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E Martin

Publications and source records attributed to E Martin.

At least 37 records · Page 2Linked to original sources
PubMed2003

Guanylyl cyclase is an ATP sensor coupling nitric oxide signaling to cell metabolism.

Defending cellular integrity against disturbances in intracellular concentrations of ATP ([ATP](i)) is predicated on coordinating the selection of substrates and their flux through metabolic pathways (metabolic signaling), ATP transfer from sites of production to utilization (energetic signaling), and the regulation of processes consuming energy (cell signaling). Whereas NO and its receptor, soluble guanylyl cyclase (sGC), are emerging as key mediators coordinating ATP supply and demand, mechanisms coupling this pathway with metabolic and energetic signaling remain undefined. Here, we demonstrate that sGC is a nucleotide sensor whose responsiveness to NO is regulated by [ATP](i). Indeed, ATP inhibits purified sGC with a K(i) predicting >60% inhibition of NO signaling in cells maintaining physiological [nucleotide](i). ATP inhibits sGC by interacting with a regulatory site that prefers ATP > GTP. Moreover, alterations in [ATP](i), by permeabilization and nucleotide clamping or inhibition of mitochondrial ATP synthase, regulate NO signaling by sGC. Thus, [ATP](i) serves as a "gain control" for NO signaling by sGC. At homeostatic [ATP](i), NO activation of sGC is repressed, whereas insults that reduce [ATP](i,) derepress sGC and amplify responses to NO. Hence, sGC forms a key synapse integrating metabolic, energetic, and cell signaling, wherein ATP is the transmitter, allosteric inhibition the coupling mechanism, and regulated accumulation of cGMP the response.

Adenosine Triphosphate↗
PubMed2003

Enhanced production of neutron-rich rare isotopes in peripheral collisions at Fermi energies.

A large enhancement in the production of neutron-rich projectile residues is observed in the reactions of a 25 MeV/nucleon 86Kr beam with the neutron-rich 124Sn and 64Ni targets relative to the predictions of the EPAX parametrization of high-energy fragmentation, as well as relative to the reaction with the less neutron-rich 112Sn target. A hybrid model based on a deep-inelastic transfer (DIT) code followed by a statistical deexcitation code accounts for part of the observed large cross sections. The DIT simulation indicates that the production of neutron-rich nuclides in these reactions is associated with peripheral nucleon exchange in which the neutron skins of the neutron-rich 124Sn and 64Ni target nuclei may play an important role. From a practical viewpoint, such reactions offer a novel synthetic avenue to access extremely neutron-rich rare isotopes towards the neutron-drip line.

Journal Article↗
PubMed2003

[The future of preclinical emergency medicine in Germany].

Against the background of an ever-increasing shortage of financial support, closure of smaller hospitals and shortage of personnel in the medical branch, the necessity of the Federal emergency system is being increasingly called into question. In reality the number of missions which are relatively indicated are clearly increasing nationwide: an emergency doctor is not absolutely necessary in many situations. However, for complex emergency situations in Germany, an emergency medical system must remain an integral component of the preclinical care system in addition to the well-trained rescue service personnel. Hereby it is less important to have more emergency medical doctors, but more important to have a higher emergency medical qualification, possibly by a reduction in the density of emergency service stations. By the introduction of a ranked assistance system and the inclusion of "first responders", the time period before the arrival of the highly qualified emergency medical doctor can be bridged by qualified paramedics and general practitioners. The impulse of the legislators, assimilation of the rescue service acts, restructuring of rescue service catchment areas and the introduction of integrated demand-oriented control stations with a consequent quality management system as well as the implementation of a medical leader rescue system can reduce costs and further improve the quality of the emergency medical rescue system.

Allied Health Personnel↗
PubMed2003

Potent thermogenic action of triiodothyroacetic acid in brown adipocytes.

Triiodothyroacetic acid (TRIAC) is a triiodothyronine (T3) metabolite with high affinity for T3 nuclear receptors. We compared the thermogenic action of TRIAC versus T3 in brown adipocytes, by studying target genes known to mediate thermogenic action: uncoupling protein 1 (UCP-1), a marker of brown adipocytes, and type II-5'deiodinase (D2), which provides the T3 required for thermogenesis. TRIAC is 10-50 times more potent than T3 at increasing the adrenergic induction of UCP-1 mRNA and D2 activities. TRIAC action on UCP-1 is exerted at the transcriptional level. In the presence of an adrenergic stimulus, TRIAC is also more potent than T3, inducing lipoprotein lipase mRNA and 5 deiodinase (D3) activity and mRNA. Maximal effects occur at very low concentrations (0.2 nM). The greater potency of TRIAC is not due to preferential cellular or nuclear uptake. Therefore, TRIAC is a potent thermogenic agent that might increase energy expenditure and regulate T3 production in brown adipocytes.

