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Biomedical subjects

D Glogar

Publications and source records attributed to D Glogar.

At least 19 recordsLinked to original sources

Increase and redistribution of cardiac mast cells in auricular thrombosis. Possible role of kit ligand.

BACKGROUND: The atrial appendage is a predilection site for thrombus formation. Mast cells (MC) are a rich source of mediators that may be involved in the regulation of thrombus formation. We examined number, distribution, and phenotype of MC in thrombosed versus unaffected auricles to elucidate their possible role in auricular thrombosis (AUTHR). METHODS AND RESULTS: Sections of atrial appendages (AUTHR, n = 14; controls (CO), n = 13) were analyzed for MC by Giemsa, toluidine blue, and berberine sulfate stains and by immunohistochemistry. Cardiac MC expressed CD antigens corresponding to the classic MC phenotype as well as tryptase, chymase, and heparin. Thrombosis was associated with a twofold increase in the number of MC in the total appendage (CO, 3.1 +/- 1.0 versus AUTHR, 6.4 +/- 1.1 MC/mm2, P < .01). Moreover, in AUTHR, a redistribution of MC to the upper endocardium was observed (AUTHR, 5.3 +/- 1.4 versus CO, 0.07 +/- 0.15 MC/mm2, P < .01). Mast cell growth factor (MGF) was expressed in the endothelium and subendothelial space of thrombosed appendages but not in the normal endocardium. Overexpression of MGF was accompanied by a weak or absent expression of the MGF receptor c-kit on redistributed MC in AUTHR. Patients with unilateral atrial appendage thrombosis did not exhibit a MC increase or redistribution in the unaffected contralateral appendage. No augmentation of other inflammatory cells was observed. Stimulation of isolated cardiac MC with MGF resulted in mediator release. CONCLUSIONS: This study provides evidence that AUTHR is associated with MC increase and redistribution and MGF overexpression. The role of redistributed MC and their mediators in the pathophysiology of atrial thrombosis requires further investigation.

Adult

Comparative assessment of right ventricular volumes and ejection fraction by thermodilution and magnetic resonance imaging in dilated cardiomyopathy.

Measurements of right ventricular (RV) ejection fraction (EF) and volumes using a new thermodilution technique were compared to serially performed magnetic resonance imaging (MRI) in 21 patients with dilated cardiomyopathy. For RVEF (%) and RV volume indices (ml/m2) the following correlation coefficients were found: RVEF r = 0.82; end-diastolic volume index (EDVI) r = 0.45; end-systolic volume index (ESVI) r = 0.65; stroke volume index (SVI) r = 0.61; all p < 0.05. However, RVEF by thermodilution was significantly lower (RVEF thermo = 31 +/- 14 vs. RVEF MRI = 50 +/- 14, p < 0.01) and RV EDV and ESVI were significantly higher compared to MRI, while SVI showed no significant difference. Exclusion of patients with atrial fibrillation (n = 8) improved the correlations (RVEF r = 0.94, EDVI r = 0.77, ESVI r = 0.87, SVI r = 0.65, all p < 0.05), but did not reduce the mean difference between both methods.

Cardiomyopathy, Dilated

[Lyme borreliosis and cardiomyopathy].

According to current opinion there is acute, self-limiting Lyme carditis, and chronic Lyme carditis. Acute Lyme carditis manifests mostly as transient conduction disorders of the heart (e.g. AV-blocking I to III), and as supraventricular and ventricular rhythm disturbances, pericarditis, myocarditis, and pancarditis in single cases. Chronic Lyme carditis is defined as a case of chronic heart failure confirmed by positive serology and endomyocardial biopsy. Anamnestic aid is rare. Neither tick-bites nor preceding or accompanying erythema chronicum migrans are constantly reported. Seropositivity and control of its specificity by western blot are indicative but no etiological proof. Even histological detection of spirochetes in endomyocardial tissue or cultivation of borrelia from endomyocardial biopsy are no final etiological proof of the respective cardial disorder. Those findings, however, are an indication for antibiotic treatment. According to the severity of the disorder, antibiotics are administered orally (penicillin or derivatives) or parenterally with penicillin or cephalosporins of the 3rd generation over 4 and 2 weeks, respectively.

Antibodies, Bacterial

The human cardiac mast cell: localization, isolation, phenotype, and functional characterization.

