Biomedical subjects

D Fröhlich

Publications and source records attributed to D Fröhlich.

At least 19 recordsLinked to original sources

PubMed2006

Inhibition of the neutrophil oxidative response by propofol: preserved in vivo function despite in vitro inhibition.

BACKGROUND AND OBJECTIVE: Propofol has been shown to inhibit a variety of functions of neutrophils in vitro, but there is a lack of in vivo data. To analyse the effects of propofol on neutrophil function in vivo we chose to investigate cataract surgery since it represents a small surgical procedure with minimal immunomodulatory effects induced by surgery. We sought to analyse any immunosuppressive effects of propofol after short-term administration in vivo in comparison to local anaesthesia as well as to in vitro effects of propofol. METHODS: The study was designed as an open randomized trial enrolling 20 patients undergoing general or local anaesthesia. The neutrophil oxidative response and propofol plasma concentration were assessed prior, during and after anaesthesia. Neutrophil function was determined flow cytometrically based on dihydrorhodamine 123 oxidation. RESULTS: Propofol concentrations which yielded a marked suppression in vitro did not alter the neutrophil oxidative response during cataract surgery in vivo. However, after local anaesthesia the neutrophil oxidative response declined to 37%, compared to the control response prior to anaesthesia. CONCLUSIONS: Although we could detect the well established suppression of neutrophil function by propofol in vitro it was not evident in vivo. This may be due to compensating effects on neutrophil function during surgery in vivo. The decline in the neutrophil oxidative response in the local anaesthesia group might be due to increased stress and catecholamine concentrations or a direct interaction of local anaesthetics with neutrophil intracellular signalling.

Adult↗

PubMed2005

Cerebrospinal fluid and neutrophil respiratory burst after subarachnoid hemorrhage.

OBJECTIVES: To investigate the effect of cerebrospinal fluid (CSF) from patients with subarachnoid hemorrhage (SAH) on the activation of polymorphonuclear neutrophils (PMN) in response to receptor-dependent stimulation with N-formyl-l-methionyl-l-leucyl-l-phenylalanine and TNFalpha or non-receptor-dependent stimulation with phorbol 12-myristate 13-acetate. METHODS: CSF from 12 patients with SAH due to ruptured cerebral aneurysm was collected. Samples of CSF were drawn at different time points. CSF from 6 healthy subjects receiving spinal anesthesia served as the control group. After stimulation of PMN the generation of reactive oxygen intermediates was analyzed on a flow cytometer. RESULTS: In the presence of CSF, PMN showed a significant suppression of the oxidative burst following stimulation compared to stimulation without CSF. The reduction of the oxidative burst following stimulation was higher in the presence of CSF from patients with SAH. After pretreatment at 56 degrees C, the extent of the suppression observed following receptor-dependent stimulation and CSF from patients with SAH was similar to that seen after stimulation with CSF from healthy individuals. CONCLUSIONS: These data show that the presence of CSF resulted in a suppression of neutrophil oxidative function. A more distinct depression was seen in the presence of CSF from patients with SAH. We suggest a complex physiological inhibitory and protective mechanism against unfavorable activation of PMN by CSF.

Adult↗

PubMed2004

Cytokine upregulation of surface antigens correlates to the priming of the neutrophil oxidative burst response.

