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Biomedical subjects

M Müller

Publications and source records attributed to M Müller.

At least 757 records · Page 42Linked to original sources
PubMed1996

RETRACTED: Cardiorespiratory changes in patients undergoing pulmonary resection using different anesthetic management techniques.

OBJECTIVE: Pulmonary resection may be associated with considerable alterations of the cardiorespiratory system. The ideal anesthetic regimen for these patients is not yet definitely determined. DESIGN: Prospective, randomized study. SETTING: Single-institutional, clinical investigation in a thoracic anesthesia department of a university hospital. PARTICIPANTS: Fifty consecutive patients scheduled for elective thoracic surgery for lung cancer. INTERVENTIONS: In 20 patients undergoing lobectomy, fentanyl/propofol/nitrous oxide/vecuronium anesthesia was used, and extubation was planned immediately after surgery (group 1A, early extubation). Another 20 patients with lobectomy were anesthetized during fentanyl/midazolam/vecuronium, and they were extubated in the intensive care unit (ICU) (group 1B, late extubation). Ten patients underwent pneumonectomy (extubation planned in the ICU) (group 2, pneumonectomy). Patients of groups 1A and 1B were selected according to a randomized sequence. MEASUREMENTS AND MAIN RESULTS: Extensive hemodynamic monitoring was performed using a pulmonary artery catheter by which right ventricular hemodynamics (right ventricular ejection fraction [RVEF], right ventricular end-systolic, and end-diastolic volumes) were additionally measured. Measurements were performed after induction of anesthesia (supine position, baseline values), before surgery (lateral position), 30 minutes after one-lung ventilation (OLV) was induced, at the end of surgery (supine position), 2 hours after surgery (in ICU), and on the morning of the first postoperative day. Pneumonectomy resulted in an increase in the pulmonary wedge pressure (from 12.2 +/- 2.9 to 18.3 +/- 3.8 mmHg) and a deterioration in right ventricular hemodynamics with a decrease in RVEF from 40.6 +/- 3.4% to 28.8 +/- 4.3% at the end of surgery. These changes were also seen on the morning of the first postoperative day. PaO2/FI02, Qs/Qt, VO2I, and DO2I were also significantly different between pneumonectomy and lobectomy patients. Intraoperatively, patients of group 1A and 1B showed almost similar cardiorespiratory data. During OLV, PaO2/FIO2 was significantly less reduced in group 1A (to 292 +/- 98 mmHg) than in group 1B (to 200 +/- 120 mmHg). Postoperatively, patients of group 1A were orientated, and physiotherapy could be started early. No relevant differences with regard to cardiorespiratory parameters were observed between group 1A and group 1B in the postoperative period until the first postoperative day. CONCLUSIONS: In comparison with lobectomy patients, pneumonectomy resulted in more pronounced and sustained deterioration in right ventricular hemodynamics. The kind of anesthesia regimen did not influence most of the cardiorespiratory parameters intraoperatively, except for Qs/Qt, which was least compromised in the propofol patients during OLV. Early extubation could safely be performed in the lobectomy patients anesthetized with propofol without showing any negative cardiorespiratory effects.

Adult↗
PubMed1996

A new method for a quantitative assessment of P-glycoprotein-related multidrug resistance in tumour cells.

A rapid, functional and quantitative diagnostic method for the estimation of the P-glycoprotein (P-gp)-dependent multidrug resistance is required in the clinical treatment of human tumours, as chemotherapy protocols and resistance-reversing agents could be applied accordingly. In the present work, by using a calcein accumulation method in combination with immunorecognition and drug-resistance studies, a new method is described for the quantitative estimation of the expression and function of the multidrug transporter. MDR1-transfected and drug-selected tumour cell lines with various levels of drug resistance were examined. The expression of P-gp and its cell-surface appearance were assessed by quantitative immunoblotting and by immunofluorescence cytometry. The transport function of the P-gp was assessed by measuring the extrusion of calcein acetoxymethyl ester (AM) with fluorometry and flow cytometry, while in parallel experiments drug resistance was directly examined in cell survival assays. The MDR1 activity factor (MAF), calculated from the calcein AM extrusion assay, is demonstrated to provide a reliable quantitative measure for MDR1 specific activity, reflecting cellular drug resistance. This relatively simple and rapid new functional P-gp assay surpasses the formerly used techniques in both sensitivity and reproducibility.

