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Biomedical subjects

R Babic

Publications and source records attributed to R Babic.

At least 37 records · Page 2Linked to original sources

Dipyridamole-dobutamine echocardiography: a novel test for the detection of milder forms of coronary artery disease.

OBJECTIVES: This study was designed to assess the clinical, hemodynamic and diagnostic effects of the addition of dobutamine to dipyridamole echocardiography. BACKGROUND: Pharmacologic stress echocardiography with either dipyridamole or dobutamine has gained acceptance because of its safety, feasibility, diagnostic accuracy and prognostic power. The main limitation of the two tests is a less than ideal sensitivity in some patient subsets, such as those with limited coronary artery disease. We hypothesized that two pharmacologic stresses might act synergistically in the induction of ischemia by combining the mechanisms of inappropriate coronary vasodilation (with dipyridamole) and an increase in myocardial oxygen consumption (with dobutamine). METHODS: One hundred fifty patients (mean [+/- SD] age 51 +/- 11 years) referred for stress echocardiography were initially studied by dipyridamole-dobutamine echocardiography. The test was stopped during the dipyridamole step in 95 patients for achievement of a predetermined end point (obvious dyssynergy induced by lower or higher dipyridamole dose), and dipyridamole-dobutamine tests were performed in 55 patients (negative dipyridamole echocardiographic test). In the same 150 patients the dobutamine echocardiographic test (up to 40 micrograms/kg body weight per min) was performed on a separate day. RESULTS: Significant coronary artery disease (> 50% diameter stenosis of at least one major coronary vessel by quantitative coronary arteriography) was present in 131 patients (one vessel in 115; two vessels in 10, three vessels in 6), with normal coronary arteriography in 19. The feasibility of the dipyridamole-dobutamine test was 96%. Self-limiting side effects occurred in 5% of patients. The peak rate-pressure product was lowest during the dipyridamole test (132 +/- 30) and was comparable during the dobutamine (186 +/- 59) and dipyridamole-dobutamine tests (179 +/- 45, p = NS vs. dobutamine; p < 0.01 vs. dipyridamole). Sensitivity was 71% for dipyridamole, 75% for dobutamine and 92% for dipyridamole-dobutamine echocardiography (dipyridamole vs. dipyridamole-dobutamine, p < 0.01; dobutamine vs. dipyridamole-dobutamine, p < 0.01; dipyridamole vs. dobutamine, p = NS), whereas specificity was 89% for dipyridamole, 79% for dobutamine and 89% for dipyridamole-dobutamine echocardiography (p = NS for all). CONCLUSIONS: Routine dobutamine addition to dipyridamole stress testing is clinically useful and well tolerated. It expands the spectrum of the disease detectable by pharmacologic stress echocardiography and allows documentation of milder forms of coronary artery disease that can be missed by conventional dipyridamole or dobutamine stress echocardiography.

Adult↗

Integrity and viability of homograft valves.

Since it has been suggested that the leaflet tissue viability influences durability after homologous valve replacement, we compared different harvest and preservation techniques in order to examine the quality and smoothness of homograft conservation. We analyzed human aortic and pulmonary valve leaflets obtained from 'heart-beating donors' (HBD) during heart transplantation and from 'non-heart-beating donors' (NHBD) during coroner's autopsies. Valves were either cryopreserved in liquid nitrogen or stored at 4 degrees C in nutrient medium similar to the procedure reported in our protocols of the homograft bank system. All grafts from NHBD had been antibiotically sterilized for 3 days beforehand. Morphological observations were made using light and electron microscopy and, in order to characterize the endothelial cell viability, a non-radioactive cell proliferation assay was used. The PGI2 secretion of the remaining endothelium was defined as the 6-keto-prostaglandin F1 alpha metabolite by an enzyme immunoassay. Observations in the scanning electron microscope revealed that, after cryopreservation, homografts show an almost confluent endothelium when processed within 24 h after harvest from HBD, but lack endothelial cells when obtained from NHBD. Cryopreserved grafts from NHBD exhibited an altered tissue structure with edema and vacuolization within the spongiosa of the leaflets as well as irreversible cell damage when examined under the light and transmission electron microscope. That the metabolic activity of HBD homografts was maintained was confirmed by proven PGI2 secretion (6150 +/- 1200 pg/3 ml M199 after cryopreservation), whereas specimens from NHBD showed a reduced (1950 +/- 730 pg/3 ml M199) and, after cryopreservation, almost no release (P < 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

The contribution of endothelial cells to hyperacute rejection in xenogeneic perfused working hearts.

