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Biomedical subjects

M R Müller

Publications and source records attributed to M R Müller.

At least 55 records · Page 3Linked to original sources

Specific activation of human mast cells by the ligand for c-kit: comparison between lung, uterus and heart mast cells.

Recent data suggest that stem cell factor (SCF or c-kit ligand, KL) is a major regulator of human mast cells (MCs). In the present study, MCs derived from the lung (n = 8), uterus (n = 14) and heart (n = 4) were analyzed for expression of c-kit receptor and for responses to recombinant SCF. MCs of all organs tested were recognized by mAbs to c-kit (YB5.B8, SR-1) as assessed by combined toluidine blue/immunofluorescence staining. Activation by rhSCF (10 ng/ml, 60 min) resulted in histamine release from lung MCs (SCF 12.8 +/- 2.7% histamine release; control 2.8 +/- 0.8%, p < 0.01), uterus MCs (SCF 16.8 +/- 5.8%; control 5.2 +/- 2.5%, p < 0.01) and heart MCs (SCF 18.4 +/- 2.6%; control 1.7 +/- 0.23%, p < 0.01). Short-term pre-incubation with rhSCF (15 min) did not result in histamine secretion (p > 0.05), but in an increase (lung 2.4 +/- 1.0 fold; uterus 2.1 +/- 1.1 fold, and heart 2.0 +/- 0.4 fold) of alpha IgE-induced mediator release (p < 0.05). The effects of SCF were dose-dependent (maximum responses at 10-100 ng/ml) and dependent on extracellular calcium. A monoclonal antibody to SCF was found to inhibit the effects of SCF on MCs. Furthermore, MCs could be desensitized specifically by pre-incubation of MCs with rhSCF in Ca-free medium. Together, these data suggest that SCF triggers mediator secretion from MCs in various organs via binding to the c-kit receptor.

Antibodies, Monoclonal↗

Minimization of hemolysis in centrifugal blood pumps: influence of different geometries.

Centrifugal blood pumps are of substantial importance for intraoperative extracorporeal circulation and for temporary cardiac assist. Their development and improvement raises many specific questions, especially on mechanical blood properties, flow distribution, and the resulting biocompatibility. In this comprehensive study the influence of various pump geometries on blood trauma was investigated. For this purpose analytical calculations, hydrodynamic performance, numerical simulation, in vitro hemolysis tests and in vivo experiments were used. The gap between rotor and housing was found to be crucial showing a distinct minimum of hemolysis at a gap of 1.5 mm (in vitro increase of plasma free hemoglobin per 100 ml plasma an hour: delta fHb/hour = 2.4 +/- 0.83 mg%/h at 1.5 mm versus 12 +/- 2.2 mg%/h at 2.5 mm; p < 0.05). Housing diameter and shape of the vanes were of less importance for blood traumatization (d = 60 mm: delta fHb/hour = 6.36 +/- 1.8 mg%/h; d = 70 mm: fHb = 7.1 +/- 1.9 mg%/h; straight radial vanes: 5.2 +/- 1.8 mg%/h; straight inclined vanes: 6.8 +/- 1.2 mg%/h; flexed vanes: 6.1 +/- 2.0 mg%/h). Three animal experiments confirmed the optimization of geometry, with a mean fHb of 2.5 to 3.2 mg% in steady state. Hydrodynamic efficiency revealed to be a necessary, but not a sufficient and sensitive criterion for hemolysis minimization (e.g. changes of eta < 10% for changes of fHb > 500%). Numerical simulation gives an improved insight in flow distribution, but can not yet be applied for quantification of blood trauma.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

[Halothane absorption by dry soda lime].