3T3 Cells↗
PubMed1996

Measurement of extracellular fluid carboplatin kinetics in melanoma metastases with microdialysis.

Clinical anti-tumour efficacy of anti-cancer drugs is a function of dose intensity, i.e. the concentration--time profile in tumour tissue. Hence, information on drug concentration profiles in tumours is of critical importance but appropriate methods for measurement are lacking. The aim of the present study was to obtain, by microdialysis sampling, concentration--time profiles in a solid tumour (melanoma) of a model anti-cancer drug, carboplatin, and thereby to assess the scope of microdialysis for tumour pharmacokinetic studies in man. Six patients with cutaneous melanoma metastases at the extremities or body trunk, scheduled to receive carboplatin (400 mg m-2 i.v.) were studied. Carboplatin concentrations were monitored in serum, intratumoral and subcutaneous tissue. Calibration of the microdialysis probes was carried out in vitro and in vivo with use of the retrodialysis method. Complete carboplatin concentration vs time profiles in tumour and subcutaneous tissue were obtained. Major pharmacokinetic parameters (maximum concentration, time to maximum concentration, area under the curve, elimination half-life) were calculated for tissues and tumour/serum concentration ratios for carboplatin were derived. Mean free concentrations of carboplatin in cutaneous melanoma metastases reached only about 50-60% of total serum levels; maximal intratumoral concentrations were 7.6 (+/-2.0; s.e.m.) microgram/ml, mean concentrations in subcutaneous tissue were similar to those in tumour. The present study demonstrates that microdialysis is a novel tool for measuring drug concentrations in solid tumours in humans in vivo and appears to be a valuable addition for pharmacokinetic/pharmacodynamic studies in oncology.

Antineoplastic Agents↗
PubMed1996

Lymphocyte apoptosis induced by CD95 (APO-1/Fas) ligand-expressing tumor cells--a mechanism of immune evasion?

The CD95 (APO-1/Fas) system is an important mediator of T-cell cytotoxicity. We investigated this system in 22 hepatocellular carcinomas (HCCs) from patients. All HCCs had partially or completely lost the expression of the CD95 receptor constitutively expressed by normal liver cells and might thus evade CD95-mediated killing. We also considered a new mechanism of immune evasion, namely, the active destruction of T-lymphocytes by tumor cells expressing CD95 ligand (CD95L). CD95L messenger RNA and protein could be detected in the HCCs. In coculture experiments, HepG2 hepatoblastoma cells, expressing CD95L mRNA after treatment with cytostatic drugs, killed CD95+ Jurkat lymphocytes. Our data suggest that tumor cells can evade immune attack by down-regulation of the CD95 receptor and killing of lymphocytes through expression of CD95L.

Antimetabolites, Antineoplastic↗
PubMed1996

First-pass uptake of methotrexate after intra-arterial bolus injection in human head and neck cancers.

The aim of this study was to quantify first-pass uptake of methotrexate into tumour and healthy tissue after intra-arterial (i.a.) injection in patients with head and neck cancers. Twenty-one patients were studied; during surgery, a bolus injection of 10 mg of 3H-labelled methotrexate was administered into the tumour-supplying artery. At 15-20 s after injection, and again 2-3 h later, a biopsy of the tumour and of surrounding healthy tissue was taken and radioactivity was measured. In 8 of 17 pretreated patients the biopsy specimens contained no tumour cells. In tumour-bearing patients, radioactivity in tumour was three times higher than in healthy tissue (P = 0.006). In tumour-negative patients there was no difference in activity between the two biopsy sites (P = 0.889). However, after 2-3 h the concentration of methotrexate in all surgical specimens returned to near background level and the initial difference between tumour-positive and tumour-negative samples was lost. Our results show that i.a. injection of methotrexate does not necessarily lead to high tumour cell exposure.

Antimetabolites, Antineoplastic↗
PubMed1996

High-pressure freezing of tissue obtained by fine-needle biopsy.

