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Biomedical subjects

A Michel

Publications and source records attributed to A Michel.

At least 55 records · Page 3Linked to original sources

The rise and fall of tuberculosis in a free-ranging chacma baboon troop in the Kruger National Park.

A single troop of free-ranging chacma baboons (Papio ursinus) was found to be infected with tuberculosis caused by Mycobacterium bovis. It is assumed that some members of the troop originally became infected when feeding on a tuberculous carcass in the veld or on tuberculous material scavenged at a nearby post mortem facility. Subsequently, apparent aerosol transmission took place while sleeping in an unused room. Oral transmission probably also occurred due to continuous contamination of the floor of this room and the common, narrow access (a train bridge crossing the Sabi River) to it with faeces and urine. A macroscopic prevalence of 50 % was found and the disease was noted to progress rapidly in infected baboons. A variety of organs had typical tuberculous lesions, of which the spleen, lungs and mesenteric lymph nodes were consistently, grossly affected. Using Restriction Fragment Length Polymorphism analysis, all but one of the baboon isolates were found to be identical to the most common African buffalo (Syncerus caffer) isolate (genotype 1) in this Park. The opportunistic sleeping facility was made inaccessible to the troop, which was forced to revert to sleeping in trees. A follow-up survey six months after closure, demonstrated that the disease had disappeared from the troop, and that no spillover infection had occurred into neighbouring troops.

Animals↗

[From data entry to data presentation at a clinical workstation--experiences with Anesthesia Information Management Systems (AIMS)].

Anesthesia Information Management Systems (AIMS) are required to supply large amounts of data for various purposes such as performance recording, quality assurance, training, operating room management and research. It was our objective to establish an AIMS that enables every member of the department to independently access queries at his/her work station and at the same time allows the presentation of data in a suitable manner in order to increase the transfer of different information to the clinical workstation. Apple Macintosh Clients (Apple Computer, Inc. Cupertino, California) and the file- and database servers were installed into the already partially existing hospital network. The most important components installed on each computer are the anesthesia documenting software NarkoData (ProLogic GmbH, Erkrath), HIS client software and a HTML browser. More than 250 queries for easy evaluation were formulated with the software Voyant (Brossco Systems, Espoo, Finland). Together with the documentation they are the evaluation module of the AIMS. Today, more than 20,000 anesthesia procedures are recorded each year at 112 decentralised workstations with the AIMS. In 1998, 90.8% of the 20,383 performed anesthetic procedures were recorded online and 9.2% entered postopeatively into the system. With a corresponding user access it is possible to receive all available patient data at each single anesthesiological workstation via HIS (diagnoses, laboratory results) anytime. The available information includes previous anesthesia records, statistics and all data available from the hospitals intranet. This additional information is of great advantage in comparison to previous working conditions. The implementation of an AIMS allowed to greatly enhance the quota but also the quality of documentation and an increased flow of information at the anesthesia workstation. The circuit between data entry and the presentation and evaluation of data, statistics and results directly available at the clinical workstation was put into practice.

Anesthesia↗

Design principles of a clinical information system for intensive care units (ICUData).

The aim of this project was to develop a cost-effective, standard-based and scalable clinical information system for use in Intensive Care Units (ICUs). The development started in 1998 at the University Giessen, Germany. Since its introduction as the basic documentation system at the ICU ward of the Department of Anesthesiology and Intensive Care Medicine in January 1999, all relevant clinical data of 1723 patients have been recorded. The implementation of the system in two further ICUs is scheduled for the year 2000. The following article describes some of the principal design goals of the system, including the medical vision that drove its interface design, and focuses on the technological underpinnings of the overall system architecture.

Computer Systems↗

Comparison of manual and automated documentation of adverse events with an Anesthesia Information Management System (AIMS).

In this study, an Anesthesia Information Management System (AIMS) is used for the comparison of manually recorded adverse events with automatically detected events from anesthesiological procedures. In 1998, data from all anesthesia procedures, including the data set for quality assurance defined by the German Society of Anesthesiology and Intensive Care Medicine (DGAI), were recorded online with the documentation software NarkoData 4 (IMESO GmbH, Hüttenberg, Germany) followed by storage into a relational database (Oracle Corporation). The occurrence of manually recorded adverse events, as defined by the DGAI, is compared with automatically detected events. Automated detection was done with SQL-statements. The following adverse events were selected: hypotension, hypertension, bradycardia, tachycardia and hypovolemia. Data obtained from 16,019 electronic anesthesia records show that in 911 patients (5.7%), one of the selected adverse events was documented manually whereas in 2,996 patients (18.7%) a adverse event was detected automatically. The incidence of automatically detected events is obviously higher compared to manually recorded events. With the help of an AIMS, automatic detection proved significant deficiencies in the manual documentation of adverse events.

