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J Boldt

Publications and source records attributed to J Boldt.

At least 235 records · Page 13Linked to original sources
PubMed1991

Replication of acetylaminofluorene-adducted plasmids in human cells: spectrum of base substitutions and evidence of excision repair.

In rats fed the liver carcinogen 2-acetylaminofluorene (AAF), the two most abundant types of DNA adduct are N-(deoxyguanosin-8-yl)-2-acetylaminofluorene and its deacetylated derivative. When plasmids carrying AAF adducts replicate in bacteria, the predominant mutations are frameshifts, whereas with deacetylated (AF) adducts, they are mainly base substitutions, just as we found when plasmids carrying AF adducts replicated in human cells. We have investigated the frequency and spectrum of mutations induced when a shuttle vector carrying AAF adducts (85% bound to the C8 position of guanine, 15% to the N2 position) replicated in human cells. The frequency induced per initial AAF adduct was higher than with AF adducts, but the kinds of mutations were similar--i.e., 85% base substitutions, principally G.C----T.A transversions. There was good correlation between the "hot spots" for mutations and hot spots for AAF adduct formation, suggesting that mutational hot spots reflect preferential binding of the carcinogen to DNA. 32P-postlabeling analysis of the adducts before and after the DNA was transfected into the human cells showed that there was no deacetylation of AAF adducts and that 85% of both types of adducts were removed within 3.5 hr, most probably by excision repair.

2-Acetylaminofluorene↗
PubMed1991

Potassium dependence for sperm-egg fusion in mice.

In this study, we examined the potassium requirements for sperm-egg fusion in mouse. Zona-free mouse eggs prepared by the method described by Boldt and Wolf were inseminated with capacitated sperm in culture media containing 0-6 mM extracellular K+, and scored for penetration. Penetration of zona-free eggs was dependent on extracellular K+, with no penetration observed under K(+)-free conditions. Media transfer experiments indicated that the lack of penetration observed was due to effects on fusion, and not on postpenetration events such as sperm head decondensation. To analyze whether the K+ effect was attributable to an effect on the sperm (i.e., occurrence of acrosome reactions), sperm were treated with the Ca2+ ionophore A23187 before insemination. Less than 5% of zona-free eggs were penetrated with ionophore-treated sperm under K(+)-free conditions, suggesting that K+ is required for fusion per se. Addition of ionophore to insemination cultures similarly did not overcome the block to fusion observed under K(+)-free conditions. The potassium channel blockers 4-aminopyridine (0.1-5 mM) and tetraethyl ammonium chloride (5-50 mM) had no inhibitory effect on fusion. These data indicate that extracellular K+ is required for sperm-egg fusion and that this requirement may not involve membrane K+ channels.

Analysis of Variance↗
PubMed1991

RETRACTED: Six different hemofiltration devices for blood conservation in cardiac surgery.

This article has been retracted: please see Elsevier Policy on Article Withdrawal (http://www.elsevier.com/locate/withdrawalpolicy). This article has been retracted at the request of the Editor. Reason: By comparing the results of this article with results reported by Berend Fedderson (Hämofiltration als blutsparendes Verfahren in der Herzchirurgie: sechs verschiedene Hämofilter im Vergleich; Niebüll, Germany; http://d-nb.info/930239350), it has been determined that experimental outcomes have been altered. Thus, the research published in this article was misrepresented to The Annals of Thoracic Surgery and the article should be retracted from the scientific record.

Aged↗
PubMed1991

Cardiorespiratory responses to hypertonic saline solution in cardiac operations.

