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D Fröhlich

Publications and source records attributed to D Fröhlich.

At least 37 records · Page 2Linked to original sources
PubMed1999

Reduced antilisterial activity of TNF-deficient bone marrow-derived macrophages is due to impaired superoxide production.

Mice deficient for TNF ligand and receptor type 1 have demonstrated the importance of TNF in the host defense against Listeria monocytogenes. To investigate the particular deficiency of macrophages derived from TNF/lymphotoxin (LT)-alpha(-/-) mice in antilisterial growth control, bone marrow-derived macrophages (BMDM) were used for in vitro infection experiments. After the combined treatment with IFN-gamma and lipopolysaccharide (LPS), production of NO by wild-type (wt) and TNF/LT-alpha(-/-) BMDM was induced to comparable levels, but only wt BMDM controlled L. monocytogenes growth efficiently. Nevertheless, inhibition of NO production led to a remarkable loss of antilisterial activity. This suggests that presence of NO is necessary but not sufficient for L. monocytogenes killing and that elimination of L. monocytogenes requires additional effector molecules. The LPS-inducible superoxide production of TNF/LT-alpha(-/-) BMDM was impaired. Accordingly both scavenging of superoxide and peroxynitrite led to reduced L. monocytogenes killing by wt BMDM. In addition, peroxynitrite was able to kill L. monocytogenes in vitro. Together these findings suggest that the defective host defense of TNF/LT-alpha-deficient mice against L. monocytogenes partially stems from reduced superoxide production of macrophages due to the absence of TNF and imply a function for peroxynitrite, the reaction product of NO and superoxide, in the intracellular killing of L. monocytogenes.

Animals↗
PubMed1999

Proteolytic destruction of functional proteins by phagocytes in human peritonitis.

BACKGROUND: Besides phagocyte-derived oxidative autoaggression, proteolytic destruction of functional proteins in the peritoneal cavity may also be involved in the pathomechanism of secondary peritonitis. To evaluate the pattern of proteolysis, 43 patients undergoing initial operation for acute peritonitis (n = 30) or scheduled abdominal lavages (Etappenlavage) for resolution of persistent peritonitis (n = 13) and 16 surgical patients with abdominal exudation without peritonitis were enrolled in our study. MATERIALS AND METHODS: Thirty blood samples and purulent exudates were taken simultaneously in each peritonitis group at the surgical interventions. Sixteen clear exudates were obtained from patients with post-operative non-infectious irritations. The following parameters were measured: (a) elastase (from neutrophils) and cathepsin B (from monocytes/macrophages); (b) alpha1-proteinase inhibitor (alpha1PI) and overall cysteine proteinase inhibitor capacity; and (c) opsonic activity and degradation products of fibrinogen, complement C3 and immunoglobulin IgG. RESULTS: Circulating levels of phagocyte proteinases and of alpha1PI were significantly elevated, whereas antigen concentrations and opsonic activity of C3 and IgG were slightly reduced in peritonitis patients compared to healthy volunteers. No degradation products were detectable in patients' blood. Discharge of phagocyte proteinases was even more pronounced in both types of peritonitis exudates. Although most of the elastase was complexed with alpha1PI, active elastase and its specific fibrinogen split product was found along with significantly reduced inhibitory capacity for elastase and cysteine proteinases. Local opsonic activity was dramatically diminished because of proteolytic degradation of C3 and IgG. Despite some phagocyte proteinase release, no destruction of functional proteins was seen in clear exudates. CONCLUSIONS: Higher values of extracellularly released phagocyte proteinases concomitant with lower opsonin activity in exudates from patients with persistent peritonitis can be taken as a further hint of the involvement of local proteolysis-induced pathomechanisms in the development of lethal multiple organ failure, which occurred more frequently in patients with persistent peritonitis (54%) than in those with acute peritonitis (27%).

