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Biomedical subjects

W Dietrich

Publications and source records attributed to W Dietrich.

At least 91 records · Page 5Linked to original sources

The influence of preoperative anticoagulation on heparin response during cardiopulmonary bypass.

The effect of preoperative anticoagulant therapy on intraoperative heparin response in patients undergoing cardiac operations was examined in a prospective study. The study included 45 patients with different preoperative anticoagulant treatments: 10 patients received treatment with phenprocoumon (a warfarin analogue) (group M), 12 patients received treatment with intravenous heparin (group Hiv), and 13 patients received treatment with subcutaneous heparin (group Hsc). The control group consisted of 10 patients who did not receive anticoagulant therapy before operation (group C). Preoperative antithrombin III activity was highest in group M (85% +/- 6%) and lowest in group Hiv (70% +/- 15%, p less than 0.05). The activated clotting time, determined 10 minutes after bolus injection of 250 IU (group M) or 375 IU heparin (all other groups), was 529 +/- 109 seconds in group C, greater than 1000 seconds in group M, 483 +/- 99 seconds in group Hsc, and 406 +/- 63 seconds in group Hiv (p less than 0.05). Heparin consumption during cardiopulmonary bypass varied between 4.6 +/- 1.4 IU/kg.min (group Hiv) and 2.6 +/- 0.9 IU/kg.min (group M) (p less than 0.05). Despite this increased heparin consumption, the patients who had received heparin before operation demonstrated increased activation of coagulation at the end of cardiopulmonary bypass (thrombin-antithrombin III complex, 19 +/- 4.1 ng/ml in group M and 61 +/- 7 ng/ml in group Hsc, p less than 0.05; cross-linked fibrin fragments, 257 +/- 92 ng/ml in group M and 875 +/- 152 ng/ml in group Hiv, p less than 0.05). Increased platelet activation was also found in patients with preoperative heparin therapy (beta-thromboglobulin at the end of cardiopulmonary bypass was 585 +/- 88 ng/ml in group M versus 1341 +/- 190 ng/ml in group Hsc, p less than 0.05). Drainage from the chest tube 24 hours after operation was 815 +/- 305 ml in group C, 644 +/- 238 ml in group M, 1133 +/- 503 ml in group Hsc, and 950 +/- 505 ml in group Hiv (p less than 0.05 for group M versus group Hsc). This study suggests that patients who receive heparin therapy before operation face a high risk of insufficient anticoagulation during cardiopulmonary bypass if standard heparin doses are used. Therefore, for patients who receive preoperative heparin therapy, a larger (500 IU/kg) initial bolus of heparin is recommended before cardiopulmonary bypass. On the other hand, patients who undergo preoperative treatment with phenprocoumon receive sufficient anticoagulative effect with a heparin bolus of 250 IU/kg.(ABSTRACT TRUNCATED AT 400 WORDS)

Antithrombin III↗

Use of the infectious disease laboratory in emergency medicine.

Until relatively recent advances in the identification of infectious agents, the emergency physician found only limited usefulness of the infectious disease laboratory. There are some tests that can provide information rapidly enough for the Emergency Department setting and new technologies that hold even greater promise for the future. The tests described in this article are currently available in most moderately sized Emergency Departments.

Bacterial Infections↗

Influence of high-dose aprotinin treatment on blood loss and coagulation patterns in patients undergoing myocardial revascularization.