Humidified soda lime is commonly used to eliminate carbon dioxide from the circulatory system. Little is known about adverse reactions to accidentally dried soda lime. Therefore, a case of unexpected absorption of halothane by dry soda lime is reported. These observations were confirmed by a simulation with relevance to anaesthetic practice. CASE REPORT. A 46-year-old ASA class I patient was scheduled for elective surgery. After induction of general anaesthesia with 500 mg thiopentone, followed by 100 mg suxamethonium, the trachea was intubated. The patient was ventilated with nitrous oxide in oxygen and 1.5 vol% of halothane for several minutes in the induction room. After being connected to a new circulatory system in the operating theatre, the patient was ventilated but, in addition inspiratory and expiratory anaesthetic gas concentrations were measured. Despite a vaporizer position of 1.5 vol% the inspiratory concentration of halothane was below 0.2 vol%. Disconnecting the tube, the typical odour of halothane was missing in the inspiratory line of the circulatory system, but was present in the fresh gas tube. Furthermore, the lower part of the soda lime canister was surprisingly hot. After removing both the absorbers, the inspiratory halothane concentration immediately normalized. The absorbers were replaced by canisters filled with fresh soda lime, and the anaesthesia was terminated without further complications. An absorption of halothane by dried soda lime was suspected. METHODS OF SIMULATION. In the first simulation four circulatory systems with two soda lime canisters each were perfused with 21 of oxygen for 48 h. In the second simulation four soda lime canisters placed in one circulatory system were perfused with 1 l for 120 h. For measurement of halothane absorption each canister was placed in a circulatory system. The canister was perfused with a fresh gas flow of 2 l of oxygen and a vaporizer position up to 1.3 vol% of halothane. By the time an equilibrium was reached, i.e., in- and outflow concentrations of halothane were equal for a 3-min period, further halothane vaporization was stopped. In a 30-s interval the soda lime temperature and the gas concentration entering and leaving the soda lime canister were registered. Subsequently, the humidity of the soda lime was determined. RESULTS. In the first simulation 6 of the 8 canisters showed a humidity of soda lime of 15.5% of 19%, with halothane being absorbed in one case. Normally, the equilibrium between in- and outflow gas concentration was reached after 3.5-4 min. In the remaining two canisters the humidity was 14% and 9%. Only a small amount of halothane vapour was absorbed. The halothane concentrations were in equilibrium after 10 to 13 min. The probes from the second simulation revealed a humidity of soda lime of 2% to 8.7%. Below a humidity of 4% the concentration of halothane leaving the canister was greatly reduced. It took 63 min to reach a steady state in the 2% humidity probe and the temperature rose to 43.1 degrees C. CONCLUSIONS. Accidental perfusion of the circulatory system with dry oxygen can cause a reduction in the humidity of soda lime. Dried soda lime delays the increase of halothane concentration in the inspiratory limb. The absorption of halothane is accompanied by an increase in the temperature of the soda lime. Therefore, in every situation lacking a sufficient anaesthetic level during inhalation anaesthesia, absorption of the vaporized anaesthetic must be excluded. Only dried soda lime can absorb halothane.

Adsorption↗

Cytotoxicity of adriamycin, idarubicin, and vincristine in acute myeloid leukemia: chemosensitization by verapamil in relation to P-glycoprotein expression.

A 4-day colorimetric tetrazolium dye (MTT) assay was used to assess the cytotoxicity of adriamycin (ADM), vincristine (VCR), and idarubicin (IDA) in blasts isolated from 37 patients with newly diagnosed and pretreated acute myeloid leukemia (AML). The effect of verapamil (VRP) as a chemosensitizer was studied in relation to the expression of the membrane efflux pump P-glycoprotein (PGP) as determined by a semiquantitative flow-cytometric proceder. A slight positive correlation was found between the fraction of cells expressing PGP and the ID50 values for ADM and VCR, but not between cellular PGP content and sensitivity to IDA. The overall data showed no significant sensitization effect of VRP. However, in specimens with more than 10% cells expressing PGP, 2 microM VRP sensitized cells to ADM and VCR significantly. The median of sensitization ratios (SRs), i.e., the ratios of cytotoxic drug ID50 in the absence/presence of VRP, were 1.89 and 2.0, respectively. No sensitizing effect of VRP on the cytotoxicity of IDA was observed. Related to the clinical status, the median fraction of PGP-positive blasts was elevated fourfold in pretreated patients (n = 16) in comparison to patients with de novo AML (n = 19). No differences in ID50 values were observed between newly diagnosed and pretreated patients. However, SRs for ADM and VCR were higher in samples of pretreated patients compared with de novo AML. PGP-mediated cellular drug resistance may thus be circumvented in leukemic blasts by application of chemosensitizers or, potentially, alternative anthracyclines.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

[Surgery of blunt heart trauma].