Adolescent↗
PubMed1999

[Cytoprotection with amifostine in the framework of radiochemotherapy in previously irradiated head and neck carcinoma].

PURPOSE: The radiotherapeutic possibilities are limited for patients with a recurrent or second head and neck cancer if the patient was already irradiated in the first therapy. In the presented study we investigated the changes of this situation due to the usage of amifostine in the case of re-irradiation (simultaneous radio-chemotherapy). PATIENTS AND METHODS: Between 1995 and 1997 we treated 14 patients with a recurrent or second malignancy of the head and neck region by a simultaneous radio-chemotherapy (20 x 1.5 Gy, Carboplatin 70 mg/m2 BSA on days 1 to 5 and 16 to 20, 500 mg amifostine prior to every carboplatin infusion). Six out of 14 patients got an additional brachytherapy (10 to 15 Gy) to increase the local dose because of a residual tumor. In 4 cases the treatment was an adjunctive one, following the surgical tumor debulking. RESULTS: We have seen 3 complete remissions (21.4%), and 8 partial remissions (57.1%). The median time of observation is 13 months now. Three out of 14 patients died, 2 because of the tumor. Hematological toxicities: side effects Grade 2 WHO were seen only in 1 patient. Acute non-hematological toxicities: mucositis Grade 0/1 in 7 patients, mucositis Grade 2 in 7 patients, dysphagia Grade 0/1 in 9 patients, dysphagia Grade 2 in 5 patients, xerostomia Grade 1 in 9 patients, xerostomia Grade 2 in 3 patients. We registrated only 1 serious late toxicity due to radio-chemotherapy: 4 months after brachytherapy a patient (with laryngectomy) developed a submental fistula. CONCLUSION: These first results suggest that the usage of amifostine offers new potential ways for re-irradiation of patients with recurrent or second malignancies in the head neck region.

Adult↗
PubMed1998

Nitrous oxide impairs the signaling of neutrophils downstream of receptors.

(1) Nitrous oxide has been shown to impair the oxidative function of neutrophils. (2) To characterize the type and the site of the drug interaction, receptor expression, cytosolic-free calcium, and H2O2 production of neutrophils were assessed using flow cytometry. (3) Nitrous oxide depresses receptor-dependent generation of H2O2 in a concentration-dependent manner. The response upon direct activation of protein kinase C (PKC) was unaffected. (4) No interference was found at the receptor sites, the linked G proteins, and the subsequent release of Ca2+, indicating a localization of the nitrous oxide interaction downstream of receptors and G proteins at or near to PKC.

Anesthetics, Inhalation↗
PubMed1998

The Fcgamma receptor-mediated respiratory burst of rolling neutrophils to cytokine-activated, immune complex-bearing endothelial cells depends on L-selectin but not on E-selectin.

Intracellular H2O2 generation, as a measure of the respiratory burst, was determined after stimulation of neutrophils by immune complex (IC)-bearing human umbilical vein endothelial cells. Under static conditions, neutrophils basically responded to the immune deposits on resting endothelial cells. The rotating shear forces of approximately 0.7 dynes/cm2, corresponding to the physiological flow in postcapillary venules, completely abolished this basal H2O2 generation. After activation of the IC-bearing endothelial layers with interleukin-1 (IL-1) or tumor necrosis factor (TNF), or both, for 4 hours, rolling adhesion of the neutrophils was induced, accompanied by considerable H2O2 production. The neutrophil respiratory burst was prominently inhibited by anti-FcgammaRIII MoAb 3G8 (72.4%), and partially by MoAb 2E1 against FcgammaRII (38.5%). Both MoAbs together inhibited the Fc-mediated H2O2 generation by 93. 4%. The respiratory burst and rolling adhesion were markedly blocked by MoAb LAM1-3 against L-selectin (91.3%), whereas the nonfunctional anti-L-selectin MoAb LAM1-14 was ineffective. F(ab)2' fragments of MoAb 7A9 against E-selectin inhibited neutrophil rolling by 98.6%, but not the respiratory burst. Moreover, rolling adhesion of neutrophils and the related oxidative burst were CD11b/CD18- independent. In summary, L-selectin has a unique auxiliary function in triggering the FcgammaR-mediated respiratory burst of rolling neutrophils to IC-bearing endothelial cells, thereby substituting CD11b/CD18 under conditions of flow.

