Analysis of cefaclor in novel chocolate-based camouflage capsules.

The determination of cefaclor in a new, complex chocolate matrix was performed by using a simple sample preparation (dispersion in dilute hydrochloric acid at 80 degrees C, centrifugation, washing with cyclohexane), followed by ion pair HPLC on a Kinetex pentafluorophenyl core-shell stationary phase with UV detection at 265 nm. We obtained good linearity (R2 = 0.9976) and precision (average RSD 0.86%) for the relevant concentration range. The preparations, although hand-made in this pilot phase, showed good uniformity of content. After being stored for four weeks in a refrigerator the preparation did not contain recognizable amounts of decomposition products.

Clinical evaluation of a simultaneous closed-loop anaesthesia control system for depth of anaesthesia and neuromuscular blockade*.

We developed a closed-loop system to control the depth of anaesthesia and neuromuscular blockade using the bispectral index and the electromyogram simultaneously and evaluated the clinical performance of this combined system for general anaesthesia. Twenty-two adult patients were included in this study. Anaesthesia was induced by a continuous infusion of remifentanil at 0.4 µg.kg(-1) .min(-1) (induction dose) and then 0.25 µg.kg(-1) .min(-1) (maintenance dose) and propofol at 2 mg.kg(-1) 3 min later. The combined automatic control was started 2 min after tracheal intubation. The depth of anaesthesia was recorded using bispectral index monitoring using a target value of 40. The target value of neuromuscular blockade, using mivacurium, was a T1/T1(0) twitch height of 10%. The precision of the system was calculated using internationally defined performance parameters. Twenty patients were included in the data analysis. The mean (SD) duration of simultaneous control was 129 (69) min. No human intervention was necessary during the computer-controlled administration of propofol and mivacurium. All patients assessed the quality of anaesthesia as 'good' to 'very good'; there were no episodes of awareness. The mean (SD) median performance error, median absolute performance error and wobble for the control of depth of anaesthesia and for neuromuscular blockade were -0.31 (1.78), 6.76 (3.45), 6.32 (2.93) and -0.38 (1.68), 3.75 (4.83), 3.63 (4.69), respectively. The simultaneous closed-loop system using propofol and mivacurium was able to maintain the target values with a high level of precision in a clinical setting.

[The Obeldicks concept. An example for a successful outpatient lifestyle intervention for overweight or obese children and adolescents]. / Das Obeldicks-Konzept. Beispiel eines erfolgreichen ambulanten Therapieprogramms für Kinder und Jugendliche mit Übergewicht oder Adipositas.

The outpatient lifestyle interventions Obeldicks (for 8- to 16-year-old obese children; 1-year intervention), Obeldicks Light (for 8- to 16-year-old overweight children; 6-month intervention), and Obeldicks Mini (for 4- to 7-year-old obese children; 1-year intervention) are based on nutrition education, physical activity, behavior therapy, and individual psychological care. Only 17% dropped out of the intervention, and 79% of the more than 1,000 participants reduced their degree of overweight. The mean SDS-BMI reduction was 0.4 (~1.5-2 kg/m(2) BMI reduction) and was associated with a significant improvement of hypertension, dyslipidemia, and disturbed glucose metabolism in the participants compared to an untreated control group. This efficiency was also proven by a multicenter randomized controlled trial. Furthermore, the quality of life of the participants improved significantly. Even 4 years after the end of intervention, the achieved weight loss was sustained. Training manuals and training seminars for professionals assist in the implementation of these lifestyle interventions at further locations.

[Feedback control of depth of anesthesia during propofol administration. Bispectral index as the controlled variable]. / Regelkreisgesteuerte Narkosetiefe bei Propofolapplikation. Verwendung des Bispektralindex als Regelungsgrösse.