Anesthesia↗

Data processing at the anesthesia workstation: from data entry to data presentation.

Main requirements for an Anesthesia Information Management System (AIMS) are the supply of additional information for the anesthesiologist at his workstation and complete documentation of the anesthetic procedure. With the implementation of an AIMS (NarkoData) and effective user support, the quality of documentation and the information flow at the anesthesia workstation could be increased. Today, more than 20,000 anesthesia procedures are annually recorded with the AIMS at 112 decentralized workstations. The network for data entry and the presentation and evaluation of data, statistics and results directly available at the clinical workstation was made operational.

Anesthesia↗

Synthesis of 9-O-substituted derivatives of 9-hydroxy-5, 6-dimethyl-6H-pyrido[4,3-b]carbazole-1-carboxylic acid (2-(dimethylamino)ethyl)amide and their 10- and 11-methyl analogues with improved antitumor activity.

Analogues of the antitumor drug S 16020-2 modified at the 9, 10, or 11 position were synthesized and evaluated in vitro and in vivo on the P388 leukemia and B16 melanoma models. Starting from 9-methoxy-5, 11-dimethyl-6H-pyrido[4,3-b]carbazole-1-carboxylic acid ethyl ester, the 11-CH3 analogue of 9-hydroxy-5,6-dimethyl-6H-pyrido[4, 3-b]carbazole-1-carboxylic (2-(dimethylamino)ethyl)amide (1), compound 4, was synthesized using a four-step sequence, whereas its 10-CH3 analogue 5 was prepared using a two-step pathway, starting from compound 1. Finally starting from the 9-OH compounds 1, 4, and 5, a series of variously 9-O-substituted derivatives were synthesized. In these series, the most active compounds resulted from esterification of the 9-OH group with various aliphatic diacids, which led to 9-O-CO-( )-COOH derivatives of 1, 4, and 5. For these compounds, the number of long-term surviving mice obtained at the optimal dose were 60-100% in the ip/iv P388 leukemia and 10-35% in the ip/ip B16 melanoma, corresponding to an improved therapeutic index with respect to 1 and 4. This high antitumor activity, with curative examples in both models, was not due to a higher cytotoxicity since these compounds were equally or slightly less potent in vitro than 1 and 4. The most active compounds were thus selected for further in vivo evaluation.

Animals↗

Electromagnetic fields in combination with elevated temperatures affect embryogenesis of Drosophila.

The effect of electromagnetic fields (50 Hz, 100 microT magnetic flux density) on Drosophila embryogenesis was tested under conditions of mild thermal stress (temperatures between 34 and 37 degrees C). When exposed to these stressor(s) for 30 min during early embryogenesis those embryos which were subjected to both electromagnetic fields and elevated temperature (costress) showed pattern anomalies more frequently than embryos subjected to thermal stress alone. Furthermore, under costress conditions development was considerably delayed in three different strains tested. The use of transgenic strains with a lacZ reporter being expressed in segmental patterns facilitated the identification and quantification of the pattern anomalies.

Animals↗

Contrasting effects of streptozotocin-induced diabetes on the in vitro relaxant properties of adenosine in rat pancreatic vascular bed and thoracic aorta.

In the present work, we have studied adenosine-induced vasodilation in streptozotocin-induced diabetic rats and compared it to that observed in normal age-matched or weight-matched animals. Experiments were performed on a vascular bed, the isolated perfused pancreas, and a large vessel, the thoracic aorta, provided from the same animal. Vasodilator activity was assessed, for isolated pancreas, as the increase in flow induced by the infusion of 2 microM adenosine for 30 min, or for noradrenaline-contracted aortae, as the relaxant response to adenosine (1 microM-1 mM). In both preparations the results obtained with selective adenosine receptors ligands (CPA, CGS 21680 and NECA) agreed with the presence of adenosine receptor of A2a subtype. In normal animals, adenosine vasodilator activity on both preparations diminished with advancing age in the rat, while diabetes was associated with a decreased or increased responsiveness to adenosine in pancreatic vascular bed or aorta, respectively. Further, the involvement of nitric oxide (NO), in relaxant responses, was evaluated by the use of the NO synthase inhibitor Nomega-nitro-L-arginine methyl ester (L-NAME). In all groups of animals, the flow rate of isolated pancreas dropped in the presence of 200 microM L-NAME, but was restored by adenosine to the level observed without L-NAME. L-NAME (10 microM) significantly reduced the dilator response to adenosine in aortic rings from diabetic animals, but not in those from normal rats. These results showed that adenosine vasorelaxant activity is significantly but differentially altered by diabetes according to the origin of the vascular preparation, and suggest that NO is involved in the vasorelaxant activity of adenosine in large vessels of diabetic animals. The potential pathophysiological role of adenosine in the vascular complications of diabetes remains to be determined.