Antigen-Antibody Complex↗
PubMed1998

Selective cytoprotection with amifostine in concurrent radiochemotherapy for head and neck cancer.

BACKGROUND: Amifostine has reduced toxicities associated with radiation therapy and platinum-based chemotherapy. In a phase II randomized trial, we investigated the ability of amifostine to reduce the toxicity of carboplatin plus radiotherapy (RCT) in patients with head and neck cancer. PATIENTS AND METHODS: Thirty-nine patients with stage III or IV squamous cell carcinomas of the head and neck received RCT (following surgery or as primary treatment). Radiotherapy was given five days per week with daily fractions of 2 Gy, up to a total dose of 60 Gy in conjunction with carboplatin 70 mg/m2 on days 1 through 5 and days 21 through 26. Eligible patients were randomised to receive RCT alone or preceded by a rapid infusion of amifostine (500 mg) on the days when carboplatin was administered. RESULTS: Patients receiving amifostine + RCT (n = 25) had significantly reduced mucositis (P = 0.0001) and xerostomia (P = 0.0001) in comparison with patients receiving RCT alone (n = 14). Additionally, patients receiving amifostine + RCT had significantly less thrombocytopenia (P = 0.001) and leukopenia (P = 0.001). At 12 months following therapy, 79% of patients receiving amifostine + RCT had no evidence of disease compared with 64% of those receiving RCT alone. CONCLUSIONS: Amifostine reduces the RCT-induced toxicities in patients with head and neck cancer and has no negative impact on antitumour efficacy.

Adult↗
PubMed1998

Nitrous oxide impairs the neutrophil oxidative response.

BACKGROUND: Nitrous oxide has been shown inconsistently to impair the oxidative function of neutrophils. The choice of the stimulus, receptor agonists, or stimuli acting independent of receptors seems to determine whether nitrous oxide impairs the oxidative functions, suggesting an interference with the cytosolic signaling of neutrophils. METHODS: Production of hydrogen peroxide by neutrophils was assessed using flow cytometric analysis. N-formyl-methionyl-leucyl-phenylalanine (FMLP), C5a, dioctanylglycerol, and phorbol-12-myristate-13-acetate were used as stimuli. In addition, the expression of receptors for FMLP and the cytosolic-free calcium response of cells were measured. RESULTS: Nitrous oxide depresses C5a- or FMLP-induced generation of reactive oxygen derivatives in a concentration-dependent manner. However, the response with direct activation of protein kinase C was unaffected. Further, the number of FMLP receptors and the cytosolic calcium response were unaffected. Inhibition of the oxidative response was not reversible within the observation period of 4 h. CONCLUSIONS: Nitrous oxide inhibited the intracellular signaling of the investigated G-protein-coupled receptors for chemotactic peptides. No interference of nitrous oxide with reduced nicotinamide adenine dinucleotide phosphate oxidase, the oxidative enzyme system of neutrophils, nor with its activation through protein kinase C was detected.

Adult↗
PubMed1998

Volatile anaesthetics induce changes in the expression of P-selectin and glycoprotein Ib on the surface of platelets in vitro.