Between 1972 and 1990 11 patients--all but one of them with multiple injuries--were treated surgically for blunt cardiac trauma caused by traffic accident in about 90%. Myocardial rupture (n = 3), laceration of the pericardial sac (n = 1), mitral insufficiency (n = 5; one of them in combination with atrial septal defect), ventricular septal defect (n = 1) and myocardial aneurysm (n = 1) occurred. Patients with myocardial rupture and pericardial laceration died within 2 h after admission to hospital; the other patients were successfully treated by mitral valve replacement (n = 4), mitral valvuloplasty and repair of ASD, suture repair of VSD and resection of myocardial aneurysm in one case, respectively. The interval to operation was 8 months to 12 years. Whereas pericardial tamponade caused by rupture of the atrial or ventricular wall and injuries of main coronary vessels require immediate surgical intervention, valve insufficiencies, septal defects or myocardial aneurysms may be mostly treated at a later date. Improvement of logistic measurements and the suspicion of blunt cardiac trauma followed by immediate surgical intervention may reduce the mortality rate in cases of cardiac rupture.

Adolescent↗

[Video-endoscopic interventions in thoracic surgery].

Between October and December 1991 we performed videoendoscopic procedures, including resection of lung tissue, on 9 patients in our thoracic surgery unit. A lung measuring 15 x 18 was extirpated in 1 patient and parietal pleurectomy was performed after complicated pneumothorax in 4 patients. In one of these cases it was necessary to close a parenchymal leak and in 3 cases bullae had to be removed. Resection was undertaken in 4 patients for peripheral lung nodules, in one of them for metastases. Two patients proceeded to conventional lobectomy immediately after the frozen section results came through. Closure of lung parenchyma was carried out by means of the new ENDO-GIA stapler. Duration of the procedure was less than one hour except in the case of one patient. In one case it was necessary to use three cannulae. In the other cases two cannulae (one for videoendoscopy and fixating instrument, one for preparation instrument and stapler) sufficed for the operation to be undertaken without difficulty. This new technique brings all the known advantages of minimal invasive intervention to patients requiring thoracic surgery.

Adult↗

[Differentiation antigens on normal bone marrow cells and following culture with growth factors in patients with acute myeloid leukemia (AML)].

In an attempt to detect residual leukemic cells during complete remission (CR), we used 4 monoclonal antibodies detecting markers at different stages of myeloid maturation. Bone marrow cells of AML patients at diagnosis/relapse or in CR were compared with normal controls at day 0 and 7, after incubation with colony stimulating factors, by the alkaline phosphatase/antialkaline phosphatase method. In AML patients at diagnosis/relapse, the expression of the early differentiation markers (CD34, HLA DR) was significantly increased and that of the late marker CD15 significantly decreased at day 0. After day 7 liquid cultures, the markers HLA DR and CD13 were significantly increased and CD15 significantly decreased. During CR a significant increase in day 7 liquid cultures of the markers HLA DR and CD13 was found compared to normal controls. These results may reflect the proliferation in culture of residual leukemic cells in CR patients.

Adolescent↗

Differential properties of cisplatin and tetraplatin with respect to cytotoxicity and perturbation of cellular glutathione levels.

We compared the cytotoxicity and the effects on the levels of cellular glutathione (GSH) of cisplatin and tetraplatin in the mouse mammary tumour cell line EMT6/P and a cisplatin-resistant variant. EMT6/CPR. EMT6/CPR showed a 2.5-fold resistance to cisplatin but no cross-resistance to tetraplatin. Basal cellular GSH levels in the resistant line were 1.7-fold those in the parent cell line. On exposure of cells to cisplatin, cellular GSH levels initially dropped in both cell lines but subsequently rose. At between 1 and 4 h after the onset of drug exposure, GSH levels were up to 2-fold the baseline levels. The cisplatin-resistant subline displayed higher GSH levels than the parent cell line at all time points. Tetraplatin failed to influence cellular GSH levels in either of the cell lines.

Animals↗

Computerized acquisition and evaluation of whole blood aggregometry data.

A special-purpose software package has been developed to acquire and analyze analog signals from a whole blood aggregometer. Up to four independent blood samples can be analyzed simultaneously or with arbitrary delays in time. The user menu ensures proper calibration prior to each measurement and provides a real-time graphic display of the signals. From analog/digital converted data, several "derived diagnostic quantities" are calculated. They are constructed with the aim to mimic the process of visual inspection of aggregometry curves and thus place the intuitive diagnostics of blood platelet function on a quantitative basis.

