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Genome-scale metabolic models are central in connecting genotypes to metabolic phenotypes. However, even for well studied organisms, such as Escherichia coli, draft networks do not contain a complete biochemical network. Missing reactions are referred to as gaps. These gaps need to be filled to enable functional analysis, and gap-filling choices influence model predictions. To investigate whether functional networks existed where all gap-filling reactions were supported by sequence similarity to annotated enzymes, four draft networks were supplemented with all reactions from the Model SEED database for which minimal sequence similarity was found in their genomes. Quadratic programming revealed that the number of reactions that could partake in a gap-filling solution was vast: 3,270 in the case of E. coli, where 72% of the metabolites in the draft network could connect a gap-filling solution. Nonetheless, no network could be completed without the inclusion of orphaned enzymes, suggesting that parts of the biochemistry integral to biomass precursor formation are uncharacterized. However, many gap-filling reactions were well determined, and the resulting networks showed improved prediction of gene essentiality compared with networks generated through canonical gap filling. In addition, gene essentiality predictions that were sensitive to poorly determined gap-filling reactions were of poor quality, suggesting that damage to the network structure resulting from the inclusion of erroneous gap-filling reactions may be predictable.

In pursuit of establishing a realistic metabolic phenotypic space, the reversibility of reactions is thermodynamically constrained in modern metabolic networks. The reversibility constraints follow from heuristic thermodynamic poise approximations that take anticipated cellular metabolite concentration ranges into account. Because constraints reduce the feasible space, draft metabolic network reconstructions may need more extensive reconciliation, and a larger number of genes may become essential. Notwithstanding ubiquitous application, the effect of reversibility constraints on the predictive capabilities of metabolic networks has not been investigated in detail. Instead, work has focused on the implementation and validation of the thermodynamic poise calculation itself. With the advance of fast linear programming-based network reconciliation, the effects of reversibility constraints on network reconciliation and gene essentiality predictions have become feasible and are the subject of this study. Networks with thermodynamically informed reversibility constraints outperformed gene essentiality predictions compared to networks that were constrained with randomly shuffled constraints. Unconstrained networks predicted gene essentiality as accurately as thermodynamically constrained networks, but predicted substantially fewer essential genes. Networks that were reconciled with sequence similarity data and strongly enforced reversibility constraints outperformed all other networks. We conclude that metabolic network analysis confirmed the validity of the thermodynamic constraints, and that thermodynamic poise information is actionable during network reconciliation.

The prosthetic supply of the hip-joint may be accompanied by the problem of venous air embolism. By including 53 orthopaedic patients having undergone total hip replacement, the influence of bone-cement as well as of the different anaesthetic techniques on the frequency of embolic phenomenons was investigated. Embolism was determined as an abrupt decrease (greater than 5 mmHg) in the end-tidal pCO2. Venous embolism often occurred with cemented endoprostheses in contrast to non-cement implantations. Patients with general anaesthesia presented more often with venous air embolism than patients with epidural anaesthesia. This might be explained by an expanding effect of nitrous oxide on air bubbles entering the vascular bed under the implantation of the shaft-prostheses. Our data stress the importance of continuous monitoring of end-tidal pCO2 for early discovery of lung embolism.

Zusammenfassung Ziel der Studie Der direkte Einfluss der Ohrakupunktur auf das subjektive Befinden in einer psychischen Belastungssituation sollte in einer Pilotstudie unter kontrollierten Bedingungen untersucht werden. Besonderes Interesse galten dem Wirkungseintritt der Ohrakupunktur sowie dem weiteren Wirkungsverlauf. Methodik Bei 30 Medizinstudenten mit Prufungsangst wurde am Abend vor einem Anatomietestat eine Ohrakupunktur durchgefuhrt. Die Probanden bekamen in 5-minutigen Intervallen vor und uber einen Zeitraum von 30 Minuten nach der Akupunktur Befindlichkeitsfragebogen ausgehandigt. Neben spezifischen Zielparametern wurden unspezifische kognitive Kontrollparameter evaluiert (insgesamt 10). Ergebnisse Im zeitlichen Verlauf zeigten sich signifikante Veranderungen insbesondere fur Faktor I (Angst/Erregung). Angst und Erregung nahmen unmittelbar nach der Ohrakupunktur (innerhalb von nur 5 Minuten) deutlich ab (p Schlussfolgerung In dieser Untersuchung wurde gezeigt, dass mit Ohrakupunktur unmittelbar Einflus auf das subjektive Befinden in psychischen Belastungssituationen genommen werden kann. Die Ohrakupunktur zeigte ihre deutlichste Wirkung schon in den ersten funf Minuten, sodass es erfolgversprechend sein konnte, sie nicht nur am Vorabend eines chirurgischen Eingriffs, sondern auch direkt praoperativ einzusetzen.

