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Biomedical subjects

E Bos

Publications and source records attributed to E Bos.

At least 73 records · Page 4Linked to original sources

Aortic root replacement with pulmonary autograft in children.

Between September 1988 and February 1993, 14 patients whose ages ranged from 3 months to 16 years (mean 11.1 +/- 4.3 years) underwent replacement of the aortic root with the autologous pulmonary root for aortic valve disease. The follow-up was 4 years (cumulative total of 25.2 patient-years). There was no early mortality. Late mortality (one patient) was 7.1% (95% confidence limits 0% to 21%). This patient had juvenile rheumatoid arthritis and died of consequent congestive heart failure with autograft failure 6 months after operation. Event-free survival after 4 years was 78.6% (95% confidence limits 50% to 95%). One patient was reoperated on because of autograft failure caused by a relapse of rheumatic fever. One patient operated on for critical neonatal aortic stenosis has subnormal exercise tolerance because of restrictive cardiomyopathy and pulmonary homograft regurgitation. The other 12 patients were in New York Heart Association functional class I at the end of follow-up. There was no prevalence of bacterial endocarditis. There were no signs of primary structural degeneration of the pulmonary autograft. During follow-up, in eight patients, increased anulus diameter of the pulmonary autograft could be demonstrated by precordial two-dimensional echocardiography, suggesting growth of the autograft. Our experience shows that aortic root replacement with the pulmonary autograft can be done with low mortality and morbidity in children with aortic valve disease. The operation seems to be contraindicated in children with juvenile rheumatoid arthritis because of the risk of recurrence of rheumatic disease in the autograft. The pulmonary autograft has also been shown to be susceptible to recurrence of rheumatic inflammation in children with a history of acute rheumatic fever. Despite pulmonary autograft replacement of the aortic valve in infants with critical valvular aortic stenosis and endocardial fibroelastosis, clinical results may be poor. Growth of the autograft is suggested by echocardiographic follow-up. We consider aortic root replacement with the pulmonary autograft the procedure of choice in children who require aortic valve replacement.

Adolescent↗

Long-term follow-up (9 to 20 years) after surgical closure of atrial septal defect at a young age.

To assess the long-term cardiac status after surgical closure of an atrial septal defect (ASD) at a young age, 104 of 135 children who consecutively underwent surgery (aged 0 to 14 years) at 1 institution between 1968 and 1980 participated in a follow-up study and underwent a complete cardiologic examination. Mean follow-up was 14.5 +/- 2.8 years. Most patients (87%) believed their health to be good or very good. At physical examination, all patients were in good health. Ninety-three patients (89%) were in sinus rhythm. Echocardiography showed that right ventricular dilatation was present in 27 patients (26%), 2 of whom had a residual ASD. Bicycle ergometry revealed that 88 patients (88%) had a normal exercise capacity. Both supraventricular and ventricular arrhythmias were observed in 67% of patients by 24-hour ambulatory electrocardiography, but only 3 (3%) had received antiarrhythmic medication, and 4 (4%) had needed a pacemaker. In the group of patients with right ventricular dilatation, the exercise capacity and prevalence of arrhythmias did not differ significantly from those in the group with a normal sized right ventricule. The outcome in patients with a secundum-type ASD was not different from that of those with a sinus venosus-type ASD. The finding of anatomic, functional or electrophysiologic abnormalities was not associated with a longer duration of follow-up.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

5-HT receptors mediating contractions of the isolated human coronary artery.

We investigated contractile responses of the isolated human coronary artery to 5-hydroxytryptamine (5-HT), washed human platelets, sumatriptan and ergotamine. 5-HT (pD2: 6.8 +/- 0.1, Emax: 47.7 +/- 6.8 mN) and platelets (effect 14.4 +/- 2.8 mN with 3.10(10) platelets/l) caused contractile responses which were attenuated by ketanserin (1 microM). In the presence of ketanserin (1 microM), both rauwolscine (1 and 10 microM) and cyanopindolol (1 and 10 microM) caused concentration-dependent additional antagonism against contractions induced by low (< or = 1 microM) concentrations of 5-HT. Sumatriptan-induced contractions (pD2: 6.2 +/- 0.1; Emax: 10.7 +/- 2.4 mN) were antagonized to a similar extent by both rauwolscine (1 microM) and cyanopindolol (1 microM) (pKB: 6.5 +/- 0.1 and 6.4 +/- 0.1, respectively) and also by metergoline (0.1 microM; pKB: 7.2 +/- 0.1). The order of potency of antagonists against sumatriptan resembles the order reported for the human saphenous vein 5-HT1D-like receptor. No significant additional antagonism by cyanopindolol (1 microM) or rauwolscine (1 microM) against platelet-induced contractile responses was observed. Ergotamine caused potent contractile responses (pD2: 8.4 +/- 0.3, Emax: 19.4 +/- 2.4 mN). It is concluded that although 5-HT2 receptors predominantly mediate 5-HT-induced contractions, the 5-HT1-like receptor seems to play a role in coronary vasospasm caused by low concentrations of 5-HT.

