vasoactive drug may be utilized in OLT patients to provide oxgen delivery without impairment of splanchnic oxygenation.     

Physiological compensation in antisense transformants: specific induction of an "ersatz" glucan endo-1,3-beta-glucosidase in plants infected with necrotizing viruses.

Plant class I glucan endo-1,3-beta-glucosidases (beta-1,3-glucanase; 1,3-beta-D-glucan glucanohydrolase, EC 3.2.1.39) have been implicated in development and defense against pathogen attack. Nevertheless, beta-1,3-glucanase deficiencies generated by antisense transformation of Nicotiana sylvestris and tobacco have little biological effect. We report here that another beta-1,3-glucanase activity is induced in these deficient mutants after infection with necrotizing viruses. Induction of class I beta-1,3-glucanase was markedly inhibited in leaves of N. sylvestris and tobacco antisense transformants infected with tobacco necrosis virus and tobacco mosaic virus, respectively. A serologically distinct beta-1,3-glucanase activity was present in the infected antisense transformants but was absent in both healthy and infected control plants and in antisense transformants treated with the stress hormone ethylene. Immunoblot analyses, localization studies, and measurements of antibody specificity indicate that this compensatory beta-1,3-glucanase activity is an intracellular enzyme different from known tobacco beta-1,3-glucanases. Therefore, plants can compensate for a deficiency in enzyme activity by producing a functionally equivalent replacement--i.e., "ersatz"--protein or proteins. The fact that compensation for beta-1,3-glucanase activity occurs in response to infection argues strongly for an important role of these enzymes in pathogenesis.     

Die analyse von aluminium im serum und urin zur überwachung emonierter personen

Zusammenfassung Die Einführnung der flammenlosen Atomabsorptionsspektrometrie in die chemische Analytik ermöglicht eine einfache quantitative Bestimmung des Aluminiums im biologischen Material. Die verwendeten Analysen-methoden und deren Zuverlässigkeitskriterien wurden beschrieben. Entsprechend der heute üblichen Verfahren zur Überwachung schwermetallexponierter Personen wurden von uns bei verschiedenen Kollektiven Aluminiumbestimmungen im Blut und Urin durchgeführt. Untersucht wurde ein Kollektiv von 110 Arbeitern eines Korund-herstellenden und -verarbeitenden Werkes. 82 dieser Arbeiter waren durch staubförmigen Korund exponiert, während 28 Personen an den Öfen zusätzlich noch Metalldämpfen ausgesetzt waxen. Die Expositionsdauer betrug im Mittel 6,9 Jahre. Als Vergleichskollektiv dienten 40 männliche nicht aluminiumexponierte Probanden. Zusädtzlich wurden 33 Dialyse-Patienten, die mit Aluminiumhydroxid (Aludrox) therapiert wurden, in die Studie einbezogen.Für die Aluminiumausscheidung im Urin errechnete sich bei den Normalpersonen eine obere Normgrenze von 30 g/l. Die Ausscheidungswerte der aluminiumexponierten Personen lagen mit einem Median von 39 g Al/l signifikant höher als das Normalkollektiv. Erwartungsgemä zeigten die dampfförmig belasteten Personen einen statistisch signifikant höheren Al-Spiegel im Urin als die staubförmig belastete Gruppe.Die Serumanalysen ergaben keine Hinweise für einen signifikanten Unterschied gegenüber Normalpersonen. Aus den Untersuchungen der Seren von nicht aluminiumexponierten Probanden errechnete sich ein oberer Grenzwert von 35 g/l. Der Serum-Aluminium-Spiegel der exponierten Personen war von der Art und Dauer der Exposition nicht beeinflut. Dagegen lagen die Aluminium-Spiegel im Serum der Dialyse-Patienten im Bereich von 6 – 254 g/l. Bei dieser Patientengruppe mit erhöhten Serum-Aluminiumwerten wurden keine klinischen Zeichen einer manifesten Toxicität gefunden. Damit kommt den Aluminiumkonzentrationen im biologischen Material der aluminiumexponierten Arbeiter keine gesundheitsgefahrdende Relevanz zu.Bei der inhalativen Aufnahme von Aluminium scheint die Menge des resorbierten und in die Blutbahn übergehenden Aluminiums gering zu sein. Hinweise für eine Akkumulation des Metalls im Organismus wurde bei Versuchen mit D-Penicillamin nicht gefunden.Aluminiumbestimmungen im Serum oder Harn sind für die Überwachung von Korund-herstellenden und -verarbeitenden Personen nach diesen Ergebnissen nicht notwendig. Bei Substanzen, wie dem Aluminium, mit geringer Resorptions-quote und groer Toleranzbreite für den menschlichen Organismus sowie ohne manifeste signifikante Gesundheitsschäden erscheint ein Biological Monitoring nicht indiziert.D 29     

La protonterapia: indicaciones y perspectivas

Protons have considerable targeting advantages in the conduct of precise conformational radiotherapy, enabling dose escalation and a better protection of critical organs. Protons differs from photons and electrons used in classical radiotherapy due to their specific physical characteristics, Bragg peak and narrow lateral penumbra. Currently, treatment of ocular melanoma, chordoma and chondrosarcoma of the base of skull and paediatric tumours are widely accepted. Others clinical indications are still being evaluated (meningioma, etc.). Generalised isocentric application and proton intensity modulation can increase the clinical indications for its use. It is a technique which, despite its current expansion, appears “restricted” because of the scarcity of equipments due to its high cost.     