Objective Monocytes play an important part in all phases of both humoral and cell-mediated immune responses. In our study, we examined the influence of various drugs used in intensive care (omeprazole, ranitidine, potassium canrenoate, furosemide, clonidine, verapamil, and metamizole) on monocyte chemotaxis in vitro. The 0,1 fold, 1 fold, and 10 fold concentrations, which are detectable in serum after a clinically efficacious bolus injection of the respective drug, were tested. Methods Using centrifugation, mononuclear cells were isolated from venous blood samples obtained from 10 healthy volunteers. Monocyte chemotaxis was determined by means of a microchemotaxis chamber. N-formyl-methionylleucylphenylalanine served as chemoattractant. Results Omeprazole, ranitidine, and potassium canrenoate did not influence monocyte chemotaxis. While the 10 fold concentrations of the clinically efficacious serum concentrations of furosemide and verapamil caused a significant inhibition, the 10 fold concentrations of the clinically efficacious serum concentrations of clonidine and metamizole significantly stimulated monocyte motility. Conclusion Clinically relevant concentrations of the drugs tested did not alter monocyte chemotaxis in vitro. However, 10 fold concentrations of the clinically efficacious serum concentrations, which might occur in vivo due to drug interaction, cumulation, altered elimination, or accidental overdose, caused an inhibition (furosemide, verapamil) or a stimulation (clonidine, metamizole). An in vitro investigation does never permit to jump to clinical conclusions. However, our study gives impulses to conduct intensive care examinations concerning the influence of drugs on monocyte functions particularly since these cells are of great prognostical importance regarding sepsis.

The transmissible spongiform encephalopathies (TSE) are known to affect humans and various animals. The bovine spongiform encephalopathy (BSE) and the human Creutzfeldt-Jacob disease (CJD) are among the most notable degenerative disorders caused by prions. Considering the BSE epidemic and the description of a new variant of Creutzfeldt-Jacob disease (nvCJD), which is probably related to bovine spongiform encephalopathy, TSE have recently gained a lot of public attention. Although the causative factors (prions, viruses) are still under discussion, none of the present concepts are explanatory for all aspects of the human CJD. CJD may present as a sporadic, genetic, or infectious illness and there is now considerable concern that bovine prions may have been passed to humans. To exclude transmission of CjD via medical products and instruments, the effectiveness of cleaning, disinfection and sterilization procedures must be firmly established. This manuscript presents an overview to anaesthesiology and intensive care medicine of recommended inactivation procedures and assessed these procedures in the light of the inactivation of prions.

Objective: Adequate volume therapy is a cornerstone for treating patients undergoing major surgery. The age-old crystalloid/colloid debate is

Polymorphonuclear leukocytes (PMNL) make an outstanding contribution to the defence against invading bacteria. We studied the effects of midazolam, droperidol, fentanyl, and alfentanil on phagocytosis and killing of Staphylococcus aureus and Escherichia coli by PMNL in vitro. Using a method described by Eggleton et al., PMNL were isolated from venous blood samples obtained from ten volunteers. The fluorescence microscopic method mentioned by Bellinati-Pires et al. was used to examine phagocytosis and killing. Whereas both midazolam and droperidol caused a significant inhibition of phagocytosis as well as bactericidal activity, fentanyl and alfentanil did not influence these PMNL functions. In order to find out whether midazolam and droperidol are able to intensify perioperative bacterial infections in vivo as well, additional clinical studies should be conducted.