Computer Graphics↗

[Embolic occlusion of arteries of the upper extremity].

Ninety-nine patients underwent embolectomy of upper extremity arteries; in 12% of the cases reoperation and in 4% amputation was necessary. Thrombosis is the cause of reocclusion of the brachial artery, based on endothelial lesions of the axillary passing into the brachial artery. At autopsy studies these andothelial lesions were verified by histological and electron-microscopical examinations in a high percentage. Therefore embolectomies should be performed very carefully by means of thin fogarty catheters. Postoperative anticoagulant therapy seems to improve the survival rate.

Adult↗

[Unilateral lung transplantation as an effective therapy in primary lung emphysema].

Unilateral lung transplantation is the treatment of choice for terminal restrictive lung disease. We report about three patients with end-stage pulmonary emphysema treated by single lung transplantation. All patients are alive 3, 6 and 7 months after the operation with good quality of life. Blood gases have normalized and lung function parameters have markedly improved. We conclude, that single lung transplantation can be an effective treatment for selected patients with end-stage obstructive lung diseases in the absence of chronic infections.

Adult↗

[Results of transverse tracheal resection in post-intubation tracheal stenoses].

Tracheal problems in form of stenosis and malacia are a calculated risk of long-term tracheal intubation. Results with conservative treatment of such problems by bougienage, laser therapy, biopsy, cryotherapy, local steroids, tracheal stenting, and tracheostomy are not satisfactory in a higher percentage of cases. Resectional therapy of benign tracheal lesions has become an established technique, which combines excellent functional results with a low complication incidence. We have treated 40 patients of 17 to 76 years of age with postintubation tracheal lesions by cross resection of the affected segment. Of these patients 40% had received conservative therapeutical steps preoperatively. The mean resection length was 3.0 cm (1.5 to 6.5 cm). The perioperative morbidity was 7.8%, mortality was 2.5%. 85% of the patients operated between 1970 and 1989 were reached for a follow-up examination with x-ray, pulmonary function test and endoscopy. The patients subjective satisfaction with the operative result was good in 85%, minor in 12% and less in 3%. The objective investigations proved very good results in 90%. Our experience confirm the good results of other authors and recommend the resection treatment for cases of postintubation tracheal lesions.

Adolescent↗

[Resection of lung metastases. Results and prognostic factors].

249 thoracotomies for lung-metastases were performed in 202 patients at the 2nd Dept. of Surgery of the Vienna University Clinic till 1989. Age ranged from 2 to 78 years, 14 patients were younger than 18 years. The primary tumour was a carcinoma in 143 cases, a sarcoma in 45 cases and a melanoma in 14 patients. The primary tumour in the young patients was osteosarcoma in 8 cases, Ewing sarcoma in 2 cases and Wilms tumour in 2 patients. With a minimal follow up period of 2.5 years the 5-years-survival after metastasectomy was 42% for patients with carcinoma and 29% for the sarcoma patients. None of the patients with melanoma survived 5 years. A significant difference was found between the carcinoma and sarcoma groups with respect to survival rate. A prognostic factor was the disease-free interval in carcinoma patients. Actuarial post-thoracotomy survival in patients with osteogenic sarcoma was 34% at 5 years and 18% in the soft-tissue sarcoma group. Size of lesion, vitality of the metastases and the disease free interval correlated with survival in the osteogenic group, whilst the number of lesions was of importance in the soft-tissue group. On account of the lesser functional morbidity and the enablement to assess both lungs for treatment, the median sternotomy is recommended for cases with bilateral lung metastases. The results justify an aggressive surgical approach for the treatment of lung metastases.

Adolescent↗

The influence of sample age on collagen-induced platelet aggregation in whole blood.

Whole blood electrical aggregometry (WBEA) has become an accepted method to gain quick information on platelet disorders. Compared to the optical method WBEA is closer to physiology and less complicated, but on the other hand more difficult to standardize. Different approaches have been attempted in the past to improve the reliability and practicability of this technique. The influence of sample age has not been defined so far. In a first step a mathematical modelling program was established, which is able to characterize the aggregation curves obtained after collagen stimulation. In a mathematical analysis various characteristics of the curve function were calculated and their sensitivity for aging investigated. Regression was performed for each characteristic, and correction factors defined. Our results indicate, that whole blood specimen for collagen induced aggregation can be used without correction factor up to 30 minutes. Data obtained with an age exceeding half an hour have to be corrected following a quadratic regression.

