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D Sauer

Publications and source records attributed to D Sauer.

At least 19 recordsLinked to original sources
PubMed2004

[Cross-validation of simple questioning methods to determine patient satisfaction with anaesthesia care].

INTRODUCTION: Evaluation of patient satisfaction with the perioperative care is an integral part of modern quality management. For this purpose simple questioning techniques are often used in clinical practise or reports of clinical trials. However, little research has been performed to investigate whether these tools and methods are useful and provide valid information. METHODS: Two-hundred patients undergoing elective surgical procedures were interviewed. Five different simple techniques or questions that have been used in the international and in the German literature throughout the last years were applied in random sequence together with the validated German translation of the QoR-9 questionnaire to measure quality of recovery. All analyses were performed descriptively. RESULTS: All investigated techniques could be answered without help by another person in 95 % up to 100 %. All simple dichotomous questions regarding satisfaction were insufficient to discriminate satisfied from less satisfied patients. A rating using grades known from the German school system (1 - 6) and a visual analogue scale (VAS; 0 - 100 mm) obtained ratings lower than the maximum possible values in 10 % and 11 % of the patients respectively. Furthermore, the flexibility that was provided by these tools was not utilized by the patients. The results of the QoR-9 questionnaire as a marker of postoperative recovery showed only a moderate correlation with ratings of patient satisfaction. CONCLUSION: Until now, there is no method or questioning technique in the German language that can be recommended for a quality assurance program. Thus, further research is needed to develop tools that provide valid information with adequate resolution to allow discrimination of patient satisfaction with perioperative care.

Adult↗
PubMed2000

Selective blockade of metabotropic glutamate receptor subtype 5 is neuroprotective.

We have used potent and selective non-competitive antagonists of metabotropic glutamate receptor subtype 5 (mGlu5) -- 2-methyl-6-phenylethynylpyridine (MPEP), [6-methyl-2-(phenylazo)-3-pyridinol] (SIB-1757) and [(E)-2-methyl-6-(2-phenylethenyl)pyridine] (SIB-1893) - to examine whether endogenous activation of this particular metabotropic glutamate receptor subtype contributes to neuronal degeneration. In cortical cultures challenged with N-methyl-D-aspartate (NMDA), all three mGlu5 receptor antagonists were neuroprotective. The effect of MPEP was highly specific because the close analogue, 3-methyl-6-phenylethynylpyridine (iso-MPEP), which did not antagonize heterologously expressed mGlu5 receptors, was devoid of activity on NMDA toxicity. Neuroprotection by mGlu5 receptor antagonists was also observed in cortical cultures challenged with a toxic concentration of beta-amyloid peptide. We have also examined the effect of mGlu5 receptor antagonists in in vivo models of excitotoxic degeneration. MPEP and SIB-1893 were neuroprotective against neuronal damage induced by intrastriatal injection of NMDA or quinolinic acid. These results indicate that mGlu5 receptors represent a suitable target for novel neuroprotective agents of potential application in neurodegenerative disorders.

Amyloid beta-Peptides↗
PubMed2000

Protective effect of a caspase inhibitor in models for cerebral ischemia in vitro and in vivo.

In primary neuronal-astrocyte cultures from mouse brain, ischemic conditions were simulated by combined oxygen-glucose deprival (OGD) for 2 hrs. This treatment resulted in near complete neuronal damage 24 hrs. later and was accompanied by DNA degradation and apoptotic nuclear morphology. Since caspases are key enzymes in the propagation and execution of programmed cell death, we evaluated the effect of the caspase inhibitor z-VAD-fmk. Damage following 2 hrs. OGD could be reduced by up to 56% with z-VAD-fmk (p<0.05). DNA-fragmentation and caspase activation has been also reported in an in vivo model of cerebral ischemia imitating human stroke. In this model the middle cerebral artery (MCA) is permanently occluded resulting in focal cerebral ischemia and subsequent infarction. Since z-VAD.fmk does not penetrate the blood-brain barrier it was applied intraventricularly as a bolus injection given 30 min. before MCA occlusion which was followed by 24 hrs. of infusion. Infarct volume was determined 48 hrs. after MCA occlusion by means of in vivo magnetic resonance imaging. Z-VAD.fmk dose dependently reduced infarct volume reaching a significant decrease of the cortical infarct by 45% when given as a 120 ng bolus followed by 40 ng/hr. infusion (p<0.05). In summary, our study supports the concept that caspase inhibitors are beneficial in brain ischemia.