Adipocytes↗
PubMed2003

[Ultrasound and local anaesthesia. Part III: ultrasound and neuroaxial local anaesthesia].

The use of ultrasound as a diagnostic tool for the visualisation of the epidural space has effects on the quality and the performance of epidural anesthesia. This work presents an overview of the recent experiences with ultrasound for epidural anesthesia and on the possibilities for ultrasound imaging techniques. The results of visualisation of the epidural space and its limiting structures obtained by various working groups are presented. We review all presently available data on the prediction of the puncture depth. The various working groups found correlations between predicted and effective puncture depth between 0.79 and 0.98 and the precision of the measurement was 57-7.7 mm. Regarding the prediction of the puncture angle there was a poor correlation ranging between 0.07 and 0.31. The precision between the measured and the punctured angles was found to be 10-13.4 degrees. In all available prospective randomised studies on the puncture effects in the lumbar epidural space, the influence of ultrasound showed a significant reduction ( p<0.03) of the puncture attempts,and we found a significant ( p<0.05) reduction in the number of puncture levels. The ultrasound-guided puncture allowed an ideal needle trajectory and a more precise application of the catheter. A significant improvement of analgesia quality ( p<0.035) and patient satisfaction ( p<0.006) could be achieved. The metaanalysis of the different studies regarding puncture quality by ultrasound-guided peridural anaesthesia showed a clear advantage for the use of imaging techniques.

Anesthesia, Epidural↗
PubMed2003

[Accessible price lists at the anaesthesiologist's workplace enhance cost consciousness as a part of process and cost optimization].

The imminent introduction of the DRG (diagnosis-related-group) system is putting hospitals in Germany under considerable pressure. This requires that personnel are efficiently allocated by optimizing organizational procedures and that the limited resources be distributed in a cost-effective manner. One prerequisite for this is a marked cost-consciousness on the part of those who "incur costs" in providing a service. To increase the awareness of costs in clinical physicians, the cost structures must be transparent. In order to achieve this goal, a project was initiated at the Department of Anaesthesiology at the University Hospital of Heidelberg, which aimed to enhance the cost-consciousness of the staff by making price lists available to anaesthesiologists at the workplace. In addition to the price lists, the 25 most expensive medications and medical products were added as an ABC analysis. The departmental staff was interviewed by questionnaire as to whether this project was reasonable. After 1 year the interview was repeated. The results of the questionnaire showed that in the opinion of the staff, price lists are an effective tool, as cost-consciousness on the part of clinical physicians can be enhanced by making price structures transparent. This is a major prerequisite for individual motivation in the cost-effective management. Although the ABC analyses demonstrate no long-term effect of the price-transparency on the cost structures, the staff showed increased cost-consciousness and individual motivation for economic tasks.

Anesthesia Department, Hospital↗
PubMed2003

[High resolution fluorescence microscopy in combination with mathematical modelling. First evidence of sub-cellular anesthetic effects on Ca2+ sparks in situ].

Volatile anesthetics used in daily clinical routine, are associated with a rare but life-threatening disease, malignant hyperthermia. To date it is well known that, with the exception of xenon and nitrous oxide, all volatile anesthetics have the potential to trigger calcium (Ca(2+)) release from the sarcoplasmic reticulum, thereby influencing the Ca(2+) homeostasis in muscle fibers. The effects of volatile anesthetics have been previously studied by recording Ca(2+)-activated force transients in muscle fibers and by quantifying the effects on isolated intracellular Ca(2+)-release channels (ryanodin receptors). The use of high resolution fluorescence microscopy methods in combination with spatio-temporal mathematical models allows the effects of volatile anesthetics on functional clusters of ryanodin receptors in mammalian skeletal muscle fibers to be studied in situ for the first time.Thus, the analysis of cellular Ca(2+)-activated force production and single channel properties in conjunction with mathematical models allows the quantification of the effects of volatile anesthetics on Ca(2+)-release in the natural physiological environment on the basis of the underlying molecular architecture. In addition to the basic understanding of alterations in the Ca(2+) homeostasis induced by volatile anesthetics in muscle and nerve cells, the results are also of direct clinical importance for the understanding of the pathogenesis of malignant hyperthermia,where ryanodin receptor mutations are currently thought to result in an increased Ca(2+) release under the influence of volatile anesthetics.

Anesthetics, Inhalation↗
PubMed2003

[Development of a questionnaire to assess the quality of the preanesthetic visit].