Intraoperative administration of the proteinase inhibitor aprotinin causes reduction in blood loss and homologous blood requirement in patients undergoing cardiac surgery. To ascertain the blood-saving effect of aprotinin and to obtain further information about the mode of action, 40 patients undergoing primary myocardial revascularization were randomly assigned to receive either aprotinin or placebo treatment. Aprotinin was given as a bolus of 2 x 10(6) kallikrein inactivator units (KIU) before surgery followed by a continuous infusion of 5 x 10(5) KIU/h during surgery. Additionally, 2 x 10(6) KIU were added to the pump prime. Strict criteria were used to obtain a homogeneous patient selection. Total blood loss was reduced from 1,431 +/- 760 ml in the control group to 738 +/- 411 ml in the aprotinin group (P less than 0.05) and the homologous blood requirement from 838 +/- 963 ml to 163 +/- 308 ml (P less than 0.05). In the control group, 2.3 +/- 2.2 U of homologous blood or blood products were given, and in the aprotinin group, 0.63 +/- 0.96 U were given (P less than 0.05). Twenty-five percent of patients in the control group and 63% in the aprotinin group did not receive banked blood or homologous blood products. The activated clotting time as an indicator of inhibition of the contact phase of coagulation was significantly increased before heparinization in the aprotinin group (141 +/- 13 s vs. 122 +/- 25 s) and remained significantly increased until heparin was neutralized after cardiopulmonary bypass (CPB).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

New aspects of steroid hormone dependent tumor growth.

Steroids are able to modulate tumor growth. These mechanisms involve probably a complex network of events which earlier were thought to be rather independent of each other. This review summarizes some new results in steroid hormone research, concerning its influence in understanding of tumor growth, above all estrogen dependent mammary tumor growth. It focuses on the following main topics situated in the centre of research at present. 1. Steroid receptors triggering the biological action of steroids are members of a superfamily of transcriptional activators with potential growth modulating properties. The DNA-binding domain of these different proteins is highly conserved. Tumor cells possibly use some of these molecules for their own growth. 2. Hormone dependent mammary tumor growth includes probably a very complex interaction of steroids with their nuclear receptors, growth factors and their membrane receptors, proteolytic enzymes and others. Tumor cells are able to secrete a lot of different proteins in response to estradiol.

Growth Substances↗

The influence of extracorporeal circulation and hemoseparation on red cell deformability and membrane proteins in coronary artery disease.

Extracorporeal circulation and hemoseparation may lead to coupled mechanical and chemical blood trauma and thus influence red cell deformability. Ten patients with coronary artery disease underwent coronary bypass. Patients' blood samples were drawn preoperatively, after extracorporeal circulation, and after hemoseparation. Ten healthy adults served as control subjects. Red blood cell deformability was determined by direct microscopic observation of red blood cells subjected to shear stresses of 1.2 to 13.3 Pa with a counter-rotating rheoscope. Red cell membrane proteins were separated by one-dimensional polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate. At 1.2 Pa, preoperative red cell deformability was significantly greater in patients with coronary artery disease than in control subjects. Neither extracorporeal circulation nor hemoseparation changed red cell deformability significantly. Electrophoretic separation of membrane proteins failed to show any quantitative or qualitative differences between patients and control subjects. Moreover RBC membrane proteins of red blood cells in the patients were not altered as a result of extracorporeal circulation or hemoseparation. The preoperatively increased red cell deformability in the patients may be drug-induced. Our data suggest that the extracorporeal circulation and hemoseparation techniques used in this study do not lead to red blood cell damage.

Blood Transfusion, Autologous↗

Autotransfusion and hemoseparation in cardiac surgery. What can be saved in cardiac reoperations and operations of thoracic aortic aneurysms?

In 149 patients, scheduled for cardiac reoperations, repair of cyanotic heart disease or resection of aneurysms of the ascending or descending aorta, the effect of intraoperative hemoseparation was studied. The amount of autologous blood which was collected before, during, and after systemic heparinisation and processed to washed packed red cells was registered. Mean packed cell quantities gained intraoperatively were: 1275 (1006-2067) ml (descending aortic aneurysm), 1800 (1186-2500) ml (ascending aortic aneurysm), 1524 (1030-1801) ml (single valve rereplacement), 1896 (1398-2368) ml (double valve rereplacement), 946 (800-1050) ml (coronary artery reoperation), 1362 (922-1455) ml (cyanotic heart disease) and 1519 (1194-2066) ml (miscellaneous cardiac operations). In 35 patients more than 2000 ml and in 14 patients more than 3000 ml packed cells were harvested. Based on body weight, relatively more packed cells could be gained in patients with cyanotic heart disease (41 ml/kg) than in the other groups (21 ml/kg). In these young patients the application of a smaller centrifuge bowl (125 ml) can be helpful. These results demonstrate that cell saving by means of a cell separator with a special suction line and collecting system can help to reduce the donor blood requirement in cardiac operations, in which large intraoperative blood loss is anticipated.