BACKGROUND: The objective of this study was to evaluate the performance of a new system for closed-loop control of propofol administration using the bispectral index (BIS) under total intravenous anesthesia in the index values of middle-to-deep depth of anaesthesia. METHODS: In this study 20 adult patients anesthetized with propofol and remifentanil were investigated. The propofol infusion was carried out using a fuzzy-PD+I controller with a target BIS value of 40. RESULTS: Closed-loop control was able to provide maintenance of anesthesia and adequate operating conditions for all patients. The following quality control criteria were calculated: median performance error (MDPE; 0.16%, SD +/-1.4%), median absolute performance error (MDAPE; 6.9%, SD +/-2.8%) and wobble (6.8%, SD +/-2.5%). CONCLUSION: The present study showed the clinical feasibility of the controller compared to existing devices regarding a high level of quality criteria of a model with an implemented fuzzy-PD+I structure controlling depth of hypnosis.

[Anaesthesiological aspects of paediatric medical care in "non-specialised departments"]. / Anästhesiologische Aspekte bei der Versorgung von Kindern in "nicht spezialisierten Abteilungen"

Paediatric perioperative care represents specific challenges related to the distinct developmental, anatomic and physiological characteristics of children, requiring specialised expertise, including pharmacology. A specially trained anaesthesia team, an appropriate environment and appropriate paediatric-sized equipment (endotracheal tubes, cannulas) represent key factors in determining the perioperative outcome for this population. Other important equipment that must be adapted to the paediatric population include: Non-invasive anaesthesia monitoring equipment (ECG, blood pressure cuff, pulse oximetry, capnography, oxygen monitor, volatile gas concentration monitor, peripheral nerve stimulator and temperature probe); as well as specialised ventilators that allow pressure- and volume-controlled ventilation with volumes as low as 20 ml, variable high frequency ventilation up to 60 breaths per minute and paediatric ventilator hose systems with automatic correction for compliance. Perioperative pain management is important in the paediatric population, with regional anaesthesia techniques (usually done under general anaesthesia) being increasingly accepted in all age groups. These techniques, however, should be performed by experienced anaesthesologists and surgeons only. If these conditions are not met, surgical procedures should not be performed except in the case of an emergency when transportation to a specialised paediatric facility cannot be done safely. This is particularly critical for premature babies, newborns, and infants up to 3 years of age.

The effect of tributyltin-oxide on earthworms, springtails, and plants in artificial and natural soils.

Chemical bioavailability in Organisation for Economic Co-operation and Development (OECD) artificial soil can contrast with bioavailability in natural soils and produce ecotoxicologic benchmarks that are not representative of species' exposure conditions in the field. Initially, reproduction and growth of earthworm and Collembolan species, and early seedling growth of a dicotyledonous plant species, in nine natural soils (with a wide range of physicochemical properties) and in OECD soil were evaluated. Soils that supported reproduction and growth of the test species were then used to investigate the toxicity of tributyltin-oxide (TBT-O). Natural soils caused greater toxicity of TBT-O to earthworms (EC(50) values varied from 0.5 to 4.7 mg/kg soil dry weight [dw]) compared with toxicity in OECD soil (EC(50) = 13.4 mg/kg dw). Collembolans were less sensitive to TBT-O than earthworms in natural soils, with EC(50) values ranging from 23.4 to 177.8 mg/kg dw. In contrast, the toxicity of TBT-O to collembolans in OECD soil (EC(50) = 104.0 mg/kg dw) was within the range of EC(50) values in natural soils. Phytotoxicity tests revealed even greater difference between the effects in natural soils (EC(50) values ranged from 10.7 to 189.2 mg/kg dw) and in OECD soil (EC(50) = 535.5 mg/kg dw) compared with results of the earthworm tests. Studies also showed that EC(50) values were a more robust end point compared with EC(10) values based on comparisons of coefficients of variation. These results show that toxicity testing should include studies with natural soils in addition to OECD soil to better reflect exposure conditions in the field.

Onset properties of mivacurium measured by mechanomyography depend on the twitch height of the adductor pollicis muscle.

