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Biomedical subjects

W Engelhardt

Publications and source records attributed to W Engelhardt.

At least 55 records · Page 3Linked to original sources
PubMed1992

[Suppression of the adrenal cortex by enoximone. A proband study with documentation of the hemodynamic course].

In contrast to the bipyridine derivatives amrinone and milrinone, the phosphodiesterase III/IV inhibitor enoximone is an imidazolone that creates the possibility of inhibiting adrenal steroid synthesis, as has already been demonstrated for other imidazoles, e.g. ketoconazole and etomidate. To clarify this point we carried out a double-blind sequential study in seven healthy volunteers. METHODS. After obtaining the approval of the ethics committee and the written consent of the volunteers, 1.25 mg/kg enoximone or saline was infused intravenously over a period of 20 min using a randomized crossover design with an interval of at least 5 days between the two trials. Twenty minutes after administration of the drug, 250 micrograms ACTH was injected. Plasma cortisol was measured prior to stimulation of the adrenal cortex and 30, 60 and 120 min afterwards; levels of aldosterone and 11-desoxy-cortisol were determined after 60 min. Standard radioimmunoassays were used. Haemodynamic parameters were measured non-invasively. RESULTS. In contrast to the placebo, enoximone resulted in a significant (P < 0.01) increase in the cardiac index (from 3.2 +/- 0.7 to 3.9 +/- 0.9 l min-1 m-2) and heart rate (from 69 +/- 11 to 81 +/- 8 min-1) and a decrease in peripheral resistance (from 1120 +/- 202 to 894 +/- 183 dyn s cm-5); blood pressure fell only slightly. Following injection of ACTH there were significant increases in cortisol (from 63 +/- 29 to 274 +/- 58 micrograms/l), aldosterone (from 86 +/- 37 to 300 +/- 105 ng/l) (both P < 0.001) and 11-desoxycortisol (from 5.3 +/- 1.2 to 9.8 +/- 4.6 micrograms/l; P < 0.05). There was no difference between enoximone and placebo at any time (P > 0.2). CONCLUSIONS. This study confirms the inodilation caused by enoximone. The normal response to ACTH rules out a direct inhibitory effect of a loading dose of 1.25 mg enoximone on the adrenal cortex. As the concentration of the major metabolite of enoximone, the sulphoxide, has been shown to surmount that of the parent drug after 40 min, this also holds true for the metabolite. We conclude that in contrast to etomidate, which causes a substantial reversible adrenal suppression after a single dose of 0.2 mg/kg, enoximone 1.25 mg/kg did not interfere with corticosteroid synthesis or release. Taking into account the metabolism and pharmacokinetics of this inodilator, there is no reason to expect an inhibitory effect even after repeated dosage.

Adrenal Cortex↗
PubMed1991

Structural requirements of the cytoplasmic domains of the human macrophage Fc gamma receptor IIa and B cell Fc gamma receptor IIb2 for the endocytosis of immune complexes.

Two isotypes of the monocyte/macrophage as well as B cell Fc gamma receptor type II (FcRIIa and FcRIIb2, respectively) mainly differ in the length (76 vs. 44 amino acids) and amino acid sequence of their cytoplasmic domains. Only the eight amino acids just behind the putative transmembrane region are identical. Despite this marked difference, both FcRII mediate endocytosis of immune complexes. To determine the functional significance of the cytoplasmic domains, we expressed truncated FcRIIa and FcRIIb2 in FcR- BHK-21 cells. Mutants of both receptors containing only one amino acid (tail-minus) of the cytoplasmic domain failed to mediate immune complex uptake. The significance of the cytoplasmic domain of the receptors could be further demonstrated using a chimeric FcRIII-FcRIIa construct. Therefore we expressed an FcRIII lacking the hydrophobic carboxyl terminus (containing the putative phosphatidyl - inositol - glycan anchor site) fused inframe to the transmembrane and cytoplasmic domain of the FcRIIa in BHK-21 cells. In contrast to the wild type FcRIII, this chimeric receptor mediated immune complex uptake indistinguishable from that mediated by the FcRIIa. Receptor mutants with relatively short cytoplasmic domains (FcRIIb2: 13, and FcRIIa: 16 amino acids) revealed, that these short amino acid stretches are sufficient to allow reduced receptor-mediated endocytosis of bound ligand. Furthermore, using FcRIIa deletion mutants with a cytoplasmic domain consisting of 62, 46, and 28 amino acids, respectively, we found that the capability of these mutants to mediate immune complex uptake decreased gradually with the truncation of the cytoplasmic tails. Thus, only short amino acid sequences of the cytoplasmic domain are sufficient to enable an, albeit reduced, receptor-mediated endocytosis.

