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Biomedical subjects

H H Scheld

Publications and source records attributed to H H Scheld.

At least 19 recordsLinked to original sources
PubMed1999

Helical CT of pulmonary nodules in patients with extrathoracic malignancy: CT-surgical correlation.

OBJECTIVE: Our aim was to assess the sensitivity of helical CT for revealing pulmonary nodules. Thoracotomy with palpation of the deflated lung, resection, and histologic examination of palpable nodules was used as the gold standard. SUBJECTS AND METHODS: Thirteen patients underwent helical CT (slice thickness, 5 mm; reconstruction intervals, 3 mm and 5 mm; interpreted by two independent observers). Subsequently, patients underwent unilateral (n = 6) or bilateral (n = 7) surgical exploration, and CT-surgical correlation of 20 lungs was performed. RESULTS: Ninety nodules were resected (61 were smaller than 6 mm; 13 were 6-10 mm; 11 were larger than 10 mm; in five nodules, the size was not recorded at surgery). Sixty-nine nodules were located in the pulmonary parenchyma and 21 in the visceral pleura. Of the 90 lesions, 43 (48%) were found on histology to represent metastases. For lesions detected by at least one observer, the sensitivity of helical CT was 69% for intrapulmonary nodules smaller than 6 mm, 95% for intrapulmonary nodules larger than or equal to 6 mm, and 100% for histologically proven intrapulmonary metastases larger than or equal to 6 mm. For lesions smaller than or equal to 10 mm, sensitivity was better using a reconstruction interval of 3 mm rather than of 5 mm. CONCLUSION: In this study, the sensitivity of helical CT exceeded the sensitivity of conventional CT in previous reports. However, because of limitations in the detection of intrapulmonary nodules smaller than 6 mm and of pleural lesions, complete surgical exploration should remain the procedure of choice in patients undergoing pulmonary metastasectomy. Preoperative helical CT should be used to guide the surgeon to lesions that are difficult to palpate.

Adult↗
PubMed1999

Inotropic effects of diadenosine tetraphosphate (AP4A) in human and animal cardiac preparations.

Diadenosine tetraphosphate (AP4A) is an endogenous compound and exerts diverse physiological effects in animal systems. However, the effects of AP4A on inotropy in ventricular cardiac preparations have not yet been studied. The effects of AP4A on force of contraction (FOC) were studied in isolated electrically driven guinea pig and human cardiac preparations. Furthermore, the effects of AP4A on L-type calcium current and [Ca]i were studied in isolated guinea pig ventricular myocytes. In guinea pig left atria, AP4A (0.1-100 microM) reduced FOC maximally by 36.5 +/- 4.3%. In guinea pig papillary muscles, AP4A (100 microM) alone was ineffective, but reduced isoproterenol-stimulated FOC maximally by 29.3 +/- 3.4%. The negative inotropic effects of AP4A in atria and papillary muscles were abolished by the A1-adenosine receptor antagonist 1, 3-dipropyl-cyclopentylxanthine. In guinea pig ventricular myocytes, AP4A (100 microM) attenuated isoproterenol-stimulated L-type calcium current and [Ca]i. In human atrial and ventricular preparations, AP4A (100 microM) alone increased FOC to 158.3 +/- 12.4% and 167.5 +/- 25.1%, respectively. These positive inotropic effects were abolished by the P2-purinoceptor antagonist suramin. On the other hand, AP4A (100 microM) reduced FOC by 27.2 +/- 7.4% in isoproterenol-stimulated human ventricular trabeculae. The latter effect was abolished by 1,3-dipropyl-cyclopentylxanthine. In summary, after beta adrenergic stimulation AP4A exerts negative inotropic effects in animal and human ventricular preparations via stimulation of A1-adenosine receptors. In contrast, AP4A alone can exert positive inotropic effects via P2-purinoceptors in human ventricular myocardium. Thus, P2-purinoceptor stimulation might be a new positive inotropic principle in the human myocardium.

Animals↗
PubMed1998

T-cell and monocyte subsets, inflammatory molecules, rejection, and hemodynamics early after cardiac transplantation.