Infusion of small volumes of hypertonic saline solution (HS) seems to be of benefit in patients with impaired perfusion. The cardiorespiratory response to a 7.2% NaCl solution prepared in hydroxyethylstarch (HES) solution was investigated prospectively in patients undergoing prolonged cardiopulmonary bypass (CPB) (HS-HES group; n = 15); 6% HES 200/0.5 solution was infused in a control group (HES group; n = 15). Volume was given preoperatively to double low pulmonary artery occlusion pressure (less than 4 mm Hg) within 20 minutes. Hemodynamics, oxygen transport variables, and pulmonary gas exchange were studied before and after infusion as well as before and after CPB. Significantly less HS-HES solution (3.06 +/- 0.2 mL/kg) than 6% HES 200/0.5 solution (10.3 +/- 0.9 mL/kg) was necessary to double baseline pulmonary artery occlusion pressure. Fluid balance during CPB was negative in the HS-HES patients (-0.05 mL/kg.min CPB) and was lowest in this group even 5 hours after CPB. Mean arterial pressure, pulmonary arterial pressure, and heart rate were without differences between the groups. Changes in cardiac index (+40%) and total systemic resistance (-25%) were significantly most pronounced in the HS-HES patients, continuing even until the end of operation. Pulmonary gas exchange (arterial oxygen tension, intrapulmonary right-to-left shunting) was least compromised in these patients, particularly after bypass. Oxygen consumption was without difference between the groups; oxygen delivery increased significantly more in the HS-HES patients due to the larger increase in cardiac output.(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiopulmonary Bypass↗
PubMed1991

Pediatric heart transplantation for congenital heart disease and cardiomyopathy.

Orthotopic heart transplantation has become an accepted therapy for adult patients with end-stage heart disease. In newborns and infants, this procedure is still controversial because of the unknown long-term results and the lack of donor organs. Since March 1988, we have performed orthotopic heart transplantation in 11 infants and children with hypoplastic left heart syndrome (n = 6), cardiomyopathy (n = 4), or congenital endocardial fibroelastosis (n = 1). The smallest infant was 3 days old and weighed 2,650 g. Four of 15 potential donors had to be refused for various medical reasons, and 4 were transferred to our hospital for organ retrieval. Seven hearts were procured remotely. We accepted weight mismatches up to 105% between donor and recipient. There were three perioperative deaths, two in patients 5 and 17 days old with hypoplastic left heart syndrome and 1 in a 2-year-old patient with a dilated cardiomyopathy. All 3 patients had drug-resistant right heart failure. A 2-year-old girl with a dilated cardiomyopathy died 2 months after transplantation owing to severe pulmonary embolism originating from the superior vena cava. The remaining 7 patients are alive and well between 1 month and 31 months after transplantation. Angiographic follow-up has not revealed signs of graft atherosclerosis at 2 years.

Cardiomyopathy, Dilated↗
PubMed1991

Does the technique of cardiopulmonary bypass affect lung water content?

Several efforts have been made to improve the technique of cardiopulmonary bypass (CPB), including the use of pulsatile flow and the modification of cannulation technique. The present study focused upon extravascular lung water (EVLW) in 60 aortocoronary bypass patients subjected to four different perfusion techniques during CPB: group 1 (n = 15): non-pulsatile flow and standard cannulation; group 2 (n = 15); pulsatile flow and standard cannulation; group 3 (n = 15): nonpulsatile flow and monoatrial cannulation (i.e., always "partial" bypass during CPB); group 4 (n = 15): pulsatile flow and monoatrial cannulation. EVLW content was measured using the double-indicator dilution technique with indocyanine green; in addition, various hemodynamic and laboratory variables were measured. Lung water content rose above normal values (mean: 5.79 +/- 0.33 ml/kg) only in the groups submitted to the standard cannulation technique, irrespective of whether the perfusion flow was pulsatile or not (group 1: + 27.4%; group 2: + 25.5%). Pulmonary gas exchange, too, was compromised only in these patients (PaO2 in group 1 -19% and in group 2 -17%; Qs/Qt in group 1 + 36 rel. % and in group 2 + 29 rel. %), whereas all patients with monoatrial cannulation and partial bypass throughout the CPB period showed no rise in EVLW content or Qs/Qt and no drop in PaO2. From the results of this study we conclude that pulsatile perfusion during open heart surgical procedure has no advantages in regard to lung water content. Monoatrial cannulation with partial bypass at all times during CPB, however, seems to be beneficial, probably owing to the maintenance of pulmonary circulation during the bypass period.