BACKGROUND: Neutrophil activation is strongly related to organ dysfunction that occurs during systemic inflammatory responses. The aim of our study was to analyze the oxidative burst response in correlation to the up- and downregulation of N-formyl-L-methionyl-L-leucyl-phenylalanine (fMLP) receptors and the surface antigens CD11b, CD62L, and CD66b as potential surrogate markers of the degree of neutrophil priming for an increased oxidative burst response induced by proinflammatory cytokines. METHODS: Blood was taken from healthy donors. Neutrophils were pretreated with cytokines (interleukin [IL]-1beta, IL-6, IL-8, granulocyte-macrophage colony-stimulating factor [GM-CSF], and tumor necrosis factor alpha [TNFalpha]; 0.01-10 ng/ml) and stimulated with fMLP (100 nM) in vitro. Functional and phenotypical parameters were quantified flow cytometrically. RESULTS: The oxidative burst response increased after priming with 0.1 ng/ml TNFalpha, 1 ng/ml GM-CSF, or 10 ng/ml IL-8. Upregulation of fMLP receptors, CD11b, and CD66b and downregulation of CD62L showed a close correlation to the oxidative burst response. Altered expression of these parameters partly reached significance at lower cytokine concentrations in comparison with the oxidative burst. IL-1beta and IL-6 had no effect. CONCLUSIONS: Our results showed that the expression of phenotypical parameters closely correlates with functional parameters in human neutrophils. Thus an up- or downregulation of antigens such as CD11b or CD62L reflects cytokine-induced functional changes.

Adult↗

PubMed2004

Thiopentone and methohexitone enantiomers do not act stereoselectively on the oxidative response in human neutrophils in vitro.

To elucidate potential stereoselective effects of single barbiturate isomers, we compared the inhibitory potency of single thiopentone enantiomers, two isomer-enriched mixtures of methohexitone and racemic mixtures of both barbiturates on the fMLP-induced neutrophil oxidative response. A suppression of the response to 50% compared to control required a 100-fold therapeutic concentration of methohexitone, while therapeutic concentrations of the thiopentone racemate led to a significant inhibition (relative fluorescence of neutrophils 0.46 +/- 0.03 compared to fMLP controls). The racemate of thiopentone produced significantly greater inhibition than the single enantiomers. Stereoselectivity in favor of one isomer could not be shown for both barbiturates. The greater inhibition by the thiopentone racemate might suggest two separate binding sites for the enantiomers which are positively coupled.

Adult↗

PubMed2003

Wave-vector-dependent exciton exchange interaction.

The exchange interaction for the yellow 1S orthoexciton in Cu2O is derived up to the order K2. The resulting exchange splittings are verified experimentally using high resolution spectroscopy. In agreement with theory the fine structure shows a characteristic dependence on the direction of the wave vector.

Journal Article↗

PubMed2003

[Status of essential trace elements in untreated carcinomas of the head and neck].

BACKGROUND: The changed mineral status is well known in different tumor types. This phenomenon has influenced the redox potential of patients suffering from solid cancers. A prospective trial was conducted to evaluate the specifics for untreated head and neck cancer patients. MATERIAL AND METHODS: We included 100 patients with advanced squamous cell carcinoma of the head and neck region before each kind of treatment. Following serum-concentrations were measured by atom absorption spectrometry: selenium, copper, zinc, and ferrum. Additionally we evaluated the activity of glutathion peroxidase and the concentration of malondialdehyde of the serum. RESULTS: 66 % of all patients have shown a decreased serum-concentration of selenium. These patients were additionally characterized by decreased activities of endogenous glutathionperoxiase. A third of all patients had decreased zinc and iron levels. Copper was found enhanced in 30 %. In trend the malondialdehyde was increasing due to decreasing selenium levels. CONCLUSIONS: Head neck cancer patients show the same characteristic trace element status as other solid tumors: decreased selenium, zinc and iron, increased copper. The therapeutic consequences of these observations are still unclear.

Adult↗

PubMed2002

Observation of coupled magnetic and electric domains.

Ferroelectromagnets are an interesting group of compounds that complement purely (anti-)ferroelectric or (anti-)ferromagnetic materials--they display simultaneous electric and magnetic order. With this coexistence they supplement materials in which magnetization can be induced by an electric field and electrical polarization by a magnetic field, a property which is termed the magnetoelectric effect. Aside from its fundamental importance, the mutual control of electric and magnetic properties is of significant interest for applications in magnetic storage media and 'spintronics'. The coupled electric and magnetic ordering in ferroelectromagnets is accompanied by the formation of domains and domain walls. However, such a cross-correlation between magnetic and electric domains has so far not been observed. Here we report spatial maps of coupled antiferromagnetic and ferroelectric domains in YMnO3, obtained by imaging with optical second harmonic generation. The coupling originates from an interaction between magnetic and electric domain walls, which leads to a configuration that is dominated by the ferroelectromagnetic product of the order parameters.