Amino Acid Chloromethyl Ketones↗
PubMed1999

Neuron-specific transgene expression of Bcl-XL but not Bcl-2 genes reduced lesion size after permanent middle cerebral artery occlusion in mice.

Protective effects after focal cerebral ischemia were assessed in transgenic mice that overexpress in a neuron-specific fashion mouse Bcl-XL or human Bcl-2. Both Bcl genes were under the control of the same mouse Thy-1 regulatory sequences resulting in very similar expression patterns in cortical neurons. Furthermore, these sequences direct lateonset (i.e. around birth) expression in brain, thus minimizing effects of transgene expression during brain development. Effects on infarct volume were measured using MRI after permanent occlusion of the middle cerebral artery (MCA). When compared to their non-transgenic littermates, Thy1mbcl-XL mice showed a significant 21% reduction in infarct size whereas Thy1hbcl-2 mice did not reveal any reduction. These findings suggest a selective protective advantage of Bcl-XL as compared with Bcl-2 in this mouse model for human stroke.

Animals↗
PubMed1999

(R,S)-4-phosphonophenylglycine, a potent and selective group III metabotropic glutamate receptor agonist, is anticonvulsive and neuroprotective in vivo.

Group III metabotropic glutamate receptors (mGluRs) are thought to modulate neurotoxicity of excitatory amino acids, via mechanisms of presynaptic inhibition, such as regulation of neurotransmitter release. Here, we describe (R,S)-4-phosphonophenylglycine (PPG) as a novel, potent, and selective agonist for group III mGluRs. In recombinant cell lines expressing the human receptors hmGluR4a, hmGluR6, hmGluR7b, or hmGluR8a, EC50 values for (R,S)-PPG of 5.2 +/- 0.7 microM, 4.7 +/- 0.9 microM, 185 +/- 42 microM, and 0.2 +/- 0.1 microM, respectively, were measured. The compound showed EC50 and IC50 values of >/=200 microM at group I and II hmGluRs and was inactive at cloned human N-methyl-D-aspartate, alpha-amino-3-hydroxy-5-methyl-isoxazole-4-propionate, and kainate receptors (>300 microM). On the other hand, it showed micromolar affinity for a Ca2+/Cl--dependent L-glutamate binding site in rat brain, similar to other phosphono-substituted amino acids like L-2-amino-4-phosphonobutyrate. In cultured cortical neurons, (R, S)-PPG provided protection against a toxic pulse of N-methyl-D-aspartate (EC50 = 12 microM), which was reversed by the group III mGluR antagonist (R,S)-alpha-methylserine-O-phosphate but not by the group II antagonist (2S)-alpha-ethylglutamate. Moreover, (R,S)-PPG protected against N-methyl-D-aspartate- and quinolinic acid-induced striatal lesions in rats and was anticonvulsive in the maximal electroshock model in mice. In contrast to the group III mGluR agonists L-2-amino-4-phosphonobutyrate and L-serine-O-phosphate, (R,S)-PPG showed no proconvulsive effects (2200 nmol i.c.v.). These data provide novel in vivo evidence for group III mGluRs as attractive targets for neuroprotective and anticonvulsive therapy. Also, (R,S)-PPG represents an attractive tool to analyze the roles of group III mGluRs in nervous system physiology and pathology.