Adenosine↗

Management of victims of urban chemical attack: the French approach.

Since the early 1980s several disasters involving mass release of toxic substances have focused the attention of different administrations and the fire services into producing protocols and guidelines for action in civilian situations. The bomb attack in the Tokyo subway, in March 1995, made it clear that a terrorist attack using highly toxic agents is now feasible. Management of disasters in the civil sector in France is based upon two interlinked plans: the Red Plan, which covers on-site organisation, and the White Plan, which concerns the interface with hospital services. Special procedures have been developed to adapt the Red and White Plans for use in the event of toxic attack and concern the deployment of emergency responding personnel, the provision of life support and antidotes in the contaminated zone, the prevention of secondary contamination and the transport and reception of victims at the hospital. Based on the established principle of pre-hospital resuscitation and well-tried assistance plans, this doctrine allows a safe and effective response to terrorist attacks as well as to other toxic release incidents.

Decontamination↗

Antiproliferative, differentiating and apoptotic effects elicited by imidazo[1,2-a]pyrazine derivatives.

1. The activity of two series of imidazo[1,2-a]pyrazine derivatives on cell proliferation and differentiation and on apoptosis was examined in relation to their effects on phosphodiesterase (PDE) activity and on purinoceptors. 2. In the first series SC-18 and SC-51 inhibited mitogen-induced 3H-thymidine incorporation in human lymphocytes. 3. The compounds of the new series PAB13, PAB23 and SCA40 inhibited the proliferation of the HEL cell line. 4. Nine imidazo[1,2-a]pyrazine derivatives of the new series have been studied on the Dami cell proliferation. SCA41 and SCA44 inhibited cell growth, SCA40 and PAB40 were moderately effective, whereas PAB12 and PAB30 were devoid of effect. The antiproliferative effects of these six non-cytotoxic compounds could not be related to their action on PDE or on purinoceptors, but rather to their lipophilicity. Conversely, for PAB13, PAB15, and PAB23, the decrease in cell number was related to their cytotoxic and apoptotic effects through their cAMP-increasing and PDE-inhibitory potency, but unrelated to an effect on purinoceptors. 5. Imidazo[1,2-a]pyrazine derivatives decreased the expression of Glycoprotein (GP)Ib in Dami cells while some of them enhanced that of GPIIb/IIIa. These effects appeared to involve inhibition of both cAMP- and cGMP-PDE. 6. These studies demonstrate the potential interest of imidazo[1,2-a]pyrazine derivatives in the query of novel anticancer drugs.

Animals↗

New imidazo(1,2-a)pyrazine derivatives with bronchodilatory and cyclic nucleotide phosphodiesterase inhibitory activities.

New imidazo[1,2-a]pyrazine derivatives have been synthesized either by direct cyclization from pyrazines or by electrophilic substitutions. The presence of electron donating groups on position 8 greatly enhances the reactivity of the heterocycle towards such reactions on position 3 of the heterocycle. The activities of these derivatives in trachealis muscle relaxation and in inhibiting cyclic nucleotide phosphodiesterase (PDE) isoenzyme types III and IV have been assessed. All compounds demonstrated significantly higher relaxant potency than theophylline. All the derivatives were moderately potent in inhibiting the type IV isoenzyme of PDE but only those with a cyano group on position 2 were potent in inhibiting the type III isoenzyme.

3',5'-Cyclic-AMP Phosphodiesterases↗

Association between the dopamine D4 receptor (DRD4) exon III polymorphism and measures of Novelty Seeking in a German population.

