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1.
Nature ; 546(7656): 129-132, 2017 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-28569799

RESUMO

X-ray free-electron lasers enable the investigation of the structure and dynamics of diverse systems, including atoms, molecules, nanocrystals and single bioparticles, under extreme conditions. Many imaging applications that target biological systems and complex materials use hard X-ray pulses with extremely high peak intensities (exceeding 1020 watts per square centimetre). However, fundamental investigations have focused mainly on the individual response of atoms and small molecules using soft X-rays with much lower intensities. Studies with intense X-ray pulses have shown that irradiated atoms reach a very high degree of ionization, owing to multiphoton absorption, which in a heteronuclear molecular system occurs predominantly locally on a heavy atom (provided that the absorption cross-section of the heavy atom is considerably larger than those of its neighbours) and is followed by efficient redistribution of the induced charge. In serial femtosecond crystallography of biological objects-an application of X-ray free-electron lasers that greatly enhances our ability to determine protein structure-the ionization of heavy atoms increases the local radiation damage that is seen in the diffraction patterns of these objects and has been suggested as a way of phasing the diffraction data. On the basis of experiments using either soft or less-intense hard X-rays, it is thought that the induced charge and associated radiation damage of atoms in polyatomic molecules can be inferred from the charge that is induced in an isolated atom under otherwise comparable irradiation conditions. Here we show that the femtosecond response of small polyatomic molecules that contain one heavy atom to ultra-intense (with intensities approaching 1020 watts per square centimetre), hard (with photon energies of 8.3 kiloelectronvolts) X-ray pulses is qualitatively different: our experimental and modelling results establish that, under these conditions, the ionization of a molecule is considerably enhanced compared to that of an individual heavy atom with the same absorption cross-section. This enhancement is driven by ultrafast charge transfer within the molecule, which refills the core holes that are created in the heavy atom, providing further targets for inner-shell ionization and resulting in the emission of more than 50 electrons during the X-ray pulse. Our results demonstrate that efficient modelling of X-ray-driven processes in complex systems at ultrahigh intensities is feasible.


Assuntos
Cristalografia/métodos , Elétrons , Lasers , Proteínas/química , Raios X , Iodo/química , Cinética , Fótons , Conformação Proteica , Eletricidade Estática , Fatores de Tempo
2.
Phys Rev Lett ; 127(9): 093202, 2021 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-34506178

RESUMO

The interaction of intense femtosecond x-ray pulses with molecules sensitively depends on the interplay between multiple photoabsorptions, Auger decay, charge rearrangement, and nuclear motion. Here, we report on a combined experimental and theoretical study of the ionization and fragmentation of iodomethane (CH_{3}I) by ultraintense (∼10^{19} W/cm^{2}) x-ray pulses at 8.3 keV, demonstrating how these dynamics depend on the x-ray pulse energy and duration. We show that the timing of multiple ionization steps leading to a particular reaction product and, thus, the product's final kinetic energy, is determined by the pulse duration rather than the pulse energy or intensity. While the overall degree of ionization is mainly defined by the pulse energy, our measurement reveals that the yield of the fragments with the highest charge states is enhanced for short pulse durations, in contrast to earlier observations for atoms and small molecules in the soft x-ray domain. We attribute this effect to a decreased charge transfer efficiency at larger internuclear separations, which are reached during longer pulses.

3.
Phys Rev Lett ; 121(13): 137403, 2018 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-30312105

RESUMO

Using ultrafast ≃2.5 fs and ≃25 fs self-amplified spontaneous emission pulses of increasing intensity and a novel experimental scheme, we report the concurrent increase of stimulated emission in the forward direction and loss of out-of-beam diffraction contrast for a Co/Pd multilayer sample. The experimental results are quantitatively accounted for by a statistical description of the pulses in conjunction with the optical Bloch equations. The dependence of the stimulated sample response on the incident intensity, coherence time, and energy jitter of the employed pulses reveals the importance of increased control of x-ray free electron laser radiation.

4.
Zentralbl Chir ; 142(4): 375-385, 2017 Aug.
Artigo em Alemão | MEDLINE | ID: mdl-27135866

RESUMO

The main focus of surgeons and anaesthesiologists during a surgical procedure is on safety and optimal treatment of the patient. Within the scope of interdisciplinary collaboration, the intraoperative communication between surgeons and anaesthesiologists is the basis of case-, findings- and surgery-phases-adapted patient management. The perioperative monitoring of patients and the implementation of diagnostic measures by anaesthesiologists are essential for optimal patient management. The results of the examinations may significantly determine the course of surgery. Therefore, it is important for surgeons to be familiar with the relevant intraoperative diagnostic measures.