Aged↗
PubMed1991

RETRACTED: Does the preparation of heparin influence anticoagulation during cardiopulmonary bypass?

Various preparations of heparin from different manufacturers are commercially available. The influence of bovine lung heparin (BLH) and porcine mucosal heparin (PMH) on anticoagulation and heparin plasma concentration was investigated in four groups of 10 patients undergoing elective aortocoronary bypass grafting either after single dose or repetitive dose (after 60 minutes) of one of these heparin preparations. Heparin plasma concentration increased significantly after injection of heparin (BLH: minimum, 1.67 U/mL; maximum, 2.10 U/mL; PMH: minimum, 1.69 U/mL; maximum, 2.15 U/mL). Sixty minutes after the initial dose, heparin plasma levels were higher in the patients who received PMH. Supplemental heparin doses 60 minutes after the loading dose increased plasma heparin concentration only with porcine mucosal heparin. Elimination of heparin in the urine was not different among the groups. Fibrinogen and antithrombin III concentrations, as well as activated clotting time (ACT; always greater than 400 seconds) and partial thromboplastin time (PTT; always greater than 300 seconds), did not differ among the groups, indicating effective anticoagulation during the bypass period with both types of heparin. It can be concluded that sufficient anticoagulation can be achieved with either kind of heparin. PMH seems to be longer acting and a repeat dose in these patients seems to be necessary only if cardiopulmonary bypass lasts longer than 90 minutes.

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PubMed1991

Influence of growth factors in defined culture medium on in vitro development of mouse embryos.

Two-cell mouse embryos were cultured in Ham's F-10 medium (Gibco, Grand Island, NY) supplemented with various concentrations of transferrin, insulin, epidermal growth factor, platelet-derived growth factor, or fibroblast growth factor. Rates of development and the cell numbers per blastocyst were compared between embryos cultured in Ham's F-10 alone versus growth factor (GF) supplemented media. Rates of development in the presence of GF were inhibited significantly in some cases, and the cell numbers per blastocyst were identical in all groups. When compared with in vivo derived blastocysts, however, all in vitro cultured embryos had significantly less cells per embryo. These results suggest that GF supplementation of media for culture of early preimplantation embryos does not stimulate the rate of embryonic development in vitro.

Animals↗
PubMed1991

[Anesthesia in heart surgery].

Today, the performance of anaesthesia in cardiac surgery is on a high quality level. It requires special knowledge of the various operative techniques, the different methods of extracorporeal circulation and haemodynamic changes of the underlying cardiological disease, as well as extensive experience in cardiac and vasoactive drugs. Heart patients are now being operated on in many departments of cardiac surgery. Over and above this patients with more or less severe cardiac diseases are being looked after in every Department of Anaesthesiology, thus, every anaesthesiologist should acquaint himself with these specific problems during his specialist training.

Adult↗
PubMed1991

Influence of hypertonic volume replacement on the microcirculation in cardiac surgery.

