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Biomedical subjects

M Havel

Publications and source records attributed to M Havel.

At least 37 records · Page 2Linked to original sources

Thoracoabdominal aneurysm repair: spinal cord protection using profound hypothermia and circulatory arrest.

Between January 1991 and February 1993, 14 patients (11 male, 3 female) between 21 and 79 years of age (median 50 years) underwent reconstruction of the thoracic (n = 7) and thoracoabdominal aorta (n = 7). Four patients had previously undergone operation of the ascending aorta, and in three patients coronary artery bypass grafting had previously been performed. All patients were operated on a via a posterolateral thoracotomy using cardiopulmonary bypass with continuous blood cardioplegia and hypothermic circulatory arrest (11 degrees C nasopharyngeal temperature, flat-EEG). All patent lower intercostal and lumbar arteries (T3 to L5) were reimplanted. The 30-day mortality after repair of the thoracic aorta was 0%; after replacement of the thoracoabdominal aorta, mortality was 28.5% (n = 2). One patient died 70 days after replacement of the thoracic aorta as a consequence of a perioperative stroke. None of the surviving 11 patients developed a permanent neurological deficit or renal or cardiac dysfunction. The average intensive care stay was 6 days for patients after replacement of the thoracic aorta and 18 days for patients after replacement of the thoracoabdominal aorta. Our results suggest that use of elective hypothermia and circulatory arrest for spinal cord protection is highly effective. We, therefore, recommend this method for complex reconstructions of the thoracoabdominal aorta.

Adult↗

Aprotinin does not decrease early graft patency after coronary artery bypass grafting despite reducing postoperative bleeding and use of donated blood.

Forty-five male patients with planned coronary artery bypass operation were randomized in a double blind fashion to receive either 6 million kallikrein inactivator units of aprotinin (high-dose group), 2 million kallikrein inactivator units of aprotinin (low-dose group), or placebo (control group). Postoperative bleeding was significantly decreased in both aprotinin groups in comparison to that in the control group (590 ml [290 to 1800 ml] high-dose group and 650 ml [280 to 1900 ml] low-dose group versus 920 ml (350 to 2700 ml) control group, p < 0.001). There was no difference between the two aprotinin groups. The need for postoperative blood transfusion was significantly lower in the aprotinin groups (1.46 [0 to 4] blood units high-dose group and 1.65 [0 to 5] blood units low-dose group versus 2.43 [0 to 7] blood units control group, p < 0.05). All patients underwent coronary angiography between the seventh and twelfth postoperative day. No difference was found among the three groups in patency of vein grafts-93.8% in the high-dose group, 94.5% in the low-dose groups, and 93.3% in the control group. Therefore, aprotinin significantly reduced postoperative bleeding and transfusion requirement after coronary artery bypass grafting without influencing early graft patency.

Aprotinin↗

[Emergency management of ruptured/dissecting aortic aneurysm--diagnosis and therapeutic strategies].

Between December 1991 and January 1994 fifteen patients with a ruptured abdominal aortic aneurysm and seven patients with a dissecting aortic aneurysm were treated in our emergency department. Dissection/rupture of an aortic aneurysm is still a dramatic event with poor outcome, whereby survival depends largely on early diagnosis. In most cases the diagnosis can be made with reasonable assurance by history taking and physical examination. The most frequent differential diagnoses are pulmonary embolism and myocardial infarction (thoracic aneurysms) and renal or biliary colic and lumbago (abdominal aneurysms). The largest delay in commencing therapy is caused by patients' hesitation to call the Emergency Medical Service. Chest X-ray, echocardiography and abdominal sonography are of high diagnostic value, computed tomography confirms the diagnosis in most cases. Our Emergency Department provides the facilities for rapid diagnosis and interdisciplinary preoperative management of dissecting/ruptured aortic aneurysms.

Adult↗

Correlation of atrial natriuretic peptide and cyclic guanosine monophosphate plasma concentrations in patients with heart disorders during rest and exercise.