Assuntos
Abdome/cirurgia , Anestesiologistas , Comunicação Interdisciplinar , Colaboração Intersetorial , Complicações Intraoperatórias/diagnóstico , Período Intraoperatório , Humanos , Monitorização Intraoperatória
5.
Anaesthesist ; 65(3): 183-9, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26886383

RESUMO

BACKGROUND: The laryngeal tube (LT) is a recommended alternative to endotracheal intubation during advanced life support (ALS). Its insertion is relatively simple; therefore, it may also serve as an alternative to bag mask ventilation (BMV) for untrained personnel performing basic life support (BLS). Data support the influence of LT on the no-flow time (NFT) compared with BMV during ALS in manikin studies. METHODS: We performed a manikin study to investigate the effect of using the LT for ventilation instead of BMV on the NFT during BLS in a prospective, randomized, single-rescuer study. All 209 participants were trained in BMV, but were inexperienced in using LT; each participant performed BLS during a 4-min time period. RESULTS: No significant difference in total NFT (LT: mean 81.1 ± 22.7 s; BMV: mean 83.2 ± 13.1 s, p = 0.414) was found; however, significant differences in the later periods of the scenario were identified. While ventilating with the LT, the proportion of chest compressions increased significantly from 67.2 to 73.2%, whereas the proportion of chest compressions increased only marginally when performing BMV. The quality of the chest compressions and the associated ventilation rate did not differ significantly. The mean tidal volume and mean minute volume were significantly lower when performing BMV. CONCLUSIONS: The NFT was significantly shorter in the later periods in a single-rescuer, cardiac arrest scenario when using an LT without previous training compared with BMV with previous training. A possible explanation for this result may be the complexity and workload of alternating tasks (e.g., time loss when reclining the head and positioning the mask for each ventilation during BMV).


Assuntos
Reanimação Cardiopulmonar/educação , Reanimação Cardiopulmonar/instrumentação , Manequins , Adulto , Suporte Vital Cardíaco Avançado , Reanimação Cardiopulmonar/métodos , Competência Clínica , Humanos , Intubação Intratraqueal , Estudos Prospectivos , Respiração Artificial , Estudantes de Medicina , Volume de Ventilação Pulmonar , Adulto Jovem
6.
Phys Rev Lett ; 114(10): 101301, 2015 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-25815919

RESUMO

We report the results of a joint analysis of data from BICEP2/Keck Array and Planck. BICEP2 and Keck Array have observed the same approximately 400 deg^{2} patch of sky centered on RA 0 h, Dec. -57.5°. The combined maps reach a depth of 57 nK deg in Stokes Q and U in a band centered at 150 GHz. Planck has observed the full sky in polarization at seven frequencies from 30 to 353 GHz, but much less deeply in any given region (1.2 µK deg in Q and U at 143 GHz). We detect 150×353 cross-correlation in B modes at high significance. We fit the single- and cross-frequency power spectra at frequencies ≥150 GHz to a lensed-ΛCDM model that includes dust and a possible contribution from inflationary gravitational waves (as parametrized by the tensor-to-scalar ratio r), using a prior on the frequency spectral behavior of polarized dust emission from previous Planck analysis of other regions of the sky. We find strong evidence for dust and no statistically significant evidence for tensor modes. We probe various model variations and extensions, including adding a synchrotron component in combination with lower frequency data, and find that these make little difference to the r constraint. Finally, we present an alternative analysis which is similar to a map-based cleaning of the dust contribution, and show that this gives similar constraints. The final result is expressed as a likelihood curve for r, and yields an upper limit r_{0.05}<0.12 at 95% confidence. Marginalizing over dust and r, lensing B modes are detected at 7.0σ significance.