The mechanisms leading to the hyperacute rejection of a vascularized xenograft are still incompletely understood. The first stage of the rejection process is when blood of the recipient comes into contact with the endothelium of the xenograft. A working heart model was used to examine endothelium-related processes and their impact on organ function. Pig hearts were perfused with porcine (autologous) or human (xenogeneic) blood. Cardiac function was evaluated by calculating the stroke work index, arteriovenous oxygen, coronary flow, and resistance. PgF1a as a marker of endothelial activation, its antagonist TXB2, and myoglobin reflecting myocardial damage were measured in the hemoperfusate. H&E and PAS staining and immunohistological demonstration of factor VIII-related antigen was performed. Xenogeneic perfused porcine hearts showed significantly less stroke work, a higher arteriovenous oxygen difference, and an increased coronary resistance. Factor VIII-related antigen could not be demonstrated immunohistologically on the endothelium after xenogeneic perfusion. PgF1a levels were significantly higher in the xenogeneic hemoperfusate, indicating endothelial cell activation. The concentration of myoglobin in the hemoperfusate remained within normal values and was similar during autologous and xenogeneic perfusion. Therefore endothelium-related processes are likely to affect the coronary circulation--thus being one mechanism leading to diminished cardiac performance during hyperacute rejection.

Acute Disease↗

[Teratoma of the umbilical cord. Case report with literature review].

A rare case of teratoma of the umbilical cord is reported. It is differentiated from acardius amorphus and compared with the nine cases reported in the literature since the first description in 1878. The clinical consequences for pregnancy of the tumour's influence on the circulation are discussed. For the first time, non-radioactive in situ hybridization of the interphase nucleus was performed in a teratoma of the umbilical cord. The results are presented and different histogenetic pathways, e.g. parthenogenetic origin of the teratoma, are debated.

Cell Transformation, Neoplastic↗

Allogeneic heart transplantation following xenogeneic bridging.

Xenografting seems to be a solution to bridge the time intervals when an essential allograft cannot be obtained. A subsequent allograft was never tried. Eight dogs (20-24 kg) of 2 years of age underwent right cervical heart transplantation. Donors were silver foxes (3-4 kg). The animals were treated by triple drug therapy consisting of cyclosporin A, methylprednisolone and azathioprine in clinical dosages. For control, six recipients received allogeneic heart transplantation (AHTP) and the identical immunosuppression. After rejection of the xenograft, a second allogeneic heart was anastomosed to the same right cervical vessels. Routine histology and immunohistology were performed. Thromboxane B2 and 6-keto-prostaglandin Fla were determined daily in peripheral blood. After final rejection sensitization of the recipient was controlled by haemagglutination tests. Survival times of the xenografts were 9.6 +/- 1.2. The subsequent hearts under the same therapy beat for 4.5 +/- 5.0 days. The average survival time of control hearts was 18 +/- 1.9 days. The five hyperacute second allografts showed signs of humoral rejection by absence of inflammation. The release of thromboxane B2 was different in hyperacute, accelerated or cellular rejection. In contrast to the long-functioning grafts, thromboxane B2 persisted during hyperacute rejection at a high level. However 6-keto-prostaglandin Fla showed no significant differences between long-time survivors and hyperacute rejecting hearts. After xenogeneic transplantation all recipients showed haemagglutinating titres between 1:4 and 1:16. Allogeneic grafts have different kinetics of rejection following xenogeneic heart transplantation (XHTP) compared with control hearts. Thromboxane B2 seems to be an important mediator in hyperacute rejection. This type of rejection is not associated with a change in 6-keto-prostaglandin Fla levels. These results indicate, that xenogeneic bridging under a common immunosuppressive regimen could lead to accelerated rejection of the following allograft. Under this condition clinical bridging is not advisable.

6-Ketoprostaglandin F1 alpha↗

Coronary arteries in the hypoplastic left heart syndrome. Histopathologic and histometrical studies and implications for surgery.

The subepicardial coronary arteries (CAs) in the hypoplastic left heart syndrome (HLHS) were studied for pathology dependent on the patency of the mitral valve and the presence of endocardial fibroelastosis (EFE) of the left ventricle (LV). Nine heart specimens with aortic and mitral atresia (group 1) were studied and compared with 19 hearts with aortic atresia and mitral stenosis (group 2) (EFE of the LV was present in all cases) and 10 normal hearts. The median age at death was 3 days. For the histological and histometrical studies, 5-mm blocks from six comparable sites of the left (L) and right (R) CAs were serially sectioned and routinely processed. The arterial size and wall thickness were measured. Macroscopically, the CAs in group 1 were normal except for the prevalence of left dominance (56%). In contrast in group 2, the CAs were thicker and tortuous. Histopathology was restricted almost exclusively to group 2 specimens (11 of 19), with the proximal LCAs being the most affected. However, eight hearts with EFE in group 2 had no structural wall changes of the CAs. Histometrically, the sizes (external diameters) of the LCAs and RCAs were similar (0.5-1.0 mm) in groups 1 and 2 and in the normal group; however, we noted an increase in percent medial thickness in group 2 specimens, especially of the LCAs. Furthermore, in some group 2 hearts, the wall thickness (intima and media) relative to the luminal size (internal radius) of proximal and middle LCAs was significantly increased, suggesting the presence of ventricle-CA communications.(ABSTRACT TRUNCATED AT 250 WORDS)