The concentration of atrial natriuretic peptide was measured in order to evaluate its importance in patients suffering from a variety of cardiac diseases. There was a correlation between plasma concentrations of atrial natriuretic peptide and its "second messenger" cyclic guanosine monophosphate (cGMP) in all of the cases examined. We investigated the relationship between atrial natriuretic peptide and cGMP plasma concentrations during rest and exercise in comparison with the scintigraphically assessed left- and right-ventricular ejection fraction in patients with chronic heart disease (n = 20), and after orthotopic heart transplantation (n = 16); plasma concentrations were also measured in healthy controls (n = 14). Atrial natriuretic peptide and cGMP concentrations showed a similar correlation during rest and exercise with r = 0.74 and r = 0.81, respectively. With the exception of patients after heart transplantation, a significant negative correlation was seen between the left ventricular ejection fraction and atrial natriuretic peptide or cGMP plasma concentrations during rest conditions (r = 0.76 or 0.58, respectively). No correlation was apparent between plasma concentrations of atrial natriuretic peptide or cGMP and the left- or right ventricular ejection fraction during exercise. The concentrations of atrial natriuretic peptide and cGMP in plasma differed significantly between healthy controls and patients during rest and exercise. It is noteworthy that atrial natriuretic peptide and cGMP concentrations were markedly higher in patients after heart transplantation than in patients suffering from chronic heart disease. Our results indicate that plasma atrial natriuretic peptide and cGMP concentrations are sensitive markers of cardiac impairment.

Atrial Natriuretic Factor↗

[Valve saving correction of aneurysms of the ascending aorta with aortic insufficiency or annular dilatation].

The current technique to correct aneurysms of the ascending aorta with incompetence of the aortic valve or dilatation of the aortic root is the implantation of a valved conduit. In many cases however structurally normal aortic leaflets are resected by this technique and patients are at the risk of complications due to mechanical heart valve prostheses and the necessary anticoagulation respectively. By resuspension of the aortic valve into the aortic prostheses similar to the technique used at implantation of homograft valves, competence of the valve can be restored and the dilatation of the aortic annulus can be prevented or even reduced. Our article describes the successful, valve sparing correction of an acute aortic dissection type A with dilatation of the aortic annulus in a 43 year old patient and in another patient with ascending aortic aneurysm with aortic insufficiency.

Adult↗

Anomalous origin of the left coronary artery: a review of surgical management in 13 patients.

Over the last decades, surgical management of anomalous left coronary artery originating from the pulmonary artery (ALCAPA) has seen a considerable evolution. Between 1965 and 1992, 13 children with age at operation ranging between 2 months and 11 years (mean 23 months) underwent one of 5 different surgical procedures: ligation (n = 3), direct aortic reimplantation (n = 7), subclavian (n = 1) or internal mammary (n = 1) artery anastomosis, or modified aortic implantation (Vigneswaran-procedure, n = 1). There were 3 early and one late deaths resulting in an overall mortality of 30.7%. Mortality was 66.7% in the ligation group, and 20% in the revascularization group (28.6% in the subgroup with direct aortic implantation). The one late death occurred 6 months after ligation. Follow-up ranges between 3 months and 21 years, mean 7.3 years. All but one survivors are in NYHA functional class I. Following operative correction, there was clear improvement in left ventricular performance. Our data give reason to suggest ALCAPA to be more frequent than considered so far. Early surgery is recommended in all patients with ALCAPA, regardless of age or symptomatic status. Reestablishment of a two-coronary system is considered the procedure of choice. All survivors require long-term follow-up controls of early recognition of residual or progressive cardiac problems.

Austria↗

[Surgical treatment of Bland-White-Garland syndrome in infants and children: experiences with revascularization techniques].

In comparison with the older technique of ligation of the anomalous coronary artery in Bland-White-Garland syndrome, the various methods of revascularisation have in common the concept of a two coronary artery system. Between 1980 and 1992, 10 children from 6 weeks to 11 years of age (mean 2 years) underwent revascularisation: direct reimplantation of the coronary ostium from the pulmonary artery to the aorta (n = 7), modified implantation with coronary artery elongation (n = 1), bypasses using subclavian artery (n = 1) or the mammary artery (n = 1). Postoperatively, 2 infants died, both following direct reimplantation, resulting in an overall mortality of 20%. There was no late death. All children but one are asymptomatic and do not require medication on follow up for between 3 months and 12 years (mean 5 years) after the procedure. Echocardiography, cardiac catheterisation, and scintigraphy show a significant improvement of left ventricular function and, as a direct consequence, a decrease in preexisting mitral insufficiency. Hence any surgical manipulation at the mitral valve should be avoided at the initial operation. As a principle, the revascularisation procedure should be performed at the earliest possible time to avoid further ischemic myocardial damage. On long-term follow-up, ventricular function and prognosis of the residual low-degree mitral insufficiency remain unclear and require regular control examinations.