7.
Klin Padiatr ; 227(4): 206-12, 2015 Jul.
Artigo em Alemão | MEDLINE | ID: mdl-25875400

RESUMO

BACKGROUND: A fast and comprehensive diagnostic by means of whole-body CT has been shown to reduce mortality in the adult trauma population. Therefore whole-body CT seems to be the standard in adult trauma-patients. Due to the higher radiation exposure of whole-body CT the use of this diagnostic toll in pediatric trauma patients is still under debate. It is not yet clear if whole-body CT in children can increase the probability of survival. METHOD: In a retrospective, multicenter study, we used the data recorded in the TraumaRegister DGU(®) to calculate the probability of survival according to the revised injury severity classification (RISC) and standardized mortality ratio (SMR). The SMR reflects the ratio of recorded to expected mortality. Included in the study were all children (1-15 years) and adults (16-50 years) with an Injury Severity Score (ISS)>9, who were directly admitted to the hospital from the scene of accident. We compared the groups of patients given whole-body CT or non-whole-body CT. Subgroup analysis was performed for children 1-9 years, children 10-15 years and adults. RESULTS: A total of 1,456 pediatric trauma patients (mean age 9.9 years) and 20,796 adults (mean age 32.7 years) were included in the study. In contrast to adult trauma patients, were the SMR in the whole-body CT group was significant lower; we observed no advantage for the whole-body CT in pediatric trauma patients. CONCLUSION: Due to the missing advantage of whole-body CT in the pediatric trauma population and the higher radiation exposure of whole-body CT a non-whole-body CT approach seems equivalent with a lower radiation exposure.


Assuntos
Traumatismo Múltiplo/diagnóstico por imagem , Sistema de Registros , Tomografia Computadorizada por Raios X/métodos , Imagem Corporal Total/métodos , Adolescente , Adulto , Criança , Pré-Escolar , Bases de Dados Factuais , Erros de Diagnóstico/prevenção & controle , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Traumatismo Múltiplo/mortalidade , Doses de Radiação , Estudos Retrospectivos , Taxa de Sobrevida , Adulto Jovem
8.
Perfusion ; 30(1): 52-9, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24743549

RESUMO

OBJECTIVES: Extracorporeal membrane oxygenation (ECMO) in patients with severe pulmonary failure is able to keep patients alive until organ regeneration, until shunting out for further diagnostic and therapeutic options or until transportation to specialized centers. Nonetheless, extracorporeal techniques require a high degree of expertise, so that a confinement to specialized centers is meaningful. Following from this requirement, the need for inter-hospital transfer of patients with severely compromised pulmonary function is rising. METHODS: We report about our experience with a portable ECMO system during inter-hospital air or ground transfer of patients with cardiopulmonary failure. RESULTS: The portable ECMO system was used for transportation to the center and in-hospital treatment in 36 patients with an average age of 53 years suffering from respiratory failure. Accordingly, the ECMO system was implanted as a veno-venous extracorporeal system. Pre-ECMO ventilation time was 5.2 (2-9) days. Twelve patients were transported to our institution by ground and 24 patients by air ambulance over a median distance of 46 km. With the assistance of the ECMO device, prompt stabilization of cardiopulmonary function could be achieved in all patients without any technical complications. Post-ECMO ventilation was 9.8 days. Weaning from the ECMO system was successful in 61% of all patients after a median device working period of 12.7 days; median ICU stay was 34 days and a survival rate of 64% of patients was achieved. Technical (8%) and device-associated bleeding (11%)/thromboembolic (8%) complication rates showed very acceptable levels. CONCLUSION: Our experience demonstrates that miniaturized, portable ECMO therapy allows location-independent, out-of-center stabilization of pulmonary compromised patients with consecutive inter-hospital transfer and further in-house treatment, so that sophisticated ECMO therapy can be offered to every patient, even in hospitals with primary healthcare.


Assuntos
Oxigenação por Membrana Extracorpórea/instrumentação , Miniaturização/instrumentação , Insuficiência Respiratória/terapia , Transporte de Pacientes , Adolescente , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento , Adulto Jovem
9.
Appl Environ Microbiol ; 80(23): 7324-36, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25239897

RESUMO

Antimicrobial photodynamic therapy (APDT) has gained increased attention as an alternative treatment approach in various medical fields. However, the effect of APDT using visible light plus water-filtered infrared A (VIS + wIRA) on oral biofilms remains unexplored. For this purpose, initial and mature oral biofilms were obtained in situ; six healthy subjects wore individual upper jaw acrylic devices with bovine enamel slabs attached to their proximal sites for 2 h or 3 days. The biofilms were incubated with 100 µg ml(-1) toluidine blue O (TB) or chlorin e6 (Ce6) and irradiated with VIS + wIRA with an energy density of 200 mW cm(-2) for 5 min. After cultivation, the CFU of half of the treated biofilm samples were quantified, whereas following live/dead staining, the other half of the samples were monitored by confocal laser scanning microscopy (CLSM). TB- and Ce6-mediated APDT yielded a significant decrease of up to 3.8 and 5.7 log10 CFU for initial and mature oral biofilms, respectively. Quantification of the stained photoinactivated microorganisms confirmed these results. Overall, CLSM revealed the diffusion of the tested photosensitizers into the deepest biofilm layers after exposure to APDT. In particular, Ce6-aided APDT presented elevated permeability and higher effectiveness in eradicating 89.62% of biofilm bacteria compared to TB-aided APDT (82.25%) after 3 days. In conclusion, antimicrobial photoinactivation using VIS + wIRA proved highly potent in eradicating oral biofilms. Since APDT excludes the development of microbial resistance, it could supplement the pharmaceutical treatment of periodontitis or peri-implantitis.