Journal Article↗

PubMed2002

["Simplified Acute Physiology Score" (SAPS II) ina the assessment of severity of illness in surgical intensive care patients].

INTRODUCTION: In 1993, Le Gall proposed a new Simplified Acute Physiology Score (SAPS II) to assess the severity of illness in intensive care patients and to predict the risk of hospital mortality using a large data base of more than 13,000 patients of different intensive care units. Up to the present time, no satisfactory form of validation for surgical intensive care patients has been available. We investigated the prognostic quality of this score system for the assessment of the severity of the illness in surgical intensive care patients. METHODS: Between October 1997 and December 1998, 310 consecutive patients were included in our study. We calculated the SAPS II score according to the published guidelines. Additionally, we calculated the risk of mortality by referring to the score. We used a receiver operating characteristics (ROC) analysis for statistical evaluation. RESULTS: The median duration of stay on our intensive care unit was 8.4 days. In all patients, the mean SAPS II was 29.9 +/- 12.7. In the survivors, calculation of mean SAPS II was 27.7 +/- 11.4. In the non-survivors, mean SAPS II was 45.7 +/- 11.2. The predicted risk of mortality was 15.7%, the actual risk of mortality was 15.8%. CONCLUSION: The SAPS II score has proved to be a good prognostic instrument in surgical intensive care patients. SAPS II is particularly effective in providing an exact estimation of the risk of death, classifying patient groups in clinical studies, epidemiological investigations, and quality assessment.

Adult↗

PubMed2002

Thiopental impairs neutrophil oxidative response by inhibition of intracellular signalling.

BACKGROUND AND OBJECTIVE: Thiopental in clinically relevant concentrations inhibits the oxidative function of neutrophils, whereas only very high, non-therapeutic concentrations of methohexital induce a similar effect. The study characterized the molecular basis of this differential action of oxy- and thiobarbiturates on neutrophils. METHODS: Neutrophils were incubated in vitro with thiopental or methohexital using concentrations within the therapeutic range. Neutrophil responses were induced using different stimuli: N-formyl-L-methionyl-L-leucyl-L-phenylalanine (FMLP), C5a and 1,2-dioctanoyl-sn-glycerol (DiC8-DAG). FMLP and C5a bind to specific G-protein-coupled receptors that share the same second messenger cascade. In contrast, DiC8-DAG, an activator of protein kinase C, bypasses the signal transduction pathway downstream of the receptors. Hydrogen peroxide production by neutrophils was assessed using flow cytometry. To characterize the localization of the interaction site, FMLP receptor expression and cytosolic-free calcium were further analysed. RESULTS: FMLP and C5a-induced hydrogen peroxide production were both significantly impaired by thiopental, but not by methohexital. When postreceptor signalling was bypassed, by stimulation with DiC8-DAG, neither thiopental nor methohexital affected hydrogen peroxide production. Additionally, neither of the barbiturates impaired the cytosolic Ca2+ response. CONCLUSIONS: We conclude that neither protein kinase C nor the hydrogen peroxide-generating enzymes are affected by thiopental or methohexital. The unimpaired Ca2+ response suggests that the function of the receptors and G-proteins were also unimpaired. Taken together, this indicates that the site of action of thiopental is in the cellular signalling upstream of protein kinase C.

Anesthetics, Intravenous↗

PubMed2001

Second harmonic generation in the centrosymmetric antiferromagnet NiO.