Animals↗
PubMed1991

[Diagnosis of malignant hyperthermia. The platelet test versus the in vitro contracture test].

An eight-year-old boy was scheduled for an orthopaedic operation with a clinically abortive reaction of malignant hyperthermia and a positive platelet test result. Since there has been no validation for this platelet test, we performed a muscle biopsy and the caffeine- halothane-contracture test (CHCT). The young patient was found to be negative (MHN) in CHCT. Furthermore, the valence and the validity of the used platelet test are discussed for diagnostic purposes. With regard to resulting consequences, first of all in respect of possibly false negative results, we suggest to investigate all patients classified by this platelet test with the accepted and established CHCT.

Blood Platelets↗
PubMed1991

[Risks and side effects of intraoperative autotransfusion].

At the Institute of Anesthesiology of the University of Würzburg, blood has routinely been replaced by autotransfusion in orthopedic and surgical patients since the mid-seventies. At present the Haemonetics-Cell-Saver 3 is used to prepare autologous erythrocyte concentrates. When using this or similar, older, autotransfusion machines, the most dangerous hazard is venous air embolism during manual use despite blood centrifugation and preparation. To avoid this danger, the connecting tube to the patient must be clamped during filling of the autotransfusion bag. During autotransfusion the connecting tube between blood centrifuge and retransfusion bag must be clamped. The time loss due to this management has to be accepted. Regarding coagulation disorders, autotransfusion of large amounts of blood resembles massive transfusion with homologous blood. To maintain coagulation, hemostaseological parameters (Quick, thrombin time, ATIII) should be analyzed at the latest after replacement of half the estimated blood volume. On principle, blood components should be substituted only according to measured values. The substitution of ATIII is most frequently necessary to decrease the hazard of vein thrombosis and pulmonary embolism in these patients. The hazard of blood contamination by suctioning of operating room air should be considered. The number of operating room personnel should be as low as possible. Additionally, the suction device could be constructed to function only when necessary and not continuously. When these safety measures are followed, risks of this effective blood-saving procedure are minimized.

Blood Coagulation Tests↗
PubMed1991

Endocytosis of human IgG:Fc receptor complexes by transfected BHK cells.

We have analyzed the mode of uptake of human beta FcRII molecules expressed in BHK cells (clone 2/14). When challenged with aggregated human IgG (ahIgG), these cells bind the ligand at 4 degrees C and endocytose the IgG: receptor complexes rapidly upon warming to 37 degrees C, as seen by fluorescence microscopy with antibodies directed against human IgG. Using 125I-labeled ahIgG, we found that 40% of the bound ligand was internalized within 15 min, and approximately 60% within 2 h. Surface replication and thin sectioning combined with immunogold labeling revealed that the ligand was taken up by coated vesicles and was transferred to the endosomal/lysosomal compartment. This was confirmed by confocal laser microscopy of cells double labeled for clathrin and ahIgG. After modulation of the coated vesicle pattern by hypertonic medium, ahIgG transport was impaired. These data show that a single isoform of human FcRII, expressed in an animal cell negative for Fc receptors, can use the coated vesicle based endocytic pathway of the host cell. Reincubation of cycloheximide-treated cells with a second batch of ligand showed that approximately 20% of the beta FcRII was recycled. This finding is in apparent contrast to the fate of the endogenous Fc receptors expressed on mouse macrophages.

Animals↗
PubMed1990

Distribution, inducibility and biological function of the cloned and expressed human beta Fc receptor II.