We have isolated and characterized the human cardiac mast cell (CMC) and compared this novel mast cell (MC type with MC obtained from uterus, skin, and lung. Heart tissue was obtained from 14 patients with cardiomyopathy (CMP, heart transplantation). CMC were isolated by enzymatic digestion using collagenase, pronase-E, hyaluronidase, and DNAse. Substantial amounts of CMC (0.5% to 1.5% of isolated cells) were found in the atrial appendages but not in ventricular digests or other sites of the heart (< 0.1%). In situ staining of atrial tissue revealed the presence of CMC in the myocardium (2.16 +/- 0.7 MC/mm2), endocardium (2.24 +/- 0.9 MC/mm2), and epicardium. As assessed by combined toluidine blue/immunofluorescence staining with monoclonal antibodies (MoAbs), isolated CMC expressed surface IgE, the receptor for stem cell factor (c-kit receptor/CD117), the p24 antigen (CD9), the Pgp-1 homing receptor (CD44), the pan leukocyte antigen (CD45), and the ICAM-1 antigen (CD54). CMC were not recognized by MoAbs to lymphocyte function associated antigen 2 (LFA-2; CD2), T-cell receptor (TcR; CD3), T4 antigen (CD4), LFA-1 alpha-chain (CD11a), C3biR alpha-chain (CD11b), CR4 alpha-chain (CD11c), LPS-R related Ag (CD14), 3-FAL/x-hapten (CD15), Fc gamma RIII (CD16), lactosylceramid (CDw17), the B-cell antigen CD19, or CR1 (CD35). In situ expression of leukocyte antigens on CMC was demonstrable by indirect immunoperoxidase staining technique and double-labeling immunohistochemistry. Almost all CMC (90%) reacted with MoAbs against tryptase and chymase and thus were MCTC. Cardiac mast cells were also stained by the heparin-binding dye Berberine sulfate and expressed measurable amounts of histamine (4.6 +/- 1.4 pg per cell). Cross linking of either IgE receptor or SCF receptor (c-kit) on CMC resulted in histamine secretion (non-specific release: < 6% of total histamine, alpha IgE induced: 12% to 52%; SCF-induced release: 9% to 18%), whereas neither substance P (a skin MC agonist) nor the basophil agonist FMLP showed an effect on CMC. Together, the CMC is an MCTC primarily located in the appendage of the atrium. This novel type of MC exhibits surface membrane antigen and functional properties similar to those of lung and uterus MC.

Antibodies, Monoclonal

Magnetic resonance imaging in the diagnosis of acute Lyme carditis.

Lyme disease is a multisystem disease, which can involve the heart causing myopericarditis. We describe 1 patient with serological and histological evidence of Lyme borreliosis and demonstration of pathologic myocardial signal enhancement in magnetic resonance imaging.

Acute Disease

Safety of concomitant potassium-sparing diuretics in angiotensin-converting enzyme inhibitor therapy in severe congestive heart failure. Xamoterol in Severe Heart Failure Study Group.

The safety of concomitant use of angiotensin-converting enzyme (ACE) inhibitors and potassium-sparing diuretics (PSD) in severe heart failure remains a controversial issue. The database of the recently reported double-blind international trial, "Xamoterol in Severe Heart Failure," was investigated to elucidate this question. Of 516 patients with New York Heart Association (NYHA) class III-IV, despite diuretics and ACE inhibitor therapy, 352 were randomized to xamoterol, a beta 1 partial agonist, and 164 were randomized to placebo. During the 13-week study, 28% of all patients (xamoterol, 104; placebo, 42) received potassium-sparing diuretics. All groups were comparable in hemodynamics and dose of other diuretics. At study end, patients with or without PSD showed no significant differences in serum K+ or creatinine, independent of xamoterol or placebo therapy. Mortality rate was consistently lower: 4.6% in patients with PSD and 8.5% in patients without PSD, although statistical significance was not reached. As compared with baseline, K+ values of 6 patients with and 17 patients without PSD had increased by > 5.0 mM at study end (p = NS); 1 patient with and 11 patients without PSD had a creatinine level > 180 microM (p = NS). For 3 patients receiving PSD, and 2 patients not receiving PSD because of renal impairment, study was discontinued because of hyperpotassemia. No significant differences were noted in long and short action or different dosages of ACE inhibitors. PSD may be administered concomitantly with ACE inhibitors, but serum K+ should be monitored as with other diuretics.

Adult

Doppler sonographic evaluation of the Duromedics-Edwards bileaflet valve at five-year follow up.

