LAUDATIO HELMUT CONRAD ZUM 90. GEBURTSTAG

Der Freie Zahnarzt -     

Successful treatment of malaria tropica with acute renal failure and cerebral involvement by plasmapheresis and hemodialysis

Summary A non-immune, 31-year-old woman developed an acute infection withPlasmodium falciparum after travelling to Kenia. The parasites proved resistant to chloroquine and sulfadoxine/pyrimethamine. The course of the disease was complicated by acute renal failure, hepatocellular damage, disorders of blood coagulation, thrombocytopenia, hemolysis and cerebral involvement. Despite a very high level of parasitemia (50% parasitized erythrocytes) a rapid clinical improvement was achieved by plasmapheresis and hemodialysis. Our experience shows that plasmapheresis and hemodialysis are excellent additive methods which rapidly improve clinical symptoms and may reduce morbidity and mortality in severe malaria tropica.

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Zusammenfassung Eine nicht-immune, 31 jährige Patientin erkrankte nach einem Keniaurlab an Malaria tropica. Die Plasmodien erwiesen sich als resistent gegenüber Chloroquin und Sulfadoxin/Pyrimethamin. Der Krankheitsverlauf war gekennzeichnet durch schwere Organkomplikationen: akutes Nierenversagen, Leberfunktionseinschränkung, Gerinnungsstörung und Thrombozytopenie, Hämolyse und zerebrale Malaria. Durch den Einsatz intensivierter Therapiemaßnahmen, wie Plasmapherese und Hämodialyse konnte trotz weiterbestehender Parasitämie von 50% eine rasche klinische Besserung bis zum Wirksamwerden der Kausaltherapie mit Chinin erreicht werden. Unsere Erfahrung zeigt, daß Plasmapherese und Hämodialyse ausgezeichnete adjuvante Therapieformen zur Verbesserung der klinischen Symptomatik bei schwerer Malaria tropica sind. Durch ihren frühzeitigen Einsatz können sie zur Verminderung der Morbidität und Mortalität bei komplizierter Malaria beitragen.

     

Viral myocarditis and coagulopathy: increased tissue factor expression and plasma thrombogenicity

We investigated the effects of viral infection on Tissue Factor (TF) expression and activity in mice within the myocardium to understand increased thrombosis during myocarditis. Mice were infected with coxsackie virus B3 (CVB3) and the hearts were collected at day 4, 8 and 28 post infection (p.i.). Myocardial TF expression and cellular activity as well as plasma activity were analyzed from CVB3 infected mice by Western blot, chromogenic Factor Xa generation assay, in situ staining for active TF and immunohistochemistry. In addition to TF expression, hemodynamic parameters were measured during the time course of infection. Furthermore, we analyzed myocardial tissues from patients with suspected inflammatory cardiomyopathy. TF protein expression was maximally 5-fold elevated 8 days p.i. in mice and remained increased on day 28 p.i. (P < 0.001 vs. non-infected controls). Alterations in TF expression were associated with fibrin deposits within the myocardium. The TF pathway inhibitor protein expression in the myocardium was not altered during myocarditis. Active cellular TF co-localized with CD3 positive cells and VCAM-1 positive endothelial cells in the myocardium. The TF expression was positively correlated with the amount of infiltrating CD3 and Mac3 positive cells (Spearman-Rho ρ = 0.749 P < 0.0001 for CD3⁺ and ρ = 0.775 P < 0.0001 for Mac3⁺; N = 35). Increased myocardial TF expression was associated with a 2-fold elevated plasma activity (P < 0.05 vs. non-infected controls). In the human hearts, the TF expression correlated postively with an endothelial cell activation marker (ρ = 0.523 P < 0.0001 for CD62E; N = 54). Viral myocarditis is a hypercoagulative state which is associated with increased myocardial TF expression and activity. Upregulation of TF contributes to a systemic activation of the coagulation cascade.