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Biomedical subjects

A Vogt

Publications and source records attributed to A Vogt.

At least 109 records · Page 6Linked to original sources
PubMed1993

Open, noncontrolled dose-finding study with a novel recombinant plasminogen activator (BM 06.022) given as a double bolus in patients with acute myocardial infarction.

The novel recombinant plasminogen activator (r-PA) (BM 06.022) is a mutant of tissue-type plasminogen activator expressed in escherichia coli which can be given as a bolus because of a prolonged half-life. The primary objective of this trial was to determine the efficacy of an intravenous r-PA double bolus (first bolus of 10 MU followed by 5 MU after 30 minutes) in patients with acute myocardial infarction. All patients received heparin intravenously and acetylsalicylic acid orally. Efficacy was assessed from infarct artery patency by coronary angiography (Thrombolysis in Myocardial Infarction trial perfusion grades 2 or 3) in 50 patients. Ninety minutes after administration of the first r-PA bolus, the infarct-related coronary artery was patent in 39 of 50 patients (78%; 95% confidence interval 64 to 88%). An angiographically confirmed reocclusion occurred in 1 patient between 90 minutes and 24 to 48 hours. The reocclusion rate was influenced by 8 interventions and 1 angiogram missing at 24 to 48 hours. Measurements of hemostatic parameters showed a decrease in fibrinogen to 37% of baseline value. There were 3 clinical reinfarctions before discharge and 2 major puncture site hemorrhages. No further serious bleeding and no serious adverse event with lethal outcome occurred. The 10 + 5 MU r-PA double bolus regimen appears to be effective with regard to patency and the success of thrombolysis. The incidence of reocclusion is very low. From the limited number of patients treated in this study, one need not be concerned about the safety profile of r-PA.

Clinical Enzyme Tests↗
PubMed1993

[Initial experiences with a recombinant human tissue thromboplastin in oral anticoagulation].

A recombinant tissue factor (rTF, Batch TFS-RD3, Baxter Diagnostics) has been assessed by plasma and capillary blood methods and compared with our working rabbit brain thromboplastin (CRB Roche, Basel, Switzerland) for its suitability in monitoring oral anticoagulant therapy. The international sensitivity index (ISI) for rTF calibrated against CRB has been found to be 0.73 and 0.69 respectively. The slope of the orthogonal regression line between log prothrombin time rTF plasma and rTF capillary blood is 0.96. Thus, we considered the ISI to be identical for both methods. International normalized ratios calculated with these assumptions, and even activity percentages assigned by a dilution curve, did not differ from the results obtained with our working thromboplastin. The human recombinant thromboplastin TFS-RD3 seems to have properties similar to currently used commercial thromboplastins. Recombinant tissue factor as a well defined preparation could make essential contributions to the standardization of prothrombin time and to the improvement of oral anticoagulant therapy.

Animals↗
PubMed1993

Impact of early perfusion status of the infarct-related artery on short-term mortality after thrombolysis for acute myocardial infarction: retrospective analysis of four German multicenter studies.

OBJECTIVE: This study evaluated the impact of early patency of the infarct-related vessel on short-term mortality after thrombolysis for acute myocardial infarction. BACKGROUND: Different thrombolytic regimens for acute myocardial infarction proved to be equally effective in large scale mortality trials despite significant differences in their efficacy with respect to early infarct-related vessel patency as shown in smaller angiographic trials. METHODS: Patients from four German multicenter studies of thrombolysis in acute myocardial infarction were retrospectively evaluated. Of 939 patients with acute myocardial infarction (duration of symptoms < 6 h) treated with thrombolysis, 907 (96.6%) had an angiogram of the infarct-related artery 90 min after the initiation of thrombolytic therapy. The perfusion status was graded according to the Thrombolysis in Myocardial Infarction (TIMI) study criteria. RESULTS: Complete reperfusion (TIMI grade 3) was found in 561 of 907 patients and partial reperfusion (TIMI grade 2) in 122 of 907. Overall, the in-hospital mortality rate was 4.6% (43 patients). In patients with complete reperfusion of the infarct-related vessel, the mortality rate was only 2.7% versus 7.1% in patients with an occluded vessel at the 90-min angiogram. This difference was highly significant in univariate as well as in multivariate analysis. In patients with partial perfusion of the infarct vessel, the mortality rate was 6.6%. CONCLUSIONS: The early perfusion status of the infarct-related artery is an independent predictor of short-term survival. However, only complete early reperfusion is associated with a reduced in-hospital mortality rate whereas patients with partial perfusion (TIMI grade 2) have a short-term prognosis similar to that of patients with persistently occluded infarct vessels. Therefore, when used as a surrogate end point for mortality, only TIMI grade 3 perfusion of the infarct vessel should be interpreted as a treatment success of thrombolysis in acute myocardial infarction.