In order to define normal flow characteristics at mid-term follow up, prospective Doppler echocardiographic studies were performed in 145 patients (mean age 49.3 years) with Duromedics-Edwards bileaflet valve prostheses (76 aortic, 55 mitral and 14 double aortic and mitral) at a mean interval of 5.2 years following operation. All patients had clinically normal prosthetic valve function and no clinical or radiographic signs of heart failure. None of the patients had severely impaired left ventricular function as assessed by cross sectional 2D echocardiography. Mean peak velocity across prostheses in the aortic position was 2.8 +/- 0.5 m/sec, corresponding to a calculated instantaneous peak pressure gradient of 31.4 +/- 10.2 mmHg. Gradients varied inversely to valve size, although differences were significant only when comparing the 19mm and 21mm versus the 27mm valve (p < 0.05). In the mitral position the mean of peak velocity was 1.8 +/- 0.3 m/sec and pressure half time was 102 +/- 14 msec, representing a calculated mean orifice size of 2.2 +/- 0.5 cm2, with no significant difference between valves of different sizes. Paravalvular regurgitation was more common in the aortic than in mitral position (39% vs. 4%, p < 0.05), although in all cases it was mild (range less than one centimeter from prosthesis ring) and clinically insignificant. We conclude that normally functioning DE valve prostheses have a predictable range of Doppler echocardiographic parameters, although the individual variability of pressure gradients and effective valve area (in mitral valves) has to be emphasized. Nevertheless, the Duromedics Edwards valve shows good hemodynamic properties at mid-term follow up.

Adolescent

[Magnetic resonance tomography in pulmonary hypertension].

We examined 23 patients with pulmonary hypertension of varying aetiology by MRI and compared the results with those of right heart catheterisation. The best correlation was obtained between right ventricular mural thickness and mean pulmonary pressure (R = 0.91, p = 0.001). There was significant correlation (R = 0.85, p = 0.001) for the diameter of the inferior vena cava, which was dilated in all patients with pulmonary hypertension. There was no significant correlation between mean pulmonary pressure and the diameters of the superior vena cava or the main pulmonary artery branches (R = 0.55 and 0.75 respectively, p less than 0.05). Amongst functional measurements there was a correlation between right ventricular ejection fraction and mean pulmonary artery pressure (R = 0.71, p = 0.001). There was no correlation between right ventricular end-systolic and end-diastolic volume. In all patients with pulmonary hypertension, dynamic flow sensitive gradient echo sequences showed the presence of tricuspid insufficiency. A further semiquantitative criterion for the presence of pulmonary hypertension in 4 patients (17%) was an abnormal signal from the main pulmonary artery in early to mid-systole shown on T1-weighted transverse sections.

Adult

Quantitative assessment of aortic regurgitation by magnetic resonance imaging.

Thirty patients with aortic regurgitation and 10 controls were examined using an 0.5 T superconducting magnet with ECG gating. In each case a multislice-multiphase spinecho study in sagittal-coronal double angulated projection (four-chamber equivalent) was performed to assess left and right ventricular volumes, ejection fraction and regurgitation fraction. Additionally, a blood-flow sensitive cine-study (gradient echo, FAME) was performed to visualize direction and area of regurgitant jet. Magnetic resonance imaging (MRI) data were compared with quantitative and qualitative assessment of aortic regurgitation by angiography, Doppler and colour flow mapping. Using the FAME mode MRI, we were able to detect the regurgitant jet as an area of signal loss within the left ventricle in all patients; moderate correlation to jet area was determined by colour flow mapping (R = 0.60, P less than 0.001). Determination of left and right ventricular end-diastolic, end-systolic and stroke volumes by MRI revealed excellent correlation with invasive data (R = 0.94, P = 0.0001). With MRI regurgitant fraction (RF) could be calculated from the difference between right and left ventricular stroke volumes, which showed good correlation with invasively determined RF (R = 0.91, P = 0.001) and with qualitative Sellers' scoring (R = 0.70, P less than 0.001), respectively. Thus MRI provides the basis for noninvasive detection and quantification of aortic regurgitation.

Adolescent

Heart rate behaviour at different stages of congestive heart failure.