Adolescent↗

Heterogeneity of endothelin/sarafotoxin receptors mediating contraction of the human isolated saphenous vein.

We investigated the effect of the ETA receptor antagonist, BQ-123 (0.1 and 1 microM), on contraction of the human isolated saphenous vein induced by endothelin-1 or sarafotoxin S6b. Contraction in response to endothelin-1 was not affected by BQ-123. In contrast, BQ-123 biphasically attenuated the contractions due to sarafotoxin S6b. These data indicate that (i) endothelin-1 induces contractions of the human saphenous vein via a non-ETA receptor and (ii) contractions in response to sarafotoxin S6b are mediated in part via a receptor different from the receptor mediating contraction due to endothelin-1.

Aged↗

Delayed-type hypersensitivity reactions to tumor-associated antigens in colon carcinoma patients immunized with an autologous tumor cell/Bacillus Calmette-Guérin vaccine.

Five different colon tumor-associated antigens (CTAA) were tested for their ability to induce an immune response in vivo and in vitro in ten colon carcinoma patients immunized with an irradiated autologous tumor cell/Bacillus Calmette-Guérin vaccine (active specific immunization) after resection of the primary tumor. The CTAA were defined by two different human monoclonal antibodies (MCA 1688 and MCA 28A32) derived by immortalization of peripheral blood B-lymphocytes from an active specific immunization patient. Delayed-type cutaneous hypersensitivity responses against a mixture of CTAA 28A32-50K and -32K were positive in seven of ten patients tested. In vitro T-cell responses upon stimulation with CTAA 28A32-32K were found to be positive in seven of ten patients and correlated with delayed-type cutaneous hypersensitivity responses to the antigen mixture. These data suggest that CTAA 28A32-32K might contain an important tumor-related T-cell epitope. Moreover, this method is suitable to define potential future candidates for antitumor vaccine development.

Animals↗

5-Hydroxytryptamine stimulates human isolated atrium but not ventricle.

Although 5-hydroxytryptamine (5-HT) elicits positive inotropic effects in the human isolated atrium via 5-HT4 receptors, no data are available about its effects in the ventricular myocardium. We investigated the inotropic effects of 5-HT in human healthy ventricular trabeculae and compared these effects with those in right atrial trabeculae. Baseline force of contraction as well as the response to noradrenaline, used to check inotropic responsiveness of the tissue, was significantly higher in ventricular (391 +/- 10 and 719 +/- 126 mg, respectively) than in atrial tissue (189 +/- 5 and 383 +/- 79 mg, respectively). However, 5-HT increased the force of contraction up to 309 +/- 82 mg at 10(-4) M in atrial trabeculae, but failed to affect the force of contraction in ventricular tissue. We conclude that, in contrast to atrial tissue, 5-HT is ineffective as a positive inotropic agent in human ventricular trabeculae. This finding obviously rules out the development of 5-HT4 receptor agonists for the treatment of heart failure, but suggests the absence of ventricular side-effects of 5-HT4 receptor (ant)agonists should these agents be used in the treatment of gastrointestinal disorders.

Heart Atria↗

Histology after stenting of human saphenous vein bypass grafts: observations from surgically excised grafts 3 to 320 days after stent implantation.

OBJECTIVES: To gain insight into the mechanism of stenting in humans and its short- and long-term implications, we studied the vascular wall of saphenous vein aortocoronary bypass grafts after implantation of the Wallstent. BACKGROUND: The implantation of a stent in aortocoronary bypass grafts may provide an alternative solution for revascularization in patients who are poor candidates for reoperation. Because human histopathologic findings after stenting with the Wallstent have not previously been described in detail, we examined graft segments that were surgically retrieved from 10 patients (21 stents) at 3 days to 10 months after implantation of the stent. METHODS: The grafts were examined by a combination of the following techniques: light microscopy, immunocytochemistry and both scanning and transmission electron microscopy. RESULTS: Early observations revealed that large amounts of platelets and leukocytes adhered to the stent wires during the first few days. At 3 months, the wires were embedded in a layered new intimal thickening, consisting of smooth muscle cells in a collagenous matrix. In addition, foam cells were abundant near the wires. Extracellular lipids and cholesterol crystals were found after 6 months. Smooth muscle cells and extracellular matrix formed the predominant component of restenosis. This new intimal thickening was lined with endothelium, in some cases showing defect intercellular junctions and abnormal adherence of leukocytes and platelets as late as 10 months after implantation. CONCLUSIONS: This type of stent is potentially thrombogenic and seems to be associated with extracellular lipid accumulation in venous aortocoronary bypass grafts.