Adolescent↗

Reduction of homologous blood requirement in cardiac surgery by intraoperative aprotinin application--clinical experience in 152 cardiac surgical patients.

The protease inhibitor aprotinin interacts with plasmin and kallikrein, which are generated in cardiac surgery during cardiopulmonary bypass (CPB). The influence of high-dose aprotinin application (2 million kallikrein inactivator units given i.v. at the beginning of anaesthesia followed by a 500,000 KIU/h infusion throughout the operation and additional 2 millions KIU added to the priming of the oxygenator) on perioperative blood loss and donor blood requirement was studied in 152 adult cardiac surgical patients. This group was compared to 317 patients having cardiac surgery without the application of aprotinin. Aprotinin reduced the homologous blood requirement by 43% (1783 +/- 100 vs 1015 +/- 131 ml, p less than 0.05), while the reduction of postoperative blood loss was 29% (1070 +/- 43 vs 761 +/- 51 ml, p less than 0.05). Fortytwo percent of the aprotinin treated patients completed their hospital stay without having any donor blood transfusion compared to 18% in the group without aprotinin. The blood saving effect was even more pronounced in operations with prolonged perfusion times. Intra- and postoperative complications were equally distributed in both groups. The blood-saving effect of aprotinin may be due to a platelet-preserving effect and/or kallikrein inhibition during CPB. There were no clinically relevant side effects related to aprotinin observed. It is concluded that high dose aprotinin therapy reduces both postoperative blood loss and homologous blood requirement, and therefore the routine application of aprotinin during cardiac surgical procedures is to be recommended.

Aprotinin↗

Reduction of blood utilization during myocardial revascularization.

The efficacy of four different blood conservation techniques in decreasing the homologous blood requirement in cardiac operations was studied prospectively in 100 patients undergoing myocardial revascularization. The patients were randomly assigned to four groups of 25 each as follows: group I, retransfusion of oxygenator blood after termination of extracorporeal circulation; group II, processing of oxygenator content by means of a cell separator; group III, predonation of autologous blood and isovolumetric substitution of hydroxyethyl starch (10 ml/kg bodyweight) after the induction of anesthesia in addition to the use of a cell separator; and group IV, predonation and the use of a cell separator plus postoperative retransfusion of shed mediastinal blood. To form homologous groups, we accepted only male patients without impairment of left ventricular function for the study. In addition, patients with internal mammary artery grafts and a duration of extracorporeal circulation less than 45 minutes or more than 90 minutes were excluded. The bank blood requirement during hospitalization was 2132 +/- 824 ml in group I, 1371 +/- 928 ml in group II, 833 +/- 599 ml in group III, and 408 +/- 559 ml in group IV. The use of blood conservation techniques resulted in reductions of homologous blood requirements of 34%, 60%, and 80%, respectively, in groups II to IV as compared with the requirement in group I. There were no complications related to autologous blood transfusion. We conclude that the use of blood conservation techniques can considerably reduce the homologous blood requirement in cardiac operations and therefore decrease transfusion-related risks.

Blood Transfusion↗

Activation of the estrogen receptor from N-nitrosomethylurea-induced rat mammary tumors.