Since the observation of an association between the dopamine D4 receptor (DRD4) exon III polymorphism and the temperament trait of Novelty Seeking,1 replication studies have yielded both positive2-5 and negative6-12 results. This raised the question whether the initial findings must be regarded as false positives.13 However, demographic or methodological differences between studies may have obscured the small effect of the DRD4 polymorphism on Novelty Seeking.14 Examination of clinical or older cohorts may have led to an underestimation of possible associations due to a restricted variation of Novelty Seeking in these cohorts. The use of different questionnaires provides another source of variation. In order to replicate the initial findings as precisely as possible, a cohort of 136 healthy, young volunteers was genotyped, and Novelty Seeking was ascertained using the TPQ.15,16 In addition, further aspects of novelty seeking behavior have been ascertained through additional trait measures. We could observe the reported association between long DRD4 alleles and significantly elevated scores (age- and sex-residualized) on the TPQ-Novelty Seeking total scale as well as on two of the subscales, Exploratory Excitability and Extravagance. The results provide further confirmation for the role of the DRD4 exon III polymorphism in modulation of Novelty Seeking. In addition, the pattern of associations between the polymorphism and other scales suggests that this polymorphism has its effect on exploratory, extravagant, and extraverted, rather than on impulsive and monotony-avoidant subtypes of Novelty Seeking.

Adult↗

Expression analysis of two gene subfamilies encoding the plasma membrane H+-ATPase in Nicotiana plumbaginifolia reveals the major transport functions of this enzyme.

The plasma membrane H+-ATPase couples ATP hydrolysis to proton transport, thereby establishing the driving force for solute transport across the plasma membrane. In Nicotiana plumbaginifolia, this enzyme is encoded by at least nine pma (plasma membrane H+-ATPase) genes. Four of these are classified into two gene subfamilies, pma1-2-3 and pma4, which are the most highly expressed in plant species. We have isolated genomic clones for pma2 and pma4. Mapping of their transcript 5' end revealed the presence of a long leader that contained small open reading frames, regulatory features typical of other pma genes. The gusA reporter gene was then used to determine the expression of pma2, pma3 and pma4 in N. tabacum. These data, together with those obtained previously for pma1, led to the following conclusions. (i) The four pma-gusA genes were all expressed in root, stem, leaf and flower organs, but each in a cell-type specific manner. Expression in these organs was confirmed at the protein level, using subfamily-specific antibodies. (ii) pma4-gusA was expressed in many cell types and notably in root hair and epidermis, in companion cells, and in guard cells, indicating that in N. plumbaginifolia the same H+-ATPase isoform might be involved in mineral nutrition, phloem loading and control of stomata aperture. (iii) The second gene subfamily is composed, in N. plumbaginifolia, of a single gene (pma4) with a wide expression pattern and, in Arabidopsis thaliana, of three genes (aha1, aha2, aha3), at least two of them having a more restrictive expression pattern. (iv) Some cell types expressed pma2 and pma4 at the same time, which encode H+-ATPases with different enzymatic properties.

Amino Acid Sequence↗

Amplification by atrial natriuretic peptide of the haemodynamic and renal responses to an acute volumic stress in the rat.