We have studied the effects of two types of volume replacement on the microcirculation in an open, controlled study in 45 patients undergoing aorto-coronary bypass grafting whose pulmonary capillary wedge pressure (PCWP) was less than 5 mm Hg. Hypertonic saline prepared in hydroxyethylstarch solution (HS-HES, n = 15) and 6% HES 200/0.5 solution (6% HES; n = 15) were infused randomly before operation in order to double the PCWP. Patients not given an infusion served as controls (n = 15). Skin microcirculatory blood flow was investigated by laser Doppler flow (LDF) measured simultaneously at the forearm and forehead before and after cardiopulmonary bypass (CPB). Less HS-HES (3.8 (SD 0.3) ml kg-1) than 6% HES-solution (9.7 (1.5) ml kg-1) was necessary to double baseline PCWP. There were no differences in heart rate and mean arterial pressure (MAP) between the groups. Cardiac index (CI) increased significantly in both volume groups (HS-HES max. +54%; 6% HES max. +30%). Systemic vascular resistance (SVR) decreased after infusion of HS-HES (-30%) and after 6% HES(-19%) and remained almost unchanged in the control group. Plasma viscosity decreased after infusion of HS-HES and increased slightly in control patients (+4%). In comparison with the 6% HES and particularly with the control group, LDF was significantly greater after infusion of HS-HES (forearm +80%; forehead +28%). LDF during CPB and thereafter was always greater than baseline values in the HS-HES group, whereas after bypass LDF was reduced in the 6% HES (-5%) and particularly in the control patients (-30%).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1991

Kinds of mutations found when a shuttle vector containing adducts of 1,6-dinitropyrene replicates in human cells.

To gain insight into the mechanisms by which carcinogens induce mutations in human cells, we have been comparing the frequency and spectrum of mutations induced when a shuttle vector, pS189, carrying covalently bound residues of structurally related carcinogens, replicates in human 293 cells. In the present study, we investigated the mutagenic effects of N-hydroxy-1-amino-6-nitropyrene, a partially reduced derivative of 1,6-dinitropyrene (1,6-DNP). The results were compared with what was found previously in the same assay with N-hydroxy-1-aminopyrene, the partially reduced derivative of 1-nitropyrene. The shuttle vector plasmids were exposed to tritiated 1-nitro-6-nitrosopyrene for 1 h in the presence of ascorbic acid, which served as a reducing agent to generate N-hydroxy-1-amino-6-nitropyrene. 32P-Postlabeling showed that only a single adduct was formed, i.e. N-(deoxyguanosin-8-yl)-1-amino-6-nitropyrene. There was a linear increase in the number of adducts per plasmid as a function of applied concentration and also in the frequency of supF mutants as a function of adducts per plasmid, reaching 58.8 x 10(-4) above a background of 0.8 x 10(-4). When the frequency of mutants induced when plasmids carrying residues of 1,6-DNP replicated in the human cells was compared with that induced by 1-NP residues, the former was 1.8 times more mutagenic than the latter. Both carcinogens induced mainly base substitutions, primarily G.C----T.A transversions; but 1,6-DNP adducts produced a significant fraction of -1 frameshifts, with most of these located in a unique run of five Gs in the gene. Polymerase termination reactions indicated that 1,6-DNP adducts were formed at every guanine, but not elsewhere in the gene. The 'hot spots' for adduct formation were not perfectly correlated with 'hot spots' for mutation induction. This indicates that the ultimate biological effect of the chemical depends not only on the number of adducts originally formed, but also on such processes as cellular DNA repair, which may remove such adducts from the plasmids before DNA replication occurs, as well as on the structure of the neighboring bases at the site of the adduct.

Base Sequence↗
PubMed1991

Blood conservation techniques and platelet function in cardiac surgery.

Postoperative alterations in platelet function induced by cardiopulmonary bypass (CPB) are of importance. The effect on platelet aggregation of three different techniques for reducing blood consumption was studied in 30 patients undergoing elective aortocoronary bypass grafting from the beginning of anesthesia until the 1st postoperative day. The patients were randomly divided into three groups, in which 1) a cell separator was used during and after CPB; 2) a hemofiltration device was used; and 3) high-dose aprotinin was used in order to reduce the need of homologous blood. A fourth group undergoing neurosurgery procedures served as a control. Platelet aggregation induced by adenosine diphosphate (concentration 0.25, 0.50, 1.0, and 2.0 microM), collagen (4 microliters/ml), and epinephrine (25 microM) was determined by the turbidimetric method. Platelet aggregation was not significantly changed in the control group, indicating that the operation itself did not impair platelet function. At the end of the operation (after retransfusion of the salvaged pump blood), the maximum aggregation and maximum gradient of aggregation induced by all three inductors were most reduced (significantly) in the cell-separator patients. On the 1st postoperative day, platelet aggregation in the hemofiltration patients and the patients treated with aprotinin had normalized. Aggregation of patients pretreated with high-dose aprotinin was not different from that of the hemofiltration patients throughout the investigation. Blood loss was significantly highest in the cell-separator group (770 +/- 400 ml on the 1st postoperative day) but was not different between the hemofiltration (390 +/- 230 ml) and the aprotinin-treated patients (260 +/- 160 ml).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1991