Halothane has been shown to inhibit platelet aggregation and may, therefore, prevent intraoperative platelet activation. The aim of this study was to compare the effects of volatile anaesthetics on platelet activation, including the transformation into an adhesive platelet phenotype. After in vitro exposure to volatile anaesthetics, the expression of the adhesion molecule P-selectin and the internalization of the receptor for the von Willebrand factor (GPlb) were analysed by flow cytometry. In contrast to desflurane or N2O, sevoflurane (> or = 0.5 MAC, P < 0.05), halothane (> or = 1.0 MAC, P < 0.01) and isoflurane (> or = 2.0 MAC, P < 0.01) induced a significantly higher expression of P-selectin on the surface of platelets, indicating the degranulation of alpha-granules. In the presence of desflurane (> or = 0.5 MAC, P < 0.05), halothane (> or = 1.0 MAC, P < 0.01), isoflurane and sevoflurane (both > or = 2.0 MAC, P < 0.01), a redistribution of GPlb occurred, indicating platelet activation. N2O had no effect. In conclusion, several of the volatile anaesthetics tested in vitro induced changes in the expression of P-selectin and GPlb, being characteristic of platelet activation. None of the anaesthetics investigated interfered with the platelet response to ADP stimulation.

Adult↗
PubMed1997

Perioperative pattern of peritoneal interleukin 8, tumour necrosis factor-alpha, and granulocyte elastase release in human secondary peritonitis.

Cytokine levels during infection and sepsis have been extensively studied in the past. In contrast to the excellent data on tumour necrosis factor alpha (TNF-alpha), interleukin 8 (IL-8), and polymorphonuclear (PMN) granulocyte elastase (PMN-E) concentrations in blood, little is known about cytokine and PMN-E levels in tissue or local fluids like abdominal exudate in secondary, purulent peritonitis of man. Therefore, the authors studied perioperative intra-abdominal levels of TNF-alpha, IL-8 and PMN-E in 21 patients with severe purulent peritonitis. The average pre-operative levels of TNF-alpha were 694 +/- 239 pg/ml in exudate and 26 +/- 6 pg/ml in plasma, for IL-8 100 +/- 34 ng/ml and 0.7 +/- 0.5 ng/ml, and for PMN-E 68 +/- 14 microg/ml and 0.7 +/- 0.1 microg/ml, respectively. Standard surgical procedures reduced the intra-abdominal concentrations of cytokines and PMN-E to as low as one tenth of the pre-operative levels. Postoperatively, TNF-alpha and IL-8 levels recovered rapidly and pre-operative levels of IL-8 were reached again after 1 h and for TNF-alpha after 8 h. PMN-E concentration remained below the initial baseline within 8 h of observation. TNF-alpha concentration, but not IL-8 or PMN-E, depended on the microbiological load of the abdominal exudate (< or > 10(3) cfu/ml). There were no significant differences in the intra-abdominal or plasma levels of cytokines or PMN-E between survivors and non-survivors at any observation time.

APACHE↗
PubMed1997

Oxidative autoaggression by phagocytes in human peritonitis.

In 60 abdominal exudates from patients with the diagnosis of either acute or persistent (chronic) peritonitis, indicators of phagocyte-derived oxidative systems (myeloperoxidase, chemiluminescence) and proteases (elastase) were measured. These exudates reveal a picture of maximal inflammatory activation. Both types of exudates (30 each) showed a significant influx of inflammatory cells, with the mean leucocyte count being 73,000 microL and 32,000 microL-1 respectively. Local myeloperoxidase concentrations were approximately 1000-fold greater than that of normal plasma. Spontaneous and elicitable chemiluminescence--indicators of phagocyte respiratory burst activity--were dramatically increased. In addition, levels of extracellularly released elastase (from neutrophils) were found to be up to about 1000-fold that of normal plasma values. Although most of the elastase detected in the exudates was complexed with alpha 1-proteinase inhibitor (alpha 1 PI), enzymatically active elastase could be measured in approximately 60% of the samples being investigated. As there was an excess of immunoreactive alpha 1 PI in these exudates, the free elastase activity implies that much of the alpha 1 PI was inactive, presumably subjected to oxidative destruction. Moreover, a trypsin-inhibitory activity to antigen ratio below 1 (mean = 0.81) in 75% of the purulent exudates indicated also partial proteolytic degradation of alpha 1 PI. In contrast, 16 clear exudates (no bacteria, white cell count below 500 microL-1) taken from the non-infected peritoneal cavity of patients undergoing intra-abdominal surgery revealed a similar permeability increase of the peritoneum but did not show relevant oxidative and proteolytic activity or destruction of alpha 1 PI compared with purulent specimens. Thus, only the inflammatory process of peritonitis appears to result in an overwhelming local phagocytic activity that initiates and maintains protease inhibitor consumption and/or inactivation. The tremendous oxidative potential found in purulent exudates may cause destruction in a wide variety of defence systems.