High-pressure freezing (HPF) permits adequate cryoimmobilization (without detectable ice crystals after freeze-substitution) of biological tissue up to a thickness of about 200 microns. Until now the preparation of tissue prior to freezing has been unsatisfactory: sizing of the tissue to the required dimensions takes minutes, during which structural alterations must occur. We demonstrate that the use of a fine-needle biopsy technique minimizes tissue damage and guarantees sample dimensions close to the optimal thickness for HPF. The tissue cores can be cryoimmobilized within 40 s of excision.

Animals↗
PubMed1996

Analysis of efficiency of two-photon versus single-photon absorption of fluorescence generation in biological objects.

Starting from basic absorption cross-section values and breakdown limitations on possible field strengths it is shown that the total exposure required for equivalent fluorescence generation by single-photon absorption (SPA) is at least an order of magnitude lower than by two-photon absorption (TPA). The difference is such that TPA may in fact in many cases offer no advantage over SPA with respect to the damage induced during fluorescence imaging of biological materials.

Absorption↗
PubMed1996

Secretion of organic anions by hepatocytes: involvement of homologues of the multidrug resistance protein.

The canalicular multispecific organic anion transporter (cMOAT) is one of at least four ATP-dependent transport systems identified so far in the canalicular membrane domain. Using mutant rat strains that lack organic anion secretion, the substrate specificity of cMOAT has been characterized. cMOAT appears to be responsible for the elimination of amphipathic anionic conjugates formed by phase II conjugation. Very recently it has been shown that the hepatocyte-specific homologue (MRP2) of the multidrug resistance protein (MRP1) functions as cMOAT in the canalicular membrane, whereas MRP1 is present in the lateral membrane only at very low levels in quiescent cells. The defective excretion of organic anions in TR- rate livers is caused by the total absence of mrp2 due to a deletion of one nucleotide in the mrp2 gene. In conclusion, the liver-specific mrp2/MRP2, a new member of the ATP-binding cassette superfamily, appears to function as cMOAT in the hepatobiliary secretion of organic anions.

ATP Binding Cassette Transporter, Subfamily B↗
PubMed1996

[Clinical relevance of mammography in men].

PURPOSE: During a period of four years 104 mammograms were performed in 89 men. Mastectomies were carried out on 23 men (group 1). 66 patients (group 2) were followed up clinically and in 15 patients serial mammograms were obtained. MATERIAL AND METHOD: In group 1 there were 5 patients with bilateral gynaecomastia, 9 with unilateral gynaecomastia and two with pseudogynaecomastia and there were 7 patients with malignancies. In group 2 there were 46 patients with bilateral gynaecomastia and 10 patients with unilateral gynaecomastia. Pseudogynaecomastia was found in 25 patients. There were 7 malignancies, of which 5 had been suspected clinically and one had been diagnosed as gynaecomastia by mammography. Two carcinomas in situ were missed clinically and also by mammography. CONCLUSION: When malignancy is not suspected on clinical grounds the first examination should be sonography, mammography being reserved for cases of doubt. Where, however, malignancy is suspected, and for follow-up, mammography retains its primary position.

Adolescent↗
PubMed1996

[Schwannoma of the obturatorius nerve as differential diagnosis in cystic adnexa tumors].

We report on a case of benign retroperitoneal schwannoma involving the obturator nerve. Discussing the difficulties of diagnosis and treatment the following became clear: 1.) Clinical examination, ultrasound and computed tomography are not helpful to differentiate a retroperitoneal schwannoma from a cystic ovarian tumour; this problem can perhaps be overcome by MR imaging. 2.) The diagnosis should be borne in mind in cases of retroperitoneal tumours of unclear origin. Appropriate surgery is necessary to avoid nerve damage and paralysis.

Aged↗
PubMed1996

[Blood supply to the liver in the human after 1 MAC desflurane in comparison with isoflurane and halothane].