Animals↗
PubMed1998

5-Aminomethylquinoxaline-2,3-diones, Part III: Arylamide derivatives as highly potent and selective glycine-site NMDA receptor antagonists.

A series of quinoxaline-2,3-diones with very high affinity to the glycine site of the NMDA receptor has been discovered. In contrast to the 7-nitro derivatives, the most potent 7-bromo substituted compounds were highly selective for the glycine site. Although none of the described compounds were active in the electroshock model in mice, 1a displayed significant protection in the quinolinic acid-induced excitotoxicity model in vivo.

Animals↗
PubMed1998

Time course of microglia activation and apoptosis in various brain regions after permanent focal cerebral ischemia in mice.

We investigated the temporal course of microglia activation in different brain regions after permanent middle cerebral artery (MCA) occlusion in mice and compared this microglia response with the appearance of apoptotic cells, Microglia activation and morphological changes of microglial cells were visualized using an immunohistochemical method with a polyclonal antibody recognizing the mouse CR3 complement receptor. Cells showing morphological and biochemical features of apoptosis were identified using the terminal deoxynucleotidyl transferase nick end-labeling (TUNEL) method and light microscopy. As early as 30 min after onset of MCA occlusion activated microglia with hypertrophic cell bodies and stout processes were detected in the periphery of the ischemic lesion as identified by diffusion-weighted magnetic resonance imaging. A wider distribution and a progressive increase in the number of activated microglia was found with increasing time. Only few TUNEL-positive cells with apoptotic features were observed within the lesion area at 6 h after onset of cerebral ischemia. From 12 h after MCA occlusion onward a tremendous increase in the number of TUNEL-positive cells was found. Within the thalamus from 24 h onward microglia cells with few processes, irregular morphology and fragmented appearance were detected. Microglia activation in the thalamus progressed up to 4 weeks after MCA occlusion, but had declined after 90 days. Neuronal degeneration in the thalamus as determined by anti-neuronal nuclei immunohistochemistry progressed from 6 days after MCA occlusion onward. Only a few TUNEL-positive cells were found in the thalamus. In summary, microglia activation both in the primary cortical lesion area and in the secondarily affected thalamus preceded the manifestation of tissue injury. These observations encourage further studies on the role of microglia in focal cerebral ischemia.

Animals↗
PubMed1998

Application of an artificial neural network to predict specific class I MHC binding peptide sequences.

Computational methods were used to predict the sequences of peptides that bind to the MHC class I molecule, K(b). The rules for predicting binding sequences, which are limited, are based on preferences for certain amino acids in certain positions of the peptide. It is apparent though, that binding can be influenced by the amino acids in all of the positions of the peptide. An artificial neural network (ANN) has the ability to simultaneously analyze the influence of all of the amino acids of the peptide and thus may improve binding predictions. ANNs were compared to statistically analyzed peptides for their abilities to predict the sequences of K(b) binding peptides. ANN systems were trained on a library of binding and nonbinding peptide sequences from a phage display library. Statistical and ANN methods identified strong binding peptides with preferred amino acids. ANNs detected more subtle binding preferences, enabling them to predict medium binding peptides. The ability to predict class I MHC molecule binding peptides is useful for immunolological therapies involving cytotoxic-T cells.

Amino Acids↗
PubMed1997

Exploration of P-type Ca2+ channels as drug targets for the treatment of epilepsy or ischemic stroke.

We investigated the neuroprotective efficacy of the P-type Ca2+ channel antagonist daurisoline against electroshock-induced convulsions in rats and mice, hypoxic/hypoglycemic-induced damage in rat hippocampal slices and brain damage induced by occlusion of the middle cerebral artery (MCA) in rats. Daurisoline applied intravenously (i.v.) (bolus of 1-60 mg/kg) reduced the spontaneous activity of rat cerebellar Purkinje cells in a dose-dependent manner, a result demonstrating activity in the brain with systemic administration of the compound. While this effect reversed rapidly in about 10-20 min following bolus-application of the drug at doses of up to 30 mg/kg, a dose of 60 mg/kg consistently induced a depression of respiration followed by death of the animals. Daurisoline administered at 10-30 mg/kg did not prevent electroshock-induced convulsions in mice or rats, nor did it reduce the neuronal damage in hippocampal slices induced by a hypoxic/hypoglycemic insult in vitro by MCA occlusion in vivo. These observations do not support the hypothesis that P-type Ca2+ channels are promising drug targets for the acute treatment of epileptic convulsions and/or ischemic stroke.