BACKGROUND: In the early period after cardiac transplantation, differential diagnosis of graft failure due to rejection, infection, and other causes is important but difficult. METHODS: In 22 consecutive patients undergoing heart transplantation, we prospectively determined levels of interleukin-6 as well as T-cell and monocyte subsets at eight points in time during biopsy and right heart catheterization and within 12 hr of echocardiography during the first 3 months after transplantation. RESULTS: Worse hemodynamic parameters, as characterized by dichotomization according to median values (pulmonary capillary wedge pressure >10 mmHg, mean pulmonary arterial pressure > 18 mmHg, pulmonary vascular resistance > 115 dyn x sec x cm(-5), right atrial pressure > 5 mmHg, cardiac index <3 L/min/m2, early mitral deceleration time < 135 msec, and isovolumic relaxation time <80 msec), were associated with higher levels of interleukin-6, C-reactive protein, polymorphonuclear cells, CD71+/CD14+ monocytes, and IgM levels and, in contrast, with lower levels of immunocompetence markers such as CD3+ T cells, CD4+ T cells, CD8+ T cells, CD3+/CD25+ T cells, CD4+/ CD45RO+ T cells, NK cells, and lower biopsy scores. CONCLUSION: Early after cardiac transplantation, elevated levels of inflammatory cells and soluble inflammatory molecules and lower levels of immunocompetence markers are associated with impaired allograft function in the absence of cellular rejection.

Adult↗
PubMed1998

Possible relationship between heat shock protein 70, cardiac hemodynamics, and survival in the early period after heart transplantation.

BACKGROUND: Heat shock proteins (HSPs) are produced by cells in response to a wide variety of stresses. To determine a possible relationship between hemodynamic parameters and HSP 70 in the early postoperative period after heart transplantation, we examined immunohistochemically the inducible HSP 70 (anti-HSP 72) response in human heart biopsies, as well as the effect of myocardial rejection on HSP. METHODS: A total of 105 routinely processed endomyocardial biopsies from 15 consecutive patients who underwent heart transplantation were examined. Analysis of hemodynamic and echocardiographic parameters were performed within 30 min and 12 hr after the biopsies. RESULTS: Immunohistochemically detected inducible HSP 70 was mainly located in the cytoplasm and nucleus/nucleolus of cardiomyocytes. Two specimens additionally showed HSP 70-positive interstitial cells and smooth muscle cells of arteries, whereas lymphocytes were consistently negative. There was a significant relation between the echocardiographically determined increased relaxation time and positive HSP 70 staining (P < 0.011). Patients with elevated right atrial pressure (P < 0.098), as well as those with increased left ventricular end systolic diameter (P < 0.06), showed a trend to higher HSP expression. Three patients who died of sepsis or multiorgan failure showed significantly higher cytoplasmic HSP 70 expression compared with 12 patients with stable clinical course. In case of rejection, significantly more patients showed no HSP expression. CONCLUSION: Although only five patients showed organ rejection, our results suggest an inverse relationship between HSP expression and rejection with the possibility of a role for HSP 70 as a graft marker to assess graft function.

Biopsy↗
PubMed1998

Transplant vasculopathy.

Transplant vasculopathy constitutes the major impediment to long-term survival in heart transplant recipients. Within the "response to immune injury" paradigm, it can best be understood as the resultant of an orchestrated recipient immune response to the initial allogenic stimulus by graft vascular endothelium. This response incorporates the elaboration of complex coordinated cytokine patterns and corresponding cell types including B-lymphocytes, T-helper1- and T-helper2-cells, cytotoxic T-cells, macrophages, and polymorphonuclear cells. These attack the alloantigenic vascular endothelium and lead, by complex cytokine signaling, to migration of donor smooth muscle cells from the media into the intima, associated with a switch from the contractile to a synthetic phenotype. In conjunction with recipient T-cells, macrophages, and lipids, the intimal fibroproliferative growth of the donor vessel is hereby initiated.

Animals↗
PubMed1998

[Effect of pre-existing lipids on calcinosis of swine heart valve bioprostheses. A study of a dynamic in vitro model].