Depressed heart rate variation has been shown to predict a high mortality rate in patients with severe congestive heart failure. To determine whether the degree of altered heart rate correlates with the clinical state, 24-h Holter monitoring was performed in 21 patients (mean ejection fraction: 18 +/- 11%) at baseline and after 6 months of oral therapy. At baseline, the overall 24-h heart rate variation and night/day heart rate ratio was reduced, depending on the NYHA functional class. The typical morphology of R-R interval histograms was a sensitive marker of the clinical state at baseline: the higher the NYHA class, the smaller the R-R interval variability and standard deviation of R-R intervals (total variability NYHA III versus II: P less than 0.05). Clinical deterioration after 6 months (n = 8) was accompanied by a tendency to further shortening of the mean total R-R interval variability (676 +/- 34 to 586 +/- 25 ms). This was shown in three patients, who were reclassified to NYHA class IV. In stable patients (n = 5) and those with clinical improvement (n = 8) no significant change in R-R variability was observed. It is concluded that variations in R-R interval histogram shapes correspond to different NYHA functional classes. While severe clinical disease progression may be associated with further reductions in the heart rate variability, improvement in the clinical state of congestive heart failure is not necessarily associated with changes in heart rate behaviour.

Adult

Doppler sonographic evaluation of the CarboMedics bileaflet valve prosthesis: one-year experience.

Between April 1989 and March 1991, 237 CarboMedics bileaflet valve prosthesis carriers (165 aortic and 72 mitral valves, mean age 54.4 years) were studied prospectively with pulsed- and continuous-wave Doppler at a mean interval of 11.4 months following surgery in order to establish ranges of normal flow velocities and pressure gradients. Physical examination revealed no signs of prosthetic dysfunction or heart failure. Postoperative left ventricular function as measured by fractional shortening was 37% for aortic valve carriers and 30% for mitral valve carriers (p = NS). Mean peak velocity (+/- SD) across the aortic valve was 2.6 m/sec (+/- 0.4) and calculated instantaneous peak pressure gradient ranged from 11 to 58 mmHg (mean 28.1 +/- 10.3). It has to be emphasized that occasional patients with normally functioning valve prostheses can show unusual high gradients. Ring diameters between 21 and 27 mm showed no significant difference with regard to flow velocities and pressure gradients, whereas in 19-mm valves, significantly higher values could be demonstrated. The 123 aortic valve carriers with normal left ventricular function (fractional shortening greater than 25%) showed significantly higher pressure gradients than the 19 patients with reduced left ventricular function (28.6 +/- 11.6 mmHg vs 16.2 +/- 5.1 mmHg, p less than 0.05). In the mitral position, the mean of peak velocity (+/- SD) was 1.7 +/- 0.4 m/sec and pressure half-time was 108 +/- 26 msec, representing a calculated valve area between 1.4 to 3.1 cm2 (mean orifice size 2.1 +/- 0.5 cm2). No significant difference between valves of different sizes was found.(ABSTRACT TRUNCATED AT 250 WORDS)

Aortic Valve

Ibopamine as a valuable adjunct and substitute for dopamine in bridging therapy before heart transplantation.

Ibopamine is an active dopamine analogue leading to improved renal perfusion and afterload reduction in heart failure. This report describes casuistic experiences in patients with severe heart failure awaiting heart transplantation. All patients could be stabilized, intravenous catecholamines be discontinued, and diuretics be reduced. Six of seven patients could be successfully transplanted. No major side effects were noted. Thus ibopamine can be a suitable adjunct for patients with endstage heart failure.

Adult

[Pimobendan (UDCG 115 BS) in long-term therapy of chronic heart failure].

Pimobendan is a positive inotropic agent with additional calcium-sensitizing effects of the phosphodiesterase III-inhibitor group. In short-term studies, beneficial hemodynamic effects have been demonstrated in patients with congestive heart failure. The aim of this prospective study was to examine the long-term effect of pimobendan (during at least 6 months) on subjective state, hemodynamic parameters, and arrhythmias in patients with congestive heart failure NYHA classes II and III. After double-blind randomization, 24 patients received pimobendan 5 mg bid or placebo orally in addition to a basic therapy (diuretics, digitalis). After 3 months, pimobendan-treated patients showed a significant clinical improvement (p < 0.03). In the placebo group, one patient underwent acute cardiac transplantation due to rapid clinical deterioration; another patient died suddenly after 5 months. No cardiac events occurred in the pimobendan group. In comparison to placebo, no proarrhythmogenic effect of pimobendan was detected. Clinical stabilization of patients in the pimobendan group was not paralleled by improvement of the hemodynamic parameters of left-ventricular performance.

Cardiac Volume

Parathyroid hormone and calcium behavior in advanced congestive heart failure.

