Search PubMed⌕ Search

Biomedical subjects

A Vogt

Publications and source records attributed to A Vogt.

At least 127 records · Page 7Linked to original sources

[Acute effects of the angiotensin converting enzyme inhibitor ramipril in patients with coronary heart disease].

We investigated the acute effect of the new long-acting ACE-inhibitor ramipril on angina-limited exercise tolerance and exercise-induced ST-depression in 18 normotensive patients with angiographically confirmed coronary artery disease in a double-blind, placebo-controlled study. Patients underwent a repeat exercise ECG 24 hours following either 5 mg ramipril p.o. or placebo. Plasma-ACE activity (nmol/min x ml) in the ramipril-group (n = 8) was significantly reduced 24 hours after 5 mg ramipril compared to placebo (n = 10): 14.0 +/- 2.0 vs 87.2 +/- 13.5, p less than 0.001. Exercise-induced ST-segment depression was not different before and after ramipril or placebo. Heart rate at rest and during angina-limited exercise was not different between the first exercise-ECG and that after ramipril or placebo, nor between the groups. Systolic arterial pressure (mmHg) was slightly, but insignificantly, lower after than before ramipril at rest (113.8 +/- 5 vs 125 +/- 6.8) and at maximal exercise, 1.5 watt/kg (150 +/- 9.4 vs 158.3 +/- 13.3). In the placebo group, blood pressure at rest and during exercise was not different before and after placebo: 126 +/- 4.7 vs 125.5 +/- 7.5 and 157.5 +/- 3.8 vs 158 +/- 3.6. Rate-pressure-product (mmHg/min x 1000) at rest prior to (8.42 +/- 0.83 and 8.95 +/- 0.51) and after ramipril or placebo (8.00 +/- 0.94 and 8.93 +/- 0.71) showed no significant difference. Similarly, rate-pressure-product at maximal exercise was equal among the groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin-Converting Enzyme Inhibitors↗

[The Borrelia titer in ENT diseases].

In 139 patients with facial paralysis, sudden hearing loss, vertigo, and lymphadenitis of the head and neck, the prevalence of borrelia burgdorferi serum antibodies was examined with the help of immunofluorescence assays for IgG- and IgM-antibodies, immunofluorescence assays after absorption of cross-reacting antibodies with treponema phagedenis, ELISA, and Western Blot. Six out of 22 patients with facial paralysis, 11 out of 72 with hearing loss, eight out of 45 with vertigo, and five out of 25 with lymphadenitis of the head and neck were seropositive. These patients were compared with a control group of 52 patients without any clinical signs of Lyme disease. The control group consisted of patients admitted for surgery of septal deformities (n = 19), squamous cell carcinomas (n = 27), and pleomorphic adenomas of the salivary glands (n = 6). In nine out of 52 patients in the control group, antibodies against Borrelia burgdorferi were detectable. According to Fisher's exact test, there was no statistical difference between the two groups as regards the prevalence of seropositive patients. Lyme disease is a doubtful major etiologic factor in facial paralysis, sudden hearing loss, or vertigo.

Adult↗

The role of cationic proteins in the pathogenesis of immune complex glomerulonephritis.

In spite of intensive endeavours, attempts to identify nephritogenic antigens in cases of immune complex glomerulonephritis have not yielded convincing results. Cationic antigens can have high affinity for the glomerular basement membrane and are prime candidates as nephritogens. They can be expected to play a role in post-infectious and in autoimmune glomerular disease. Histones show great promise in the latter case: we are able to demonstrate (1) a high affinity for the glomerular basement membrane and (2) their ability to promote glomerular deposition of anionic antigens as an additional target. Histones were detectable in glomerular deposits in two murine models of glomerulonephritis: the spontaneous lupus-like disease of NZB/W F1 mice and in graft-versus-host disease. We propose that histones may be responsible for the induction of glomerulonephritis in lupus-like syndromes, as well as other types of autoimmune renal disease. As an analogue, histone-like proteins from micro-organisms may also be responsible for glomerular disease in post-infectious nephritis.

Animals↗

Improved thrombolysis with a modified dose regimen of recombinant tissue-type plasminogen activator.