Calcification is one of the main causes of failure of porcine bioprosthetic heart valves, a problem which has not been satisfactorily solved to date. Previous studies have shown that calcification is decreased in porcine heart valves that have undergone treatment for lipid extraction. The relation between lipid distribution and calcification of seven new commercially available porcine bioprosthetic heart valves (St. Jude Medical, Bioimplant) is assessed by Sudan red III staining to show preexisting lipids. All porcine bioprosthetic valves contained lipids to different degrees. Five valves were subjected to the pulsatile accelerated calcification process for 4 weeks. Distribution and level of calcification were evaluated by radiography and compared to the Sudan red-stained fatty areas. Comparison of the calcifications detected by radiography and the macroscopically detected lipids showed a coincidence of 57-66%. Two porcine bioprosthetic valves were histologically prepared and stained with Hematoxylin and von Kossa's stain, respectively. By light microscopy, the von Kossa staining revealed microcalcifications and polarizing microscopic investigation showed birefractive substances in areas with lipid deposits. These preexisting substances in porcine valve tissue may play a determinative role in the calcification of the tissue. Substantial studies are necessary to further determine the role of preexisting lipids in calcification.

Animals↗
PubMed1998

Cerebral and systemic embolization during left ventricular support with the Novacor N100 device.

BACKGROUND: Patients undergoing implantation of left ventricular assist systems (LVAS) are prone to thromboembolic complications. We analyzed the incidence, clinical findings, and outcome of neurologic and systemic thromboembolic events (TE) in patients with the Novacor N100 LVAS. In a subset of patients, transcranial Doppler sonography was used to detect microembolic signals. METHODS: Thirty-six patients underwent implantation of a Novacor N100 LVAS for various reasons. The surgical procedure was elective in 18 patients and scheduled on an urgent or emergency basis in another 18 patients. The assist period lasted from 17 to 336 days (109 +/- 88 days); 22 patients were forwarded to heart transplantation after being supported for 140 +/- 87 days. RESULTS: Clinical cerebral embolism was evident in 17 patients (47%). Thromboembolic events were singular in 8 and multiple in 9 patients; in the latter up to 10 TE occurred (mean +/- SD, 1.4 +/- 2 TE). Leading neurologic symptoms were unilateral hemiplegia in 11, as well as ocular symptoms and aphasia in 12 patients each. Noncerebral TE were detected in 4 patients, 2 of whom underwent an emergency operation for intestinal and iliac artery occlusion. The incidence of TE did not correlate strongly with the interval of LVAS support. Cerebral computed tomography confirmed lesions in 58% of patients. Transcranial Doppler sonography detected microembolic signals on 67% of all recordings, with the microembolic signals being more frequent on days with clinically manifest TE. The outcomes were good, as only 2 patients suffer from neurologic sequelae. CONCLUSIONS: Thromboembolism is still a major threat for patients with LVAS implantation. Neurologic sequelae are frequent but have a favorable prognosis, and systemic complications occur considerably less often. Patient selection, adequate anticoagulation, and transcranial Doppler sonography may help to reduce the incidence of TE.

Adult↗
PubMed1998

Neonatal mechanical bridging to total orthotopic heart transplantation.

BACKGROUND: Until recently, newborns with medically intractable cardiac failure caused by congenital malformations were mostly doomed to death because of the severity of the disease, which precludes a palliative operation, or because of fatal deterioration before availability of a suitable donor heart. METHODS: The recently developed paracorporeal pneumatically driven Medos HIA ventricular assist device offers a therapeutic option for these small infants because it is manufactured in various sizes and is even suitable for cardiac assistance in neonates with a body surface area less than 0.3 m2. RESULTS: We report our initial experience with this device, which we used for univentricular bridging to total orthotopic cardiac transplantation in 3 infants. The device was inserted to support the left ventricle in two instances and to support the right heart in one. Successful bridging to transplantation was achieved in 2 infants for periods of 2 and 7 weeks. CONCLUSIONS: Our experience demonstrates the feasibility of univentricular mechanical support followed by successful cardiac transplantation in infants and newborns.

Aortic Valve Stenosis↗
PubMed1998

In vitro testing of bioprostheses: influence of mechanical stresses and lipids on calcification.