Assuntos
Bactérias/efeitos da radiação , Fenômenos Fisiológicos Bacterianos/efeitos da radiação , Biofilmes/efeitos da radiação , Raios Infravermelhos , Luz , Viabilidade Microbiana/efeitos da radiação , Boca/microbiologia , Animais , Antibacterianos/metabolismo , Bovinos , Contagem de Colônia Microbiana , Voluntários Saudáveis , Humanos , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/metabolismo , Coloração e Rotulagem , Resultado do Tratamento
10.
Perfusion ; 29(3): 200-9, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-23996694

RESUMO

The use of extracorporeal membrane oxygenation (ECMO) is becoming a popular tool in the treatment of cardiogenic shock. We present two case reports where classical veno-arterial peripherally cannulated ECMO therapy proved insufficient with profuse cerebral hypoxemia. After augmenting the setting into veno-veno-arterial ECMO, we achieved a remarkable improvement of all oxygenation parameters. The simultaneous use of veno-venous and veno-arterial ECMO might display as a novel strategy to counteract the coronary and cerebral hypoxemia in veno-arterial ECMO therapy in patients with therapy-refractory cardiogenic shock or in combined cardiopulmonary failure. In this manuscript, the veno-veno-arterial ECMO setup is described in full detail and different venous cannulas are discussed.


Assuntos
Oxigenação por Membrana Extracorpórea/métodos , Hipóxia Encefálica/cirurgia , Choque Cardiogênico/cirurgia , Idoso , Feminino , Humanos , Hipóxia Encefálica/complicações , Hipóxia Encefálica/fisiopatologia , Masculino , Pessoa de Meia-Idade , Choque Cardiogênico/complicações , Choque Cardiogênico/fisiopatologia
11.
Cytokine ; 61(1): 97-103, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23026294

RESUMO

Fractalkine is a unique member of the CX3C chemokine family by unfolding its potential through the chemokine (C-X3-C motif) receptor 1 (CX3CR1) with dual function acting both as an adhesion molecule and a soluble chemokine. The regulation of this chemokine is still not clear. Therefore, we were interested in the regulation of fractalkine and of CX3CR1 in experimental sepsis. In addition, we investigated the role of NF-κB for the regulation of fractalkine and of CX3CR1. Using a mouse model of cecal ligation and puncture (CLP)-induced sepsis, we found elevated fractalkine mRNA levels in the heart, lung, kidney, and liver, as well as increased plasma levels 24 and 48h after CLP, respectively. In parallel, CLP resulted in a significant downregulation of CX3CR1 mRNA receptor expression in all investigated murine tissues. Septic mice that were pretreated with the selective NF-κB inhibitor pyrrolidine dithiocarbamate (PDTC) were found to have a decreased liberation of proinflammtory cytokines such as TNF-α, IL-1ß, IL-6, or IFN-γ. Further PDTC pretreatment attenuated CLP-induced downregulation of CX3CR1 mRNA as well as CLP-induced upregulation of fractalkine mRNA expression in the heart, lung, kidney, liver, and the increase in fractalkine plasma levels of septic mice. In addition, CLP-induced downregulation of renal CX3CR1 protein expression was inhibited by PDTC-pretreatment. Taken together, our data indicate a CLP-induced inverse regulation of the expression between the relating ligand and the receptor with an upregulation of fractalkine and downregulation of CX3CR1, which seems to be mediated by the transcripting factor NF-κB likely via reduced liberation of proinflammtory cytokines in the whole murine organism.


Assuntos
Quimiocina CX3CL1/metabolismo , NF-kappa B/metabolismo , Pirrolidinas/farmacologia , Receptores de Quimiocinas/metabolismo , Sepse/imunologia , Tiocarbamatos/farmacologia , Animais , Receptor 1 de Quimiocina CX3C , Ceco/patologia , Ceco/cirurgia , Quimiocina CX3CL1/biossíntese , Quimiocina CX3CL1/genética , Modelos Animais de Doenças , Regulação para Baixo , Interferon gama/metabolismo , Interleucina-1beta/metabolismo , Interleucina-6/metabolismo , Ligadura , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Punções , Pirrolidinas/uso terapêutico , RNA Mensageiro/sangue , Receptores de Quimiocinas/biossíntese , Receptores de Quimiocinas/genética , Tiocarbamatos/uso terapêutico , Fator de Necrose Tumoral alfa/metabolismo
12.
Cytokine ; 62(1): 52-7, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23498057