To improve further the patency rate of infarct-related coronary arteries, the following accelerated dosage regimen of recombinant tissue-type plasminogen activator (rt-PA) was administered to 80 patients with acute myocardial infarction of less than or equal to 6 h duration: 15 mg intravenous bolus, 50 mg infusion over 30 min and 35 mg infusion over the following 60 min. After coronary angiography at 90 min coronary angioplasty was performed in 16 patients and additional thrombolysis in 3 patients. Six patients were not included in the final angiographic analysis, mostly because of borderline ST segment elevations, in order to avoid overestimation of the efficacy of this dose regimen. Four of these had a patent infarct artery; no early angiogram was performed on two. Sixty minutes after the start of infusion, 54 (74%) of 73 patients had a patent infarct-related artery (Thrombolysis in Myocardial Infarction [TIMI] grade 2 or 3) as did 67 (91%) of 74 patients at 90 min. At 24 h, 61 (92.4%) of 66 patients showed a patent infarct artery. Recurrent myocardial ischemia was noted in 12 patients, 7 (9.4%) of whom experienced reinfarction during the hospital stay. Minor local bleeding complications were observed in 14 patients (17.5%). There were four in-hospital cardiac deaths; one patient who underwent additional thrombolysis for recurrent ischemia died from bleeding complications. These results show that a rapid infusion of 100 mg of rt-PA over 90 min yields a high early patency rate of the infarct-related artery without an increase in reocclusion rate and adverse reactions.

Adult↗

N-terminal amino acid sequence of the Borrelia burgdorferi flagellin.

The 41 kDa flagellar protein of Borrelia burgdorferi appears to be an immunodominant antigen producing an early and strong response in most, if not all, individuals during infection in humans. It would represent a very good antigen for serodiagnosis of Lyme disease, if its crossreactivity with flagella of other bacteria was low. To gain information on this point we isolated the B. burgdorferi flagellin by preparative two-dimensional electrophoresis for N-terminal amino acid analysis. By comparing the N-terminal amino acid sequences of flagellar proteins from other eubacteria we found that the first six out of twenty nine amino acids were identical to the Treponema pallidum and Treponema phagedenis 'class B' flagellins. All 29 N-terminal residues exhibited a moderate inter-genus homology (44-55%), in contrast to the high degree (67-95%) of inter-species conservation of the treponemal 'class B' flagellar N-terminal sequences. There was little similarity to other flagellins except the B. subtilis flagellar protein.

Amino Acid Sequence↗

Histones have high affinity for the glomerular basement membrane. Relevance for immune complex formation in lupus nephritis.

An effort has been made to integrate insights on charge-based interactions in immune complex glomerulonephritis with nuclear antigen involvement in lupus nephritis. Attention was focussed on the histones, a group of highly cationic nuclear constituents, which could be expected to bind to fixed anionic sites present in the glomerular basement membrane (GBM). We demonstrated that all histone subfractions, prepared according to Johns (4), have a high affinity for GBM and the basement membrane of peritubular capillaries. Tissue uptake of 125I-labeled histones was measured by injecting 200 micrograms of each fraction into the left kidney via the aorta and measuring organ uptake after 15 min. In glomeruli isolated from the left kidneys, the following quantities of histones were found: f1, 13 micrograms; f2a (f2al + f2a2), 17 micrograms; f2b, 17 micrograms; and f3, 32 micrograms. Kinetic studies of glomerular binding showed that f1 disappeared much more rapidly than f2a. The high affinity of histones (pI between 10.5 and 11.0; mol wt 10,000-22,000) for the GBM correlates well with their ability to form aggregates (mol wt greater than 100,000) for comparison lysozyme (pI 11, mol wt 14,000), which does not aggregate spontaneously bound poorly (0.4 micrograms in isolated glomeruli). The quantity of histones and lysozyme found in the isolated glomeruli paralleled their in vitro affinity for a Heparin-Sepharose column (gradient elution studies). This gel matrix contains the sulfated, highly anionic polysaccharide heparin, which is similar to the negatively charged heparan sulfate present in the GBM. Lysozyme eluted with 0.15 M NaCl, f1 with 1 M NaCl, and f2a, f2b, and f3 could not be fully desorbed even with 2 M NaCl; 6 M guanidine-HCl was necessary. Two further findings of great relevance for the concept of induction of immune complex glomerulonephritis by histones were: (a) glomerular-bound histone was accessible for specific antibody given intravenously; and (b) prior binding of histones promoted glomerular deposition of anionic antigens, as could be shown with ssDNA fragments. These data justify the proposal that glomerular deposition of histones can induce immune complex formation, start an inflammatory process, and produce tissue damage.