BACKGROUND: Structural valve deterioration of bioprostheses is mainly caused by the progressive development of calcification. Mechanical stresses or lipid deposits in porcine aortic leaflets have been proposed as major factors contributing to the calcification process. METHODS: A new test protocol consisting of nondestructive holographic interferometry, which allows a quantitative deformation analysis of heart valves, and accelerated dynamic in vitro calcification was used. The rapid calcification fluid contained a final combined calcium and phosphorus concentration of 130 (mg/dL)2 in barbital buffer solution. The calcification of 32 bioprostheses donated by different manufacturers (SJM Bioimplant, Biocor standard, Biocor No-React, Carpentier-Edwards SAV, Bravo, pericardial prototype) was assessed after up to 25 x 10(6) cycles by microradiography and the areas of calcification were compared with the holographic interferograms. The distribution of lipid droplets of four porcine prostheses were visualized by Sudan III stain before the calcification process. RESULTS: Most of the tested bioprostheses had areas presenting with stress concentrations, and the dynamic in vitro testing resulted in leaflet calcification corresponding to the holographic irregularities. A strong correlation between calcification and stress distribution or lipid accumulation was found (r = 0.72; r = 0.81, respectively). After 19 x 10(6) cycles, the Carpentier-Edwards SAV and the pericardial valves had significantly less calcification than other prostheses tested (p = 0.003), but the variation among individual prostheses from the same manufacturer was even more pronounced. CONCLUSIONS: Mechanical stresses or lipid accumulation seems to play an important role in the calcification process of bioprostheses. Quality control of bioprosthetic valves using holographic interferometry has the potential to predict calcification before implantation.

Aortic Valve↗
PubMed1998

Successful treatment of a Novacor LVAD malfunction without repeat sternotomy.

Implantable left-ventricular assist devices have been remarkably free of mechanical failures. We describe an uncommon Novacor N100 PCq LVAS malfunction caused by an internal short circuit of the device due to urine aspiration via the vent line. Device replacement was managed via a subcostal approach without sternotomy. Patient recovery was uneventful and successful transplantation was performed one month after the device exchange.

Adult↗
PubMed1998

Suppression of panel-reactive antibodies by treatment with mycophenolate mofetil.

"Panel Reactive Antibody" (PRA) testing is commonly used to assess the pretransplant antibody status in order to estimate the risk of an adverse humoral response following transplantation. We report on a female patient with end-stage cardiac failure suffering from acute myocarditis who underwent implantation of a left-ventricular assist device (Novacor, Baxter Healthcare Corp. Oakland, CA). During evaluation for heart transplantation, a PRA level of 50-70% was detected. After treatment with mycophenolate mofetil at a dosage of 2 g daily, PRA levels declined within one week to 0-5%, and remained low after discontinuation of the immunosuppressive drug. We feel that pretreatment of patients with elevated PRA levels with mycophenolate mofetil is well justified.

Acute Disease↗
PubMed1998

Effect of platelet inhibitors on thromboembolism after implantation of a Novacor N100--preliminary results.

BACKGROUND: Left-ventricular assist device implantation (LVAD) is still associated with thromboembolism as the optimal anticoagulation is still unclear. We report on the effects of adding platelet inhibitors to our anticoagulation regimen in our Novacor LVAD program. METHODS: Oral platelet aggregation inhibitors (aspirin 330 mg + dipyridamole 75 mg, three times per day) were added to the heparin/phenprocoumon treatment in 9 patients starting on postoperative day 3 to 7 (group A). Of the previous 41 patients, the last 20 patients served as a control group (group B), to reduce any learning curve effect. RESULTS: The mean interval of mechanical support between the two groups was comparable (group A vs B: 148 +/- 127 vs 104 +/- 61 days, n.s.). Accordingly, the cumulative support was much lower in group A (1051 days) as compared to group B (2091 days). In group B, 10 patients (50%) developed clinically evident thromboembolism. The number of events ranged from 1 to 10 (mean 1.4 +/- 2.3), with a total of 32. With addition of platelet inhibitors, the incidence of cerebral embolism dramatically dropped, as only one patient presented with transient ischemic attacks in group A (p < 0.05). Thoracic bleeding as defined by excessive drainage losses requiring redo thoracotomy did not increase (group A vs B: 22% vs 20%, n.s.). CONCLUSION: Addition of platelet inhibitors to heparin/phenprocoumon effectively prevents thromboembolism. However, platelet inhibitors should be postponed until sufficient hemostasis is achieved, since too early administration is associated with an increased risk of bleeding.

Anticoagulants↗
PubMed1998

Identification and expression of a novel isoform of cAMP response element modulator in the human heart.