The activation of the estrogen receptor (ER) from N-nitrosomethylurea (NMU)-induced rat mammary tumors was studied in vitro. The activation of the receptor induced by heating of the cytosol containing occupied ER was measured by a 3-4-fold increase of receptor binding to nuclei in comparison with the nuclear binding of the nonactivated ER. The activation of the ER was further shown by alteration of the elution profile from DEAE-cellulose. A shift of the receptor peak from 234 mM (Peak II, nonactivated ER) to 70 mM (Peak I, activated ER) phosphate buffer could be obtained. The overall recoveries of activated ER following chromatography on DEAE-cellulose were significantly lower than the recoveries of the nonactivated ER, 71 and 85%, respectively. Binding of the activated ER to nuclei and chromatography of the supernatant which is not able to bind to nuclei on DEAE-cellulose resulted in a decrease of Peak I and in an increase of the overall recovery. These findings suggest that the nuclear bound ER consists of two parts. One is represented partially by Peak I of the elution profile and the other one by that part of the receptor which can not be eluted from the column under the conditions used. Furthermore, the dissociation of tritiated estradiol (E3H) from the nonactivated ER followed a two component exponential function whereas after activation a monophasic dissociation curve could be observed. The mean half times for the dissociation of E3H from the activated and nonactivated ER were 101 and 7.2 min, respectively. Finally, the nonactivated molybdate stabilized ER sedimented in 5-20% sucrose density gradients as two peaks, one at 9.5 S and the other at 4 S. After activation of the ER only the smaller 4 S peak was evident. Molybdate inhibited the activation of the ER measured by nuclear binding assays, sucrose density gradient analysis, dissociation kinetics or ion exchange chromatography but not completely in every case.

Animals↗

The only inositol tetrakisphosphate detectable in avian erythrocytes is the isomer lacking phosphate at position 3: a NMR study.

Avian red blood cells contain a millimolar amount of inositol polyphosphate which plays a role as an allosteric effector of hemoglobin. We confirmed the structure of this substance by NMR techniques as purely myo-inositol 1,3,4,5,6-pentakisphosphate. Based on present knowledge this effector is synthesized from inositol trisphosphate by successive phosphorylation. In a search for biosynthetic and degradative intermediates of inositol pentakisphosphate we found only one inositol tetrakisphosphate isomer. Its structure was unambiguously assigned by proton, 13C- and 31P-NMR to myo-inositol 1,4,5,6-tetrakisphosphate. As in mammalian cells the major inositol tetrakisphosphate isomer is myo-inositol 1,3,4,5-tetrakisphosphate, there seem to be differences between avian red blood cells and mammalian cells in the routes of inositol polyphosphate formation and/or degradation.

Animals↗

Ethylene oxide in dialyzer rinsing fluid: effect of rinsing technique, dialyzer storage time, and potting compound.

Ethylene oxide (ETO) is recognized as one of the main causes of dialyzer-associated hypersensitivity reactions. We studied the amount of ETO in the rinsing fluid of ETO-sterilized hollow-fiber dialyzers as a function of rinsing technique, dialyzer storage time, and the amount of potting compound (known to be an ETO reservoir) in the dialyzer. The results suggested that the initial 500 ml of rinsing fluid removes much of the residual ETO in the dialyzer. Ethylene oxide extraction was enhanced substantially by rinsing at 37 degrees C versus 5 degrees C. However, considerable amounts of ETO remained in the dialyzer after an initial 500 ml rinse, some of which could be removed by rinsing with an additional 1,500 ml. High concentrations of ETO were measured in fluid that had been recirculated through the dialyzer for 10 min or longer and in fluid that had been allowed to remain in the dialyzer for 10 min under zero-flow conditions. The amount of ETO in the rinsing fluid decreased markedly as the dialyzer storage time was increased from 4 to 8 weeks and in dialyzers in which a portion of the potting compound had been replaced with a polycarbonate ring. Our results suggest that the dose of ETO administered to the patient at the outset of dialysis can be minimized by rinsing the dialyzer with 2 L of fluid at 37 degrees C and by avoiding administration of rinsing fluid that has been allowed to remain in contact with the dialyzer for more than several minutes. Use of a long storage interval and use of dialyzers containing reduced amounts of potting material will also reduce the ETO load.