[Hemodynamic effects of enoximone--comparative studies of heart surgery patients].

Treatment of depressed myocardial pump function during cardiac surgery is usually based on catecholamines. Development of selective phosphodiesterase (PDE)-III-inhibitors such as enoximone seems to be an interesting aspect in treating myocardial dysfunction in this situation. In patients undergoing aorto-coronary bypass grafting, who where unable to be weaned from cardiopulmonary bypass (CPB) without pharmacologic support, i.v. injection of enoximone (0.5 mg/kg) resulted in significant better hemodynamics than after infusion of dobutamine in comparable patients. The mechanisms for improvement in ventricular function induced by enoximone appear to be enhanced contractility, owing to its positive inotropic effects, and a decrease in ventricular outflow resistance, resulting from peripheral vasodilation. The positive hemodynamic effects in patients additionally treated with catecholamines (epinephrine) may be of particular interest in patients with beta-receptor down-regulation phenomenon.

Blood Pressure↗
PubMed1990

The new phosphodiesterase inhibitor enoximone in patients following cardiac surgery--pharmacokinetics and influence on parameters of coagulation.

Enoximone is a selective inhibitor of the phosphodiesterase-III enzyme (PDE-III) and possesses positive inotropic and vasodilatory properties. The PDE-inhibitor amrinone has been associated with adverse effects on coagulation by decreasing platelets. To investigate the influence of enoximone on hemostasis, 18 patients undergoing elective aorto-coronary bypass grafting and receiving enoximone were compared to a control group (n = 18). In addition, the plasma levels of enoximone and its major metabolite (enoximone-sulfoxide) were studied following a single injection (0.5 mg/kg) and during a continuous infusion (5 and 10 micrograms/kg.min) before, during and after extracorporeal circulation (ECC). No difference between study and control groups was found for the parameters of coagulation during the investigation period; in particular there were no differences in platelet count and platelet function (thrombelastography). Following the single bolus, peak plasma levels decreased during ECC to ineffective levels. Continuous infusion, however, maintained effective plasma levels of enoximone; sulfoxide levels were twice as high as enoximone concentrations up until the end of the investigation period. It is concluded that enoximone can be judged to be safe in respect to its effects on coagulation even following ECC and at relatively high doses. The use of continuous infusion results in plasma levels which remain at an effective concentration through to the time that the patient is transferred to the intensive care unit.

Aged↗
PubMed1990

Comparative effects of enoximone and theophylline on plasma catecholamines and haemodynamics in cardiosurgical patients.

The release of endogenous catecholamines in aorto-coronary bypass graft patients receiving either 0.5 mg/kg enoximone (n = 10), 4.0 mg/kg theophylline (n = 10) or saline solution (control, n = 10) has been studied, as well as certain haemodynamic parameters. Adrenaline (A) and noradrenaline (NA) concentrations were not significantly changed by the administration of enoximone. Theophylline caused a small increase in NA (+40% in the 1st min) and a marked increase in A (approximately +7000% in the 1st min), which still remained elevated at the end of the investigation period (+220% in the 30th min). The major haemodynamic effects of enoximone were a significant increase in cardiac index (CI; +35%) and a decrease in pulmonary capillary wedge pressure (PCWP; -27%), pulmonary artery pressure (PAP; -21%), RVEDV and RVESV, while the heart rate (HR) remained almost unchanged. The dominant haemodynamic effects of theophylline were an increase in HR (+26%; arrhythmia in 3 patients), PAP (+22%), and RVEDV (+19%), while RVESV (+26%), MAP (-16%), CI (-14%), and RVEF (-15%) fell significantly. It is concluded that the haemodynamic actions of enoximone are not mediated by catecholamine release, whereas the adverse cardiovascular effects of theophylline might partly be explained by the significant increase in plasma adrenaline.