RESUMO

To investigate the effects of the commonly-used immunomodulators l-glutamine, l-alanine, and the combination of both l-alanyl-l-glutamine (Dipeptamin(®)) on intracellular expression of IL-6, IL-8, and TNF-α during endotoxemia, lipopolysaccharide (LPS)-stimulated human monocytes in a whole blood system were investigated by flow cytometry. Whole blood of twenty-seven healthy volunteers was stimulated with LPS and incubated with three different amino acid solutions (1. l-glutamine, 2. l-alanine, 3. l-alanyl-l-glutamine, each concentration 2 mM, 5 mM, incubation time 3 h). CD14(+) monocytes were phenotyped in whole-blood and intracellular expression of cytokines was assessed by flow cytometry. Our investigations showed for the first time in whole blood probes, imitating best physiologically present cellular interactions, that l-glutamine caused a dose-independent inhibitory effect on IL-6 and TNF-α production in human monocytes stimulated with LPS. However, l-alanine had contrary effects on IL-6 expression, significantly upregulating expression of IL-6 in LPS-treated monocytes. The impact of l-alanine on the expression of TNF-α was comparable with glutamine. Neither amino acid was able to affect IL-8 production in LPS-stimulated monocytes. The combination of both did not influence significantly IL-6 and IL-8 expression in monocytes during endotoxemia, however strongly reduced TNF-α production. For the regulation of TNF-α, l-glutamine, l-alanine and the combination of both show a congruent and exponentiated downregulating effect during endotoxemia, for the modulation of IL-6, l-glutamine and l-alanine featured opposite regulation leading to a canceling impact of each other when recombining both amino acids.


Assuntos
Alanina/farmacologia , Glutamina/farmacologia , Interleucina-6/metabolismo , Interleucina-8/metabolismo , Lipopolissacarídeos/farmacologia , Monócitos/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Adulto , Dipeptídeos/farmacologia , Endotoxemia/sangue , Citometria de Fluxo , Humanos , Interleucina-6/sangue , Interleucina-8/sangue , Espaço Intracelular/metabolismo , Monócitos/efeitos dos fármacos , Fator de Necrose Tumoral alfa/sangue
13.
Transfus Med ; 23(6): 407-15, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23962029

RESUMO

AIM(S): In this article, we aimed to investigate plasma Factor XIII levels after extracorporeal circulation in cardiac surgery by thromboelastometric detection, as extracorporeal circulation causes various coagulation disorders due to the exposure of blood to artificial surfaces, inflammatory induction and mechanical destruction of platelets and coagulation factors, which may particularly affect factors with long half-lives, such as Factor XIII. BACKGROUND: Since transfusion algorithms are often empirical and laboratory analysis of Factor XIII plasma levels may not be available 24 h a day, bed-side testing using rotational thromboelastometry (ROTEM) could offer a splendid option to define the cause of excessive peri-operative bleeding disorders in general and Factor XIII levels in particular in a timely manner and thus facilitating exact substitution therapy. METHODS: In this trial, we investigated 25 cardiac surgery patients with extracorporeal bypass times over 100 min. Standard laboratory and ROTEM analyses were performed post-operatively at the time of intensive care unit admission and 6 h later. We implemented EXTEM with additional Factor XIII (teenTEM) as additional test by adding 0·625 IU Factor XIII to standard EXTEM reagents. RESULTS: In this observational study, we could not demonstrate a correlation between Factor XIII and MCFEXTEM , CFTEXTEM or MLEXTEM . Neither Factor XIII plasma levels nor MCFEXTEM could predict blood loss. In accordance with previous findings, we were able to demonstrate increased maximum clot firmness (MCF), decreased clot formation time and decreased maximum lysis by adding Factor XIII in vitro (teenTEM vs EXTEM) indicating an improvement in the coagulation process. As shown before, we also found a strong correlation between MCF and platelet and fibrinogen plasma levels. CONCLUSION: In summary, 'teenTEM' test does not seem to detect Factor XIII deficient patients in cardiac surgery. Furthermore, post-operative blood loss could not be predicted neither by ROTEM nor by laboratory analysis of Factor XIII. In vitro administration of Factor XIII appears to improve laboratory measures of haemostasis.