INTRODUCTION: The influence of the twitch height of the adductor pollicis muscle during baseline measurements on the pharmacodynamic parameters of mivacurium was prospectively evaluated. PATIENTS AND METHODS: Fifty adult patients were anaesthetized with propofol and alfentanil. Neuromuscular function was monitored mechanomyographically by measuring the force of the adductor pollicis muscle following stimulation of the ulnar nerve. Following a stabilization period of 20 min, the individual twitch height of the adductor pollicis muscle was determined before a single bolus of mivacurium (75 microg kg-1) was administered. Patients were divided into two groups. The data of patients whose thumb adduction force was below the median value of all patients were the 'low force' group (9.1 +/- 1.4 N) and the data of all other patients were the 'high force' group (13.7 +/- 1.8 N). RESULTS: In the 'high force' group, maximum neuromuscular blockade of mivacurium was deeper (0.97 +/- 0.05 vs. 0.93 +/- 0.06; P < 0.05) and onset faster (2.9 +/- 1.1 min vs. 4.0 +/- 1.2 min; P < 0.05). Neuromuscular recovery did not differ between the groups. CONCLUSION: The different onset speeds reflect either different sensitivity to neuromuscular blocking agents with respect to patients' muscle power or a problem of the mechanomyographic measuring technique.

[Depth of anaesthesia during intubation: comparison between propofol and thiopentone]. / Narkosetiefe bei Intubation : Vergleich zwischen Propofol und Thiopental.

In order to study the depth of anaesthesia during endotracheal intubation, 30 patients received either thiopentone or propofol for anaesthesia induction. The BIS value as a parameter for the depth of anaesthesia and the rate pressure product (RPP) were acquired online. Patients who received thiopentone for anaesthesia induction showed significantly higher BIS values at the moment of intubation and reached BIS values >60 significantly more frequently than patients receiving propofol. The RPP in the propofol group lay significantly below that of the thiopentone patients. For all patients there was an mean increase in BIS values of 8 index points and an increase in the RPP. Therefore, BIS values around 50 should be achieved before intubation in order to avoid the critical BIS value for awareness of >60 despite the increase caused by the intubation procedure. Within 24 h of intubation all patients were interviewed for possible signs of awareness. None of the patients was able to remember the intubation or reported other experiences that indicated an unconscious awareness. Nevertheless, the progress of BIS values in a standardized intubation as performed in the normal clinical routine, shows that the use of thiopentone for initiating anaesthesia results in a very flat level of anaesthesia during intubation. The risk for patients to experience awareness should therefore, not be underestimated. Therefore, when using thiopentone it is recommended to also use a rapid acting muscle relaxant or to select a high ED95 to compensate for the flat level of anaesthesia. Alternatively, repetetive boluses of the hypnotic shortly before intubation should be considered or to revert to propofol. The dosage and pharmacokinetics of the analgesic should also be taken into consideration because an insufficient analgesia leads to a faster flattening of the depth of anaesthesia.

Comparison of invasive and less-invasive techniques of cardiac output measurement under different haemodynamic conditions in a pig model.

BACKGROUND AND OBJECTIVE: Despite the introduction of various less-invasive concepts of cardiac output measurement, pulmonary arterial thermodilution is still the most common measurement technique. METHODS: This prospective controlled study was designed to compare different methods of cardiac output measurement simultaneously. Pulmonary arterial thermodilution, transpulmonary thermodilution (PiCCO), trans-oesophageal echo-Doppler probe (HemoSonic) and partial carbon dioxide rebreathing technique (NICO monitor) were evaluated against a peri-aortic transit-time flow-probe as reference method in a clinically relevant animal model. After approval from the Local Ethics Committee on Animal Research, the investigations were conducted in nine anesthetized domestic pigs. Systemic haemodynamics were modulated systematically by the application of catecholamines, caval occlusion and exsanguination. Statistical analysis was performed with Bland-Altman and linear regression. RESULTS: A total of 366 paired cardiac output measurements were carried out at a reference cardiac output between 0.5 and 7 L min(-1). The correlation coefficients for pulmonary arterial and transpulmonary thermodilution against reference were 0.93 and 0.95, for trans-oesophageal Doppler and partial rebreathing technique 0.84 and 0.77. Pulmonary arterial thermodilution and transpulmonary thermodilution showed comparable bias and limits of agreement. Where HemoSonic showed an overestimation of cardiac output at a higher precision, NICO overestimated low and underestimated higher cardiac output values. CONCLUSIONS: Our data suggest that pulmonary arterial thermodilution and PiCCO may be interchangeably used for cardiac output measurement even under acute haemodynamic changes. The method described by Bland and Altman demonstrated an overestimation of cardiac output for both thermodilution methods. HemoSonic and NICO offer non-invasive alternatives and complementary monitoring tools in numerous clinical situations. Trend monitoring and haemodynamic optimizing can be applied sufficiently, when absolute measures are judged critically in a clinical context. The use of the NICO system seems to be limited during acute circulatory changes.