Anastomosis, Surgical↗

Early activation of hemostasis during cardiopulmonary bypass: evidence for thrombin mediated hyperfibrinolysis.

In 14 consecutive patients undergoing cardiopulmonary bypass for coronary bypass surgery the time course of coagulation and fibrinolysis markers were measured, e. g. plasma levels of thrombin-antithrombin III (TAT) complexes, cross-linked fibrin degradation products (XIFDP) and plasmin-alpha 2-antiplasmin complexes (PAP). TAT levels exceeded the 90% baseline percentile already during CPB (after opening of aortic clamp) in 10 patients, whereas PAP and XIFDP exceeded their 90% percentile in only one patient at this time. Concerning fibrinolysis markers PAP and XIFDP the majority of patients showed elevations higher than their 90% baseline percentile only 1 h postoperation. Correlation analysis revealed significant dependencies between TAT levels during and at the end of CPB and PAP levels 1 h postoperation (R = 0.55 and R = 0.56 respectively). Furthermore, 1 h postoperation XIFDP levels were significantly correlated with both TAT and PAP. Peak XIFDP levels at the same time correlated with blood loss via thoracic drains (R = 0.56). Thus, we suggest that hyperfibrinolysis in patients undergoing CPB is at least partly due to hypercoagulation. Clinically, this may implicate that intensified anticoagulation could prevent hyperfibrinolysis and reduce postoperative blood loss.

Adult↗

Transesophageal echocardiography in the emergency surgical management of patients with aortic dissection.

The diagnostic accuracy and benefit of transesophageal echocardiography were investigated in 32 patients with suspected aortic dissection. Results of transesophageal echocardiography were compared with surgical assessment. The Stanford classification was used for differentiation of dissection type. Examination time was 5 to 15 minutes. Twenty-eight patients were correctly identified to have aortic dissection; four patients had nondissecting aneurysms of the ascending aorta. Both sensitivity and specificity for detection of aortic dissection were 100%. Type of dissection was misdiagnosed in one patient. Classification of dissection type was correct in 96%. The primary entry site was correctly identified in 25 patients (89%). Aortic regurgitation was found in 57% of patients. Pericardial effusion was detected in 21%, with tamponade in one patient. Myocardial infarction was suggested by transesophageal echocardiography in 7%, and 14% had significantly reduced left ventricular function. Eight patients underwent operation based on transesophageal echocardiography alone. Intraoperative transesophageal echocardiography, performed in 20 patients, verified retrograde flow in the true lumen after femoral cannulation. Transesophageal echocardiography documented postrepair persistence of the intimal flap in aortic segments that were not operated on in all patients. Secondary tears and flow in the false lumen were detected in 35% of patients. We conclude that transesophageal echocardiography allows expedient and accurate diagnosis and classification of aortic dissection, and we recommend it as the primary bedside diagnostic modality. It can especially identify patients requiring surgical intervention without further delay caused by other diagnostic procedures.

Adult↗

New aspects of the degeneration of bioprosthetic heart valves after long-term implantation.

Bioprosthetic heart valves removed 76 to 150 months after implantation were morphologically investigated to correlate structural alterations with clinical failure modes. Traditional morphologic methods of evaluating valvular heterografts, such as microradiography and electron microscopy, were complemented by undecalcified ground sections, a new technique for analyzing the distribution of mineral deposits. Apart from well-investigated mechanisms that accelerate tissue degeneration, our observations point to additional facts: (1) phagocytosis of collagen fibrils and elastic material by macrophages and foreign body giant cells in areas near tears and perforations and (2) initial calcification indicated by delicate crystals in the intercellular space arranged in close relation to the periodicity of the cross-striation pattern of collagen fibrils. The present report not only calls attention to degenerative changes that are enhanced by mechanical stress but also underlines phagocytosis as an important mechanism in the destruction of bioprosthetic heart valves.

Bioprosthesis↗

The progression of mild acute cardiac rejection evaluated by risk factor analysis. The impact of maintenance steroids and serum creatinine.