Assuntos
Procedimentos Cirúrgicos Cardíacos , Circulação Extracorpórea , Fator VIII/metabolismo , Tromboelastografia/métodos , Idoso , Idoso de 80 Anos ou mais , Fator VIII/análise , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Hemorragia Pós-Operatória/sangue , Hemorragia Pós-Operatória/prevenção & controle
15.
Radiat Res ; 199(6): 535-555, 2023 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-37310880

RESUMO

Tools for radiation exposure reconstruction are required to support the medical management of radiation victims in radiological or nuclear incidents. Different biological and physical dosimetry assays can be used for various exposure scenarios to estimate the dose of ionizing radiation a person has absorbed. Regular validation of the techniques through inter-laboratory comparisons (ILC) is essential to guarantee high quality results. In the current RENEB inter-laboratory comparison, the performance quality of established cytogenetic assays [dicentric chromosome assay (DCA), cytokinesis-block micronucleus assay (CBMN), stable chromosomal translocation assay (FISH) and premature chromosome condensation assay (PCC)] was tested in comparison to molecular biological assays [gamma-H2AX foci (gH2AX), gene expression (GE)] and physical dosimetry-based assays [electron paramagnetic resonance (EPR), optically or thermally stimulated luminescence (LUM)]. Three blinded coded samples (e.g., blood, enamel or mobiles) were exposed to 0, 1.2 or 3.5 Gy X-ray reference doses (240 kVp, 1 Gy/min). These doses roughly correspond to clinically relevant groups of unexposed to low exposed (0-1 Gy), moderately exposed (1-2 Gy, no severe acute health effects expected) and highly exposed individuals (>2 Gy, requiring early intensive medical care). In the frame of the current RENEB inter-laboratory comparison, samples were sent to 86 specialized teams in 46 organizations from 27 nations for dose estimation and identification of three clinically relevant groups. The time for sending early crude reports and more precise reports was documented for each laboratory and assay where possible. The quality of dose estimates was analyzed with three different levels of granularity, 1. by calculating the frequency of correctly reported clinically relevant dose categories, 2. by determining the number of dose estimates within the uncertainty intervals recommended for triage dosimetry (±0.5 Gy or ±1.0 Gy for doses <2.5 Gy or >2.5 Gy), and 3. by calculating the absolute difference (AD) of estimated doses relative to the reference doses. In total, 554 dose estimates were submitted within the 6-week period given before the exercise was closed. For samples processed with the highest priority, earliest dose estimates/categories were reported within 5-10 h of receipt for GE, gH2AX, LUM, EPR, 2-3 days for DCA, CBMN and within 6-7 days for the FISH assay. For the unirradiated control sample, the categorization in the correct clinically relevant group (0-1 Gy) as well as the allocation to the triage uncertainty interval was, with the exception of a few outliers, successfully performed for all assays. For the 3.5 Gy sample the percentage of correct classifications to the clinically relevant group (≥2 Gy) was between 89-100% for all assays, with the exception of gH2AX. For the 1.2 Gy sample, an exact allocation to the clinically relevant group was more difficult and 0-50% or 0-48% of the estimates were wrongly classified into the lowest or highest dose categories, respectively. For the irradiated samples, the correct allocation to the triage uncertainty intervals varied considerably between assays for the 1.2 Gy (29-76%) and 3.5 Gy (17-100%) samples. While a systematic shift towards higher doses was observed for the cytogenetic-based assays, extreme outliers exceeding the reference doses 2-6 fold were observed for EPR, FISH and GE assays. These outliers were related to a particular material examined (tooth enamel for EPR assay, reported as kerma in enamel, but when converted into the proper quantity, i.e. to kerma in air, expected dose estimates could be recalculated in most cases), the level of experience of the teams (FISH) and methodological uncertainties (GE). This was the first RENEB ILC where everything, from blood sampling to irradiation and shipment of the samples, was organized and realized at the same institution, for several biological and physical retrospective dosimetry assays. Almost all assays appeared comparably applicable for the identification of unexposed and highly exposed individuals and the allocation of medical relevant groups, with the latter requiring medical support for the acute radiation scenario simulated in this exercise. However, extreme outliers or a systematic shift of dose estimates have been observed for some assays. Possible reasons will be discussed in the assay specific papers of this special issue. In summary, this ILC clearly demonstrates the need to conduct regular exercises to identify research needs, but also to identify technical problems and to optimize the design of future ILCs.