Detection of human hantavirus infections in Lithuania.

BACKGROUND: In Europe certain hantaviruses are known to cause hemorrhagic fever with renal syndrome of different severity. The objective of the present investigation was to study the presence of hantavirus infections in Lithuania. MATERIAL AND METHODS: Two different serum panels from cancer patients (n = 438) and blood donors (n = 299) from Lithuania were tested by monoclonal antibody capture IgG ELISA using yeast-expressed recombinant nucleocapsid (rN) proteins of Puumala virus (PUUV), Hantaan virus (HTNV) and Dobrava virus (DOBV). The reactivity of ELISA-positive sera was proven in Western blot tests using various hantavirus rN proteins. Selected serum samples were further analyzed by focus reduction neutralization assays. RESULTS: In the IgG ELISA 39 sera from the cancer patients and four sera from blood donors were found to be reactive with at least one of the rN proteins. By immunoblot using the three yeast-expressed rN proteins, the ELISA reactivity of 36 of 39 and two of four serum samples from cancer patients and blood donors, respectively, was confirmed; this corresponds to a seroprevalence of 8.2% and 0.7%, respectively. In ELISA, the majority of the samples reacted exclusively with rN proteins of HTNV and DOBV (31 of 36 and one of two in the two groups). In the group of sera selected for serotyping by focus reduction neutralization assay, this dominance was confirmed by the identification of eight DOBV but only four PUUV infections. No infection by HTNV or another hantavirus besides DOBV and PUUV was verified. Anti-hantavirus-positive human sera were detected in all seven investigated counties of Lithuania. CONCLUSION: In Lithuania at least two hantaviruses, DOBV and PUUV, circulate and cause human infections. Additional investigations are needed to study the seroprevalence more precisely and to search for clinical cases of hantavirus infections.

[Feedback control of muscle relaxation with a varying on-off controller using cisatracurium]. / Regelkreisgesteuerte Muskelrelaxation mit einem modifizierten Zweipunktregler mit Cisatracurium.

BACKGROUND: Under clinical conditions constant neuromuscular blockade can also be maintained by a simple closed-loop system. However, delayed onset time, non-linearity of the dose-response curve and different sensitivity to muscle relaxants for each patient are limiting factors. METHODS: In 20 patients who underwent elective surgical procedures under continuous propofol/alfentanil anaesthesia and relaxation with cisatracurium, the maintenance of an electromyographically controlled cisatracurium block of 90% was achieved by a varying on-off control system. Using an own computer-aided measuring device, the course of the neuromuscular blockade and deviations from the desired neuromuscular block were registered. RESULTS: Over a period of 64.2+/-14.0 min, neuromuscular block could be controlled on average at a T(1)-level of 10% (90% block). The mean error of the deviation of the obtained neuromuscular blockade from the set-point was -1.6+/-0.9% on average. To maintain this neuromuscular blockade, a dose rate of 1.4+/-0.9 micro g x kg(-1) x min(-1) cisatracurium was necessary. CONCLUSIONS: It can be concluded that a simple closed-loop system allows the safe use of the intermediate term muscle relaxant cisatracurium for the performance of surgical procedures.

[The syringe pump as actuator--a practical application problem of feedback control systems]. / Die Spritzenpumpe als Stellglied--Ein Problem im praktischen Einsatz regelkreisgesteuerter Systeme.