Adolescent↗
PubMed1997

Laryngeal mask airway and uncuffed tracheal tubes are equally effective for low flow or closed system anaesthesia in children.

Low flow and closed system anaesthesia have considerable advantages in economy, limited atmospheric pollution, and maintenance of humidification and temperature. To benefit from these techniques leakage from the breathing system should be as low as possible. The sealing of the airway is crucial to ensure this. Therefore, we have investigated in 30 children, aged 2-6 yr, the effectiveness of the laryngeal mask airway (LMA) and the uncuffed tracheal tube (TT) for closed system paediatric anaesthesia, during positive pressure ventilation, in a prospective, randomized study. Ventilation was adequate in all cases with both devices. Loss of gas from the breathing system was less than 100 ml min-1 in 13 (87%) patients in the LMA and in 12 (80%) patients in the TT group, with a maximum of approximately 700 ml min-1 in the TT and approximately 350 ml min-1 in the LMA group. We conclude that the airway sealing with both devices was tight enough to perform low flow or closed system anaesthesia in paediatric patients aged 2-6 yr.

Anesthesia, Closed-Circuit↗
PubMed1996

Thiopentone and propofol, but not methohexitone nor midazolam, inhibit neutrophil oxidative responses to the bacterial peptide FMLP.

The effects of different anaesthetics on the neutrophil oxidative response in vitro are compared. Neutrophils were stimulated with small amounts of the bacterial peptide N-formyl-L-methionyl-L-leucyl-phenylalanine as a physiological, receptor-dependent stimulus. A new flow cytometry-based method capable of detecting the small amounts of H2O2 generated by neutrophils in a heterogeneous all-or-none response following submaximal stimulation with N-formyl-L-methionyl-L-leucyl-phenylalanine was used. Propofol and thiopentone suppressed the respiratory burst significantly (P < 0.05 and P < 0.01) in therapeutic concentrations, while midazolam and methohexitone inhibited significantly (P < 0.01) only at concentrations greater than the therapeutic range. Impairment of the neutrophil response was primarily because of a reduction in the number of neutrophils participating in the respiratory burst and not of a proportional decrease of the fluorescence of all neutrophils.

Adult↗
PubMed1996

[Occupational exposure in the operating room by isoflurane when using the laryngeal mask].

Success of intraocular surgery depends in part on low intraocular pressure, sufficient muscle relaxation during the operative period, and avoidance of coughing during emergence from anaesthesia. Isoflurane (ISO) guarantees deep anaesthesia and Laryngeal Mask Airway (LM) makes emergence smoother than when using conventional endotracheal intubation. Occupational exposure to isoflurane appears unavoidable near the potential main source of leakage, the "patient's mouth". Due to the short distance between the patient's mouth and the working area, the risk of exposure for the surgeon could be high. Traces of anesthetic gases may cause various negative effects on the health of the personnel. Higher abortion rates are reported on in recent literature. The aim of this study was to quantify trace amounts of ISO and then to compare these values with international threshold limits. In this study, trace concentrations of ISO were measured directly by means of a high sensitive photoacoustic infrared spectrometry analyser. Measurements were done continuously every 120 seconds at the working places of the surgeon, anaesthetist and the assisting nurse. One possible leakage source, the patient's mouth, was also analysed. 10 cataract operations under general anaesthesia were included in the study. All the measured values were low, the majority under 2 ppm isoflurane. The national threshold values (10 ppm) were not exceeded. We conclude that the use of the LMA in ventilated patients is not associated with high concentrations of isoflurane in the working environment of the operating theatre personnel during eye surgery. Trace concentrations of isoflurane using the LMA are comparable with those using ET under these working conditions. Under other working conditions, higher concentrations may be expected should therefore be controlled.