1. The purpose of the present study was to test the effects of synthetic atrial natriuretic peptide (ANP) on renal haemodynamics and excretory capacities of salt and water in the rat during an 'acute volumic stress', which was induced by brisk disturbances of the circulatory volume. 2. To this end, 29 anaesthetized male Wistar rats were rapidly injected with 1 mL of 0.85% NaCl, repeated twice at 60 s intervals. The injectates contained no ANP (n = 5) or 1 x 0.25 (n = 6), 3 x 0.25 (n = 6), 1 x 2.5 (n = 6) or 3 x 2.5 micrograms (n = 6) ANP, added to the first injectate only (1 x) or to each injectate (3 x). Renal blood flow (RBF) was continuously measured with an electromagnetic flow transducer. 3. Renal blood flow increased transiently (approximately 30 s) by approximately 13% (P < 0.05) during each injection of saline without ANP. Addition of 0.25 or 2.5 micrograms ANP to the first injectate enhanced RBF by 21 and 35%, respectively (both P < 0.05), but did not modify the time sequence. Furthermore, addition of 0.25 microgram ANP to the second and third injectate produced an almost similar change in RBF at the end of each injection (delta RBF = 20 and 17%, respectively). In contrast, the addition of 2.5 micrograms ANP to the second and third injectate did not produce the same changes in RBF observed at the end of the first injection. The amplitude of the change in RBF was then similar to the increase in RBF induced by 1 mL saline without ANP. Mean arterial pressure (MAP) did not change significantly during repeated injections of saline alone or with addition of 0.25 microgram ANP to the first injectate. However, MAP decreased significantly (by 5, 9 and 9 mmHg) after the injection of 3 x 0.25, 1 x 2.5 or 3 x 2.5 micrograms ANP, respectively. 4. Sodium excretion was rapidly increased from 2.600 +/- 0.654 to 9.330 +/- 1.322 mumol/min after injection of 3 x 1 mL of 0.85% NaCl (P < 0.05). Thereafter, sodium excretion remained enhanced throughout the experiment, so that 70% of the sodium load injected was recovered at the end of the experiment. Atrial natriuretic peptide added to the injectates further elevated the maximal responses in diuresis and natriuresis induced by saline injections without ANP (P < 0.001). A maximal effect was observed after the addition of 2.5 micrograms ANP to the first saline solution. When the amount of sodium excreted was calculated by integrating the areas under the curve of the natriuretic responses, a relationship was established as a function of the amount of ANP added to the saline solutions. It was characterized by a threshold in the presence of 2.5 micrograms ANP added to the first injectate when the integration period was limited to 4 min 30 s and 14 min 30 s after starting the first injection of the varying test solutions. When the integration period was extended until the end of the experiment (2 h), the amount of sodium excreted in each group was further enhanced, especially after injection of 3 x 1 mL of 0.85% NaCl without ANP or with 1 x 0.25 and 3 x 0.25 microgram ANP. Differences in sodium excretion between groups were attenuated (P < 0.054, ANOVA). 5. In conclusion, our results demonstrate differential effects of synthetic ANP on renal vascular reactivity and excretory capacity. These effects were superimposed on changes induced by acute volumic stress. In particular, effects of saline injections on renal vascular compliance were amplified in the presence of ANP added in varying amounts to the injectates. This amplification was limited to 2.5 micrograms ANP.

Animals↗

[Experiences fo three year's routine operation of an anesthesia information management system (AIMS) at a university clinic in Giessin].

PURPOSE: In 1994, the Department of Anaesthesiology and Intensive Care Medicine of the Justus Liebig University at Giessen decided to install an Anaesthesia Information Management System (AIMS). Individual aspects and results from routine operation are presented, demonstrating the quality of the documentation and the value of information at the anaesthesiological workstation. The paper discusses which adaptations are necessary according to the experience gathered. METHODS: For the installation of the system Apple Macintosh Clients (Apple Computer, Inc., Cupertino, California) and a File Server were integrated into the partially existing hospital network. The hospital network had to be enlarged during the project according to the Anaesthesiological requirements. The software of the Hospital Information System (HIS) and an HTML browser were installed at individual workstation computers in addition to the Anaesthesia documentation software NarkoData (ProLogic GmbH, Erkrath). The remote control software Timbuktu (Farallon, Alameda, USA) has been added to facilitate remote administration. The file administration programme FileWave (Wave Research, Berkeley, USA) is used for file distribution. Since 1995, all anaesthesia procedures have been documented with the system, either by online or postoperative recording. Since 1997, the recorded information has been stored in a relational Oracle 7 data bank (Oracle Corporation). RESULTS: From 1995 to 1997, 60,405 anaesthesiological procedures have been recorded with the help of this AIMS at 111 decentralised workstations. In 1997, 87.8% of the 21,130 performed anaesthesia procedures have been recorded online with the system and 12.2% postoperatively. From 1995 to 1997, the number of recorded procedures increased by 6.4% from 19,854 to 21,130. Because of lacking interfaces at some patient monitoring stations, the automatic recording of patient data could only be implemented at 69 workstations (62%). With the corresponding access rights, important patient information from the HIS (diagnoses, laboratory results, etc.), records of previous Anaesthesia procedures, numerous statistics, and the whole information from the hospital's intranet (including e-mail) are available at the anaesthesiological workstation at any time. CONCLUSION: The implementation of the AIMS and an effective user support have been able to increase significantly the quality of documentation, the flow of information at the anaesthesia workplace and the number of recorded Anaesthesia procedures. All recorded data can be analysed immediately The expansion of the automatic data transfer from the patient monitoring, interfaces to other computer subsystems of the hospital and a practicable evaluation programme are necessary for further enhancing the efficiency of the AIMS.

Anesthesiology↗