Cardiac Catheterization↗
PubMed1990

RETRACTED: Acute preoperative plasmapheresis and established blood conservation techniques.

Plasmapheresis performed weeks before an operation producing autologous plasma has proved to be of benefit in elective operations. First experiences in acute plasmapheresis, which is performed immediately before the operation, have been reported recently. When acute plasmapheresis is used in cardiac operations, however, it must be viewed in connection with other techniques for reducing blood consumption such as the Cell Saver (CS) and ultrafiltration devices. In 60 patients undergoing elective aortocoronary bypass grafting, acute plasmapheresis was performed, producing either platelet-poor plasma or platelet-rich plasma, in combination with either the Cell Saver or hemofiltration. Fluid balance during cardiopulmonary bypass was significantly lower in the hemofiltration patients. Postoperatively, none of these patients received donor blood, whereas 4 patients of the Cell-Saver groups needed packed red blood cells. AT-III, fibrinogen, the number of platelets, albumin, total protein, and colloid osmotic pressure were less compromised when hemofiltration was used in combination with acute plasmapheresis in contrast to combination with the Cell-Saver technique. Plasma hemoglobin was without differences during the investigation period, and polymorphonuclear elastase was less increased when platelet-rich plasma was produced preoperatively. On the first postoperative day, most of the differences between the groups had already disappeared. We conclude that when acute plasmapheresis is used in cardiac operations, discarding of plasma by the Cell Saver should be avoided and ultrafiltration devices should replace centrifugation techniques for blood conservation.

Blood Coagulation Factors↗
PubMed1990

Enoximone treatment of impaired myocardial function during cardiac surgery: combined effects with epinephrine.

Enoximone belongs to a new class of noncatecholamine-positive inotropes, which selectively inhibit phosphodiesterase type III and increase cyclic AMP (cAMP). This study was performed in 30 coronary artery surgery patients with impaired myocardial function (ejection fraction [EF] less than 50%). The study's two purposes were to investigate the hemodynamic effects of enoximone, 0.5 mg/kg, administered following induction of anesthesia (phase I), and to assess whether enoximone can potentiate the actions of sympathomimetic agents during weaning from cardiopulmonary bypass (CPB) (phase II). Starting with already reduced hemodynamics, induction of anesthesia led to a further deterioration of blood pressure and cardiac output (CO). Administration of enoximone produced a significant increase in cardiac index (CI) (+47%), whereas pulmonary capillary wedge pressure (PCWP) (-37%), pulmonary artery pressure (PAP) (-17%), and systemic vascular resistance (SVR) (-17%) were significantly reduced. Heart rate (HR) was not increased, and no dysrhythmias occurred during the investigation. The hemodynamic effects were maintained for 30 minutes until the start of the operation. In phase II, where weaning from CPB was not possible without pharmacological support, either enoximone (0.5 mg/kg) + epinephrine (0.1 micrograms/kg/min) or only epinephrine (same dosage) was randomly selected. Weaning was successful in both groups, but the combined therapy produced a larger increase in cl and a more pronounced decrease of the elevated filling pressure (PCWP). PAP was not changed in the combined therapy group, but increased in the patients receiving epinephrine alone. It is concluded that enoximone has beneficial hemodynamic effects in the perioperative period, and that potentiation of the effects of epinephrine in severe heart failure may be one of the drug's most useful features.

Aged↗