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Biomedical subjects

C Sauer

Publications and source records attributed to C Sauer.

At least 19 recordsLinked to original sources

[Three-week multimodal inpatient treatment of children with chronic pain. First results of the long-term follow-up].

OBJECTIVE: In children and adolescents we investigated the impact of a 3-week inpatient multimodal pain therapy on subjective burden of life, pain intensity, and number of days off from school 3, 6, or 12 months later. METHODS: At the beginning of therapy (inpatient setting) and 3, 6, and 12 months thereafter (outpatient setting) we collected the respective data using standardized questionnaires. For statistical analysis we used Wilcoxon's signed rank test. A p <0.05 was regarded as statistically significant. RESULTS: A total of 72 patients aged 7.5-18.2 years suffering daily pain entered the study, most of them being diagnosed with somatoform pain disease. After 3, 6, and 12 months, 65, 27, and 30 patients could be reevaluated. Mean pain intensity of the week before data acquisition was significantly less than at the beginning (2.9, 2.3, and 2.9 vs 6.3) as was the mean number of days off from school due to pain during the 4-week period before each day of data acquisition (1.8, 1.5, and 1.4 vs 9.2). Mean subjective burden of life was significantly less than at the beginning (24.5, 22.0, and 25.8 vs 37.8). CONCLUSION: Outpatient multimodal pain therapy has a sustained impact on children and adolescents suffering from chronic pain.

Adolescent↗

Primary mouse hepatocytes for systems biology approaches: a standardized in vitro system for modelling of signal transduction pathways.

Complex cellular networks regulate regeneration, detoxification and differentiation of hepatocytes. By combining experimental data with mathematical modelling, systems biology holds great promises to elucidate the key regulatory mechanisms involved and predict targets for efficient intervention. For the generation of high-quality quantitative data suitable for mathematical modelling a standardised in vitro system is essential. Therefore the authors developed standard operating procedures for the preparation and cultivation of primary mouse hepatocytes. To reliably monitor the dynamic induction of signalling pathways, the authors established starvation conditions and evaluated the extent of starvation-associated stress by quantifying several metabolic functions of cultured primary hepatocytes, namely activities of glutathione-S-transferase, glutamine synthetase, CYP3A as well as secretion of lactate and urea into the culture medium. Establishment of constant metabolic activities after an initial decrease compared with freshly isolated hepatocytes showed that the cultured hepatocytes achieve a new equilibrium state that was not affected by our starving conditions. To verify the highly reproducible dynamic activation of signalling pathways in the in vitro system, the authors examined the JAK-STAT, SMAD, PI3 kinase, MAP kinase, NF-kappaB and Wnt/beta-catenin signalling pathways. For the induction of gp130, JAK1 and STAT3 phosphorylation IL6 was used, whereas TGFbeta was applied to activate the phosphorylation of SMAD1, SMAD2 and SMAD3. Both Akt/PKB and ERK1/2 phosphorylation were stimulated by the addition of hepatocyte growth factor. The time-dependent induction of a pool of signalling competent beta-catenin was monitored in response to the inhibition of GSK3beta. To analyse whether phosphorylation is actually leading to transcriptional responses, luciferase reporter gene constructs driven by multiple copies of TGFbeta-responsive motives were applied, demonstrating a dose-dependent increase in luciferase activity. Moreover, the induction of apoptosis by the TNF-like cytokine Fas ligand was studied in the in vitro system. Thus, the mouse hepatocyte in vitro system provides an important basis for the generation of high-quality quantitative data under standardised cell culture conditions that is essential to elucidate critical hepatocellular functions by the systems biology approach.

Animals↗

4-Epidoxycycline: an alternative to doxycycline to control gene expression in conditional mouse models.

Since the pioneering work by Gossen and Bujard in 1992 demonstrating the usefulness of the Escherichia coli derived tet resistance operon for regulating gene expression a large collection of doxycycline-controlled transgenic mice has been established. Gene switching in eukaryotic tissue culture cells or mice requires administration of tetracycline, anhydrotetracycline or doxycycline to efficiently inactivate the transactivator protein tTA (TET-OFF system) or alternatively to activate the reverse transactivator protein rtTA (TET-ON system). However, the antibiotic activity of doxycycline can create an imbalance of the intestinal flora, resulting in diarrhoea and in a smaller number of animals in colitis. Previous studies reported that 4-epidoxycycline (4-ED), a hepatic metabolite of doxycycline, does not function as an antibiotic in mice. This gave us the idea that 4-ED might be useful for controlling gene expression in mice without the unwanted antibiotic side effect. To study the applicability of 4-ED for control of gene expression we used cell lines expressing the oncogene HER2 under control of tTA (TET-OFF) as well as rtTA (TET-ON). 4-ED and doxycycline were similarly efficient in switching on or -off HER2 expression. In vivo we used a conditional mouse model that allows switching off HER2 in tumor tissue. We show that (i) doxycycline, 7.5mg/ml in drinking water (used as a positive control), (ii) 4-ED, 7.5mg/ml in drinking water, (iii) 4-ED, 10mg/kg body weight, s.c., and (iv) anhydrotetracycline, 10mg/kg, s.c. (used as a second positive control), were similarly efficient. Using mice with tumor volumes of 1.6cm(3) all four schedules led to a tumor remission of more than 95% within 7 days. In conclusion, 4-ED is similarly efficient as doxycycline to control gene expression in vitro and in mice. Since 4-ED lacks the antibiotic activity of doxycycline it may help to avoid adverse side effects and selection of resistant bacteria.