Blood Preservation↗

Acute effects of anticonvulsant drugs on gonadotropin-stimulated and precursor-supported androgen production in the rat testis.

The possibility of direct inhibition of testicular endocrine function by carbamazepine, phenytoin, or valproate was tested using the rat Leydig cell model in vitro in order to find whether such an effect could contribute to the reduction of plasma free testosterone levels reported in male patients who take antiepileptic medications. With maximally stimulating concentrations of human choriogonadotropin (hCG) or cyclic AMP, testosterone formation was inhibited by 50% in the presence of 40 microM carbamazepine, 350 microM phenytoin, or greater than 1 mM valproate. With submaximally stimulating concentrations of hCG, leading to physiological testosterone secretion rates, half-maximal inhibition occurred in the presence of 15 microM carbamazepine, 180 microM phenytoin, or 900 microM valproate. Only the values for carbamazepine were in the clinically therapeutic range. Further investigation revealed that carbamazepine acted primarily at a target between cyclic AMP formation and cholesterol conversion to androgens. In contrast, phenytoin acted by competitive interaction at the cytochrome P450XVII which converts progesterone to androgens. Valproate had by far the lowest potential to generate adverse effects in this endocrine system.

Androgens↗

Treatment of postpneumonectomy empyema.

Postpneumonectomy empyema with or without (bronchopleural) fistula is an infrequent but serious, and often life-threatening complication. In 20 of our patients postpneumonectomy empyema was discovered. The time interval between original operation and discovery of the empyema varied from 9 days to 9 years. In two cases, the empyema had been found and treated initially at another hospital but not adequately, so that at the time of treatment by us the bronchopleural fistula had already been present for 8 and 19 years. In 13 cases a bronchial stump fistula was discovered. In five patients the fistula was successfully closed endoscopically with glue. In one patient closure was performed by transmediastinal stump resection, in three patients with a fistula thoracoplasty was performed. In three patients we achieved closure by transposition of pedicled muscle flaps. In one of these patients a septic condition could be mastered by performing window thoracotomy. Two patients without fistula were successfully treated with irrigation, and two further patients with thoracostomy. In one patient recovery was achieved by medication after puncture. Two patients died of sepsis and after thoracoplasty. If a fistula is present, drainage with irrigation and endoscopical glueing should be the initial treatment. This should be followed by resection of the bronchial stump. If there is no fistula or if the stump is too short thoracostomy is the treatment of choice. If it is not successful thoracoplasty has to be performed.

Adhesives↗

Beneficial effect of iloprost on early pulmonary function after lung preservation with modified eurocollins solution.

Prostacyclin (PGI2) has proven beneficial effects on organ preservation. Iloprost (ZK 36 374), a stable synthetic analogue with a longer half-life of 14 minutes is reported to have less hypotensive effects than PGI2 while offering increased cytoprotective and antiaggregation action. In this study its effects on lung-preservation were investigated. The heart lung block of 12 Beagle dogs was harvested after flushing of the pulmonary artery with 60 ml/kg modified Eurocollins (MEC) solution, the left lung was stored for 4 hours and then transplanted into 12 weight-matched dogs. Prior to operation the animals were randomized into two groups with MEC solution as the only preservative in group A and an additional i.v. infusion of 1 microgram/kg/min Iloprost during 15 minutes prior to flushing and 15 micrograms/kg Iloprost administered to the perfusate in group B. Arterial pO2, alveolo-arterial oxygen difference (AaDO2) and pulmonary artery pressure (PAP) of the transplanted lungs were measured 1, 4, 12, and 24 hours after transplantation during occlusion of the contralateral pulmonal artery. The application of Iloprost resulted in a significant improvement of pO2 (p = 0.047), AaDO2 (p = 0.002) and PAP (p = 0.018) after 1 hour. Results in group B at later time points were improved without reaching statistical significance. Iloprost therefore showed beneficial effects on pulmonary function early after lung preservation with MEC.

Animals↗