Alkaloids↗
PubMed1996

Reduction of excitotoxicity-induced brain damage by the competitive NMDA antagonist CGP 40116: a longitudinal study using diffusion-weighted imaging.

The cerebroprotective properties of the competitive N-methyl-D-aspartate (NMDA) antagonist CGP 40116 were evaluated in a rat model of excitotoxicity-induced brain damage using direct intrastriatal injection of quinolinic acid and subsequent (5 or 45 min later) i.p. administration of the drug. Diffusion-weighted magnetic resonance imaging (DWI) was used to follow the temporal lesion growth during the acute phase (4 h) and T2-weighted MRI (T2WI) to quantify vasogenic edema extent 2 days later. For control animals, we found a rapid increase in lesion volume during the first hour followed by a moderate growth over the following hours. The DWI-visible hyperintensity was partially reversible after treatment with CGP 40116. The onset of action of CGP 40116 was immediate. The final outcome (63% reduction of lesion volume within 2-4 h post-surgery) was independent of the time of drug administration. DWI data after 4 h correlated well with those obtained by T2WI 2 days later. DWI is a valuable method for early prediction of the outcome of therapeutic interventions of excitotoxic insults.

2-Amino-5-phosphonovalerate↗
PubMed1996

Autoimmune hemolytic anemia following T cell-depleted allogeneic bone marrow transplantation.

The development of immune-mediated hemolytic anemia is a well-recognized complication after allogeneic bone marrow transplantation (BMT). The majority of reported cases, however, have been alloimmune in origin due to ABO or minor red blood cell antigen incompatibilities between the donor and recipient. In this study, we report seven adult patients who developed autoimmune hemolytic anemia (AIHA) between June 1985 and January 1993. These patients were identified from a total of 236 adult patients who received T cell-depleted (TCD) grafts as graft-versus-host disease (GVHD) prophylaxis. The onset of AIHA was at a median of 10 months (range 7-25 months) post-transplant and occurred in 5% of all patients transplanted with TCD grafts who survived at least 6 months. Six patients had a warm reacting autoantibody, while one patient had a cold-reacting antibody with a thermal amplitude up to 30 degrees C. All were receiving immunosuppressive treatment for GVHD at the time of diagnosis. Initial treatment in all patients consisted of steroids. Three of the seven had a partial response while the four remaining patients failed to respond to corticosteroids. Splenectomy was performed in three patients with two partial responses. Four patients were treated with additional therapeutic interventions, including plasmapheresis, immunoglobulin infusions, staphylococcus protein A column, or other immunosuppressive agents. In five cases, erythropoietin was administered as adjunctive treatment to maintain adequate hematocrit levels. Two patients are presently in complete remission after prolonged courses of steroids, while a third patient has compensated hemolysis requiring low-dose steroids. Four patients died due to either infectious complications or disseminated intravascular coagulation secondary to cold agglutinin disease. These data indicate that AIHA is a clinically significant and not infrequent complication in allogeneic marrow transplant recipients. The response to conventional treatment is generally unsatisfactory as even patients who ultimately remit require prolonged courses of immunosuppressive therapy.

Adolescent↗
PubMed1995

The competitive NMDA antagonist CGP 40116 permanently reduces brain damage after middle cerebral artery occlusion in rats.