Assuntos
Bioensaio , Coleta de Amostras Sanguíneas , Estudos Retrospectivos , Citocinese , Espectroscopia de Ressonância de Spin Eletrônica
16.
Radiat Res ; 199(6): 556-570, 2023 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-37018160

RESUMO

After large-scale radiation accidents where many individuals are suspected to be exposed to ionizing radiation, biological and physical retrospective dosimetry assays are important tools to aid clinical decision making by categorizing individuals into unexposed/minimally, moderately or highly exposed groups. Quality-controlled inter-laboratory comparisons of simulated accident scenarios are regularly performed in the frame of the European legal association RENEB (Running the European Network of Biological and Physical retrospective Dosimetry) to optimize international networking and emergency readiness in case of large-scale radiation events. In total 33 laboratories from 22 countries around the world participated in the current RENEB inter-laboratory comparison 2021 for the dicentric chromosome assay. Blood was irradiated in vitro with X rays (240 kVp, 13 mA, ∼75 keV, 1 Gy/min) to simulate an acute, homogeneous whole-body exposure. Three blood samples (no. 1: 0 Gy, no. 2: 1.2 Gy, no. 3: 3.5 Gy) were sent to each participant and the task was to culture samples, to prepare slides and to assess radiation doses based on the observed dicentric yields from 50 manually or 150 semi-automatically scored metaphases (triage mode scoring). Approximately two-thirds of the participants applied calibration curves from irradiations with γ rays and about 1/3 from irradiations with X rays with varying energies. The categorization of the samples in clinically relevant groups corresponding to individuals that were unexposed/minimally (0-1 Gy), moderately (1-2 Gy) or highly exposed (>2 Gy) was successfully performed by all participants for sample no. 1 and no. 3 and by ≥74% for sample no. 2. However, while most participants estimated a dose of exactly 0 Gy for the sham-irradiated sample, the precise dose estimates of the samples irradiated with doses >0 Gy were systematically higher than the corresponding reference doses and showed a median deviation of 0.5 Gy (sample no. 2) and 0.95 Gy (sample no. 3) for manual scoring. By converting doses estimated based on γ-ray calibration curves to X-ray doses of a comparable mean photon energy as used in this exercise, the median deviation decreased to 0.27 Gy (sample no. 2) and 0.6 Gy (sample no. 3). The main aim of biological dosimetry in the case of a large-scale event is the categorization of individuals into clinically relevant groups, to aid clinical decision making. This task was successfully performed by all participants for the 0 Gy and 3.5 Gy samples and by 74% (manual scoring) and 80% (semiautomatic scoring) for the 1.2 Gy sample. Due to the accuracy of the dicentric chromosome assay and the high number of participating laboratories, a systematic shift of the dose estimates could be revealed. Differences in radiation quality (X ray vs. γ ray) between the test samples and the applied dose effect curves can partly explain the systematic shift. There might be several additional reasons for the observed bias (e.g., donor effects, transport, experimental conditions or the irradiation setup) and the analysis of these reasons provides great opportunities for future research. The participation of laboratories from countries around the world gave the opportunity to compare the results on an international level.


Assuntos
Aberrações Cromossômicas , Liberação Nociva de Radioativos , Humanos , Estudos Retrospectivos , Radiometria/métodos , Bioensaio/métodos , Cromossomos , Relação Dose-Resposta à Radiação
17.
Anaesthesist ; 61(6): 503-11, 2012 Jun.
Artigo em Alemão | MEDLINE | ID: mdl-22695777

RESUMO

An Addisonian crisis marks an acute adrenocortical failure which can be caused by decompensation of a chronic insufficiency due to stress, an infarct or bleeding of the adrenal cortex and also abrupt termination of a long-term glucocorticoid medication. This article reports the case of a 25-year-old patient with Crohn's disease who suffered an Addisonian crisis with hypotension, hyponatriemia and hypoglycemia during an emergency laparotomy after he had terminated prednisolone medication on his own authority. This necessitated an aggressive volume therapy in addition to an initial therapy with 100 mg hydrocortisone, 8 g glucose and a continuous administration of catecholamines. Under this treatment regimen hemodynamic stabilization was achieved. Reduction of the administration of hydrocortisone after 3 days resulted in cardiovascular insufficiency which required an escalation of the hydrocortisone substitution.