In end-stage human heart failure, excessive beta-adrenergic stimulation of the cAMP-dependent signaling pathway due to enhanced endogenous catecholamines is hypothesized to contribute to expressional alterations of myocardial regulatory proteins. The cAMP response element modulator (CREM) regulates the transcription of cAMP-responsive genes and might be involved in the regulation of cardiac gene expression. Using the reverse transcription polymerase chain reaction, we identified a novel CREM mRNA, CREM-Ib deltaC-X, in the human heart. Overexpression of CREM-Ib deltaC-X decreased cAMP response element (CRE) -mediated gene transcription in HIT-T15 cells, and this activity was assigned to the part of the sequence encoding putative internally translated proteins. Two of three possible internally translated proteins were immunologically identified in cells overexpressing CREM-Ib deltaC-X tagged with the hemagglutinin epitope of the influenza virus. Both proteins were expressed in bacteria and showed CRE-specific DNA binding, formation of heterodimers with the cAMP response element binding protein (CREB), and inhibition of CREB's binding to the CRE. CREM expression was detected on the mRNA and protein levels in the human heart. We conclude that CREM-Ib deltaC-X generates internally translated repressors of CRE-mediated gene transcription, suggesting the first example for the existence and function of human cardiac CREM.

Animals↗
PubMed1998

Relation of urokinase-type plasminogen activator expression to presence and severity of atherosclerotic lesions in human coronary arteries.

Urokinase-type plasminogen activator (UPA) has been implicated in a broad spectrum of pathological processes - e.g. cell adhesion, migration and proliferation and matrix remodeling - that are considered important features of atherogenesis and plaque disruption. In this study, we have analyzed the content and expression of UPA in human coronary arteries and its relation to the presence and severity of atherosclerotic lesions. Segments of coronary arteries obtained from human heart explants (n = 15) were classified by the presence and types of atherosclerotic lesions. UPA was quantitatively determined in protein extracts of the intimal and medial layers. In situ hybridization and immunohistochemical analyses were performed on serial sections of representative tissue specimens. UPA was detected in the extracts as pro-UPA, UPA complexed to plasminogen activator inhibitor-1, or as otherwise inactive UPA antigen, but not in the active two-chain form. Both functional and total UPA were increased several-fold in extracts of advanced lesions, while the ratios of functional over total UPA showed the opposite trend suggesting enhanced UPA inactivation and turnover. UPA expression in early atherosclerotic lesions was particularly prominent in areas of proliferating SMCs in the abluminal part of the neointima, whereas in advanced lesions UPA was widely expressed in macrophage-rich areas adjacent to the rims and shoulder regions of the necrotic cores. The results strongly suggest a causal involvement of UPA in coronary atherogenesis and its clinical outcome.

Coronary Artery Disease↗
PubMed1998

Holographic interferometry and in vitro calcification: comparing pericardial versus porcine bioprostheses.

BACKGROUND AND AIMS OF THE STUDY: Structural valve deterioration of bioprostheses is mainly caused by progressive calcification. It has not yet been convincingly demonstrated whether pericardial or porcine bioprostheses are more prone to calcification. METHODS: A previously described in vitro test protocol consisting of non-destructive holographic interferometry, which permits quantitative deformation analysis of heart valves and accelerated dynamic calcification in vitro was used to evaluate five stented pericardial bioprostheses of different sizes and design (three or two leaflets) from one manufacturer. The extent of calcification was assessed after up to 20 x 10(6) cycles in the valve tester by microradiography, and areas of calcification were compared by holographic interferometry using computerized image processing. Calcification was confirmed by EDX-analysis and Von Kossa staining. Results were compared with in vitro testing of 25 porcine bioprostheses from different manufacturers. RESULTS: The tested pericardial bioprostheses had an individual distribution of mechanical stresses detectable by holographic interferometry, which resulted in different calcification of valve leaflets. A strong correlation between calcification and stress distribution was found (correspondence of affected areas: 82.3 +/- 10.1%, r = 0.97). Variability in calcification and stress distribution, respectively, of pericardial valves compared well with our findings for porcine prostheses. Overall, the extent of leaflet calcification was not statistically different for pericardial and porcine bioprostheses (p = 0.21). CONCLUSIONS: The biological material of bioprostheses (pericardial versus porcine) does not seem to be the crucial factor in the calcification process. Mechanical stresses detectable by holographic interferometry have a more pronounced impact and predict calcification of individual prostheses, at least in the in vitro setting.

Animals↗