In this study we evaluated the effect of the competitive N-methyl-D-aspartate (NMDA) antagonist D-(E)-4-(3-phosphonoprop-2-enyl)piperazine-2-carboxylic acid (CGP 40116) on both early (2 days) and late (28 days) ischemic brain damage in a rodent model of focal cerebral ischemia by means of magnetic resonance imaging (MRI) and conventional histology. Immediately after occlusion of the left middle cerebral artery (MCA), rats received either CGP 40116 (20 mg/kg i.p.) or isotonic saline. Two MRI scans were performed in each animal 2 and 28 days after MCA occlusion. After the second scan, rats were perfusion fixed for histological evaluation. The volume of lesioned brain tissue as determined by MRI or histology was calculated from the damaged area in single sections and the distance between them. CGP 40116 reduced acute infarct volume as measured by MRI 2 days after MCA occlusion by 44% (p < 0.05, analysis of variance). After 28 days the lesion detected by MRI was still significantly smaller in the drug-treated animals. This finding was confirmed by the histological analysis showing a 64% reduction in the volume of brain atrophy in the CGP 40116 group (p < 0.05, analysis of variance). There was a good correlation between the MRI data and the results of the histological evaluation (r = 0.9). Our results indicate that (a) the competitive NMDA antagonist CGP 40116 permanently protects brain tissue from the consequences of cerebral ischemia in a rat model for human stroke and (b) early and late pathological changes can be accurately measured by MRI.

2-Amino-5-phosphonovalerate↗
PubMed1994

Relation between myocardial infarct location and stroke.

OBJECTIVES: We sought to compare the likelihood of stroke in patients with anterior versus nonanterior myocardial infarction. BACKGROUND: The association between anterior infarction and left ventricular thrombus has led to the assumption that embolization from thrombi is an important cause of stroke in patients with anterior infarction. We hypothesized that if anterior infarction is a cause of left ventricular thrombi, the number of strokes should be disproportionately higher in patients with anterior than nonanterior infarction. METHODS: We performed a retrospective analysis of 2,466 patients randomized from day 3 to day 15 after infarction as part of a multicenter placebo-controlled study of diltiazem to prevent cardiac death or myocardial infarction. Any acute focal cerebral disorder resulting in localizing findings characterized as a stroke or transient ischemic attack was considered an event. RESULTS: Of 91 events during a follow-up period of 12 to 52 months, 23 (3.2%) occurred in 724 patients with an anterior and 68 (3.9%) in 1,742 patients with a nonanterior myocardial infarction (relative risk 0.81; 95% confidence interval 0.51 to 1.30). Power analysis revealed that the negativity of the study was not the result of inadequate sample size. Life table analysis showed no difference in cumulative event rate (p = 0.42) according to site of infarction. Cox regression analysis showed that of 10 clinical covariates, only systolic blood pressure was predictive of stroke (p < 0.001). The use of warfarin did not contribute to the model. Finally, the addition of site of infarction (anterior vs. nonanterior) did not contribute significantly to the Cox model. CONCLUSIONS: Although there is a significant incidence of stroke after acute myocardial infarction, there is no relation between the occurrence of stroke and site of infarction. These data do not support the presumed causal relation between anterior myocardial infarction, thrombus and stroke.

Adult↗
PubMed1994

The competitive NMDA receptor antagonist CGP 40116 is a potent neuroprotectant in a rat model of focal cerebral ischemia.

Focal cerebral ischemia was induced in rats by permanent occlusion of the left middle cerebral artery (MCA). The cerebroprotective properties of the competitive NMDA antagonist CGP 40116 were evaluated in that model and compared to the neuroprotective effects of MK 801, D-CPPene and CGS 19755 under the same experimental conditions. Infarct volume was assessed using in vivo magnetic resonance imaging. The rank order of potency for the NMDA antagonists tested was MK 801 > CGP 40116 approximately D-CPPene > CGS 19755. CGP 40116 dose-dependently reduced the volume of cortical infarction, with an ED50 of 11 mg/kg i.v., and its cerebroprotective efficacy was comparable to that of MK 801. Neuroprotection by CGP 40116 was still apparent when treatment was started 30 minutes after MCA occlusion. It is concluded that CGP 40116 is an effective cerebroprotectant with potential clinical utility for amelioration of focal cerebral ischemic damage.

2-Amino-5-phosphonovalerate↗
PubMed1993

Characterization of the cerebroprotective efficacy of the competitive NMDA receptor antagonist CGP40116 in a rat model of focal cerebral ischemia: an in vivo magnetic resonance imaging study.

The cerebroprotective properties of the competitive NMDA antagonist D-(E)-2-amino-4-methyl-5-phosphono-3-pentenoic acid (CGP 40116) were evaluated in a rat model of focal cerebral ischemia. CGP 40116 (5-40 mg/kg i.v.) was injected immediately following permanent occlusion of the left middle cerebral artery (MCA). MK 801 (1 or 3 mg/kg i.v.), D-CPPene (20 mg/kg i.v.), and CGS 19755 (40 mg/kg i.v.) were used for comparison. Lesion volume was assessed using in vivo magnetic resonance imaging, which in initial experiments with parallel histological determinations proved to be an accurate method for the measurement of brain infarction and the determination of a cerebroprotective drug effect. CGP 40116 dose-dependently reduced the volume of cortical infarction, with an ED50 of 11 mg/kg i.v. and a maximal effect equivalent to a 62% reduction in cortical edema volume. Its cerebroprotective efficacy was thus comparable to that of MK 801. The rank order of potency for the NMDA antagonists was MK 801 > CGP 40116 approximately D-CPPene > CGS 19755. Neuroprotection by CGP 40116 was still apparent when treatment was started 30 min after MCA occlusion. It is concluded that CGP 40116 is an effective cerebroprotectant with potential clinical utility for amelioration of focal cerebral ischemic damage.

2-Amino-5-phosphonovalerate↗
PubMed1992

Differing effects of alpha-difluoromethylornithine and CGP 40116 on polyamine levels and infarct volume in a rat model of focal cerebral ischaemia.

Focal cerebral ischaemia was induced in rats by occlusion of the left middle cerebral artery. Two days later, infarct volume was determined by magnetic resonance imaging and the concentrations of the polyamines putrescine (PU), spermine and spermidine by HPLC. In control (occluded) animals, PU levels were elevated in infarcted and non-infarcted areas of the left hemisphere. Treatment with the ornithine decarboxylase (ODC) inhibitor alpha-difluoromethylornithine, prevented the ischaemia-induced increase in tissue PU without affecting infarct volume. Conversely, administration of the N-methyl-D-aspartate (NMDA) receptor antagonist CGP 40116 decreased cortical infarction without changing the tissue content of PU. We conclude that there is no direct link between NMDA receptor activation and brain PU, or PU and post-ischaemic tissue damage, and that inhibitors of ODC are not cerebroprotective in this animal model of stroke.

2-Amino-5-phosphonovalerate↗
PubMed1992

Evaluation of quinolinic acid induced excitotoxic neurodegeneration in rat striatum by quantitative magnetic resonance imaging in vivo.

Excitotoxic neurodegeneration in the rat striatum was induced by direct injection of quinolinic acid. The degree of damage was evaluated in vivo 1 day later by quantitative magnetic resonance imaging (MRI) and 7 days later in the same animals by measuring the activities of the neuronal marker enzymes choline acetyltransferase and glutamic acid decarboxylase. Striatal damage assessed using the two approaches was highly correlated. Moreover the cerebroprotective efficacy of the N-methyl-D-aspartate receptor antagonist CGP 40116 was indistinguishable based on all analytical parameters. MRI, however, was more reproducible than the enzymatic methods and was faster and simpler for routine analyses of excitotoxic damage and cerebroprotection in vivo.

2-Amino-5-phosphonovalerate↗