In the current study a questionnaire was developed to evaluate the preanesthetic visit to prepare patients for general anesthesia with regard to the effects on in-hospital quality of care. The questionnaire consists of one part pertaining to patient satisfaction and one part pertaining to the information gained from the preanesthetic visit. In a first phase, the questionnaire was generated and then validated in 104 patients undergoing general or vascular surgery at the University of Heidelberg, Germany. As a result of the pretest evaluation, the preliminary pool of questions could be reduced. Consequently, the final questionnaire is composed of six questions on patient satisfaction and six questions on information gained after the preanesthetic visit as well as one question regarding the number of preanesthetic consultations prior to general anesthesia. In the part of the questionnaire on patient satisfaction, responses can be given on a 6-point scale ranging from -3 (statement is not correct) to +3 (statement is correct). The scores -3 to +3 are assigned 1-6 points, in order to calculate a total sum score to measure patient satisfaction. The part on information gained contains multiple-choice questions with four possible answers, of which only one is correct. Analogous to the measurement of patient satisfaction, a total sum score can be calculated to evaluate the information gain after the preanesthetic visit. The present study shows the suitability of a questionnaire to evaluate the quality of health care after the preanesthetic visit with the parameters patient satisfaction and information gain. Such a questionnaire can be used to compare different premedication techniques and, thus, might contribute to improve the quality of health care.

Adult↗
PubMed2003

[Preoperative fasting. An update].

In Germany the predominant standard of preoperative care for elective surgery is fasting after midnight, with the aim of reducing the risk of pulmonary aspiration. However, for the past several years the scientific evidence supporting such a practice has been challenged. Experimental and clinical studies prove a reliable gastric emptying within 2 h suggesting that, particularly for limited intake of clear fluids up to 2 h preoperatively, there would be no increased risk for the patient. In addition, the general incidence of pulmonary aspiration during general anaesthesia (before induction, during surgery and during recovery) is extremely low, has a good prognosis and is more a consequence of insufficient airway protection and/or inadequate anaesthetic depth rather than due to the patient's fasting state. Therefore, primarily to decrease perioperative discomfort for patients, several national anaesthesia societies have changed their guidelines for preoperative fasting. They recommend a more liberal policy regarding per os intake of both liquid and solid food, with consideration of certain conditions and contraindications. The following article reviews the literature and gives an overview of the scientific background on which the national guidelines are based. The intention of this review is to propose recommendations for preoperative fasting regarding clear fluids for Germany as well.

Fasting↗
PubMed2003

Pronounced arterial collateralization was induced after permanent rat cerebral four-vessel occlusion. Relation to neuropathology and capillary ultrastructure.

The present study investigates chronic changes in cerebral arterial vessel system, microvasculature, and brain histopathology using an adult rat model based on permanent and stepwise occlusion of four cerebral vessels. Digital subtraction angiography (DSA) was performed to study chronic changes in arterial cerebral vessel system after permanent vessel occlusion. Long-lasting functional changes such as NMDA-, AMPA- and GABA(A)-receptor binding were detected in hippocampus and dentate gyrus using autoradiography. Structural changes in cerebral capillaries were investigated using light- and electron microscopy. Chronic cerebral oligemia did not cause any significant changes in the densities of excitatory glutamate and inhibitory GABA(A) receptors. By electron microscopy we could document, however, that most capillaries in vessel-occluded animals shrank, the endothelial cells were prominent with enlarged nuclei and increased cytoplasm, and the basal membrane was thickened. In contrast to the degenerative changes in brain capillaries, pronounced arterial collateralization was disclosed by DSA after chronic brain vessel occlusion. The model of chronic occlusion of four cerebral vessels is characterized by capillary degeneration and arterial collateralization proceeding in parallel. Thus, this rat model may be useful in investigations of long-lasting compensatory mechanisms contributing to cerebrovascular or neurodegenerative disorders.

Angiography, Digital Subtraction↗
PubMed2003

[Study of theoretical cases of intensity-modulated beams with step-and-shoot technique].

To initiate Intensity-Modulated Radiation Therapy (IMRT) in our department, theoretical cases were used as a training, to define methods of measurements and to verify the software by comparing results of calculation and measurement on a PMMA phantom. Irradiation was performed with 6 and 25 MV X-rays from a linear accelerator. For measurements, films and ionization chambers have been chosen. The comparison between calculations and measurements shows some discrepancies at the level of junctions and also in areas of low doses especially when many segments were used. These theoretical cases provide a first step on the way towards treatments with intensity modulation.

Bias↗
PubMed2003

Osteopontin polymorphisms and disease course in multiple sclerosis.

