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.     

Management of emergencies in adults with congenital cardiac disease

The aim of the study was to assess the quantity and nature of emergencies affecting adults with congenital cardiac disease (CCD) and evaluate infrastructural requirements for adequate management. There is an increasing number of adults with CCD requiring specialized complex care. This multicenter study evaluated all emergency admissions to 1 of 5 centers for adults with CCD within 1 year. Within 1 year, there were 1,033 admissions of adults with CCD, and 201 (160 patients; age 16 to 71 years) were emergencies. Underlying cardiac anomalies were univentricular heart (22%), complete transposition (14%), tetralogy of Fallot (21%), and others (43%). Seventy percent of patients had undergone previous cardiac surgery. The main reason for acute admission was cardiovascular (arrhythmia, heart failure, syncope, aortic dissection, and endocarditis). Diagnostic procedures most often assigned were echocardiography (n = 223), chest x-ray (n = 95), Holter electrocardiography (n = 85), cardiac catheterization/electrophysiologic study (n = 39), and others (n = 143). Forty-six patients underwent surgery (cardiovascular n = 41, general n = 5) or electrophysiologic treatment (n = 41). One hundred twenty-six of 201 emergencies (63%) required cooperation with another specialized department: surgery (n = 46), internal medicine (n = 42), neurology (n = 12), ophthalmology (n = 6), otorhinolaryngology (n = 5), gynecology (n = 5), psychiatry (n = 4), radiology (n = 3), dermatology (n = 2), and orthopedics (n = 2). In conclusion, physicians and consultants attending adult patients with CCD need a high degree of specialized experience concerning the cardiac anomaly to manage emergencies properly. Furthermore, a wide range of noncardiac diagnostic and therapeutic procedures must be available. Data support the demand for a multidisciplinary approach in specialized centers for adequate care of adults with CCD.     

Cardiac perforation following transcatheter PFO closure.

From December 1998 to August 2001, transcatheter closure of patent foramen ovale (PFO) with an Amplatzer PFO occluder has been successfully performed in our center in 102 patients without severe complications. We are reporting the first known case of cardiac perforation by an Amplatzer PFO occluder.     

Antibodies against lepirudin are polyspecific and recognize epitopes on bivalirudin

Bivalirudin is a synthetic antithrombin sharing a sequence of 11 amino acids with the recombinant hirudin lepirudin. We investigated whether antilepirudin antibodies recognize epitopes on bivalirudin. Antilepirudin antibody-positive sera of 43 patients, treated with lepirudin for heparin-induced thrombocytopenia, were analyzed. Lepirudin- and bivalirudin-coated microtiter plates were used for antibody testing in an enzyme-linked immunosorbent assay (ELISA) system. Of the 43 sera-containing antibodies binding to lepirudin, 22 (51.2%) contained antibodies that also recognized bivalirudin. Binding of these antibodies to bivalirudin was inhibited by more than 70% by preincubation with high doses of bivalirudin. However, if lepirudin-coated microtiter plates were used, high concentrations of bivalirudin inhibited only 2 of the 43 positive sera by more than 30%. Therefore antihirudin antibodies must be polyspecific. The clinical consequences of this cross-reactivity are unknown but bivalirudin, targeted by antibodies of patients treated with lepirudin previously, could potentially boost antibody titers in such patients or even trigger an immune response by itself. Clinically significant antibody formation in response to bivalirudin monotherapy has not been observed, however. Yet, as lepirudin and antilepirudin antibodies have recently been implicated in severe anaphylactic reactions, caution is warranted when using bivalirudin in patients previously treated with lepirudin.     

Peer environment mediates parental history and individual risk in the etiology of cannabis use disorder in boys: a 10-year prospective study

Previous research has shown that a trait termed neurobehavior disinhibition (ND) measured in childhood predicts substance use disorder by young adulthood. The present investigation extends these findings by determining the degree to which peer environment mediates the association between ND and development of cannabis use disorder (CUD). ND was measured in a sample of 216 boys 10-12 years of age. The peer environment was assessed at age 16. Current CUD was determined at age 22. Paternal and maternal SUD predicted son's ND which, in turn, predicted son's peer environment and, subsequently, son's cannabis use frequency and CUD. Peer environment mediated the association between ND and cannabis use and ND and CUD. Maternal and paternal SUD predicted the peer environment. Parental SUD, son's ND, and son's peer environment predicted CUD at age 22 with 84% accuracy.