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Biomedical subjects

H Osterhues

Publications and source records attributed to H Osterhues.

12 recordsLinked to original sources

Loco-regional thrombolysis for deep vein thrombosis: fact or fiction? A study of hemostatic parameters.

Loco-regional thrombolysis for deep-vein thrombosis (DVT) has been claimed to be equally effective and safe compared with systemic thrombolysis. It is not known whether a loco-regional thrombolytic effect exists and of what it might consist. To investigate this issue, we studied eight patients with DVT undergoing loco-regional thrombolysis with 20 mg alteplase infused over 4 h in a dorsal foot-vein of the affected leg, while the leg was kept tightly bandaged; alteplase infusions were repeated every 24 h, the number of therapy cycles (TC) was seven, and full-dose heparin was given. For coagulation analyses, 'loco-regional' blood samples were taken from a vein of the affected leg and 'systemic' samples were taken from an antecubital vein. After a median number of six TC, good partial reperfusion was achieved in 4/8 patients, moderate partial reperfusion in 2/8, major bleedings occurred in 2/8, and minor bleedings in 1/8 patients. During the first TC, recombinant tissue-type plasminogen activator (rtPA) activity and antigen, as well as FgDPs and d-dimers, were elevated significantly loco-regionally over systemic values, and a complete breakdown of plasmin-inhibitor activity occurred with only a slight systemic reduction; no other differences were found. During successive TC, differences in rtPA-activity and -antigen levels decreased, and no significant differences were found for all other parameters. Thus, a local fibrinolytic effect was demonstrable during loco-regional thrombolysis for DVT; the magnitude of this effect diminished during successive TC, giving rise to the hypothesis that the fibrinolytic efficacy may be decreased due to growing, antifibrinolytic activity. The preserved, loco-regional plasmin-inhibitor activities during the later TC, in contrast to the complete breakdown during the first TC, suggest that part of the enhanced antifibrinolytic activity is due to loco-regionally increased plasmin-inhibitor activity. The ultimate goal of loco-regional thrombolysis, the induction of local fibrinolysis without systemic effects, has not, however, been achieved.

Adult↗

Direct enzyme immunometric measurement of plasma big endothelin-I concentrations and correlation with indicators of left ventricular function.

Recent studies have suggested that the plasma concentrations of endothelin-1, a potent vasoconstrictive peptide, are increased in patients with congestive heart failure. This study aimed to evaluate a new direct ELISA for big endothelin-1 (the precursor of endothelin-1), in comparison with a big endothelin-1 ELISA using plasma sample extraction, and to investigate whether plasma big endothelin-1 concentrations correlate with indicators of left ventricular function. The direct ELISA yielded significantly (P < 0.001) lower results than the assay with extracted samples (0.9 +/- 0.5 pmol/L vs 2.7 +/- 1.9 pmol/L; n = 90); however, the results of the two assays were closely correlated (r = 0.86, P < 0.001). Plasma big endothelin-1 concentrations exhibited a significant (P < 0.001) negative correlation (r = -0.46, r = -0.40) with the left ventricular ejection fraction and a significant positive correlation (r = 0.40, P < 0.001; r = 0.36, P < 0.01) with the left ventricular end-diastolic pressure and the left ventricular end-diastolic (r = 0.42, r = 0.38, P < 0.001) and end-systolic (r = 0.52, r = 0.47, P < 0.001) volume indices. Plasma big endothelin-1 concentrations were notably greater in patients with New York Heart Association (NYHA) class II-IV symptoms than in patients without cardiac disease or in patients categorized to NYHA class I. These data suggest that plasma big endothelin-1 concentrations, measured by a direct ELISA, correlate with hemodynamic indicators and symptoms of left ventricular dysfunction.

Adult↗

Signal-averaged electrocardiogram in patients with insulin-dependent (type 1) diabetes mellitus with and without diabetic neuropathy.

The purpose of this study was to investigate the presence of ventricular late potentials derived from signal-averaged ECG in patients with IDDM with and without diabetic neuropathy. Eighty patients with IDDM but without evidence of cardiac disease and 80 age-matched healthy control subjects were investigated. The corrected QT interval was measured from the standard surface electrocardiogram. Ventricular late potentials were derived from signal-averaged electrocardiogram. Out of the 80 diabetic patients, 20 had an autonomic neuropathy, 20 had an isolated peripheral neuropathy, and 40 had no symptoms of neuropathy. The corrected QT interval was significantly prolonged in patients with an autonomic neuropathy as compared with the control group (436 +/- 23 ms(x 5) vs 384 +/- 23 ms(x 5), p < 0.001). In the other patient groups there was no significant prolongation of the corrected QT interval. Ventricular late potentials were present in 3 diabetic patients with an isolated peripheral neuropathy and in 1 control subject (NS). No diabetic patient with an autonomic neuropathy had ventricular late potentials. Our data did not indicate an increased incidence of ventricular late potentials derived from signal-averaged electrocardiogram in diabetic patients independent of a coexisting diabetic neuropathy or a prolonged corrected QT interval.