Osteopontin (OPN), also known as early T-cell activating gene (Eta-1), has been recently shown to be a critical factor in the progression of experimental autoimmune encephalomyelitis, and perhaps multiple sclerosis (MS). Here we investigated whether the 327T/C, 795C/T, 1128A/G or 1284A/C single-nucleotide polymorphisms in the OPN gene were correlated with susceptibility or any of the several clinical end points in a cohort of 821 MS patients. Overall, we observed no evidence of genetic association between the OPN polymorphisms and MS. Although not reaching statistical significance, a modest trend for association with disease course was detected in patients carrying at least one wild-type 1284A allele, suggesting an effect on disease course. Patients with this genotype were less likely to have a mild disease course and were at increased risk for a secondary-progressive clinical type.

Adult↗
PubMed2003

Validation of intensity modulation on a commercial treatment planning system.

For two years now, a study on intensity modulated radiotherapy (IMRT) has been in progress at the Antoine Lacassagne Hospital Center for Cancer Therapy (in Nice) in collaboration with the University of Nice-Sophia Antipolis. The kind of intensity modulation that was used is the "step and shoot" technique in which the modulated beam is created both by adding andjoining elementary fields. Before carrying out clinical tests, several problems regarding the production of modulated beams has to be mastered. The current developments of our study enable us to dosimetrically produce (in water phantom and in the PMMA phantom) complexmodulated whose segmentation was calculated by one commercial treatment planning system (TPS). Nevertheless, we showed and studied some critical discrepancies between standard clinical calculations and the calculations using field segmentation. We showed that with nonoptimal conditions of segmentation the discrepancies, which are due to the type of algorithm used, could bring about significant errors inside the field of up to 10% of maximum dose. Another point of our study is the quantification and resolution of differences between measurements and calculations due to the internal segmentation of calculated modulated fields and their realization on Linac. Once again, in none optimal conditions of segmentation and inside the field we obtained discrepancies up to 20% of maximum dose between calculations using field segmentation and measurements. That was mainly due to the tongue and groove effect and penumbra phenomena. This study allows us to show that the discrepancies between segmentation calculations and standard clinical calculations should be solved by the use of penumbra models during segmentation calculations. We will introduce both the study and its near-future perspectives.

Algorithms↗
PubMed2003

The Cdx2 homeobox gene has a tumour suppressor function in the distal colon in addition to a homeotic role during gut development.

BACKGROUND: During development, the homeobox gene Cdx2 exerts a homeotic function, providing the positional information necessary for correct specification of the midgut endoderm. This is illustrated by the non-neoplastic gastric-type heteroplasias present at birth in the pericaecal region of Cdx2(+/-) mice. Furthermore, intestinal expression of Cdx2 continues throughout life but diminishes in colorectal cancers compared with adjacent normal tissue, suggesting a role in tumorigenesis. AIM: To investigate the consequence of altered Cdx2 expression on colon tumour initiation and/or progression. METHODS: Heterozygous Cdx2(+/-) mice were analysed for spontaneous malignant tumours and for tumour development after treatment with a DNA mutagen, azoxymethane. RESULTS: Cdx2(+/-) mice did not spontaneously develop malignant tumours. After azoxymethane treatment, the gastric-like heteroplasias in the pericaecal region did not evolve into cancer indicating that they are not precancerous lesions. However, azoxymethane treated Cdx2(+/-) mice developed tumours specifically in the distal colon 12 weeks after azoxymethane treatment whereas no tumours were found in wild-type littermates at this stage. Histopathological and molecular analyses indicated that these tumours were invasive adenocarcinomas that recapitulated the malignant sequence observed in the majority of sporadic colorectal cancers in human. In addition, we found that the colonic epithelium was less sensitive to radiation induced apoptosis in Cdx2(+/-) than in wild-type mice. CONCLUSION: This study provides the first experimental evidence that Cdx2 is a tumour suppressor gene involved in cancer progression in the distal colon. This action in adults is functionally and geographically distinct from its homeotic role during gut development.

Adenocarcinoma↗
PubMed2002

Inaudible functional MRI using a truly mute gradient echo sequence.

We performed functional MRI experiments using a mute version of a gradient echo sequence on adult volunteers using either a simple visual stimulus (flicker goggles: 4 subjects) or an auditory stimulus (music: 4 subjects). Because the mute sequence delivers fewer images per unit time than a fast echo planar imaging (EPI) sequence, we explored our data using a parametric ANOVA test and a non-parametric Wilcoxon-Mann-Whitney test in addition to performing a cross-correlation analysis. All three methods were in close agreement regarding the location of the BOLD contrast signal change. We demonstrated that, using appropriate statistical analysis, functional MRI using an MR sequence that is acoustically inaudible to the subject is feasible. Furthermore compared with the "silent" event-related procedures involving an EPI protocol, our mGE protocol compares favourably with respect to experiment time and the BOLD signal.

Acoustic Stimulation↗