Animals↗

Frequencies of Borrelia burgdorferi-reactive T lymphocytes in Lyme arthritis.

Using a limiting dilution system, frequencies of Borrelia burgdorferi-reactive T cells were determined in the blood and synovial fluid of four patients with chronic Lyme arthritis (LA), one patient with acrodermatitis chronica atrophicans (ACA), two patients with other inflammatory joint diseases, and two healthy individuals. B. burgdorferi-reactive precursor T cells ranged from 1/750 to 1/8220 in case of LA and ACA patients and from 1/820 to 1/31 400 in case of controls. In vivo activated B. burgdorferi-reactive T cells were almost absent in control subjects. With one exception, they were detected in LA patients at frequencies ranging from 1/1 300 to 1/15 400. Interestingly, even after successful antibiotic therapy of LA patients, similar frequencies of in vivo activated B. burgdorferi-reactive T cells were observed in the peripheral blood, provided that low cell concentrations were used for culture. At higher cell numbers, the fraction of B. burgdorferi-reactive T cells apparently dropped, suggesting regulatory phenomena.

Adult↗

Ultrastructural studies in passive in situ immune complex glomerulonephritis. A rat model for membranous glomerulonephritis.

Morphologic studies were performed in a passive model of in situ immune complex glomerulonephritis in rats. The formation and fate of subepithelial immune complexes as well as the role of glomerular polyanion in the induction of disease were examined. Unilateral in situ immune complex glomerulonephritis was induced in rats by perfusion of cationised horse spleen ferritin (pI greater than 9.5) (400 micrograms/rat) into the left kidney followed by systemic injection of 0.2 ml (= 400 micrograms precipitating antibody) of sheep anti-ferritin antiserum 2 h later. This schedule induced glomerulonephritis with proteinuria (mean maximum 100 mg/24 h between the 5th and the 12th day). Rats were sacrificed at intervals between 1 h and 42 days after induction of glomerulonephritis, samples of renal tissue were examined by light, immunofluorescence and electron microscopy (including staining of anionic sites by polyethyleneimine). The lesion induced closely resembled that of membranous glomerulonephritis in man as massive subepithelial deposits were seen with very little cellular infiltration or proliferation. The antigen (ferritin) deposits were initially located subepithelially; from 2 weeks onwards intramembranous deposits in the thickened basement membrane were present, the apparent translocation being due to excessive newly synthesised basement membrane material which encloses the deposits. A loss of anionic sites in the lamina rara interna, lamina rara externa and on the epithelial cell surface coat preceded the development of proteinuria.

Animals↗

[Diagnosis of toxoplasmosis in pregnancy].

Even today, toxoplasmosis infection during pregnancy is an unsolved problem. In studies of 2206 pregnant women, toxoplasmosis specific IgM-antibodies have been detected in 69 cases (3.1%). Using more sophisticated serological techniques only 12 active toxoplasmosis cases needing therapy remained. Decisive discrimination criteria of the various tests were exact time of the examination as well as the level of the antibody titer. Although only 12 toxoplasmosis infections were treated, no connatal infections have been observed. On the other hand, in some outpatients, referred to our clinic, cases of severe connatal toxoplasmosis infections were found although they had undergone therapy. To solve the problem of toxoplasmosis, we recommend a general screening before pregnancy if possible. For optimal results of this screening, serologic reference laboratories and efficient sonography units must be established to obtain, when required, umbilical venous blood.

Animals↗

[Macromolecular basis of filtration and immune complex pathogenesis in the glomerulus].