In spite of the fact that inversion is a symmetry operation of both the crystalline and the magnetic lattice of NiO, second harmonic generation (SHG) has been observed below the Néel temperature. A spectroscopic study shows that the signal is due to combined magnetic-dipole and electric-dipole transitions between the (3d)(8) levels of the Ni(2+) ion in the crystal field. The SHG is resonant in both the incoming and the outgoing light waves and thus greatly enhanced. A quadratic coupling of the nonlinear polarization to the order parameter was found. This allows the investigation of individual domains.

Journal Article↗

PubMed2001

A new endotoxin adsorber: first clinical application.

In an open, uncontrolled pilot study, 5 men and 1 woman with suspected gram-negative sepsis were treated with a new whole-blood endotoxin adsorption system. Lipopolysaccharide (LPS) adsorption was carried out by hemoperfusion over high-affinity polymethacrylate-bound albumin (Fresenius Endotoxin Adsorber EN 500). All patients suffered from endotoxemia (>20 pg/ml LAL) and met at least two systemic inflammatory response syndrome (SIRS) criteria. Four patients suffered from pneumonia due to mechanical ventilation, one from peritonitis, and one from pneumonia and peritonitis. Endotoxin adsorption was very well tolerated, and efficient LPS removal was shown in all patients. Apache II score immediately before immunoadsorption was 23.5 and was 22.3 after the last treatment. All 6 critically ill patients improved substantially and were discharged from the intensive care unit. LPS whole blood immunoadsorption is a promising new method. No side effects have been observed thus far. A large controlled study to prove clinical efficacy in patients with severe sepsis is under way.

APACHE↗

PubMed2001

[Extravasation of contrast media in brain parenchyma and cerebrospinal fluid space after CT or DSA of thorax or abdomen].

PURPOSE: Analysis of clinical and CT findings in patients with signs of disruption of the blood-brain or blood-CSF barrier after i.v. or i.a. administration of non-ionic contrast media. METHODS: 1. Retrospective analysis of 8 patients with clinical and CT findings of disruption of the blood-brain or blood-CSF barrier after i.v. or i.a. administration of non-ionic contrast media (200-450 ml). 2. Prospective analysis of 30 intensive care patients with sepsis and suspected abscess, who underwent CT of the chest and abdomen with 240 ml of a non-ionic contrast medium followed by cranial CT to rule out septic lesions. RESULTS: The retrospective analysis proved that disruption of the blood-brain barrier may occur in elderly patients with risk factors after injection of higher amounts of contrast media. In the prospective study, equivalent CT phenomena were observed in 3 of 30 patients with sepsis. CONCLUSIONS: Hypoxemic and toxics damage to the blood-brain barrier as well as higher amounts of contrast media may result in extravasation of contrast medium into the CSF space, which can be demonstrated by CT. For differential diagnosis, the clinical symptoms and CT patterns of a disruption of the blood-brain or blood-CSF barrier should be known.

Adult↗

PubMed2001

Gene variants of the bactericidal/permeability increasing protein and lipopolysaccharide binding protein in sepsis patients: gender-specific genetic predisposition to sepsis.

OBJECTIVES: To determine whether the genotype frequencies of the five bi-allelic polymorphisms in the bactericidal/permeability increasing protein (BPI) (Lys216 --> Glu; PstI polymorphism in intron 5; silent mutation G545 --> C) and the lipopolysaccharide binding protein (LBP) (Cys98 --> Gly; Pro436 --> Leu) are associated with the incidence and lethality of sepsis. DESIGN: Case control study of patients with sepsis. SETTING: Intensive care units within university hospitals. PATIENTS: A total of 204 patients diagnosed with sepsis and 250 healthy blood donors. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Short DNA fragments containing the polymorphic sites of the LBP and BPI locus were amplified by the polymerase chain reaction or mismatched polymerase chain reaction. The individual polymorphisms were determined with the appropriate restriction enzyme digestions and subsequent agarose gel electrophoresis. The presence of LBP genotypes with the less frequent Gly98 allele was found to be associated with sepsis (p < .02) in male patients, but not in females. Patients which were homozygote for either of the rare Gly98 (n = 6) and/or Leu436 (n = 5) LBP alleles, furthermore, exclusively were nonsurvivors of sepsis. The genotype frequencies in the BPI gene did not differ between patients and control individuals. CONCLUSIONS: Our findings suggest that common polymorphisms in the gene for LBP in combination with male gender are associated with an increased risk for the development of sepsis and, furthermore, may be linked to an unfavorable outcome. These data support the important immunomodulatory role of LBP in Gram-negative sepsis and suggest that genetic testing may be helpful for the identification of patients with an unfavorable response to Gram-negative infection.