Adult↗
PubMed1993

Intrathecal antibody synthesis in Lyme neuroborreliosis: use of recombinant p41 and a 14-kDa flagellin fragment in ELISA.

The intrathecal synthesis of IgM and IgG antibodies to Borrelia burgdorferi sonicate, to recombinant flagellin (41 kDa) and to a tryptic peptide of the flagellin (14-kDa fragment) was determined by ELISA in paired cerebrospinal fluid (CSF) and serum samples from 35 patients with Lyme neuroborreliosis (LNB) and in 10 patients with neurosyphilis. The antibody index (AI = QBb/QIg) was calculated from the ratio between CSF/serum quotients for specific antibodies (QBb) and total immunoglobulins (QIg). For the examination of IgG antibodies, the sonicate ELISA was performed with and without pre-absorption with Treponema phagedenis. Of 35 patients with LNB, 31 had intrathecal IgG response to B. burgdorferi demonstrated by sonicate ELISA (24 after absorption of cross-reactive antibodies), 29 had a response demonstrated by flagellin ELISA and 21 of 35 by 14-kDa ELISA. In patients with neurosyphilis the AI (IgG) was elevated in the sonicate ELISA in 7 of 10 samples (none of 10 after absorption of cross-reactive antibodies), in the flagellin ELISA in 5 of 10 samples and in the 14-kDa ELISA in none of 10 samples. Intrathecal synthesis of IgM antibodies to B. burgdorferi was demonstrated in patients with neuroborreliosis by sonicate ELISA in 20 of 35 samples, by flagellin ELISA in 16 of 35 samples and by 14-kDa ELISA in 9 of 35 samples. No intrathecal synthesis of B. burgdorferi-specific IgM could be detected by any assay in patients with neurosyphilis.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

[Mitral insufficiency after percutaneous balloon valvuloplasty in mitral stenosis. Incidence and progression].

Percutaneous balloon valvoplasty of the mitral valve was performed in 126 patients (24 men, 102 women; mean age 55.0 +/- 12.1 years) with mitral stenosis. The mean transmitral valve gradient fell from 12.4 +/- 6.1 to 6.0 +/- 3.2 mmHg, while the valve opening area increased from 1.0 +/- 0.2 to 1.55 +/- 0.3 cm2. After percutaneous balloon valvoplasty 36 patients still had no mitral regurgitation, while the grade of mitral regurgitation remained the same in 47 (grade I: n = 35; grade I: n = 12). Mitral regurgitation, previously not present, occurred in 25 patients, but was severe in only three (grade III: n = 1; grade IV: n = 2). Previously present mitral regurgitation increased in 18 of 65 patients, in four to grade III, in one to grade IV. In three patients acute grade IV mitral regurgitation resulted from a tear in a leaflet of a fibrotic valve which was not or only slightly calcified, requiring emergency surgery. Followup observations over 16.9 (1-60) months showed no change in most patients, but three developed mitral regurgitation. The latter underwent elective surgery, as did one patient with acute mitral regurgitation. Thus a total of seven patients (5.6%) required surgery for mitral regurgitation after percutaneous balloon valvoplasty.

Adolescent↗
PubMed1992

Improved thrombolysis in acute myocardial infarction with front-loaded administration of alteplase: results of the rt-PA-APSAC patency study (TAPS)

Thrombolysis with recombinant tissue-type plasminogen activator (rt-PA) and anisoylated plasminogen streptokinase activator (APSAC) in myocardial infarction has been proved to reduce mortality. A new front-loaded infusion regimen of 100 mg of rt-PA with an initial bolus dose of 15 mg followed by an infusion of 50 mg over 30 min and 35 mg over 60 min has been reported to yield higher patency rates than those achieved with standard regimens of thrombolytic treatment. The effects of this front-loaded administration of rt-PA versus those obtained with APSAC on early patency and reocclusion of infarct-related coronary arteries were investigated in a randomized multicenter trial in 421 patients with acute myocardial infarction. Coronary angiography 90 min after the start of treatment revealed a patent infarct-related artery (Thrombolysis in Myocardial Infarction [TIMI] grade 2 or 3) in 84.4% of 199 patients given rt-PA versus 70.3% of 202 patients given APSAC (p = 0.0007). Early reocclusion within 24 to 48 h was documented in 10.3% of 174 patients given rt-PA versus 2.5% of 163 patients given APSAC. Late reocclusion within 21 days was observed in 2.6% of 152 patients given rt-PA versus 6.3% of 159 patients given APSAC. There were 5 in-hospital deaths (2.4%) in the rt-PA group and 17 deaths (8.1%) in the APSAC group (p = 0.0095). The reinfarction rate was 3.8% and 4.8%, respectively. Peak serum creatine kinase and left ventricular ejection fraction at follow-up angiography were essentially identical in both treatment groups. There were more bleeding complications after APSAC (45% vs. 31%, p = 0.0019).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Purification and characterization of a tryptic peptide of Borrelia burgdorferi flagellin, which reduces cross-reactivity in immunoblots and ELISA.