Aortic Valve↗

[Primary extranodal non-Hodgkin lymphoma of the stomach. Value of surgery within the scope of a multimodality treatment concept].

The clinical course of 22 patients was analyzed in a retrospective study; all of these were suffering from malignant lymphoma of the stomach and most underwent radical resection as the only therapeutic measure. A unrelated effect on the survival rate was found in a high-grade malignancy metastatic disease of celiac lymph nodes (stage II2E) and tumor size. On the basis of the presented data we assume that low-grade malignant lymphomas stages IE can be cured by radical resection. In stage II1E and II2E we recommend multi-disciplinary treatment strategy with radical resection followed by radiation therapy in low-grade malignancy or chemotherapy in high-grade malignancy.

Adult↗

Fibrin-fibronectin compounds in human ovarian tumor ascites and their possible relation to the tumor stroma.

Covalently linked heterogeneous fibrin-fibronectin compounds were detected in ascitic fluid of 31 patients with advanced ovarian cystadenocarcinoma by means of enzyme-linked immunosorbent assay techniques, immunoaffinity chromatography, and Western blot analysis. Deposition of fibrin and fibronectin could also be demonstrated immunohistochemically in Carnoy-fixed tissue sections. Fibrin and fibronectin were found in the tumor stroma within tumor nests and more prominently in stroma surrounding the tumor nests. The association of fibrin and fibronectin was especially pronounced in the stroma surrounding the tumor islands. Fibronectin was also found to be associated with stroma cells. Areas within the tumor stroma showed superimposed staining for both fibrin and fibronectin supporting the assumption that the covalently linked fibrin-fibronectin conjugates found in ascitic fluid may stem from the provisional tumor stroma by proteolytic release.

Ascitic Fluid↗

Complete thrombotic obliteration of the ascending aorta and the aortic arch as a cause of acute heart failure in a newborn.

Thrombosis of the great vessels, and especially of the aorta, is rare in neonates. We report a case with thrombosis of the ascending aorta, aortic arch, brachiocephalic trunk and subclavian artery. Clinically, severe heart failure occurred on the 1st day of life and the diagnosis was confirmed by echocardiography and cardiac catheterization, including angiocardiography. Left ventricular function was found to be extremely depressed. An infusion with prostaglandin E1 was initiated in order to improve the systemic circulation by dilating the arterial duct. The infant died of neurological complications prior to surgery.

Aorta↗

Competition of coronary arteries and ventriculo-coronary arterial communications in pulmonary atresia with intact ventricular septum.

Pulmonary atresia with intact ventricular septum can be complicated by the presence of large ventriculo-coronary arterial communications which disturb normal myocardial perfusion. In the selection of patients for surgery the presence of these communications provides an additional problem. On the basis of previous cineangiocardiographic study, we performed a histopathological study of 16 cases. Twelve presented with ventriculo-coronary arterial communications and four only showed myocardial sinusoids. A tripartite right ventricle was seen in the latter group but not exclusively. It is shown that subepicardial coronary arterial pathology is exclusively present in cases with ventriculo-coronary arterial communications although not solely at a connection site between a communication and an artery. The affected coronary artery is itself focally abnormal and hypoplastic and can be blocked or even absent. The interruption of such an artery can also occur after birth and not necessarily at a site of connection with a communication. This implies that infants with communications either already have a coronary circulation partly or completely dependent on ventriculo-coronary arterial communications at birth or can develop such a condition in time. This hazard to myocardial perfusion, often compromised by a large "steal" from the aorta to the right ventricle, limits the choice of surgical procedures.

Child, Preschool↗

[Tumor-associated antigens and fibrin derivatives as reaction products of ovarian cancer].