Coronary Artery Bypass↗

Surgical treatment of congenital bronchopulmonary disease in children.

From 1987 to 1992, 22 children (age 0 days-14 years) were operated for congenital bronchopulmonary disease. One patient had a hamartoma. Four children had a bronchogenic cyst, in 1 patient combined with an esophageal duplication. Intrapulmonary sequestration was diagnosed in 3 children; one of whom had an esophageal duplication as well. Four children had localized emphysema. In 1 patient histology showed rhabdomyosarcoma. A lobectomy was performed following chemotherapy but recurrence was not resectable at a third thoracotomy. Ten patients had cystic adenomatoid malformation, 6 were dependent on artificial ventilation before surgery. Three patients with cystic adenomatoid malformation died in hospital: 2 after pneumonectomy who were shown to have bilateral disease and 1 died after bilobectomy and was shown to have a hypoplastic contralateral lung. Hospital morbidity involved 1 patient with recurrent pneumothorax, 2 with atelectasis of the operated lung and 3 with prolonged artificial ventilation. Late mortality involved 1 patient due to pulmonary rhabdomyosarcoma. After 1-26 months of follow-up there were no late complications. Adequate multidisciplinary treatment allows acceptable mortality and low morbidity in surgery for congenital bronchopulmonary disease in children.

Adolescent↗

Chylothorax as a complication of harvesting the left internal thoracic artery in coronary artery bypass surgery.

A patient is described with chylothorax after harvesting the left internal thoracic artery for coronary artery bypass surgery. Conservative treatment with a medium chain triglycerides diet and tube thoracostomy was not only unsuccessful, but also resulted in the complications of malnutrition and empyema. We recommend early surgical treatment of chylothorax after coronary bypass surgery with the use of an internal thoracic artery.

Adult↗

Behavioural and emotional problems in children and adolescents with congenital heart disease.

Behavioural/emotional problems were assessed at least nine years after surgical correction for congenital heart disease (ConHD) in childhood. Parents of 144 10-15-year-old ConHD-children completed the Child Behavior Checklist (CBCL) and 179, 11-17-year-old, ConHD-adolescents completed the Youth Self-Report (YSR). On the CBCL and YSR ConHD-children and adolescents obtained significantly higher problem scores than same-aged peers from normative reference groups. No significant differences were found between problem scores for different cardiac diagnostic groups. A negative correlation was found between CBCL total problem scores and IQ-scores of ConHD-children; for YSR total problem scores no such relationship was found.

Adaptation, Psychological↗

Effects of histamine on porcine isolated myocardium: differentiation from effects on human tissue.

Inotropic effects of histamine have been studied extensively in many species, but data on porcine myocardium, often used as a model for human heart, are not available. We investigated inotropic effects of histamine on atrial and ventricular trabeculae obtained from porcine hearts. For comparison, we also evaluated the effects of histamine on human myocardium. Histamine caused concentration-dependent increases in contractile force in porcine and human atrial tissue [at 1 x 10(-3) M: 267 +/- 70 and 317 +/- 81 mg, or 133 +/- 17 and 85 +/- 12% of the response to 1 x 10(-5) M norepinephrine (NE), respectively], as well as in porcine and human ventricular tissue (at 1 x 10(-3) M: 592 +/- 148 and 773 +/- 203 mg, or 68 +/- 13 and 122 +/- 61% of response to 1 x 10(-5) M NE, respectively). Cimetidine, but not mepyramine, antagonized the contractile effects of histamine in porcine and human atrial tissue and in human ventricular tissue. In contrast, the histamine-induced positive inotropic effect in porcine ventricular tissue was antagonized by mepyramine but not by cimetidine. Propranolol failed to block the inotropic effect of histamine in all four tissues. These results indicate that, as with human atrial trabeculae, the positive inotropic effect on porcine atrial trabeculae is mediated by H2 receptors. In contrast to human ventricular trabeculae, however, the positive inotropic effect on porcine ventricular trabeculae appears to be mediated by H1 receptors.

Adolescent↗

Altered specificity of alloreactive cardiac graft-infiltrating cells by prophylactic treatment with OKT3 or horse antilymphocyte globulin.