In man the early immune response in Lyme disease is primarily directed against the endoflagellin antigen. Isolated flagellar protein of Borrelia burgdorferi suggests itself as a suitable test antigen. However, cross-reactivity between flagellins of B. burgdorferi, Escherichia coli, Bacillus subtilis, Proteus mirabilis and Salmonella typhimurium was demonstrated by immunoblotting and ELISA with polyclonal rabbit-hyperimmune-sera. Tryptic cleavage of recombinant B. burgdorferi 41 kDa flagellin, expressed in E. coli, produced a peptide fragment which was recognized exclusively by antisera to Borrelia species. This peptide was designated as the 14 kDa fragment due to its migratory behaviour in SDS-PAGE. The fragment is part of the variable region of the flagellin, as proven by amino acid sequencing. The flagellin peptide was employed as an antigen in ELISA and immunoblot assays, testing the polyclonal sera mentioned above. The specificity was superior to that obtained with the intact recombinant flagellin.

Amino Acid Sequence↗
PubMed1992

Glomerular immune deposits in murine lupus models may contain histones.

Two types of lupus mice, NZB/NZW F1 female hybrids and mice with graft-versus-host disease (GVHD), were studied. Histones H3 and H2A were detected by immunofluorescence in glomeruli of 22/22 proteinuric GVHD and 8/12 proteinuric NZB/W F1 female mice; in non-proteinuric animals, 3/5 GVHD and 2/27 NZB/W F1 female were positive. Using antibodies to histone peptides it was shown that mainly the N-terminal regions of histones H3 and H2A were exposed in glomerular deposits. Western blot analysis revealed antibodies to histone subfractions in sera of 33/34 lupus mice that developed proteinuria. This study provides evidence that histones are involved in the pathogenesis of lupus nephritis.

Animals↗
PubMed1991

[Percutaneous balloon valvuloplasty in mitral stenosis].

Between June 1986 and June 1989, percutaneous balloon valvuloplasty (PBV), using the transseptal, single-balloon technique, was performed in 50 consecutive patients (38 women and 12 men; mean age 54 +/- 14 years) with mitral stenosis. The procedure was technically successful in 48 patients (in one patient the atrial septum could not be crossed, in the other cardiac tamponade occurred). The mean diastolic gradient was decreased from 12.5 +/- 6.6 to 6.1 +/- 3.1 mmHg, mean pulmonary artery pressure (PAP) reduced from 29 +/- 12 to 22 +/- 6 mmHg, and valve opening area increased from 1.0 +/- 0.25 to 1.6 +/- 0.4 cm2. Redilatation had to be undertaken in four patients because of restenosis. Commissurotomy had to be performed in one patient, valve replacement in nine (restenosis in 4, poor primary results in 3, increase in regurgitation in 2). One patient died of a noncardiac cause. Follow-up observations for an average of 14 (3-36) months indicated in 30 of the remaining 33 patients without additional intervention a stable clinical improvement of at least one class (NYHA classification), as well as stable haemodynamic findings (gradient: 6.0 +/- 2.7 mmHg, valve opening area 1.5 +/- 0.3 cm, PAP 23 +/- 7 mmHg. Thus PBV achieved, at least in the medium term, clinical improvement in about two thirds of patients, and an operation was avoided.

Adolescent↗
PubMed1991

Surface charge distribution is a determinant of antigen deposition in the renal glomerulus: studies employing 'charge-hybrid' molecules.

The deposition of antigens and immune complexes (IC) in the renal glomerulus is charge-dependent. The demonstration that molecules of net anionic charge, but with discrete positively charged regions, exhibit affinity for the glomerular basement membrane (GBM) extends this concept. Charge hybrid (polar) molecules were constructed by covalently coupling small polycations (lysozyme or linear poly-L-lysine chains with a mean of 17 and 20 residues) to larger polyanions (ovalbumin or human serum albumin (HSA]. Although the products were of overall net anionic charge they still bound to glomerular structures. Immunofluorescence studies performed after i.v. injection of the samples into rats revealed that HSA:poly-L-lysine had the highest affinity. Radioisotopic measurements showed uptake of HSA:poly-L-lysine to be a function of the number of lysine residues; binding of HSA:poly-L-lysine20 was 2.5 times higher than HSA:poly-L-lysine17 (P less than 0.01). Prior injection of a small competing polycation (polyethyleneimine 1200) reduced uptake of HSA:poly-L-lysine by 75%, indicating the charge-based nature of the interaction. HSA:poly-L-lysine20 alone was effectively eliminated from the glomeruli within 72 h. Administration of HSA:poly-L-lysine followed by anti-HSA antibody induced immune complex formation in the capillary wall, giving rise to a granular immunofluorescence pattern and discrete subendothelial and subepithelial deposits. Molecules with polar structure do occur naturally and may contribute to immune complex formation in glomerulonephritis.