The detection of tumour-associated antigens in blood, ascites fluid, and tissue by the use of monoclonal antibodies establishes new aspects for the course control of ovarian cancer therapy and the evaluation of tumour-associated fibrinolysis. Monoclonal antibodies to the cross-linking site of fibrin derivatives in an enzyme immunoassay (D-dimer-ELISA) allow to compare quantitative results of fibrinolysis products with different tumour markers and the clinical tumour situation. In a prospective follow-up-study in 102 patients with epithelial ovarian carcinoma Ca 125, D-dimer, TPA, Ca 19-9, and CEA were investigated as tumour markers. Specificity (control group 61 gynaecologic patients with benign diseases) and sensitivity were compared in sensitivity-specificity diagrams (receiver operating characteristic curves) for different clinical tumour situations (preoperative, S0-S3). Applying a limit value of normal range, indicated in parentheses, the specificity of Ca 125 (greater than 65 mu/ml) amounts to 100%, D-dimer (greater than 700 ng/ml) 100%, TPA (greater than 120 mu/ml) 90%, CEA (greater than 5 ng/ml) 96%, Ca 19-9 (greater than 37 mu/ml) 98%. In the same sequence, sensitivity values came to 91%, 82%, 65%, 8% and 19% in manifest tumour situations. Antigen-concentration levels and frequency of pathological values depend on the degree of tumour disease. The results of seroimmunodiagnostic methods correlate with the clinical tumour situation: In 11 of 12 cases clinical tumour progression or relapse were accompanied by increasing concentrations of Ca 125 and D-dimer. In 21 cases of second-look laparotomies, tumour marker values in the normal range were often found not to be conclusive for diagnosing a tumour-free situation. The predictive value for true negative results amounted to only 18%. Immunohistochemical investigations and plasma-ascites diffusion ratios of antigens indicate that enrichment occurs in ascites. Fibrin deposition often surrounds tumour plugs and is found in interstitional tissue, whereas Ca 125 is expressed mainly at tumour cell surface. The histochemical image reflects fibrin as a tumour surrounding antigen and Ca 125 as a tumour-originated antigen. Clinical relevant serodiagnostic methods for ovarian cancer are brought about by the monoclonal detection of the investigated antigens.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗

Myocardial salvage prior to emergency coronary bypass surgery for PTCA-induced coronary occlusion.

The possibility of prolonged, selective coronary perfusion via angioplasty catheters was evaluated. A pump was developed featuring minimal hemolysis even at high pump pressures. Pressure requirements differed greatly between various catheter types. Catheter-induced hemolysis did not correlate with pump pressure and was mainly due to a turbulent jet effect through sideholes. In 20 of 22 closed-chest dogs, myocardial ischemia could be greatly reduced or completely prevented for over 2 hours after proximal LAD or Cx occlusion. With flow rates between 1 and 2.5 ml/min/kg body weight and using the ECG and coronary venous O2 saturation for rate adjustment, pressure within the selectively perfused vessel never reached critical values. Thus, with the appropriate equipment, prolonged coronary perfusion is feasible. In some cases of percutaneous transluminal coronary angioplasty-(PTCA) induced coronary occlusion, it may prevent ischemic myocardial damage between PTCA-induced acute coronary occlusion and subsequent surgical revascularization.

Journal Article↗

[Selective continuous coronary perfusion via an angioplasty catheter following acute vascular occlusion].

Since surgical revascularisation after PTCA-induced acute coronary occlusion in the majority of cases is delayed by at least 2 hours, we assessed the possibility of selective, volume-controlled coronary perfusion via the still indwelling angioplasty catheter for such a prolonged period using an external pump. Because of the high pressures required to provide adequate flow through many of the currently used catheters, an AC independent, pressure and volume controlled pump was developed which does not cause substantial hemolysis even at pressures beyond 10 atm. During in vitro tests the pressure-flow-rate relations and the degree of hemolysis and blood count changes were determined for various catheters. The previous catheters with a fixed wire tip caused excessive hemolysis which rendered prolonged coronary perfusion prohibitive. But even with the more recent catheters the presence of side holes near the catheter tip may at times cause significant hemolysis. In 20 out of 22 dogs the anterior descending (n = 18) or circumflex (n = 2) coronary artery was selectively perfused for 2 hours following balloon occlusion. The perfusion rate was adjusted according to the occurrence of ischemic signs in the ECG and for a drop in the coronary venous oxygen saturation which was monitored with a fiberoptic catheter. The intraluminal pressure within the selectively perfused vessel was recorded continuously but not used for adjustment of the perfusion rate. In no case was there a critical pressure increase in the selectively perfused vessel. When perfusion of the occluded vessel was stopped after 2 hours, massive myocardial ischemia developed which was reversible with resumption of perfusion. Using an adequate pump and the more recent, steerable angioplasty catheters which should not have side holes near the tip, selective coronary perfusion can be performed for at least 2 hours and is capable of preventing myocardial ischemia.

Angioplasty, Balloon↗