Parathyroid hormone (PTH) regulates the content of calcium and thus exerts an effect on myocardial function. Abnormal secretion of PTH has been sporadically reported to be associated with depressed mechanical performance of the heart muscle. In the present study, we first measured PTH levels at baseline in 27 consecutive patients with advanced congestive heart failure (LVEF: 17 +/- 9%): five patients (18.5%) revealed elevated PTH levels, one case of hypoparathyroidism was discovered. Furthermore, nine unselected patients underwent symptom-limited exercise stress test leading to an increase in mean pulmonary artery pressure from 25.6 +/- 15 at baseline to 41.2 +/- 18 mm Hg at peak exercise. In contrast to observations in healthy subjects, in heart failure patients both mean PTH and blood calcium concentrations did not change significantly during peak exercise or recovery. Moreover, patients with the lowest left-ventricular ejection fraction showed a decrease in PTH during maximal stress. We conclude that abnormal baseline PTH secretion is common in patients with advanced congestive heart failure. More importantly, these studies show that PTH release is depressed under stress conditions, possibly indicating a dysfunction of the parathyroid gland in severe heart failure.

Adult

[Direct diagnosis of the atherosclerotic vascular wall: possibilities and limits of intravascular ultrasound].

The clinical application of intravascular ultrasound still awaits established criteria for the interpretation of normal and diseased arterial wall structures. The aim of this preclinical study was to evaluate sonographic features of normal and atherosclerotic human arteries in vitro and to correlate these findings with histological cross-sections. Seventy-four segments from 33 human postmortem arteries of various anatomic locations were studied in saline solution using a mechanical 20-MHz transducer in a 6F catheter. In normal arteries, close correlations were found between sonographic and morphometric measurements of total wall thickness (r = 0.89), lumen circumference (r = 0.99), and of lumen area (r = 0.89, all p less than 0.001). Of 29 histologically verified atherosclerotic lesions, 19 were calcified, and all of them were correctly diagnosed with IVUS; however, acoustic shadowing prevented quantitative plaque evaluation. Of 10 fibromuscular lesions, six (60%) were correctly diagnosed with IVUS, using either direct morphologic criteria (n = 4) or indirect signs of vessel wall irregularity (n = 2), while the remainder (n = 4) were missed by IVUS due to a similar echodensity compared with the surrounding tissue. Thus, there was an overall sensitivity of 86% for the detection of atherosclerotic lesions by IVUS. In animal experiments in vivo, the feasibility of high-quality-imaging in pulsatile arteries was confirmed and pathologic changes in vein grafts were visualized. We conclude that IVUS carries the potential to directly assess arterial wall changes in vivo. The method appears very sensitive in the detection of calcified plaque, whereas fibromuscular lesions may often not be readily distinguished from normal surrounding tissue. This may limit the clinical usefulness of IVUS at the present time.

Adult

Platelet survival in patients with dilated cardiomyopathy.

Dilated cardiomyopathy is associated with thromboembolic complications, which correlate poorly, however, with a visible left ventricular thrombus. Therefore, this study was performed to assess whether an abnormality of platelet function in vivo can be detected in patients with dilated cardiomyopathy. Platelet survival was measured after autologous labeling with indium-111 oxine in 28 patients with dilated cardiomyopathy and angiographically normal coronary arteries (mean ejection fraction 21 +/- 9% [standard deviation], range 4 to 39%) and in nine patients with coronary artery disease and similar left ventricular dysfunction (mean ejection fraction 21 +/- 10%). Plasma levels of beta-thromboglobulin and platelet factor 4 were measured in patients with idiopathic cardiomyopathy (n = 15) and platelet scintigraphic images of the heart (n = 24) were obtained in subsets of both patient groups. Platelet survival was significantly and similarly shortened in patients with idiopathic and ischemic cardiomyopathy (67 +/- 34 and 55 +/- 24 h, respectively) compared to controls (209 +/- 9 h, n = 12; p less than 0.001). Of the two platelet-specific proteins, beta-thromboglobulin was increased in the patients compared with controls (42 +/- 17 versus 22 +/- 6 ng/ml, p less than 0.001). Platelet scintigraphy 24 h (n = 24) and/or 48 h (n = 9) after labeling showed a diffuse pattern of enhanced platelet uptake over the heart which varied in intensity among patients, but which was never seen in controls (n = 6). This increased platelet uptake was similar in patients with idiopathic and ischemic cardiomyopathy but did not correlate with either ejection fraction or cardiothoracic ratio.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult