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Biomedical subjects

P Bischoff

Publications and source records attributed to P Bischoff.

At least 19 recordsLinked to original sources

Monitoring methods: SNAP.

The SNAP electroencephalogram (EEG) monitor, described as an interesting, innovative EEG tool that samples raw EEG signals and uses its own unique algorithm, analyses both high- (80-420 Hz) and low- (0-20 Hz) frequency components of the signal. This is termed the SNAP index, and it ranges from 100 (arbitrarily representing the fully awake state) to 0 to provide functional data points for patient management. The SNAP is the first commercial EEG-monitoring tool to use Personal Digital Assistant computer technology. The first version of SNAP index was introduced in 2002, and so far there has been little experience with the SNAP device reported in the literature. Compared with other EEG devices, there is no evidence that SNAP is superior to others in generating more specific information about 'depth of sedation'. Moreover, the influence of high-frequency electromyographic activity on the SNAP needs to be clarified.

Algorithms↗

Ruthenium (II)-derived organometallic compounds induce cytostatic and cytotoxic effects on mammalian cancer cell lines through p53-dependent and p53-independent mechanisms.

The metallic compound cisplatin has been used for many years to treat various human cancers. Here, we describe the cytostatic and cytotoxic properties of a new class of organometallic compounds that contain a ruthenium (II) atom covalently linked to carbon and nitrogen atoms. We found that several ruthenium-derived compounds (RDCs) led to G1 arrest and induced apoptosis in tumor cell lines derived from glioblastomas, neuroblastomas, and lymphoid tumors at least as efficiently as cisplatin. We further analyzed the signaling pathways underlying these effects, and we showed that both RDCs and cisplatin induced p53 and p73 protein levels but with different intensities and kinetics. This accumulation of p53 and p73 proteins correlated with an increase in p21 and Bax expression, two p53 target genes linked to cell growth arrest and apoptosis. However, in contrast to cisplatin-induced apoptosis, overexpression of DeltaNp73, a p53 and p73 dominant-negative isoform, only partly reduced RDC-induced apoptosis, suggesting p53-dependent and p53-independent modes of action. This observation was further confirmed by the ability of RDC to induce apoptosis in p53-/- cells. Altogether, this study highlights key cellular and molecular features of RDCs and suggests that further development of this new class of compounds may contribute to improve future chemotherapeutic protocols.

Animals↗

[Fundus quiz 2004].

Six cases with characteristic fundus pathologies are presented and discussed using multiple choice questions.

Adult↗

Simultaneous fluorescein and indocyanine green angiography for exudative macular degeneration.

BACKGROUND: The present study investigates how often a simultaneous fluorescein and indocyanine green (ICG) angiography had therapeutic consequences and if it is useful as a clinical routine diagnostic tool. PATIENTS AND METHODS: 502 consecutive simultaneous angiographies in eyes with exudative macular degeneration were retrospectively studied. RESULTS: A classic extra- or juxtafoveolar choroidal neovascularisation (CNV) was found in 3.5 % of the eyes. A subfoveal predominantly classic CNV was present in 19 % of the angiographies. ICG angiography showed a vascular network in 3 % of the eyes with occult CNV in fluorescein angiography. A neovascularisation supplied by retinal vessels (retinal angiomatous proliferation) was found in 9 % and a polypoidal choroidal vasculopathy (PCV) in 6 %. Other plaques or hot spots were visible in 4 %. In 11 eyes with progressive exudation from PCV and threatening of the fovea, laser treatment was successfully performed. CONCLUSIONS: Combined angiography identifies treatable PCV. Advantages of a combined procedure (easier logistics, no missing of treatable cases) and arguments for a two step procedure with ICG angiography only in selected cases (lower costs, lower rate of adverse reactions) must be weighed against each other.

Adult↗

SNAP index and Bispectral index during different states of propofol/remifentanil anaesthesia.

The accuracy of the new SNAP index with the Bispectral index (BIS) to distinguish different states of propofol/remifentanil anaesthesia was compared in 19 female patients who were undergoing minor gynaecological surgery. Comparisons of the SNAP index, BIS, spectral edge frequency, mean arterial blood pressure and heart rate were performed. The ability of all parameters to distinguish between the steps of anaesthesia -awake vs. loss of response, awake vs. anaesthesia, anaesthesia vs. first reaction and anaesthesia vs. extubation - were analysed with the prediction probability. The prediction probability to differentiate between two interesting nuances of anaesthetic states -loss of response vs. first reaction - was calculated. Only the BIS showed no overlap between the investigated steps of anaesthesia. Both the SNAP index and BIS failed to differentiate the nuances of anaesthesia. The SNAP index and BIS were superior to mean arterial blood pressure and heart rate and spectral edge frequency in distinguishing between different steps of anaesthesia with propofol and remifentanil and provided useful additional information.

Adult↗

Bispectral index and A-line AAI index as guidance for desflurane-remifentanil anaesthesia compared with a standard practice group: a multicentre study.

BACKGROUND: This study was designed to investigate the impact of bispectral index (BIS) or A-line AAI index (based on middle-latency auditory evoked potential) monitoring on recovery times and drug consumption when compared with standard anaesthetic practice during desflurane-remifentanil anaesthesia. METHODS: After having obtained approval from the institutional review board and written informed consent, 200 adult patients undergoing minor surgical procedures were randomized to receive a desflurane-remifentanil anaesthetic controlled either solely by clinical parameters or by BIS or AAI to the following target values: during maintenance of anaesthesia to a value of '50' (BIS) or '30' (AAI), 15 min before the end of surgery to '60' (BIS) or '45' (AAI). Recovery times and drug consumption were recorded by a blinded investigator. RESULTS: Compared with standard practice, patients with BIS or AAI monitoring needed similar desflurane concentrations (standard practice 2.9 [0.5] vol%, BIS 3.3 [0.9] vol%, AAI 2.6 [0.5] vol%), and had similar recovery times (open eyes 5.6 [2.5] min, 5.9 [3.4] min, 5.0 [3.1] min; extubation 6.3 [2.4] min, 6.6 [3.5] min, 5.6 [3.0] min; stating name 7.3 [2.4] min, 7.6 [3.5] min, 7.3 [6.6] min). CONCLUSIONS: Compared with standard anaesthetic practice BIS and AAI guided titration to the used target ranges did not result in a reduction of desflurane consumption or recovery times during minor surgery with use of remifentanil.

Adolescent↗

[Fundus quiz 2003].

6 cases with pathognomonic fundus pathologies are presented and discussed using multiple-choice questions.

Adult↗

[SNAP-index and bispectral index during induction of anaesthesia with propofol and remifentanil].

OBJECTIVE: Measurement of "depth of anesthesia" is of enormous interest to the anesthesiologist. New monitor systems, based on the electroencephalogram (EEG) were developed. The aim of the present study was to compare the SNAP index and the Bispectral index during induction of anesthesia with propofol and remifentanil. METHODS: After IRB approval and written informed consent we investigated 19 female patients during minor gynecologic surgery. Target controlled infusion (TCI) of propofol was increased in a step-by-step mode (0.5 micro g/kg) every 1 min until the patients lost response to the modified Observer's Assessment of Alertness/Sedation scale (MOAAS). 5 min after the patient lost response remifentanil 0.4 micro g/kg/min was started. Every 20 s SNAP index, BIS, spectral edge frequency, mean arterial blood pressure, heart rate and MOASS were recorded. Prediction probability ( P(K)) was used to analyze the relationship of MOAAS, TCI propofol, and all investigated parameters. Changes after start of remifentanil were analyzed with Friedman and Wilcoxon test. RESULTS: SNAP index ( P(K) = 0.91) and BIS ( P(K) = 1.0) were able to distinguish reliably between MOAAS = 5 and MOAAS = 0. Start of remifentanil infusion resulted in statistically significant changes for all parameters except the SNAP index (p > 0,05). CONCLUSIONS: SNAP index and BIS were reliable parameters to distinguish different levels of sedation, but SNAP index was not able to reflect the analgesic potency of remifentanil during propofol infusion.

Anesthesia, Intravenous↗

Cisplatin enhances the cytotoxicity of fast neutrons in a murine lymphoma cell line.

The utilization of high linear energy transfer (LET) radiations, such as fast neutrons or carbon ions (hadrontherapy), offers promising perspectives in radiotherapy. While it is well known that by combining radiotherapy and chemotherapy, important therapeutic advantages can be obtained to cure cancer, there have been, so far, very few investigations on the effects of treatments combining an irradiation with high-LET particles and cancer drugs. The present study was therefore undertaken to examine the effects of exposure to 65 MeV fast neutrons combined with cisplatin in a murine T cell lymphoma (RDM4) in vitro. The cells were irradiated at doses ranging from 2 to 8 Gy without or with addition of cisplatin shortly before the irradiation, at concentrations between 0.3 and 12.5 micro M. These treatments were applied concomitantly. Proliferation and apoptosis were assessed at different time intervals thereafter. The combination of irradiation with cisplatin was found to be more cytotoxic than either treatment alone. Furthermore, the cytotoxicity induced by this cotreatment resulted not only from apoptosis but also from other forms of cell death.

Animals↗

Acute heart failure during spinal surgery in a boy with Duchenne muscular dystrophy.

Patients with Duchenne muscular dystrophy (DMD) are at high risk of perioperative complications. DMD may be accompanied by heart failure resulting from dystrophic involvement of the myocardium, which can be subclinical in the early stages of the disease. This case demonstrates that a normal preoperative ECG and echocardiograph cannot exclude the development of heart failure during anaesthesia in DMD patients undergoing major surgery.

Acute Disease↗

Quality of perioperative AEP--variability of expert ratings.

BACKGROUND: Previous studies suggest that auditory evoked potentials (AEP) may be used to monitor anaesthetic depth. However, during surgery and anaesthesia, the quality of AEP recordings may be reduced by artefacts. This can affect the interpretation of the data and complicate the use of the method. We assessed differences in expert ratings of the signal quality of perioperatively recorded AEPs. METHODS: Signal quality of 180 randomly selected AEP, recorded perioperatively during a European multicentre study, was rated independently by five experts as 'invalid' (0), 'poor' (1), or 'good' (2). Average (n=5) quality rating was calculated for each signal. Differences between quality ratings of the five experts were calculated for each AEP: inter-rater variability (IRV) was calculated as the difference between the worst and best classification of a signal. RESULTS: Average signal quality of 57% of the AEPs was rated as 'invalid', 39% as 'poor', and only 4% as 'good'. IRV was 0 in only 6%, 1 in 62%, and 2 in 32% of the AEP, that is in 32% one expert said signal quality was good, whereas a different expert thought the identical signal was invalid. CONCLUSIONS: There is poor agreement between experts regarding the signal quality of perioperatively recorded AEPs and, as a consequence, results obtained by one expert may not easily be reproduced by a different expert. This limits the use of visual AEP analysis to indicate anaesthetic depth and may affect the comparability of AEP studies, where waveforms were analysed by different experts. An objective automated method for AEP analysis could solve this problem.

Adult↗

Induction of apoptosis by high linear energy transfer radiation: role of p531.

The involvement of the tumor suppressor p53 gene in the sensitivity of many cell types towards low linear energy transfer (LET) radiation is now well established. However, little information is available on the relationship between p53 status of tumor cells and their ability to undergo apoptosis following exposure to high-LET radiation. Here we present the results of experiments carried out with the human lymphoblastoid cell line TK6 and its p53 knock-out counterpart NH32. Cells were irradiated at doses ranging from 0.25 to 8 Gy with fast neutrons (65 MeV), carbon ions (95 MeV/nucleon), and X rays (15 MV). For both cell lines, the occurrence of apoptosis, determined by the quantification of hypodiploid particles as well as the activation of several caspases, was compared with their sensitivity towards high-LET radiation. Results indicate that p53 is involved in the response of TK6 cells to fast neutrons and carbon ions, as measured by cell proliferation and occurrence of apoptosis. However, p53-deficient cells are still able to undergo apoptosis following irradiation. This suggests that heavy ions and fast neutrons induce cellular damage that is not under the control of p53. The involvement of executioner caspases in high-LET radiation induced apoptosis was also evaluated by use of specific inhibitors.

Apoptosis↗

Involvement of TP53 in apoptosis induced in human lymphoblastoid cells by fast neutrons.

We investigated the involvement of TP53 in apoptosis induced by fast neutrons in cells of three human B-lymphoblast cell lines derived from the same donor and differing in TP53 status: TK6 (wild-type TP53), WTK1 (mutant TP53) and NH32 (knockout TP53). Cells were exposed to X rays or to fast neutrons at doses ranging from 0.5 to 8 Gy. Apoptosis was determined by measurements of the sub-G0 /G1-phase DNA content and by the externalization of phosphatidylserine. Fast neutrons induced extensive apoptosis in TK6 cells, as shown by the formation of hypodiploid particles, the externalization of phosphatidylserine, and the activation of caspases. In contrast, cell death was triggered at a significantly lower rate in cells lacking functional TP53. However, TP53-independent cell death also expressed the morphological and biochemical hallmarks of apoptosis. Proliferation tests and clonogenic assays showed that fast neutrons can nevertheless kill WTK1 and NH32 cells efficiently. The absence of functional TP53 only delays radiation-induced cell death, which is also mediated by caspases. These results indicate that fast-neutron irradiation activates two pathways to apoptosis and that the greater relative biological effectiveness of fast neutrons reflects mainly an increase in clonogenic cell death.

Apoptosis↗

[Induction of apoptosis of splenic lymphocytes in mice by accelerated carbon ions].

To assess the capacity of heavy ions to induce apoptosis in lymphocytes, mice have been irradiated with accelerated carbon ions (95 MeV/nucleon) at doses ranging from 0.1 to 4 Gy. Their spleens were removed 24 h later and gently dissociated to prepare a single cell suspension. Mononuclear cells were then maintained in culture at 37 degrees C, and the occurrence of apoptosis in these cells was analysed 24 h later. Lymphocytes were also irradiated in vitro, in the presence of Ac-DEVD-CHO, a potent caspase-3 and -7 inhibitor. Results from three experiments performed at the Grand Accelerateur National d'Ions Lourds (GANIL, Caen, France) are reported here. They indicate that carbon ions induce a marked, dose-dependent, reduction of the spleen weight and cellularity. However, in sharp contrast with spleen cells prepared from X-ray irradiated mice, only a slight increase of apoptosis is evidenced in cultured lymphocytes from mice irradiated with heavy ions. The significance of such results is discussed. So far, few data exist concerning the biological effects of heavy ions, in particular their capacity to induce apoptosis in lymphocytes; the present study provides useful clues for further investigations.

Animals↗

Caspase-3-like activity determines the type of cell death following ionizing radiation in MOLT-4 human leukaemia cells.

Caspases, a family of cysteine proteases, play a central role in the pathways leading to apoptosis. Recently, it has been reported that a broad spectrum inhibitor of caspases, the tripeptide Z-VAD-fmk, induced a switch from apoptosis to necrosis in dexamethasone-treated B lymphocytes and thymocytes. As such a cell death conversion could increase the efficiency of radiation therapy and in order to identify the caspases involved in this cell death transition, we investigated the effects of caspase-3-related proteases inhibition in irradiated MOLT-4 cells. Cells were pretreated with Ac-DEVD-CHO, an inhibitor of caspase-3-like activity, and submitted to X-rays at doses ranging from 1 to 4 Gy. Our results show that the inhibition of caspase-3-like activity prevents completely the appearance of the classical hallmarks of apoptosis such as internucleosomal DNA fragmentation or hypodiploid particles formation and partially the externalization of phosphatidylserine. However, this was not accompanied by any persistent increase in cell survival. Instead, irradiated cells treated by this inhibitor exhibited characteristics of a necrotic cell death. Therefore, functional caspase-3-subfamily not only appears as key proteases in the execution of the apoptotic process, but their activity may also influence the type of cell death following an exposure to ionizing radiation.

Annexin A5↗