Frühbehandlung des akuten Myokardinfarktes: Umsetzung von Therapierichtlinien in den klinischen Alltag,MITRA-Pilotphase

Clinical Research in Cardiology - MITRA (Maximale Individuelle TheRapie beim Akuten Myokardinfarkt) ist eine Anwendungsbeobachtung für den stationären und poststationären Verlauf...     

Protease nexin-2/amyloid beta protein precursor. A tight-binding inhibitor of coagulation factor IXa.

Protease nexin-2/amyloid beta protein precursor (PN-2/A beta PP) is an abundant, secreted platelet protein which is a potent inhibitor of coagulation Factor XIa. We examined other potential anticoagulant activities of PN-2/A beta PP. Purified Kunitz protease inhibitor domain of PN-2/A beta PP and PN-2/A beta PP itself were found to prolong the coagulation time of plasma and pure Factor IXa. The Kunitz protease inhibitor domain also inhibited the ability of Factor IXa to activate Factor X. PN-2/A beta PP inhibited Factor IXa with a Ki of 7.9 to 3.9 x 10(-11) M in the absence and presence of heparin, respectively. When the second-order rate constant of PN-2/A beta PP's inhibition of Factor IXa (2.7 x 10(8) M-1min-1) was compared to that of antithrombin III (3.8 x 10(6) M-1min-1), PN-2/A beta PP was at least a 71-fold more potent inhibitor of Factor IXa than antithrombin III. PN-2/A beta PP formed a complex with Factor IXa as detected by gel filtration and ELISA. The finding that PN-2/A beta PP is a potent inhibitor of Factor IXa could help to explain the spontaneous intracerebral hemorrhages seen in patients with hereditary cerebral hemorrhage with amyloidosis Dutch-type where there is an extensive accumulation of PN-2/A beta PP in their cerebral blood vessels.     

Studies on drug monitoring in thrice and once daily treatment with aminoglycosides

Objectives To investigate at what time the peak level should be determined under conventional thrice daily (t.i.d.) administration of the aminoglycoside netilmicin and to study its serum concentrations under once daily (od) treatment to define the required daily dose and to gain information about convenient drug monitoring.Design The design of the study was a consecutive sample trial.Setting The study took place in a university hospital.Patients 41 intubated patients of a surgical ICU who received netilmicin as a short-term infusion over 30 min for life-threatening infections were included in the study.Interventions In 21 patients netilmicin was administered t.i.d. The virtual peak levels which had been determined by pharmacokinetic dosage calculation were compared with the serum concentrations obtained directly after the administration as well as after 15, 30, 60 and 180 min. In 20 patients the netilmicin serum concentrations during od treatment were determined directly before and immediately after the application as well as 0.5, 1, 3, 7 and 12 h later. To achieve a virtual peak level of 25 mg/l and a trough level of 0.5 mg/l individual adjustment of the dosage based on pharmacokinetic calculations was performed.Measurements and results In t.i.d. treatment the serum concentration measured after 30 min was closest to the virtual peak level; therefore, this is the best time to determine the peak level. In od treatment the required daily dose was 7.86 mg/kg body weight (median) in patients with normal renal function. During od dosing the trough level was extremely important in drug monitoring, whereas determination of the high peak level was of doubtful value.Conclusions The peak level should be determined during t.i.d. administration at 30 min. In od treatment the initial daily dose should be 7 mg/kg body weight; in drug monitoring the trough level is very important.     

Expression of phosphorylcholine-specific B cells during murine development

The TEPC 15 (T15) clonotype, a putatively germline antibody specificity, does not appear in the neonatal B-cell repertoire until approximately 1 wk of age. This report extends this observation by the demonstration that (a) the T15 clonotype follows similar kinetics of appearance in germfree as well as conventionally-reared mice; (b) maternal influences and genetic background play a minor role in the development of the T15 clonotype since CBFI neonates raised by C57BL/6 or BALB/c mothers acquire the T15 clonotype at the same time in ontogeny as BALB/c neonates; (c) the lack of phosphorylcholine (PC)-specific B cells shortly after birth is reflected in a dearth of PC-binding cells in the neonate as well; and (d) no PC-specifc B cells are found in 19-day fetal liver or in bone marrow until 7 days of life, coincident with their appearance in the spleen. These findings, along with a previous report that PC-specific splenic B cells are tolerizable as late as day 10 after birth, confirm the invariant, late occurrence of the T15 clonotype and support a highly- ordered, rigorously predetermined mechanism for the acquisition of the B- cell repertoire. The results are discussed in light of other studies on the ontogeny of B-cell specificity, and in terms of the implications on the mechanism by which antibody diversity is generated.     

Heterogeneity of human red cell autoantibodies assessed by isoelectric focusing

Human red cell (RBC) autoantibodies may be the products of a single lymphocyte clone or of a restricted number of clones. For insight into the clonal distribution of human RBC autoantibodies, serum fractions from 28 individuals with various forms of autoimmune hemolytic anemia (AHA) and two nonanemic individuals with positive direct antiglobulin tests were separated by isoelectric focusing (IEF), and RBC binding in each fraction was quantitated with a solid-phase radioimmunoassay. IEF fractions of serum from normal volunteers and patients with nonimmune hemolytic anemia served as controls. These studies indicate that RBC antibodies are found in a restricted number of IEF fractions in sera from some patients with immune hemolytic anemia. IEF fractions containing RBC-binding activity vary among patients with idiopathic AHA, and distinct patterns of binding activity are found in serum from some patients with AHA associated with alphamethyldopa and procainamide or with B-cell immunoproliferative diseases. These findings suggest that the mechanism leading to autoantibody production may differ among patients with the various forms of immune hemolytic anemia.     

Spontaneous rupture of renal allografts (author's transl)]

Spontaneous rupture of an allografted kidney is not such a rare complication of kidney transplantation. In our series 5.2% of the transplanted kidneys ruptured spontaneously. The condition is an acute emergency characterized by the triad, acute abdomen, swelling in the region of the transplant and haemorrhagic shock. The aetiology of transplant rupture seems to be multifactorial, but the superimposition of an acute rejection episode on ischaemic tubular damage with acute renal failure was found to be the most important combination of events leading to transplant rupture in our patients. Exceptionally precise immunological monitoring in the early phases following transplantation and early aggressive therapy of an acute rejection crisis associated with acute renal failure should prevent allograft rupture.