Polymorphonuclear leukocytes (PMNL) are important components of the immunological defence system which protects the human organism from invading bacteria. Using a fluorescence microscopic method, we examined the influence of propofol and its solvent intralipid on phagocytosis and killing of Staphylococcus aureus and Escherichia coli by PMNL in vitro. Propofol inhibited (Por = 0.001) phagocytosis of Staphylococcus aureus as well as Escherichia coli. Killing of Staphylococcus aureus (Por = 0.001) and of Escherichia coli (Por = 0.01) was suppressed. Intralipid, by itself, impaired phagocytosis of Escherichia coli (Por = 0.05). Apart from that, intralipid produced no relevant effects. Additional clinical studies regarding the influence of propofol on PMNL function are recommended.

The green picoalga Ostreococcus is emerging as a simple plant model organism, and two species, O. lucimarinus and O. tauri, have now been sequenced and annotated manually. To evaluate the completeness of the metabolic annotation of both species, metabolic networks of O. lucimarinus and O. tauri were reconstructed from the KEGG database, thermodynamically constrained, elementally balanced, and functionally evaluated. The draft networks contained extensive gaps and, in the case of O. tauri, no biomass components could be produced due to an incomplete Calvin cycle. To find and remove gaps from the networks, an extensive reference biochemical reaction database was assembled using a stepwise approach that minimized the inclusion of microbial reactions. Gaps were then removed from both Ostreococcus networks using two existing gap-filling methodologies. In the first method, a bottom-up approach, a minimal list of reactions was added to each model to enable the production of all metabolites included in our biomass equation. In the second method, a top-down approach, all reactions in the reference database were added to the target networks and subsequently trimmed away based on the sequence alignment scores of identified orthologues. Because current gap-filling methods do not produce unique solutions, a quality metric that includes a weighting for phylogenetic distance and sequence similarity was developed to distinguish between gap-filling results automatically. The draft O. lucimarinus and O. tauri networks required the addition of 56 and 70 reactions, respectively, in order to produce the same biomass precursor metabolites that were produced by our plant reference database.

Polymorphonuclear leukocytes (PMNL) play an important part in protecting against invading bacteria. It is known that some anaesthetics may impair PMNL functions, thus possibly promoting infection. We investigated the effect of fentanyl and alfentanil on superoxide anion production, hydrogen peroxide generation, and activity of released myeloperoxidase in vitro. However, the two opioids did not have any significant influence on the tested PMNL functions.

OBJECTIVE: Polymorphonuclear neutrophile leucocytes (PMNL) play an important role in the defence against bacterial infections. It is known that some anaesthetics are able to disturb PMNL functions. We examined the influence of midazolam and flunitrazepam on the activity of the bactericidal enzymes lysozyme and beta-glucuronidase released from PMNL in vitro. METHODS: As described before [4], PMNL were isolated from venous blood samples obtained from 10 healthy male volunteers. PMNL stimulation and measurement of lysozyme and beta-glucuronidase activities were conducted according to the description by Metcalf et al. [5]. The BIOMED-system [8] was used for statistical evaluation. RESULTS: Neither midazolam nor flunitrazepam caused any statistically important alteration of lysozyme activity. However, clinically relevant concentrations of both benzodiazepines significantly enhanced beta-glucuronidase activity. The additives of flunitrazepam did not play any role. CONCLUSION: Surprisingly enough, midazolam and flunitrazepam increased the activity of beta-glucuronidase released from PMNL in vitro. At present, this result can neither be explained nor can its importance be estimated. On the other hand, the benzodiazepines did not relevantly influence lysozyme activity.

Monocytes play a very important part in humoral as well as in cell-mediated immunity. At present, however, the knowledge of the influence of anaesthetic agents on the functions of monocytes is limited. In the present study, the effects of thiopentone, methohexitone, ketamine, midazolam, droperidol, propofol, etomidate, and fentanyl on monocyte chemotaxis were examined in vitro using a 48-well microchemotaxis chamber. Clinically relevant concentrations of ketamine, midazolam, and droperidol significantly (P < or = 0.05) inhibited chemotaxis. For that reason, it is possible that these anaesthetics impair the immunological system in vivo. This possibility should be further examined.