The natural course of mild acute cardiac allograft rejection (MAR) under cyclosporine-based therapy is generally considered benign, and usually antirejection therapy is not instituted. The present study was undertaken to determine the frequency of and the risk factors for progression of MAR into a clinically significant (moderate or severe) rejection on subsequent endomyocardial biopsy (EMB). Among 167 cardiac recipients, transplanted from 3/1984 to 4/1990, MAR under cyclosporine-based therapy was diagnosed on 220 EMBs. Depending upon the outcome on the subsequent EMB, MAR was categorized as progressive or nonprogressive. This served as the dependent variable for a stepwise logistic regression analysis evaluating 11 covariates as potential risk factors: perioperative antibody prophylaxis (ATG vs. OKT3), maintenance therapy, underlying disease, HLA-mismatches for A- and B + DR-loci, serum creatinine (mg/dl) and cyclosporine HPLC blood level (ng/ml) at diagnosis of MAR and at subsequent biopsy, recipient age, donor age. 40 (18.2%) of 220 MARs became progressive as opposed to 37 (7.3%) of a control cohort of 507 negative EMBs (P less than 0.0001). Stepwise logistic regression yielded the type of maintenance therapy (P = 0.0019) and serum creatinine level at diagnosis of MAR (P = 0.0615) as independent predictors of progression of MAR. After adjustment for influence of maintenance therapy and serum creatinine none of the cyclosporine variables provided any additional information. MARs without maintenance steroids and low serum creatinine levels had the highest risk (37.2% observed incidence) to develop moderate or severe rejection on subsequent EMB. This analysis supports evidence that diagnosis of MAR on EMB is associated with a considerable high progression rate into clinically significant rejection when compared to negative EMBs. Progression particularly occurs in MAR under steroid-free maintenance therapy and suggests early augmentation of immunosuppression. In terms of progression of MAR serum creatinine values, obviously indicating cyclosporine nephrotoxicity, appear to reflect the extent of cyclosporine-mediated immunosuppressive activity more properly than parameters of its bioavailability by measuring cyclosporine HPLC blood levels.

Adrenal Cortex Hormones↗

The monoclonal HBA-71 antibody modulates proliferation of thymocytes and Ewing's sarcoma cells by interfering with the action of insulin-like growth factor I.

The monoclonal HBA-71 antibody recognizes a Ewing's sarcoma associated antigen, which is also highly expressed on the cell surface of human cortical thymocytes and islets of Langerhans among normal tissues. The antibody was found to inhibit partially the growth of ES tumor cell lines and to trigger proliferation in thymocyte cultures. The influence of growth factors and the effect of the HBA-71 antibody was further investigated in the present study. The growth of ES tumor cells was demonstrated to be dependent on the presence of insulin-like growth factor I or insulin. The HBA-71 antibody (25 micrograms/ml) enhanced the growth stimulatory effect of IGF-I under serum-free conditions. The expression of the HBA-71 epitope is modulated positively by IGF-I and insulin and negatively by dexamethasone and human growth hormone in ES/PNET tumor cells and thymocytes. IGF-I either alone or in combination with HBA-71 stimulated the proliferation of thymocytes under serum-free conditions whereas in complete medium, IGF-I stimulated thymidine incorporation and the HBA-71 antibody either alone or in the presence of IGF-I showed inhibitory activity most likely due to down-regulation of the receptor. These data demonstrate the important role of IGF-I in the growth of ES/PNET tumor cells as well in the proliferative activity of HBA-71 positive normal thymocytes. The biological activity of IGF-I in malignant thymocytes, pancreas tumors, fetal muscle, brain, granulosa and Sertoli cells has been documented in the literature.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Effect of intraoperative aprotinin administration on postoperative bleeding in patients undergoing cardiopulmonary bypass operation.

To study the hemostyptic effect of aprotinin (Trasylol) in patients undergoing extracorporeal circulation for coronary artery bypass operations, we randomized 12 of 24 patients to receive aprotinin in high dosage (about 800 mg) during extracorporeal circulation. From the resulting two groups each, one patient was excluded from the study because of postoperative myocardial infarction (control group) and surgical hemorrhage (aprotinin group) leading to a second operation. Although heparin was used for anticoagulation in all 22 patients, all had a marked increase in plasma levels of thrombin-antithrombin III complexes during extracorporeal circulation, indicating an intravasal activation of coagulation. By monitoring the plasma levels of fibrin degradation products in patients without aprotinin therapy, we recorded a concomitant hyperfibrinolysis significantly less pronounced in patients receiving aprotinin (p less than 0.005). The mean total postoperative blood loss was lower in patients receiving aprotinin (620 ml) than in control patients (1000 ml; p less than 0.03). The results confirm previous reports of a hemostyptic effect of aprotinin in cardiac operations. This effect is probably due to a prevention of hyperfibrinolysis.