OBJECTIVE: Objective of this investigation was to compare the effects of the new inhalation agent desflurane with equipotent doses of isoflurane and halothane on hepatic blood flow (tHBF). METHODS: 36 Patients scheduled for elective aortocoronary bypass grafting were enrolled to the study. tHBF was assessed by plasma clearance and hepatic extraction of indocyanine green, and standard haemodynamic parameters were measured by thermodilution technique. The measurements were performed awake and after intubation at equilibration of 1 MAC. All measurements were terminated before skin incision. RESULTS: We found a significant decrease of tHBF in all patients regardless of the inhalation agent used (H 918 ml/min +/- 107 to 625 ml/min +/- 181, I 930 ml/min +/- 195 to 637 ml/min +/- 137, D 940 ml/min +/- 129 to 677 ml/min +/- 122). The tHBF in relation to cardiac output also decreased significantly (H 17% +/- 5 to 14% +/- 3, I 16% +/- 3 to 14% +/- 5, D 20% +/- 5 to 18% +/- 6). No difference was seen between the groups according to tHBF and haemodynamics. CONCLUSION: The results of this study suggest that all inhalation agents included in the study significantly decreased tHBF during anaesthesia with the concentration of 1 MAC.

Aged↗
PubMed1996

Oral cadmium exposure of adults in Germany. 1: Cadmium content of foodstuffs and beverages.

The cadmium contents of 94 and 105 foodstuffs bought in six-fold repetition in 1988 and in nine-fold repetition in 1991, respectively were analysed within the framework of a market-basket study. These foodstuffs were typical of German eating habits. Additionally, 170 samples of drinking water were investigated. The cadmium concentrations of the foodstuffs were comparable with results of recent studies carried out in Europe and North America. Fruit, milk and dairy products, sugar and sugar-rich foodstuffs as well as beverages showed mean cadmium contents < or = 5 ng/g fresh matter or ng/ml, respectively. The cadmium content of meat, sausage, fish and tinned fish was also low. Pork and beef, the most important kinds of meat, contained 5.4 and 2.5 ng/g on average. The majority of the vegetables investigated, including potatoes, had cadmium concentrations < 25 ng/g. However, individuals samples of lettuce showed very high cadmium levels. The cadmium content of bread, cakes and pastries as well as farinaceous products were within the range of 20-40 ng/g. The most important bread, cakes and pastries (wheat and rye bread, toasted bread, rolls) contained 25-35 ng/g. A median cadmium concentration of 0.2 micrograms/l was found in the drinking water. As expected, liver and kidneys showed the highest cadmium levels of 73 and 204 ng/g, respectively on average.

Adult↗
PubMed1996

Mapping of an autoreactive epitope within glutamate decarboxylase using a diabetes-associated human monoclonal autoantibody and an epitope cDNA library.

Glutamate decarboxylase (GAD65) is a major autoantigen in insulin-dependent diabetes (IDDM) and the neurological disorder Stiff-Man-Syndrome (SMS). We derived a human monoclonal autoantibody (MICA 2) from peripheral blood of a patient newly diagnosed with IDDM, which reacted with GAD65 in Western blots. This indicated that a linear epitope is recognized by MICA 2. Using an epitope cDNA library we mapped the MICA 2 epitope to a contiguous stretch of 26 amino acids (506-531) in the C-terminus of GAD65. Neither blocking experiments with synthetic peptides nor analysis of overlapping decapeptides expressed as fusion proteins allowed us to further narrow down the epitope to the typical size of linear epitopes of 6-8 amino acids. We suggest that a miniconformational epitope provided by amino acids 506-531 is recognized by MICA 2, which withstands SDS gel electrophoresis without destruction or partially refolds during the Western blot procedure. A sequence homology with human heat shock protein 60 (HSP60) maps to this region of GAD65 but no cross-reactivity of MICA 2 with HSP60 occurred. Our data demonstrate that reactivity of an antibody in Western blots does not necessarily define a classic linear epitope of 6-8 amino acids and describe a new autoreactive epitope in GAD65 different from those reported for sera from patients with SMS.

Amino Acid Sequence↗
PubMed1996

The effects of albumin versus hydroxyethyl starch solution on cardiorespiratory and circulatory variables in critically ill patients.