Assuntos
Doença de Addison/etiologia , Complicações Intraoperatórias/etiologia , Doença de Addison/fisiopatologia , Doença de Addison/terapia , Testes de Função do Córtex Suprarrenal , Adulto , Anestesia , Anti-Inflamatórios/efeitos adversos , Volume Sanguíneo , Catecolaminas/uso terapêutico , Cuidados Críticos , Estado Terminal , Doença de Crohn/cirurgia , Hidratação , Humanos , Hidrocortisona/uso terapêutico , Complicações Intraoperatórias/fisiopatologia , Complicações Intraoperatórias/terapia , Laparotomia , Masculino , Prednisolona/efeitos adversos , Desequilíbrio Hidroeletrolítico/complicações , Desequilíbrio Hidroeletrolítico/terapia
18.
Anaesthesist ; 61(9): 792-814, 2012 Sep.
Artigo em Alemão | MEDLINE | ID: mdl-22955889

RESUMO

Acute subarachnoid hemorrhage (SAH) is a severe and acute life-threatening cerebrovascular disease. Approximately 80% of all acute non-traumatic SAHs are the result of a ruptured cerebrovascular aneurysm. Despite advances in diagnosis and treatment a high morbidity and mortality still exists. Apart from the primary cerebral damage there are also secondary complications, such as vasospasm, rebleeding, hydrocephalus, cerebral edema or hydrocephalus. For an appropriate therapy an understanding of the extensive pathophysiology, the options in diagnostics and therapy and the complications of the disease are essential. Anesthesiologists are decisively involved in the therapy of the primary and secondary damages and subsequently in the outcome as well. This article provides an overview of the perioperative and intensive care management of patients with SAH.


Assuntos
Hemorragia Subaracnóidea/terapia , Anticoagulantes/uso terapêutico , Angiografia Cerebral , Cuidados Críticos , Cardiopatias/complicações , Humanos , Hidrocefalia/complicações , Hipertensão Intracraniana/etiologia , Pneumopatias/etiologia , Pneumopatias/terapia , Angiografia por Ressonância Magnética , Procedimentos Neurocirúrgicos , Fatores de Risco , Hemorragia Subaracnóidea/complicações , Hemorragia Subaracnóidea/diagnóstico , Hemorragia Subaracnóidea/epidemiologia , Hemorragia Subaracnóidea/fisiopatologia , Vasoespasmo Intracraniano/etiologia , Desequilíbrio Hidroeletrolítico/etiologia
19.
Anaesthesist ; 59(8): 682-99, 2010 Aug.
Artigo em Alemão | MEDLINE | ID: mdl-20694713

RESUMO

Acute renal failure (ARF) is clinically defined as an abrupt, but in principle reversible deterioration of glomerular and tubular function. Regarding pathophysiology, ARF is caused by ischemic renal conditions and toxic mediators. Sepsis is the most common cause of ARF in the intensive care unit and ARF is an independent risk factor for lethality of septic patients. Interventions to protect the kidneys against ARF include preliminary optimization of renal perfusion by volume load with cristalloid solutions and the administration of vasopressors. Daily maximum permissible dosages for colloids should not be exceeded and hyperoncotic colloid solutions should be generally avoided. Dopamine in "renal dosage" is nowadays obsolete. Loop diuretics produce diuresis and can be beneficial to extrarenal organs by improving fluid homeostasis, however diuretics do not improve kidney function and outcome. Therefore, diuretics are not indicated for patients with imminent or existing ARF. Septic patients with ARF can be treated by intermittent and continuous forms of renal replacement therapy, whereas continuous convective and intermittent diffusive methods are equivalent when utilizing an ultrafiltration rate > or =20 ml/h*kg body weight or a therapeutic interval > or =3 times/week.


Assuntos
Injúria Renal Aguda/etiologia , Insuficiência de Múltiplos Órgãos/etiologia , Sepse/complicações , Injúria Renal Aguda/epidemiologia , Injúria Renal Aguda/fisiopatologia , Coloides/administração & dosagem , Coloides/efeitos adversos , Coloides/uso terapêutico , Diuréticos/uso terapêutico , Humanos , Isquemia/complicações , Rim/fisiopatologia , Insuficiência de Múltiplos Órgãos/fisiopatologia , Prognóstico , Diálise Renal , Terapia de Substituição Renal , Sepse/epidemiologia , Sepse/fisiopatologia
20.
J Surg Oncol ; 100(4): 297-301, 2009 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-19697426

RESUMO

Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (HIPEC) has become an important tool in the management of patients with peritoneal malignancies. It is a complex surgical procedure with significant fluid loss during debulking leading to relevant pathophysiological alterations and therefore a challenge for anesthesiologists and critical care physicians. This review summarizes perioperative changes in hemodynamics, oxygen supply, coagulation, hematopoetic parameters and fluid status during cytoreductive surgery and HIPEC and how to deal with these pathophysiological alterations.


Assuntos
Assistência Perioperatória/métodos , Neoplasias Peritoneais/cirurgia , Coagulação Sanguínea/fisiologia , Sistema Hematopoético/fisiologia , Hemodinâmica/fisiologia , Humanos , Consumo de Oxigênio/fisiologia , Neoplasias Peritoneais/fisiopatologia
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