Ethylene Oxide↗

Classification of the papillomaviruses--mapping the genome.

Papillomaviruses form one genus of the Papovaviridae family. They share common antigenic determinants and their DNAs cross-hybridize under conditions of low stringency. The classification of papillomaviruses is at present based on the host range and the relatedness of the nucleic acids. Isolates are considered independent types if there is less than 50% cross-hybridization in the liquid phase according to a standard protocol. At least 31 human and six bovine papillomavirus types can be differentiated on this basis. The host range does not reflect the natural relationship between the viruses. Subgenera, which differ in biological properties, can be distinguished in outline. Data on overall sequence homology are insufficient for a meaningful classification because two types of virus may be closely related within one genome region and rather heterogeneous in other areas. Some new isolates appear as intermediates between previously well-separated types and complicate the system. A reasonable classification of such types of papillomavirus should be based on homologies between genes that are relevant for differences in the biology of the viruses. A functional mapping of the rather uniformly organized, colinear genomes of papillomaviruses has been started. Genetic studies with bovine papillomavirus type 1 have assigned functions in replication, transformation, gene expression and capsid synthesis to individual open reading frames.

Amino Acid Sequence↗

Differential regulation of papilloma virus early gene expression in transformed fibroblasts and carcinoma cell lines.

Treatment of bovine papilloma virus (BPV) 1-transformed mouse fibroblasts with cycloheximide led to a 10-fold increase in the amount of viral transcripts, after as little as 1 h of protein synthesis inhibition. Northern blots revealed no qualitative changes in the RNA pattern. Nuclear run-on experiments showed about a 7-fold increase in specific transcriptional activity after cycloheximide treatment. The half-life of BPV1 mRNA was twice as long as in untreated controls. These results indicate that both RNA synthesis and degradation of viral RNA are controlled by labile proteins. Cycloheximide stimulation turned out to be independent of the BPV1 E2 gene activity which enhances viral transcription. Cycloheximide treatment had no effect on the amount of human papilloma virus (HPV) 18 transcripts in cervical carcinoma derived HeLa and C4-1 cells. Transcription of HPV16 in the cervical carcinoma line SiHa was likewise unaffected. The differential regulation of transcription in transformed fibroblasts and cancer-derived cells, and the significance for malignant conversion are discussed.

Amino Acid Sequence↗

Binding of estrogen receptor from N-nitrosomethylurea-induced rat mammary tumors to nuclei.

The binding of the cytoplasmic estrogen receptor (ERc) from N-nitrosomethylurea (NMU)-induced rat mammary tumors to the nucleus using a cell-free system is described. All tumors studied were estrogen-receptor-positive and most of them were hormone-dependent. Sixty-two percent of all tumors investigated (n = 134) decreased in size more than 30% 4-5 days after ovariectomy. Brief heating of the cytosol loaded with tritiated estradiol induced activation of the ERc measured by an increase of nuclear binding activity. Temperature-dependent activation was evident in every case. The optimal time and temperature of activation were 15-60 min at 30 degrees C. After denaturation of the ERc by heating for 20 min at 56 degrees C only small parts of free estradiol could be bound to nuclei. Mg2+ ions and EDTA inhibited the nuclear binding of the receptor. The nuclear binding assay was performed for 1 hr at 0-4 degrees C. After this time the activated ERc was bound nearly maximally to nuclei. Under optimized conditions 50-60% of the ERc could be bound to nuclei maximally. Using the same medium for the preparation of crude and purified nuclei the binding of the receptor to both kinds of nuclei was similar. Na2MoO4 prevented the activation of the ERc from NMU-tumors completely but did not influence the binding of the previously activated receptor to nuclei.

Animals↗