Graft-infiltrating lymphocytes from patients who were prophylactically treated with OKT3 or horse antilymphocyte globulin (H-ALG) were found to have different specificity patterns from those in the control group that received cyclosporine from the day of transplantation. This prophylactic treatment led to a significant decrease of the HLA-DR-directed cytotoxicity, while the cytolytic response against HLA-class I mismatches was hardly affected. In H-ALG patients without rejection, the percentages of class I-reactive cultures were found to be lower than in the other treatment groups, which was mainly due to a lower percentage of HLA-B--reactive cultures. In CsA and OKT3 patients, cytotoxic T cells were rather directed to HLA-B mismatches than to HLA-A antigens, while in H-ALG patients no difference in HLA-A and B-directed cytotoxicity was found. Our data suggest that OKT3 and H-ALG influence the specificity of the T cell allorepertoire, resulting in a decreased frequency of class II-specific cytotoxic T cells after transplantation. H-ALG also has a downregulating influence on the CTL response against HLA class I (HLA-B) antigens. In some patients a fast regeneration of these cells occurs, which results in a higher rejection incidence during the first posttransplant year.

Antilymphocyte Serum↗

The significance of complete serological testing for hepatitis B in heart valve banking.

Allograft heart valves obtained from donor hearts have been cryopreserved in the Heart Valve Bank in Rotterdam for transplantation purposes. In contrast to hepatitis B screening of organ donors, which consists of only a rapid HBV surface antigen (HBsAg) assay, tissue donors can be screened more completely for hepatitis B virus (HBV) by HBsAg and antibodies against HBV core antigen (anti-HBc) tests, and when necessary, anti-HBs and HBV-DNA tests. The value of this complete HBV screening was investigated by evaluation of the HBV screening results of 676 donor sera. HBsAg was positive in 1 serum. Anti-HBc was positive in 63 sera, of which 52 also had positive antibodies against HBV surface antigen (anti-HBs) tests (no risk of transmission) and 10 had negative anti-HBs tests. In 3 cases with a negative anti-HBs test the HBV-DNA test was positive (risk of transmission). In 3 cases not enough serum was available to perform all tests, resulting in a total of 7 rejected donors. Single HBsAg testing would have resulted in the rejection of only 1 donor. In the presented group of selected donors, approximately 0.5% of the HBsAg-negative donors were lower-level chronic carriers of hepatitis B. Complete HBV screening decreases the risk of transmission of hepatitis B in allograft heart valve transplantation.

DNA, Viral↗

The detection of cytotoxic T cells with high-affinity receptors for donor antigens in the transplanted heart as a prognostic factor for graft rejection.

Alloreactive T lymphocytes are the initiators and effectors of acute rejection of organ transplants, and T cells with high-affinity receptors for antigen might be especially implicated in this process. It has been shown that the cytotoxic capacity of CTL with low affinity for alloantigens can be inhibited with CD8 mAb, while high-affinity CTL are not affected. To investigate whether the presence of such high-affinity cells in human heart transplants may be predictive for acute rejection, we analyzed their frequency in cultures derived from endomyocardial biopsies in 19 patients, 9 of whom had never experienced acute rejection and 10 who had had one or more rejection episodes. IN the rejectors, already before histological signs of rejection (myocyte damage) had developed, significantly higher donor-reactive CTL frequencies were found compared with the nonrejectors (medians of 10,586 vs 1,169 reactive cells per 10(6) tested cells, P = 0.002). After CD8 inhibition, the difference between rejectors and nonrejectors was even more pronounced (P < 0.001). In patients with rejection, the number of CD8-resistant, high-affinity CTL was higher than 1000 per million cells in all cases, while in patients who had never experienced rejection this number was less than 1000. As these CTL characteristics are already present before the first histological signs of rejection have developed, this might be used as a prognostic factors.

Antibodies, Monoclonal↗

Malondialdehyde and glutathione production in isolated perfused human and rat hearts.