Analysis of Variance↗
PubMed1991

[Heparin-induced thrombocytopenia. Perspectives in a therapeutic dilemma].

Severe heparin-induced thrombocytopenia (HIT) is a complication of heparin treatment with a frequency of about 0.5% of the treated patients. It is attributed to an immune mechanism leading to the production of heparin-associated antibodies which bind to the platelets and cause their elimination through consumption, sometimes accompanied by thromboembolic episodes. Therapeutically HIT represents a dilemma since heparin administration must be stopped immediately, whereas anticoagulation is acutely indicated in order to avoid thrombotic complications. Two such cases with this dilemma are illustrated. The diagnosis of HIT was made using platelet aggregation studies and flow cytometry techniques for the detection of heparin-associated platelet antibodies. Therapeutically, low molecular weight heparins were administered with success. Besides the diagnostic problems other available therapeutic solutions are discussed.

Aged↗
PubMed1991

Complement and monocytes are essential for provoking glomerular injury in passive Heymann nephritis in rats. Terminal complement components are not the sole mediators of proteinuria.

Complement but not polymorphonuclear granulocytes (PMN) causes glomerular injury in passive Heymann nephritis in rats. We have now identified monocytes as another important mediator in this model. Passive Heymann nephritis was induced in Wistar rats by intravenous injection of sheep anti-rat Fx1A antiserum. Four groups (all receiving anti-rat Fx1A antiserum) were studied: (a) rats given normal sheep globulin (nephritic controls), (b) rats given sheep anti-rat PMN globulin (PMN-depleted), (c) rats given sheep anti-rat monocyte globulin (monocyte-depleted), (d) rats injected with cobra venom factor (complement-depleted). In vitro specificity controls for anti-cell antisera were made by cytotoxicity tests and inhibition of phagocytosis. In vivo specificity controls were performed in heterologous Masugi nephritis (PMN-dependent) and accelerated Masugi nephritis (monocyte-dependent). Complement and monocyte depletion significantly delayed the onset of proteinuria (p less than 0.001 versus nephritic controls on day 5), PMN depletion had no significant effect. Monocyte infiltration was seen in control nephritic rats, but monocyte depletion prevented this influx. In the monocyte-depleted group, no differences in glomerular deposition of C3, C9, and C5b-9 were seen in comparison to the nephritic control rats. Serum C3 levels were comparable in groups a, b, and c, the complement system was biologically active in the monocyte depleted-group (c), and the amount of anti-Fx1A antibody bound was the same in all groups. This shows that, besides complement, monocytes are required for induction of renal damage in passive Heymann nephritis. The concept of a sole role for complement in glomerular immune injury involving subepithelial immune deposits should be reconsidered.

Animals↗
PubMed1990

Isolation of an outer membrane protein complex from Borrelia burgdorferi by n-butanol extraction and high-performance ion-exchange chromatography.

Borrelia burgdorferi, the causative agent of Lyme disease, expresses two major membrane proteins, designated outer surface proteins A and B, which are of antigenic relevance, especially in the chronic phase of Lyme disease. Both proteins exhibit strain-related molecular weight variation. A method is described for obtaining these proteins from the bacterial membrane, without the use of detergents, by a combination of n-butanol extraction and cation-exchange chromatography on a Mono S fast protein liquid chromatographic column. This method yields up to five times larger amounts of the proteins in aqueous solution than previously described protocols, which applied ionic or non-ionic detergents. A comparison of extracts obtained by this method from different Borrelia burgdorferi strains is reported.

1-Butanol↗
PubMed1990

[The laboratory diagnosis of Borrelia burgdorferi infection].

The multiplicity of the clinical appearance of Lyme disease makes it necessary to confirm the diagnosis by detecting the pathogen or specific antibodies. Isolation of the pathogen from infected tissue or body fluids is difficult, so that, to date, only serology is feasible for routine diagnosis. In view of a lack of standardisation of borrelia serology, the clinician must expect false negative, and--even more so--false-positive, results. Future laboratory diagnosis should be markedly improved by nucleic acid hybridisation for the detection of the pathogen, and the use of specific immunodominant antigens for antibody detection.

Antibodies, Bacterial↗