Acute-Phase Proteins↗

PubMed2001

ApoE-containing high density lipoproteins and phospholipid transfer protein activity increase in patients with a systemic inflammatory response.

High density lipoproteins (HDL) mediate reverse cholesterol transport as well as the clearance of oxidation products or inflammatory mediators, thereby contributing to tissue integrity. The decrease in HDL in inflammation has been attributed to decreased lecithin:cholesterol acyltransferase activity, whereas the role of phospholipid transfer protein (PLTP) and cholesteryl ester transfer protein has not been analyzed in detail. We have studied the activities of HDL-modifying proteins and the heterogeneity of HDL in healthy control subjects and three groups of postsurgery patients: no bacterial infection (group 1), bacterial focus and systemic inflammatory response (group 2), and severe sepsis (group 3). For all patients, a decrease in total HDL could be demonstrated, with a loss of mainly large, apolipoprotein A-I (apoA-I) HDL particles, an almost total loss of apoC-I, and an increase in apoE HDL (200-500 kDa), which did not contain significant amounts of apoA-I, apoA-II, or apoC-I. PLTP activity was increased in patients of groups 2 and 3, paralleled by a redistribution of PLTP into a population of small (120- to 200-kDa) particles, probably representing PLTP homodimers or lipid-complexed PLTP. In summary, the increase in apoE HDL and PLTP activity may improve the delivery of energy substrates and phospholipids to tissues that must maintain cellular membrane homeostasis under conditions of inflammatory stress.

Adult↗

PubMed2000

[Prevention of radiation-induced diarrhea by smectite. Results of a double-blind randomized, placebo-controlled multicenter study].

PURPOSE: Diarrhea and abdominal pain are well-known side effects abdominal or pelvic of radiation therapy that may lead to interruption of treatment in serious cases. In recent trials the silicate smectite has proven a promising drug in the prophylaxis of these adverse events. The presented trial aimed at the verification of earlier studies and the evaluation of a dose-effect relationship. PATIENTS AND METHODS: Between April 1994 and May 1995, a total of 176 patients obtaining radiotherapy of the pelvis or the abdomen were evaluated in a double-blind, randomized placebo-controlled investigation regarding the prophylactic effect of smectite (= Colina) against radiotherapy-induced diarrhea. During the whole period of radiotherapy 85 patients obtained 2 x 6 g smectite daily and 91 patients received 2 x 6 g placebo. The primary end point of the analysis was the time to the first appearance of diarrhea (> or = 3 pappy stools). RESULTS: All 176 patients were evaluated according to an intent-to-treat analysis. There was no significant difference between the prophylactic effects of smectite and placebo. For an explorative post-hoc analysis the total study group was split up into 2 subgroups, one with an irradiated small bowel volume < or = 837.5 ml, the other with a small bowel volume > 837.5 ml (median); the analysis indicated that the first subgroup showed a benefit for the smectite-treated patients in contrast to the placebo treatment (32 vs. 18 calendar days to the first appearance of diarrhea). This benefit was statistically not significant. CONCLUSION: Prophylactic application of smectite during irradiation of the pelvis and the abdomen can delay the development of radiotherapy-induced diarrhea, a statistical significance could not be verified neither in the total study group nor in the post-hoc subgroup analysis.