Administration, Oral↗

Emergency airway management by non-anaesthesia house officers--a comparison of three strategies.

OBJECTIVES: The purpose of this study was to determine effects of different airway devices and tidal volumes on lung ventilation and gastric inflation in an unprotected airway. METHODS: Thirty one non-anaesthesia house officers volunteered for the study, and ventilated a bench model simulating an unintubated respiratory arrest patient with bag-valve-facemask, laryngeal mask airway, and combitube using paediatric and adult self inflating bags. RESULTS: The paediatric versus adult self inflating bag resulted with the laryngeal mask airway and combitube in significantly (p<0.001) lower mean (SEM) lung tidal volumes (376 (30) v 653 (47) ml, and 368 (28) v 727 (53) ml, respectively). Gastric inflation was zero with the combitube; and 0 (0) v 8 (3) ml with the laryngeal mask airway with low versus large tidal volumes. The paediatric versus adult self inflating bag with the bag-valve-facemask resulted in comparable lung tidal volumes (245 (19) v 271 (33) ml; p=NS); but significantly (p<0.001) lower gastric tidal volume (149 (11) v 272 (24) ml). CONCLUSIONS: The paediatric self inflating bag may be an option to reduce the risk of gastric inflation when using the laryngeal mask airway, and especially, the bag-valve-facemask. Both the laryngeal mask airway and combitube proved to be valid alternatives for the bag-valve-facemask in this experimental model.

Adult↗

Systematic relationships and cospeciation of bacterial endosymbionts and their carpenter ant host species: proposal of the new taxon Candidatus Blochmannia gen. nov.

The systematic relationships of intracellular bacteria of 13 Camponotus species (carpenter ants) from America and Europe were compared to those of their hosts. Phylogenetic trees of the bacteria and the ants were based on 16S rDNA (rrs) gene sequences and mitochondrial cytochrome oxidase subunit I (COI) gene sequences, respectively. The bacterial endosymbionts of Camponotus spp. form a distinct lineage in the y-subclass of the Proteobacteria. The taxa most closely related to these bacteria are endosymbionts of aphids and the tsetse fly. The bacterial and host phylogenies deduced from the sequence data show a high degree of congruence, providing significant evidence for cospeciation of the bacteria and the ants and a maternal transmission route of the symbionts. The cloned rrs genes of the endosymbionts contain putative intervening sequences (IVSs) with a much lower G+C content than the mean of the respective rrs genes. By in situ hybridization specific 16S rDNA oligonucleotide probes verified the presence of the bacteria within tissues of three of the eukaryotic hosts. It is proposed that the endosymbionts of these three carpenter ants be assigned to a new taxon 'Candidatus Blochmannia gen. nov.' with the symbionts of the individual ants being species named according to their host, 'Candidatus Blochmannia floridanus sp. nov.', 'Candidatus Blochmannia herculeanus sp. nov.' and 'Candidatus Blochmannia rufipes sp. nov.'.

Animals↗

Airway management during cardiopulmonary resuscitation--a comparative study of bag-valve-mask, laryngeal mask airway and combitube in a bench model.

Gastric inflation and subsequent regurgitation are a potential risk of ventilation during cardiopulmonary resuscitation (CPR). In respect of recent investigations, principal respiratory components such as respiratory system compliance, resistance and lower esophageal sphincter pressure were adapted according to CPR situations. The purpose of our study was to assess lung ventilation and gastric inflation when performing ventilation with bag-valve-mask, laryngeal mask airway, and combitube in a bench model simulating an unintubated cardiac arrest patient. Twenty-one student nurses, without any experience in basic life support measures, ventilated the bench model with all three devices. Mean ( +/- S.D.) gastric inflation with the laryngeal mask airway (seven cases) was significantly lower than with the bag-valve-mask (0.6 +/- 0.8 vs 3.0 +/- 2.11 min(-1), P < 0.01). There was no gastric inflation when ventilation was performed with the combitube. Only seven of 21 volunteers exceeded 1-min lung volumes of > 5 1 when using the bag-valve-mask, whereas mean (+/-S.D.) 1-min lung volumes with both laryngeal mask airway and combitube were significantly higher (laryngeal mask airway 15.0+/-6.61, combitube 16.6 +/- 6.81 vs bag-valve-mask 4.8 +/- 2.71, P < 0.01). The time for insertion was significantly faster with both bag-valve-mask and laryngeal mask airway compared with the combitube (median: bag valve mask 22 s, laryngeal mask airway 37 s vs combitube 70 s, P < 0.01). This may tip the scales towards using the laryngeal mask airway during basic life support airway management. In conclusion, our data suggests that both laryngeal mask airway and combitube may be appropriate alternatives for airway management in the first few minutes of CPR.