Sufficient intravascular fluid therapy is of major importance in the treatment of the critically ill patient. The present study assessed whether the cardiorespiratory response of long-term volume replacement with low-molecular weight (LMW) hydroxyethyl starch solution (HES) differs from that of human albumin (HA). According to a randomized sequence, 30 trauma patients (injury severity score [ISS] between 15 and 30) and 30 sepsis patients (secondary to major general surgery) received either 10% HES (mean molecular weight 200,000 daltons; HES trauma [n = 15], HES sepsis [n = 15]) or human albumin 20% (HA trauma [n = 15], HA sepsis [n = 15]) over 5 days to keep pulmonary capillary wedge pressure (PCWP) between 12 and 18 mm Hg. Cardiorespiratory variables were measured by a pulmonary artery catheter on the day of inclusion into the study and daily during the next 5 days. Gastric intramucosal pH (pHi) was measured by tonometry. Central venous pressure and PCWP were comparable within the subgroups (trauma/sepsis) throughout the entire study period. In the trauma patients, cardiac index (CI), oxygen consumption index (VO2I), and oxygen delivery index (DO2I), significantly increased only in the HES-treated patients. In the sepsis patients, CI, VO2I, and DO2I increased and remained higher than baseline only in the HES group (P < 0.01). Right ventricular ejection fraction (RVEF) was reduced (< 40%) in the HA patients and increased only in the HES patients (from 34% +/- 4% to 42% +/- 3%; P < 0.05). pHi remained normal (> 7.35) in both trauma groups and in the HES-treated sepsis patients. In the HA sepsis group, pH, decreased (> 7.20) within the study period (7.15 +/- 0.12 on Day 4), indicating deteriorated splanchnic perfusion. We conclude that long-term intravascular fluid therapy with HA in traumatized and sepsis patients has no advantages in comparison to LMW-HES. In both groups, volume replacement with HES even resulted in improved systemic hemodynamics. Decrease in pHi in the sepsis patients was blunted by HES infusion indicating improved splanchnic perfusion by this regimen of volume therapy.

Adult↗
PubMed1996

Influence of long-term continuous intravenous administration of pentoxifylline on endothelial-related coagulation in critically ill patients.

OBJECTIVE: To determine the influence of pentoxifylline on endothelial-associated coagulation. DESIGN: Prospective, randomized, placebo-controlled study. SETTING: A surgical intensive care unit of a university hospital. PATIENTS: Consecutive patients (n = 60) with trauma or sepsis secondary to major (nontrauma) surgery. All patients received controlled mechanical ventilation. INTERVENTIONS: According to a randomized sequence, the patients either received pentoxifylline continuously over 5 days (1.5 mg/kg/hr iv) (trauma-pentoxifylline group [n = 15], sepsis-pentoxifylline group [n=15] or saline solution as placebo (trauma-control group [n = 15], sepsis-control group [n = 15]. MEASUREMENTS AND MAIN RESULTS: In addition to the standard coagulation screen, thrombomodulin, protein C, (free) protein S, and thrombin-antithrombin plasma concentrations were measured by enzyme-linked immunosorbent assays. Intensive care therapy, hemodynamics, and changes of Acute Physiology and Chronic Health Evaluation II score were comparable for pentoxifylline-treated and nontreated patients. An average dose of 2.5 g/day of pentoxifylline (range 2.2 to 2.9) was infused into the pentoxifylline-treated patients. At baseline, plasma thrombomodulin concentrations were higher in the septic patients than in the trauma patients. Thrombomodulin plasma concentrations increased significantly more in the control patients (trauma: from 38.9 +/- 10.5 to 59.9 +/- 10.1 ng/mL; sepsis: from 49.7 +/- 12.1 to 72.3 +/- 11.2 ng/mL) than in the pentoxifylline-treated patients (trauma: from 37.9 +/- 11.9 to 50.2 +/- 9.2 ng/mL; sepsis from 51.9 +/- 10.1 to 63.3 +/- 10.2). Starting from similar baseline values, protein C concentration increased significantly more in the sepsis-pentoxifylline patients (from 52.0 +/- 11.1% to 69.1 +/- 11.1%) than in the untreated septic patients (from 50.1 +/- 10.0% to 52.5 +/- 9.5%). There were no significant differences between the pentoxifylline-treated and nontreated groups for protein S and thrombin-antithrombin concentrations. Standard coagulation parameters (fibrinogen, activated partial thromboplastin time, antithrombin III) did not differ between these groups either. CONCLUSIONS: Continuous intravenous administration of pentoxifylline for 5 days beneficially influenced the thrombomodulin/protein C/protein S system in both the trauma and septic patients.

APACHE↗