Abdomen↗

PubMed2000

Less adrenergic activation during cataract surgery with total intravenous than with local anesthesia.

BACKGROUND: Previous studies reported that, contrary to local anesthesia, cataract surgery under inhalational anesthesia is associated with substantial adrenergic activation. We tested the hypothesis that total intravenous anesthesia (TIVA) with propofol and alfentanil produces less or comparable adrenergic activation during cataract surgery than local anesthesia. METHODS: Patients were randomly assigned to peribulbar local block (n=10) or TIVA (n=10). The heart rate, blood pressure, plasma concentrations of catecholamines, cortisol, and glucose were assessed at seven pre-, intra-, and post-operative time points. RESULTS: In the patients given local anesthesia, plasma concentrations of epinephrine, norepinephrine and cortisol did not change significantly. In contrast, plasma epinephrine decreased by roughly 66% during TIVA: from 45+/-16 to 15+/-8 pg/ml. Plasma norepinephrine concentration decreased by roughly 50%, from 462+/-265 to a minimum value of 219+/-6 pg/ml and plasma cortisol concentrations decreased by roughly 61%, from 16.4 ng/ml to 6.4 ng/ml. Blood pressure and heart rates remained near baseline values during local anesthesia. In contrast, systolic blood pressure decreased by 30% and heart rate by 12 beats/min during TIVA. CONCLUSION: The presented study and available data clearly suggest that local anesthesia produces the best adrenergic and hemodynamic stability during cataract surgery. Contrary to previously reported results on inhalational anesthesia (thiopentone/enflurane), the TIVA regimen used effectively prevents the adrenergic and metabolic response during cataract surgery.

Adult↗

PubMed2000

The common functional C(-159)T polymorphism within the promoter region of the lipopolysaccharide receptor CD14 is not associated with sepsis development or mortality.

Sepsis is characterised by a systemic inflammatory response to bacterial products during infection, which interestingly both in humans and animal models is gender associated with a higher susceptibility of males than females. The CD14 receptor is involved in activation of cells by lipopolysaccharides released from Gram-negative bacteria and, as recently shown, also by products of Gram-positive bacteria (e.g., peptidoglycans and lipoteichoic acid). The functional relevance of a C(-159)T CD14 polymorphism recently has been shown based on correlation of the T allele to higher plasma levels of soluble CD14, and higher membrane expression on monocytes. We, therefore, now analysed this CD14 polymorphism in 204 patients with severe sepsis and 247 controls. No significant difference of allele frequencies was observed between sepsis patients and controls neither for males nor females. Mortality also was not associated with the polymorphism studied. This may suggest that other mechanisms for lipopolysaccharide recognition, such as the recently described Toll-like receptors are important for inflammatory cell activation in sepsis.

Adolescent↗

PubMed2000

[Radiotherapy of hidradenitis suppurativa--still valid today?].

PURPOSE: In a retrospective analysis the efficacy of radiotherapy in the treatment of hidradenitis suppurativa was assessed. PATIENTS AND METHODS: Data from 231 patients undergoing radiotherapy for hidradenitis suppurativa in the last years in 2 hospitals were analyzed. The patients were treated with an orthovoltage therapy unit with 175 kV, 0.5 mm copper-filtering. The single doses reached from 0.5 Gy to 1.5 Gy up to total doses between 3.0 Gy and 8.0 Gy in one series. In chronic recurrent disease 2 or more series with a total dose of more than 10.0 Gy were given. RESULTS: Complete relief of symptoms at the end of radiotherapy was achieved in 89 patients (38%). In 92 patients (40%) there was clear improvement of symptoms. Only 2 patients did not react to radiotherapy. No side effects of radiotherapy occurred. CONCLUSION: Radiotherapy should be given more consideration as a treatment option for hidradenitis suppurativa.

Adult↗