Adult↗

Smaller tidal volumes during cardiopulmonary resuscitation: comparison of adult and paediatric self-inflatable bags with three different ventilatory devices.

Gastric inflation and subsequent regurgitation of stomach contents is a major hazard of bag-valve-face mask ventilation during the basic life support phase of cardiopulmonary resuscitation (CPR). Recent investigations suggested that use of a paediatric self-inflating bag may reduce stomach inflation while ensuring sufficient lung ventilation. The purpose of our study was to examine whether use of a paediatric self-inflating bag in association with laryngeal mask airway, combitube, and bag-valve-face mask may provide adequate lung ventilation, while reducing the risk of gastric inflation in a bench model simulating the initial phase of CPR. Sixteen intensive care unit registered nurses volunteered for our study. Use of a paediatric versus adult self-inflating bag resulted in a significantly (P < 0.01) lower mean (+/- S.D.) tidal lung volume with both the laryngeal mask airway and combitube (laryngeal mask airway 349 +/- 149 ml versus 725 +/- 266 ml, combitube 389 +/- 113 ml versus 1061 +/- 451 ml). Lung tidal volumes were below the European Resuscitation Council recommendation with both self-inflatable bags in the bag-valve-face mask group (paediatric versus adult self-inflatable bag 256 +/- 77 ml versus 334 +/- 125 ml). Esophageal tidal volumes were significantly (P < 0.05) lower using the paediatric self-inflatable bag in the bag-valve-face mask group; almost no gastric inflation occurred with the laryngeal mask airway, and none with the combitube. In conclusion, use of the paediatric self-inflating bag may reduce gastric inflation, but measured lung tidal volumes are below the European Resuscitation Council recommendation when used with either, the laryngeal mask airway, combitube, or bag-valve-face mask.

Adult↗

Lessons from a failed information systems initiative: issues for complex organisations.

Organisational issues are now recognised as key factors in the effective use of information technology (IT). This paper extends our knowledge of these issues for large complex distributed organisations. It is based on an analysis of the failure of a large IT system selected by a major state public health service for Statewide implementation. The system selected was well proven overseas, was implemented through a pilot process, yet was withdrawn because it did not meet requirements. The issues which are dealt with include the nature of the organisation and its interaction with the implementation strategy, the nature of decision-making, the contrast between the incentives and perspectives at different levels, ownership of the program, management of skills and the impact of instability and complexity. The option of decentralised IT management is raised and the advantages of common systems discussed. A proposal is ventured for managing such developments while maintaining essential commonality. The paper demonstrates that the environment of large complex distributed organisations introduces a complex of issues that are not normally considered in implementation strategy.

Attitude to Computers↗

An L-type calcium-channel gene mutated in incomplete X-linked congenital stationary night blindness.

The locus for the incomplete form of X-linked congenital stationary night blindness (CSNB2) maps to a 1.1-Mb region in Xp11.23 between markers DXS722 and DXS255. We identified a retina-specific calcium channel alpha1-subunit gene (CACNA1F) in this region, consisting of 48 exons encoding 1966 amino acids and showing high homology to L-type calcium channel alpha1-subunits. Mutation analysis in 13 families with CSNB2 revealed nine different mutations in 10 families, including three nonsense and one frameshift mutation. These data indicate that aberrations in a voltage-gated calcium channel, presumably causing a decrease in neurotransmitter release from photoreceptor presynaptic terminals, are a frequent cause of CSNB2.

Amino Acid Sequence↗

Analysis of DNA damage recovery processes in the adaptive response to ionizing radiation in human lymphocytes.

It has been frequently suggested that the adaptive response to ionizing radiation involves the induction of a chromosomal repair mechanism. Although several lines of evidence favour this assumption, direct proof is lacking. We have chosen to study this question with the help of the comet assay. Lymphocytes from three human donors were given an adapting dose of 0.05 Gy 16 h after mitogenic stimulation and a challenging dose of 2 Gy 5 h thereafter. While a portion of the cells was removed from the cultures for the comet assay, remaining cells were harvested at 52 h culture time and screened for chromosomal aberrations. In some experiments an analysis of cell proliferation was additionally carried out by flow cytometry. In the comet assay a reduced level of initial damage and an increased repair capacity was observed in the adapted + challenged cells; however, this did not result in a reduction of the aberration frequencies. No effect of the adapting dose on cell proliferation was detectable. The analysis of comet distributions revealed that the observed enhanced repair capacity was due to the presence of a subpopulation of slowly repairing cells in the challenged lymphocytes and the lack of such a subpopulation in the adapted + challenged cells. We assume that the slowly repairing cells were quiescent G0 lymphocytes which were removed from the adapted + challenged cell population, probably by apoptotic-like processes.

Adaptation, Physiological↗