Based on a computer simulation programme, the accuracy of the Graseby 3400 syringe pump was tested for its use in a feedback control system of the neuromuscular block. Firstly, a calculation of errors to determine the difference between the target and actual flow rates was carried out. Next, the characteristic curves of the syringe pump were determined under different flow and sampling rates to correct the application software of the feedback controller with a view to obtaining the correct flow rates online. It was discovered that, particularly with short 12 s sampling rates, dose-dependent errors of almost 100% were provable. Therefore, the application of a robust controller and integration of the characteristic curves at the outlet of the controller software are required. For the adoption of syringe pumps in medical feedback control systems, definite determination of the actual infusion quantity using an exact calculation of errors is required. Especially in cases of short sampling rates in combination with low infusion quantities, the syringe pump comes almost to a standstill, which results in extreme differences between target and actual flow rates.

[Quantitative assessment of neuromuscular block of the orbicularis oculi muscle]. / Quantitative Erfassung der neuromuskulären Blockade des Musculus orbicularis oculi.

In a prospective clinical study neuromuscular block at the orbicular ocular muscle was examined qualitatively and quantitatively by an AMG approach. The signals were recorded, visualized and evaluated simultaneously under PC-support after TOF-stimulation in 20 s intervals. Fifty ASA I and II patients were included into the study. After oral premedication with midazolam 10-15 mg, anaesthesia was induced with propofol 2 mg/kg and alfentanil 0.02 mg/kg and maintained by means of propofol 6-8 mg/kg/h and alfentanil 0.02 mg/kg/h. After intubation and signal stabilization, mivacurium 0.75 mg/kg was administered and neuromuscular blockade was recorded online. The measured acceleration at the orbicular ocular muscle amounted 0.9 g on average. Maximal neuromuscular block was registered at 78.5% and the TOF-ratio of 0.8 was achieved after 14.1 min. The low values of the AMG-signals of the orbicular ocular muscle requiring very high technical demands on the measuring instrument. Additional problems arise through the considerable temporal expenditure for discovering the optimal location of stimulation. During the AMG monitoring the position dependence of the measured values of the sensors must be taken into consideration. These technical problems restrict the suitability of the AMG at the orbicular ocular muscle as a quantitative neuromuscular monitoring tool.

[Oral and rectal premedication of children with midazolam]]. / Orale und rektale Prämedikation von Kindern mit Midazolam.

Premedication in children continues to be a problem in anaesthesiology. Apart from the application of premedication drugs, a strongly committed anaesthetist and sound psychological work are decisive prerequisites for adequate premedication. In this randomized study, 329 children aged between 1 and 14 who were scheduled for small surgical procedures were examined. Based on the results of a preliminary trial using different dosages of midazolam, the children were premedicated either orally with 0.4 mg/kg BW midazolam or with 0.3 mg/kg BW midazolam as a rectal solution and the premedication effect was recorded according to the classification of Lindgren. These reduced doses of midazolam, which were much lower than those described in the literature, led to very good premedication effects, too. Regarding cardiovascular behaviour, an increasing anxiolysis and the effect of premedication led to a significant decline in mean arterial blood pressure and heart frequency. The circulatory changes that occurred were at no time clinically relevant in any child, and therefore no treatment was needed. Based on the measured oxygen saturation, no significant respiratory changes were seen during the observation period. The frequency and extent of the registered side-effects were classified as slight. Side-effects such as singultus, salivation and ataxia/gesticulations were of no danger during the entire perioperative period.

[Clinical administration of muscle relaxants for intubation]. / Der klinische Einsatz von Muskelrelaxanzien zur Intubation.