A cDNA encoding the human beta Fc gamma receptor II (FcRII) was isolated from a placental cDNA library. Analysis of the predicted amino acid sequence indicates that this receptor is synthesized with a 42-amino acid leader sequence. The mature protein consists of 249 amino acids. The leader sequence and the cytoplasmic domain are strikingly different from the CDw32 antigen but show great homology to the mouse beta 2FcR. RNA blot analysis of human cells using CDw32 and beta FcRII-specific DNA fragments demonstrated one beta FcRII transcript (1.7 kb) in B cells and in HL-60 cells which were induced to differentiate along a monocyte-macrophage pathway by phorbol 12-myristate 13-acetate treatment. Under these conditions the CDw32 transcripts (2.5 and 1.7 kb) are induced to a minor extent in HL-60 cells. In contrast, the 2.5-kb CDw32 transcript is strongly induced in HL-60 cells which have been induced to differentiate into granulocytes by exposure to dimethylsulfoxide. To determine the biological properties of the beta FcRII, we expressed the antigen in FcR- hamster cells. Only immune complexes but not monomeric human IgG were bound significantly. Bound ligand was efficiently internalized within 15 min and it was then found in vesicular structures. Thus the low-affinity beta FcRII is able to internalize ligands without cooperation with any other FcR.

Amino Acid Sequence↗
PubMed1990

Organization of human FcRII and FcRII-like (beta FcRII) genes: structural homology to HLA class I and class II genes.

Genomic EMBL 3 DNA clones representing part of the human Fc gamma receptor II and the beta Fc gamma receptor II genes were characterized. One of them contains the first five exons including the 5' flanking region of the beta FcRII gene. The signal peptide, the extracellular domains, the putative membrane spanning region, and the first amino acids of the cytoplasmic region encoded by these five exons are spread over approximately 11 kb. Another genomic DNA clone comprises four exons encoding the second extracellular domain and the transmembrane and cytoplasmic regions of the FcRII. Alignment of the genomic DNA clones reveals that these FcR genes are identically organized. Comparison of the corresponding regions of these clones shows that not only the exons are strikingly homologous but also the splice junctions and parts of the intervening sequences are conserved. Furthermore, the genomic organization of FcRII and HLA-class I resemble each other.

Antigens, Differentiation↗
PubMed1990

New site for pacemaker generators in children.

Bipolar pacemaker implantation was performed in three children, aged 5, 6 and 9 years. The two epimyocardial fishhook pacing electrodes were inserted through different incisions. After resection of the anterior part of the 5th and 6th rib, the generator was placed into a pocket with the posterior wall resulting from the remaining periostium/perichondrium and the anterior wall consisting of the isolated intercostal and pectoral muscle. The leads were brought in extrapleurally and connected to the generator. The operations were conducted without perioperative and late postoperative complications.

Child↗
PubMed1990

Transient transcatheter balloon closure of patent foramen ovale following surgical repair of critical pulmonary stenosis.

Severe cyanosis resulting from postoperative atrial right-to-left shunt is a life-threatening complication. We present a technique of transient transcatheter balloon closure of a patent foramen ovale in a newborn operated on for critical pulmonary stenosis, where the foramen ovale had been left open intraoperatively. Cardiac catheterization was performed under echocardiographic control in the intensive care unit and the foramen ovale was occluded with a water-filled balloon-catheter. Significant improvement of arterial oxygen tension allowed delayed definitive surgical closure in a second step. Unfortunately, the child developed right-sided pneumothorax postoperatively and died of cardiopulmonary failure. Nevertheless, this procedure seems a suitable way to relieve atrial right-to-left shunt temporarily until definitive surgical closure can be performed.

Anastomosis, Surgical↗
PubMed1990

[Coronary aneurysm following Kawasaki syndrome].

In 10 boys with coronary aneurysms following Kawasaki syndrome echocardiography was performed and compared to angiography with respect to its reliability in detecting coronary aneurysms. All patients had central aneurysms of the left coronary artery which were visualized by echocardiography. In contrast, only two of six central aneurysms of the right coronary artery were detected echocardiographically. None of four leftsided and five rightsided peripheral coronary aneurysms were seen by echocardiography. There was no correlation between severity of coronary lesions and the score of Asai and Kusakawa estimating the risk of aneurysms on clinical grounds. Regression of coronary aneurysms was observed in seven, persistence in two, and progression in one patient, respectively, within 7-27 months. All children are doing well without clinical evidence of myocardial ischemia. We conclude from our experience that involvement of coronary arteries is unlikely if the central parts of the left coronary artery, which can be well visualized by echocardiography, are inconspicuous. In case echocardiography suggests a coronary aneurysm we recommend angiographic investigation in order to visualize the peripheral coronary arteries.

Aspirin↗
PubMed1989

[Pulmonary segmental artery angiography in intensive care patients].