Air Pollutants, Occupational↗
PubMed1995

The predictive value of four scoring systems in liver transplant recipients.

OBJECTIVE: To compare 4 general severity classification scoring systems concerning prognosis of outcome in 123 liver transplant recipients. The compared scoring systems were: the mortality prediction model (admission model and 24 h model); the simplified acute physiology score; the acute physiology and chronic health evaluation (Apache II) and the acute organ systems failure score. DESIGN: Retrospective, consecutive sample. SETTING: Adult intensive care unit in a university hospital. PATIENTS: 123 adult liver allograft recipients after admission to the intensive care unit. MEASUREMENTS AND MAIN RESULTS: The scoring systems were calculated as described by the authors to classify the severity of illness after admission of the allograft recipients to the intensive care unit. The mean and median values of survivors and the group of patients, that died during hospital stay were compared. Receiver-operating characteristics were plotted for all scoring systems and the areas under the curves of receiver-operating characteristics were calculated. The predictive value of the 4 scoring systems was tested using a variety of sensitivity analyses. The mortality prediction model (24 h model) was found to have a high significance (p < 0.001) in predicting mortality and showed the greatest area under the curve (0.829). Simplified acute physiology score (p < 0.001) and acute physiology and chronic health evaluation (Apache II) (p < 0.01) had a high significance as well, but did not hit the level of prognosis of mortality prediction model, as shown in the area under the curves. Accordingly, sensitivity was highest in MPM-24 h (83%), followed by SAPS (72%) and Apache II (71%). MPM-24 h had a total misclassification rate of 22% (SAPS = 32%, Apache II = 33%). MPM-admission failed in predicting mortality (sensitivity = 52%). Organ systems failure score seemed not to be useful in liver transplant recipients. CONCLUSION: General disease classification systems, such as the mortality prediction model, simplified acute physiology score or acute physiology and chronic health evaluation are good mortality prediction models in patients after liver transplantation. We suggest that there is no need for improvement of a special scoring system.

Adolescent↗
PubMed1995

[Comparison of APACHE-II AND APACHE-III for classification of disease severity of intensive care patients].

The Acute Physiology and Chronic Health Evaluation model (APACHE II, APACHE III) is used to describe the severity of illness and predict the outcome in critically ill patients. APACHE III, introduced in 1991, has not yet been validated in Europe. We calculated APACHE II and APACHE III scores in patients after admission to the intensive care unit (ICU) and compared the prognostic value on hospital mortality. METHOD. One hundred fifty patients with stay of over 24 h were enrolled in the study and prospectively and consecutively investigated. APACHE II and III scores were calculated as described by the authors. The mean and median values of the survivors were compared with the non-surviving group (Mann-Whitney U test). Receiver operating characteristics (ROC analysis) and the areas under the ROC curves were plotted. RESULTS. Of the 150 patients, 34 died during their hospital stay (22.7%). The mean and median APACHE II and III scores were significantly higher (P < 0.001) in the non-surviving group. The area under the ROC curve was higher for APACHE III (0.899) compared to APACHE II (0.847). CONCLUSIONS. APACHE II and APACHE III were both found to have good prognostic value in general ICU patients. Our results suggest that the APACHE III version includes a more precise prediction of hospital mortality than APACHE II. A new aspect of APACHE III is an expanded modification of the Glasgow Coma Scale to assess neurologic derangements.

APACHE↗