Donor treatment with mycophenolate mofetil: protection against ischemia-reperfusion injury in the rat

BACKGROUND: Mycophenolic acid, the active metabolite of mycophenolate mofetil, inhibits the glycosylation of cell membrane glycoproteins. We hypothesized that impaired glycosylation of cell adhesion molecules on endothelial cells in vivo results in decreased susceptibility to inflammation or immunogenicity after allogeneic transplantation. METHODS: The expression of mannose residues on cultured rat endothelial cells was examined after stimulation with interleukin 1 in the presence or absence of mycophenolic acid using labeled Galanthus nivalis agglutinin. The in vitro adhesion of blood leukocytes to heart tissue was examined using peripheral blood leukocytes of recipient origin and sections of donor heart tissue exposed to ischemia-reperfusion injury after pretreatment with vehicle or mycophenolic mofetil. (LEWxBN)F1 donor rats were treated with 20 or 60 mg/kg/day of mycophenolate mofetil for 1 or 2 weeks followed by transplantation of the heart into Lewis recipients after storage in heparin-containing normal saline for either 10 min at 4 degrees C or 120 min at room temperature. RESULTS: Endothelial cells stimulated in vitro with interleukin 1 showed an increase in a population of strongly mannose-positive cells, which was prevented by the addition of mycophenolic acid during the culture. The in vitro adhesion of peripheral blood leukocytes to cardiac tissue sections exposed to prolonged storage and reperfusion was significantly less if the donor had been treated with mycophenolate mofetil. Treatment of cardiac graft donors with mycophenolate mofetil protected the graft against early graft failure after prolonged storage at room temperature, because the mean graft survival was 9.4+/-0.6 days for grafts that came from donors treated with mycophenolate mofetil versus 1.2+/-0.9 days (P<0.05) for grafts that came from vehicle-treated donors. Donor pretreatment with mycophenolate mofetil did not affect the survival time of heart grafts transplanted after 15 min of standard cold storage or the survival of grafts transplanted into presensitized recipients. CONCLUSION: Donor treatment with mycophenolate mofetil protects cardiac grafts against primary nonfunction after prolonged tepid storage, which may be related to the inhibition of glycosylation of cell adhesion molecules involved in ischemia-reperfusion injury.     

Administration of prostacyclin after liver transplantation: a placebo controlled randomized trial

The shortage of suitable organs for liver grafts is responsible for the use of marginal donors for liver transplantation (OLT). If these liver grafts function poorly initially after OLT, a supportive therapy is necessary. The purpose of this study was to evaluate the effects of prostacyclin (PGI2) on postoperative liver graft function after OLT. A total of 30 adult recipients of primary OLT were randomized to either receive PGI2 (4 ng/kg per min body weight, n = 15) or a placebo for 6 d. To evaluate regional splanchnic oxygenation a fiberoptic pulmonary-artery catheter was inserted into a hepatic vein and the difference between mixed venous oxygen content and hepatic venous oxygen content was determined (deltaO2). Measurements were performed directly after transplantation and at 6, 12, 24 and 48 h postoperatively. A significant correlation between deltaO2 and the level of transaminases (ALT/AST) was observed 24 and 48 h after transplantation (p < 0.05). PGI2 treatment induced a significant decrease in deltaO2 after 24 and 48 h after reperfusion (p < 0.05). Peak AST levels tended to be lower in the PGI2 treatment group (418 +/- 99 vs. 638 +/- 156 U/L, p < 0.1). These results suggest that administration of PGI2 after OLT improves hepatic-splanchnic oxygenation and may thereby reduce reperfusion injury after OLT.     

Venous complications after orthotopic liver transplantation

Complications involving the portal vein or the vena cava, are rare after orthotopic liver transplantation. We report on the incidence and treatment of venous complications following 1000 orthotopic liver transplantations in 911 patients. Twenty-six of the adult patients (2.7%) suffered from portal complications after transplantation, whereas complications of the vena cava were observed in only 17 patients (1.8%). Technical problems or recurrence of the underlying disease (e.g. Budd-Chiari syndrome) accounted for the majority of complications of the vena cava, whereas alteration of the vessel wall or splenectomy during transplantation could be identified as important risk factors for portal vein complications. In patients undergoing modification of the standard end-to-end veno-venous anastomosis of the portal vein due to pathological changes of the vessel wall, complications occurred in 8.3%, whereas only 2.4% of patients who received a standard anastomosis of the portal vein experienced complications of the portal vein. Furthermore, splenectomy during transplantation was also associated with an increased incidence of portal vein complications (10.5 vs. 2.2% in patients without splenectomy). Treatment was dependent on the signs and symptoms of the patients, and varied considerably between patients with portal vein complications and patients suffering from complications of the vena cava. Complications of the vena cava led to retransplantation in about one-third of the patients, whereas in patients with occlusion of the portal vein, retransplantation was necessary in only 15%, and more than half of the patients suffering from portal vein complications did not require any treatment at all. Usually, treatment of patients with portal vein complications only became necessary when additional complications such as arterial occlusion or bile duct injuries occurred.