Adolescent↗

Increased endothelin release by cultured human smooth muscle cells from atherosclerotic coronary arteries.

OBJECTIVES: Endothelin, a 21-amino acid peptide initially purified from the medium of cultured endothelial cells, is a potent vasoconstrictor exerting its effects predominantly in a paracrine or autocrine manner. Recent data indicate that endothelin is also synthesized by cultured vascular smooth muscle cells and that endothelin is an effective stimulator of smooth muscle cell proliferation. This study aimed to investigate the endothelin release of cultured human smooth muscle cells, isolated from coronary plaques and from normal coronary tunica media, and to determine circulating endothelin concentrations in patients with coronary artery disease compared to control subjects. METHODS: Coronary plaque material was extracted by thrombendarterectomy during aorto-coronary bypass grafting (n = 19). Segments of normal coronary arteries were obtained at autopsy (n = 33). Cells were isolated by enzymatic disaggregation and identified as smooth muscle cells with antibodies against smooth muscle alpha-actin. Venous blood samples were drawn from patients with coronary artery disease undergoing cardiac catheterization (n = 32) and from control subjects (n = 38). Endothelin concentrations in culture medium and in plasma samples were measured by radioimmunoassay after Sep Pak C18 extraction. RESULTS: Cultured smooth muscle cells, isolated from coronary plaques, released a significantly (P < 0.001) higher amount of immunoreactive endothelin into the culture medium (39.2 +/- 3.9 pg/10(4) cells, mean +/- s.e.m., 31 supernatant samples) than smooth muscle cells from normal coronary tunica media (3.9 +/- 0.8 pg/10(4) cells, 28 samples). Circulating endothelin concentrations were slightly elevated (P < 0.01) in patients with coronary artery disease (3.8 +/- 0.2 pg/ml) compared to control subjects (3.0 +/- 0.2 pg/ml). CONCLUSIONS: These data suggest that the endothelin production is markedly increased in smooth muscle cells of coronary atherosclerotic plaques. The enhanced endothelin release may stimulate smooth muscle cell proliferation in a paracrine or autocrine manner and thus may contribute to the development or progression of coronary artery disease.

Cells, Cultured↗

QRS morphologies of the surface ECG of nonsustained ventricular tachycardias during holter monitoring compared with QRS morphologies of spontaneous sustained ventricular tachycardias.

The purpose of this study was to compare electrocardiographic (ECG) morphologies of nonsustained ventricular tachycardias (VTs) during Holter monitoring with the ECG morphology of documented, sustained, monomorphic VTs during the spontaneous event of tachycardia in 14 patients (9 with coronary artery disease), in whom a sustained, spontaneous monomorphic VT had been documented in a 12-lead ECG. All patients had a 24-hour Holter ECG without antiarrhythmic medication. Channel 1 of the Holter ECG was compared with leads V1, V2, and V3, and channel 2 with leads V4, V5, and V6. The Holter ECG of 10 patients in whom the QRS complex during sinus rhythm was similar to the QRS complex in the corresponding ECG leads was accepted for analysis. In 8 of the 10 patients, nonsustained VTs were detected during Holter monitoring. In one of these eight, the ECG morphology of at least one nonsustained VT in the Holter recordings was identical with the sustained VTs. Thus, incidences and ECG morphologies of nonsustained VTs during Holter monitoring do not correlate closely with those of spontaneous sustained monomorphic VTs. Therefore, most ventricular runs during Holter monitoring may have a mechanism different from that of spontaneous sustained VTs.

Adult↗

A prescreening system for potential antiproliferative agents: implications for local treatment strategies of postangioplasty restenosis.