Muscle relaxants are used for tracheal intubation, surgical procedures and in the intensive care unit. This review describes muscle relaxants available in Germany, with special focus on their use in endotracheal intubation. We compare the advantages and disadvantages of succinylcholine (the only depolarising agent) with those of short- and intermediate-acting non-depolarising agents in an attempt to define the characteristics of the ideal muscle relaxant. The effective doses required to attain 95% neuromuscular block and maximum effect (onset time) are compared for adults and children. It is documented that, with non-depolarising agents, increasing the dose and using either the priming or timing principle possibly reduce the onset time of neuromuscular block during a rapid sequence induction. The advantages and disadvantages of using non-depolarising instead of depolarising agents are discussed using data from our studies and those of other research groups. Possible side-effects due to the chemical structure and the necessary dosage for intubation of different agents are also discussed. Two points are emphasized: firstly, the use of non-depolarising agents for intubation requires the possibility of safe ventilation of the patient via mask, and, secondly, it is important that procedures be performed by an experienced anaesthetist.

Overexpression of the transcriptional repressor FoxD3 prevents neural crest formation in Xenopus embryos.

Xenopus FoxD3 (XFD-6) is an intron-less gene initially expressed within the Spemann organizer and later in premigratory neural crest cells. Based upon sequence and expression pattern comparisons, it represents the Xenopus orthologue to zebrafish fkd6, chicken CWH-3 and mammalian HFH-2 (genesis). Early expression of FoxD3 is activated by the Wnt-pathway and inhibited by BMP signalling. Ectopic overexpression of FoxD3 leads to an enlargement of the neural plate concomitant with a failure in neural crest formation, loss of anterior structures, lack of closure of the neural tube and severe defects in somitogenesis. Phenotypic variation is accompanied by down-regulation of neural crest markers, including Xslug, Xtwist and Xcadherin-11. FoxD3 also inhibits its own expression, thereby acting in a negative autoregulatory loop. By injections of VP16 and engrailed fusions we can demonstrate that FoxD3 acts as a negative transcriptional regulator; this repressive function strictly requires the presence of the winged helix domain. Transplantation experiments show that FoxD3 overexpressing cells from the prospective neural crest do neither differentiate nor migrate.

Expression of the highly conserved RNA binding protein KOC in embryogenesis.

The human KOC gene which is highly expressed in cancer shows typical structural features of an RNA binding protein. We analyzed the temporal and spatial expression pattern of KOC in mouse embryos at different gestational ages. The expression of KOC seems to be ubiquitous at early stages. During advanced gestation highest KOC expression occurs in the gut, pancreas, kidney, and in the developing brain. The expression pattern of KOC was compared to its Xenopus homologue Vg1-RBP during frog development. Similar expression was found in these organs suggesting an important functional role of the homologous proteins in embryonic development.

Identification of genetic determinants for the hemolytic activity of Streptococcus agalactiae by ISS1 transposition.

Streptococcus agalactiae is a poorly transformable bacterium and studies of molecular mechanisms are difficult due to the limitations of genetic tools. Employing the novel pGh9:ISS1 transposition vector we generated plasmid-based mutant libraries of S. agalactiae strains O90R and AC475 by random chromosomal integration. A screen for mutants with a nonhemolytic phenotype on sheep blood agar led to the identification of a genetic locus harboring several genes that are essential for the hemolytic function and pigment production of S. agalactiae. Nucleotide sequence analysis of nonhemolytic mutants revealed that four mutants had distinct insertion sites in a single genetic locus of 7 kb that was subsequently designated cyl. Eight different open reading frames were identified: cylX, cylD, cylG, acpC, cylZ, cylA, cylB, and cylE, coding for predicted proteins with molecular masses of 11, 33, 26, 11, 15, 35, 32, and 78 kDa, respectively. The deduced amino acid sequence of the protein encoded by cylA harbors a conserved ATP-binding cassette (ABC) motif, and the predicted proteins encoded by cylA and cylB have significant similarities to the nucleotide binding and transmembrane proteins of typical ABC transporter systems. Transcription analysis by reverse transcription-PCR suggests that cylX to cylE are part of an operon. The requirement of acpC and cylZABE for hemolysin production of S. agalactiae was confirmed either by targeted mutagenesis with the vector pGh5, complementation studies with pAT28, or analysis of insertion elements in naturally occurring nonhemolytic mutants.