Fractional clearance and ultrastructural studies produce results consistent with the idea that the glomerular filtration barrier is a heteroporous membrane. The majority of the pores being small, excluding molecules like serum albumin and larger moieties, while a low number of pores allow the passage of molecules as big as dimeric ferritin, in very restricted quantities. Cationic macromolecules, of a size which should effectively exclude them from the filtration process, readily gain access to all three layers of the GBM. Depending on charge (pI) and size they can in fact exhibit significant affinity for negatively charged structures in both laminae rarae. In addition, polycations can mediate the glomerular deposition of anionic macromolecules, for example DNA-fragments, by diminishing charge repulsion. A prerequisite for the local formation of glomerular immune complexes is that at least one of the reaction partners has an affinity for the GBM. Antigens bound to structures in the laminae rarae are accessible for circulating antibody. Immune complexes formed with cationic antigen in the lamina rara interna are transferred to the subepithelial region with time. Antigen and antibody molecules can penetrate the lamina densa only in dissociated form. The persistence of glomerular immune complexes can be explained by antigen-antibody lattice formation within the network of proteoglycan chains, followed by covalent binding between components of the complex and structures of the GBM.

Animals↗

[Follow-up after dilatation of congenital and acquired aortic stenosis].

Until 31 December 1987, a total of 85 transfemoral balloon valvuloplasties (TBV) had been performed for aortic valve stenosis, on 25 patients with noncalcified congenital and 58 (aged 66 +/- 10 years) with acquired (calcified) stenosis. The procedure had to be repeated in two infants because of early re-stenosis. The systolic transvalvular pressure gradient was reduced from 93 +/- 29 (mean +/- SD) to 51 +/- 20 mm Hg in acquired stenoses, and from 87 +/- 24 to 44 +/- 15 mm Hg in congenital stenoses. Invasive pressure measurements in 16 patients with acquired stenosis 3-11 months (mean of 8 months) post-TBV demonstrated partial or complete re-stenosis in all patients. In contrast, only 3 of 17 patients with congenital stenosis had significant re-stenosis 4-38 months (mean of 16 months) after TBV. These results demonstrate that TBV gives similar immediate results in acquired, calcified and congenital, non-calcified aortic stenosis. However, the intermediate and long-term results are much better in the congenital form, because re-stenosis is rare, whereas the primary success failed to persist in any of the patients with the acquired form.

Adolescent↗

[Polymyalgia rheumatica following Borrelia infection].

The case of a 84-year old woman is presented who developed a polymyalgia rheumatica/giant cell arteritis (PMR/GCA)-syndrome following a tick bite. Elevated titers of IgG-antibodies (indirect immunofluorescence and ELISA) as well as IgM (Immunoblot) against Borrelia burgdorferi antigens were found in her serum. When a total of 19 patients with PMR/GCA-syndrome was tested serologically, elevated or borderline IgG-titers against Borrelia antigens were detected in 12 of them (= 63%). Hence, Borrelia infection may be viewed as a potential trigger mechanism of a PMR/GCA-syndrome.

Aged↗

Acute effects of the new angiotensin converting enzyme inhibitor ramipril on hemodynamics and carotid sinus baroreflex activity in congestive heart failure.

The hemodynamic effects of a single dose of 5 mg of ramipril, a new angiotensin converting enzyme inhibitor, were investigated in 10 patients with chronic congestive heart failure. Arterial blood pressure and total peripheral resistance were decreased by approximately 12% without causing reflex tachycardia. A highly significant decrease occurred in mean pulmonary artery and pulmonary capillary wedge pressures. These hemodynamic changes were equally pronounced at rest and during exercise on a bicycle ergometer; the effect was of the same magnitude 5 and 24 hours after medication. Angiotensin converting enzyme activity in plasma was nearly completely inhibited after 5 hours and remained at about 12% of control after 24 hours. Cardiac index, which was normal before treatment, remained unaffected. Thus, ramipril induced a balanced reduction of left ventricular pre- and afterload. The activity of the carotid sinus baroreflex was investigated in 8 of the patients using the neck suction technique before and 24 hours after ramipril. The reflex bradycardia during stimulation of the baroreceptors was significantly increased by ramipril, whereas the decrease in blood pressure remained essentially unaffected. Ramipril induced a selective sensitization of the parasympathetic baroreceptor heart rate reflex without influencing the sympathetically mediated peripheral vasodilatation. This effect may be responsible for the lack of reflex tachycardia in spite of the decrease in blood pressure.

Angiotensin-Converting Enzyme Inhibitors↗