The indication for wedge angiograms in intensive-care patients within the scope of X-ray chest examination is outlined. The obligatory wedge angiogram in patients with Swan-Ganz catheter is redundant. 4 indications for this special examination are specified. As a new possibility for differentiating between the ventral or dorsal course of pulmonary vessels, an inverse ratio of arborization angles is outlined for the first time.

Catheterization, Swan-Ganz↗
PubMed1989

[ECG-controlled placement of central venous catheters in patients with atrial fibrillation].

Some workers state that sinus rhythm is essential for electrocardiographic placement of central venous catheters. We performed a prospective study to compare location control by ECG and by chest X-ray in 40 patients with absolute arrhythmia and atrial fibrillation. The criteria accepted as allowing the assumption of an intracardiac position of the catheter tip were: (1) Abrupt appearance of high-voltage P-waves when the right atrium (RA) was entered and their brisk disappearance when pulling the catheter back into the vena cava superior (VCS) and/or (2) a change in configuration and voltage of the QRS complex on withdrawal of the catheter from the right ventricle (RV). After establishment of an intracardiac position, the catheter was withdrawn until the ECG changed to show a trace identical to that seen before it had entered the heart. Then, in this study, the correct central venous position was confirmed by chest X-ray. The intravascular ECG revealed a correct placement of the catheter tip in the VCS in all patients but one. In this patient who had severe dysrhythmia, an intracardiac ECG could not be obtained, although the chest X-ray showed a correct position of the catheter in the VCS. While false-negative results (where an intracardiac catheter position cannot be documented although the catheter is in a central venous position) occasionally do occur, false-positive results (with ECG suggesting an intracardiac location read, though the catheter tip is actually in a peripheral vein) are virtually impossible.(ABSTRACT TRUNCATED AT 250 WORDS)

Atrial Fibrillation↗
PubMed1989

[Central venous catheterization with an incorporated J-wire and contamination protective sleeves for rapid venous catheterization of the external jugular vein].

The external jugular vein can easily be identified in most patients and provides an alternative access to the superior vena cava. Unfortunately, advancement of the catheter may be hampered for anatomical reasons, e.g. the presence of valves. Use of a flexible guide-wire with curved tip (J-wire), as first proposed by Blitt et al., results in a significant increase in the rate of successful cannulations. This method necessitates tedious surgical draping, however, that may not always be practicable. Therefore, a catheter was developed that is wrapped in a protective sleeve and contains a J-wire instead of the common plastic mandrin, thus making contamination during insertion impossible.

Catheterization, Central Venous↗
PubMed1988

Open comparative study with treatment-refractory depressed patients: electroconvulsive therapy--anesthetic therapy with isoflurane (preliminary report).

Isoflurane is the only routine volatile anesthetic which leads to a burst-suppression EEG in nontoxic concentrations and for which no memory impairments can be expected subsequent to anesthesia. After electrically induced spike-wave activity in electroconvulsive therapy (ECT), a brief period of a very flat EEG can be observed. This phenomenon may be closely related to the therapeutic effects of ECT. The results which have been achieved up to now in comparing ECT to anesthetic therapy with isoflurane, without seizures being induced, are presented.

Adult↗
PubMed1988

[The course of myocarditis in childhood].

Seventeen patients, aged from 2 days to 16 1/2 years, all suffering from acute myocarditis, were observed between 1975 and 1987. At the onset of the acute infection all patients had a severe disfunction of the left ventricle. Two patients died after hospital admission. Death occurred after one day and after five days, respectively. Postmortem examination showed inflammatory reaction within the myocardium with cellular infiltrates in both cases, and a variable degree of myocardial necrosis in one. The remaining 15 patients had follow-up check-ups between 2 months and 8.25 years later. Electrocardiographic abnormalities disappeared within 3 month in all patients, and the reduced fractional shortening of the left ventricle became normal in 80% of the patients after 5.5 months. At the last follow-ups one patient showed dilated cardiomyopathy. The other patients showed complete recovery regarding their functional capacity and regarding other clinical findings even though 50% still had some minor abnormalities in the echocardiogram and on the chest x-ray. Based on the findings of this follow-up investigation, the prognosis of acute myocarditis in childhood seems as being favourable, although some residual myocardial damage may occur. In most cases this residual myocardial damage is clinically and functionally insignificant. However, in some rare cases, significant chronic myocardial damage will be found.

Acute Disease↗