BACKGROUND: Recent advances in the understanding of the biology of restenosis indicate that it is predominantly caused by a multifactorial stimulation of smooth muscle cell proliferation. The aim of this study was to investigate the in vitro effect of five potential antiproliferative agents on smooth muscle cells from human atherosclerotic femoral arteries. METHODS AND RESULTS: Primary stenosing plaque material of 24 patients (aged 63 +/- 14 years) and restenosing plaque material of 7 patients (aged 65 +/- 9 years) was selectively extracted from femoral arteries by the Simpson atherectomy device. Cells were isolated by enzymatic disaggregation and identified as smooth muscle cells by positive reaction with smooth muscle alpha-actin. Dalteparin sodium (0.001-100 anti-Xa units/ml), cyclosporine A (0.005-500 micrograms/ml), colchicine (0.00004-4 pg/ml), etoposide (0.002-200 micrograms/ml), and doxorubicin (0.0005-50 micrograms/ml) were added to the cultures. Six days after seeding, cells were trypsinized and cell number was measured by a cell counter. All five agents tested exhibited a significant inhibition of smooth muscle cell proliferation (P < 0.001). After an incubation time of 48 h, the cytoskeletal components, alpha-actin, vimentin, and microtubules were investigated. At peak concentrations, all five tested agents except dalteparin sodium caused severe damage to the cytoskeleton. CONCLUSIONS: All five potential antiproliferative agents exhibited a significant inhibition of smooth muscle cell proliferation. The development of new intravascular delivery systems may open the way for local antiproliferative treatment strategies in interventional cardiology.

Actins↗

Corticosteroid agents inhibit proliferation of smooth muscle cells from human atherosclerotic arteries in vitro.

We studied the in vitro effect of steroid agents on smooth muscle cells from human atherosclerotic arteries. Recent advances in the understanding of the biology of restenosis indicate that restenosis is predominantly caused by a multifactorial stimulation of smooth muscle cell proliferation. Primary stenosing plaque material of 24 patients (aged 63 +/- 14 years) and restenosing plaque material of 7 patients (aged 65 +/- 9 years) was selectively extracted from femoral arteries by the Simpson atherectomy device. Cells were isolated by enzymatic disaggregation and identified as smooth muscle cells by positive reaction with smooth muscle alpha-actin. The steroid agents prednisolone (0.0075-750 micrograms/ml), hydrocortisone (0.0125-1250 micrograms/ml), and dexamethasone (0.0004-40 micrograms/ml) were added to the cultures. Six days after seeding the cells were trypsinized and the cell number was measured by a cell counter. All three steroid agents exhibited a significant antiproliferative effect on smooth muscle cell proliferation. At high concentrations of hydrocortisone, cytoskeletal elements of smooth muscle cells such as actin, microtubules, and vimentin, were largely altered. Our data indicate that the proliferation of smooth muscle cells from human atherosclerotic arteries in vitro can be inhibited by steroid agents and thus may open the way for local post-angioplasty treatment strategies.

Actins↗

[Localization of premature and ectopic ventricular depolarization using a new nuclear medicine tomographic technique].

In planar radionuclide ventriculography (RNV) identification of the site of initial contraction is possibly by the Fourier phase. First clinical experiences will be presented with a new integrated tomographic technique--ISPECT--in noninvasively assessing the site of ectopic or premature ventricular depolarization. In six patients Fourier phases of RNV and ISPECT were performed and compared in five with results from the corresponding electrophysiologic study. It was possible to exactly localize the beginning of mechanical contraction in the two orthogonal planes: during pacemaker stimulation at the apex of the right ventricle, at the lateral border of a large aneurysm during ventricular tachycardia, and at the site of three of five WPW bundles. In the other two bundles the site of first contraction was near the area found during invasive mapping procedure. Thus, this new ISPECT approach together with planar radionuclide imaging may help in noninvasively localizing the site of ectopic and premature depolarization in addition to surface ECG.

Adult↗

Silent ischaemia in asymptomatic 'healthy' individuals with coronary risk factors.

On the occasion of a routine medical check-up 256 out of 1100 individuals with an accumulation of coronary risk factors were screened for silent myocardial ischaemia by exercise testing and Holter monitoring. Of these individuals 5.5% had a pathological exercise test, 7.4% had ischaemia-like events on the Holter ECG, 11.3% had at least one pathological test, but only 1.6% had ischaemic signs in both ECG tests. The outcome of the ECG tests appears to be independent of the type and the total number of risk factors. To date, 13 of the 29 individuals with a positive test have undergone thallium myocardial imaging: only three individuals had signs of ischaemia. Holter monitoring and exercise ECG show comparable results in this population. The pathological ECG findings were only partly confirmed by the thallium test. The follow-up will show the prognostic significance of the ECG changes.

Coronary Disease↗