Antithrombin III↗

[Orthotopic heart transplantation at the 2d Surgical Department of the University of Vienna: 4-year experience].

Between March 1984 and August 1988, 89 orthotopic cardiac transplants were performed in 87 patients at the Second Department of Surgery, University of Vienna. 2 patients underwent retransplantation and 3 patients received previously a total artificial heart bridge. Recipients were immunosuppressed with low dose cyclosporine, azathioprine and since May 1986 with additional low dose prednisolone; all patients were supplemented perioperatively with either ATG or OKT3. 1-year survival rates continuously increased from 33% in 1984 to 88% in 1987 (p = 0.07). The one-year survival rate in recipients given double drug therapy (cyclosporine and azathioprine) was 43% as compared with 77% on triple therapy (cyclosporine, azathioprine and prednisolone, p = 0.003). Acute rejection was the leading cause of death. These data indicate that the substantial improvement in survival rates is attributable to augmented immunosuppression and to improved patient management and recipient selection.

Adolescent↗

Ewing's-sarcoma-associated HBA-71 tumor antigen represents a new differentiation marker of human thymocytes.

The monoclonal HBA-71 antibody recognizes a new human tumor-associated antigen of Ewing's sarcoma and peripheral neuroectodermal tumors, which is also expressed in some normal tissues, including thymus, islets of Langerhans, ependyme, adenohypophysis, Sertoli/Leydig and granulosa cells. Besides a tumor-specific reciprocal chromosomal translocation t (11:22), the expression of the HBA-71 antigen is the only marker which can be used for reliable differential diagnosis of these rare malignancies of childhood and adolescence among other small round cell tumors. The HBA-71 antigen is further characterized here by ultrastructural, functional and cell-matrix interaction studies. In immunohistochemical staining the HBA-71 reacted with the cell surface of human cortical thymocytes. The HBA-71 antigen was also found to be localized at the cell-surface glycocalyx of tumor cells using immunogold staining and electron microscopy. A panel of additional monoclonal antibodies with reactivity patterns similar to those of the HBA-71 antibody was obtained by immunization of mice with ES cell lines and boostering with thymocytes. The HBA-71 antibody triggers proliferation of thymocytes and to a lesser extent also stimulates peripheral mononuclear blood cells. Antibody-induced thymocyte cultures exhibit the phenotype of immature, CD3low thymocytes with uniform and stable expression of the HBA-71 antigen. In contrast to the thymocytes the HBA-71 antibody has an inhibitory effect on the continuous growth of the HBA-71+ tumor cell lines. The HBA-71 antigen may be involved in the regulation of growth of the positive normal and malignant tissues. Positive modulation of the antigen expression was induced in Ewing's sarcoma cell lines in response to insulin, insulin-like growth factor I (IGF-I) and by interaction of the cells with the extracellular matrix.

Animals↗

Expression of a new human THY-1 related antigen in Ewing's sarcoma and peripheral neuroectodermal tumors.

Ewing's sarcoma (ES), peripheral neuroectodermal tumor (PNET) and Askin's tumor of the chest wall share a reciprocal chromosomal translocation between the long arms of chromosomes 11 and 22 (q23-24; q12). In the absence of other distinguishing features this specific translocation is regarded as marker of a common and neuroectodermal origin for these rare tumors. A monoclonal antibody (HBA-71) developed in our laboratory has been found to recognize an unique ES and PNET associated antigen, which is also expressed in some normal tissues, including thymus, bone marrow, islets of Langerhans, ependyma and adenohypophysis. It is shown in this study that this HBA-71 antigen is closely related to the murine THY-1 antigens, major cell surface glycoproteins of thymocytes and brain in mice and rat. Both antigens have similar molecular ratios (18,000), amino acid compositions and sensitivity to tryptic digestion, show high cell surface expression, and binding of the appropriate antibodies to HBA-71 antigen triggers proliferation in thymocytes. The HBA-71 epitope may represent a primitive neuroectodermal marker of ES/PNET, or its expression may be directly linked to the reciprocal translocation invariably associated with HBA-71-positive ES and PNET tumors, which maps to the same region of chromosome 11 (q23-24) as the human Thy-1 gene.

Amino Acids↗