A number of studies show the relation between oxygen-derived free radicals and cardiac ischemia/reperfusion injury. However, little is known about oxidative stress in the human heart, which can be measured by oxidized glutathione (GSSG) and malondialdehyde (MDA) formation. Furthermore, data on MDA production by rat hearts are controversial, possibly because of the use of the aspecific thiobarbituric acid assay. Therefore, GSSG and MDA were measured, with colorimetric and high-performance liquid chromatographic assays, respectively, in buffer-perfused explanted human hearts and normal rat hearts made temporarily ischemic. Human hearts received cardioplegia; rat hearts were studied in a control and an ischemic group with or without cardioplegia. Baseline GSSG release was < 0.01 nmol.min-1.g wet wt-1 in both species. During reperfusion, GSSG release from human hearts and from ischemic and cardioplegic/ischemic rat hearts peaked at 0.24 +/- 0.12, 1.1 +/- 0.4, and 0.19 +/- 0.04 nmol.min-1.g-1, respectively. MDA was undetectable (< 0.02 nmol.min-1.g-1) in the effluent of both species and in human hearts (< 4 nmol/g protein). Rat heart reduced glutathione levels decreased 32% as a consequence of cardioplegia and ischemia. Cardioplegia induced a 41% (P = .08) decrease in rat heart MDA content, whereas cumene hydroperoxide increased it 3.6 times (P < .01). Thus, after ischemia human and rat hearts release GSSG, indicating that oxidative stress has occurred. Apparently, lipid peroxidation takes place in normal rat hearts, decreases after cardioplegia, but does not increase after ischemia/reperfusion. Human hearts lack MDA under normoxic and ischemic conditions. This novel finding seems to reflect a low MDA-forming potential in both situations.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Specific sequelae after Fontan operation at mid- and long-term follow-up. Arrhythmia, liver dysfunction, and coagulation disorders.

Patients who have undergone a Fontan-type operation usually have an elevated systemic venous pressure. To determine the sequelae of this nonphysiologic condition, we evaluated 66 patients 1 to 14 years after a Fontan-type operation. Fifty-one patients were apparently in good clinical condition, and 15 patients had symptoms and were restricted in their daily life. Bicycle exercise capacity, tested in 41 patients, ranged from 50% to 110% (mean 85%) of the predicted value for length. In 16 patients, a decreased capacity (< 85%) was, among others, related to arrhythmias and the presence of protein-losing enteropathy. A 24-hour ambulatory electrocardiogram was available in 56 patients and found to be normal in 32 (57%) patients. Arrhythmias were present in 21 patients, six of whom had symptoms. Three patients had previous pacemaker implantation. One or more abnormalities in liver enzyme and function tests were present in 40 patients (61%) and in coagulation factors in 46 patients (69%). The most pronounced was a protein C deficiency, a known thrombotic risk factor, present in 41 patients. The occurrence of arrhythmias increased with time of follow-up (p < 0.004), the occurrence of protein C deficiency decreased with time (p < 0.0001), and the occurrence of abnormal liver enzyme and function tests was not related to time of follow-up. With regard to age at operation, arrhythmias did not occur in patients who underwent operation at a mean age of 4 +/- 1.9 years (standard deviation), in contrast to patients who underwent operation at a mean age of 7.6 +/- 4 years (standard deviation) (p < 0.001). The occurrence of the two other types of sequelae was not related to the age at operation. With regard to the type of operation, only patients with a valved right atrium-to-pulmonary artery connection had a higher prevalence of arrhythmias than patients with a nonvalved or direct right atrium-to-pulmonary artery connection (p < or = 0.001). The latter patients also had a higher prevalence of protein C deficiency (p < or = 0.001). No relationship was found among the other types of operation, the underlying structure, or the hemodynamic condition measured at rest and the presence of arrhythmias, abnormal liver enzyme and function tests, or protein C deficiency. This point survey shows that even patients with an apparently good clinical condition are at risk for arrhythmias, abnormal liver enzyme and function tests, and coagulation factor abnormalities. Serial statement of affairs is recommended to ensure that adequate preventive measures can be taken.

Adolescent↗

Wild-type mouse p53 down-regulates transcription from different virus enhancer/promoters.

The protein encoded by the tumour-suppressor gene p53 can complex with SV40 virus large T antigen, the adenovirus E1B 58-kDa protein and the E6 protein of human papillomavirus type 16. The functions of these complexes are unclear, but there is some evidence to suggest that binding of p53 to these viral proteins may inactivate p53 function. Recent reports have shown that p53 is involved in regulation of transcription. We have considered the possibility that p53 may regulate transcription of viral genes important for virus replication and/or transformation. Inactivation of p53 function by formation of such complexes might then permit correct expression of these viral genes. Since p53 can bind to the SV40 virus enhancer/promoter, we have investigated the effect of p53 on transcription from this promoter and report here that mouse p53 is a potent repressor of the SV40 enhancer/promoter. Mutations within p53 severely inhibited this activity and provided some evidence to show that the N-terminus of p53 contains residues essential for this function. We also show that mouse p53 represses transcription from the promoters of viruses that do not express proteins that complex with p53: the human cytomegalovirus early promoter and the Rous sarcoma virus long terminal repeat. By studying the effect of p53 on transcription in different cell lines, we show that the effects of p53 on promoters may be cell type specific.

Animals↗