Monocytes play an important part in all phases of both humoral and cell-mediated immune responses. In our study, we examined the influence of various drugs used in intensive care (omeprazole, ranitidine, potassium canrenoate, furosemide, clonidine, verapamil, and metamizole) on monocyte chemotaxis in vitro. The 0,1 fold, 1 fold, and 10 fold concentrations, which are detectable in serum after a clinically efficacious bolus injection of the respective drug, were tested.Using centrifugation, mononuclear cells were isolated from venous blood samples obtained from 10 healthy volunteers. Monocyte chemotaxis was determined by means of a microchemotaxis chamber. N-formyl-methionylleucylphenylalanine served as chemoattractant.Omeprazole, ranitidine, and potassium canrenoate did not influence monocyte chemotaxis. While the 10 fold concentrations of the clinically efficacious serum concentrations of furosemide and verapamil caused a significant inhibition, the 10 fold concentrations of the clinically efficacious serum concentrations of clonidine and metamizole significantly stimulated monocyte motility.Clinically relevant concentrations of the drugs tested did not alter monocyte chemotaxis in vitro. However, 10 fold concentrations of the clinically efficacious serum concentrations, which might occur in vivo due to drug interaction, cumulation, altered elimination, or accidental overdose, caused an inhibition (furosemide, verapamil) or a stimulation (clonidine, metamizole). An in vitro investigation does never permit to jump to clinical conclusions. However, our study gives impulses to conduct intensive care examinations concerning the influence of drugs on monocyte functions particularly since these cells are of great prognostical importance regarding sepsis.

In an experimental design the pain reduction effect of acupuncture is studied and compared to the treatment of a classical acupuncture point and a point of the Yamamoto New Scalp Acupuncture (YNSA).Experimental pain stimuli (32 per test person) were set in 42 test persons at the upper calcaneus edge and pain reduction was checked intra-individually by using the following variations of treatment: Acupuncture YNSA basis-point D, Acupuncture at the classical point Xiao Chang Shu = Bl 27, Acupuncture at a placebo point of the head, Acupuncture at a placebo point of the gluteal region.Evaluation of the data as well as a statistical investigation using a bi-factoral variance analysis with repeated measurements of 2 respectively 1 factor yielded following results: There are highly significant differences concerning pain reduction through the stimulation of the YNSA basis-point D and the acupuncture at the classical point Bl 27 (p0,0007). There are also highly significant differences concerning the verum and the placebo treatment (p0,00006). Further hypothesis of controlling the experimental design were tested.On the whole, the investigation shows that there is a marked difference between the verum and placebo treatment as well as a difference between the acupuncture of the YNSA basis-point D and the classical acupuncture point Xiao Chang Shu (Bl 27) with regard to pain reduction induced by experimental stimuli at the calcaneus. These differences are significant.

Transposon mutagenesis, in combination with parallel sequencing, is becoming a powerful tool for en-masse mutant analysis. A probability generating function was used to explain observed miniHimar transposon insertion patterns, and gene essentiality calls were made by transposon insertion frequency analysis (TIFA). TIFA incorporated the observed genome and sequence motif bias of the miniHimar transposon. The gene essentiality calls were compared to: 1) previous genome-wide direct gene-essentiality assignments; and, 2) flux balance analysis (FBA) predictions from an existing genome-scale metabolic model of Shewanella oneidensis MR-1. A three-way comparison between FBA, TIFA, and the direct essentiality calls was made to validate the TIFA approach. The refinement in the interpretation of observed transposon insertions demonstrated that genes without insertions are not necessarily essential, and that genes that contain insertions are not always nonessential. The TIFA calls were in reasonable agreement with direct essentiality calls for S. oneidensis, but agreed more closely with E. coli essentiality calls for orthologs. The TIFA gene essentiality calls were in good agreement with the MR-1 FBA essentiality predictions, and the agreement between TIFA and FBA predictions was substantially better than between the FBA and the direct gene essentiality predictions., Author Summary Metabolic modeling techniques play a central role in rational design of industrial strains, personalized medicine, and automated network reconstruction. However, due to the large size of models, very few have been comprehensively tested using single gene knockout mutants for every gene in the model. Such a genetic test could evaluate whether genes that for a given condition are predicted to be essential by a model, are indeed essential in reality (and vice versa). We developed a new probability-based technology that identifies the essentiality of genes from observed transposon insertion data. This data was acquired by pooling tens of thousands of transposon mutants, and localizing the insertion locations all at once by using massive parallel sequencing. We utilized this gene essentiality data for the genome-scale genetic validation of a metabolic model. For instance: our work identified nonessential genes that were predicted to be essential for growth by an existing metabolic model of Shewanella oneidensis, highlighting incomplete areas within this metabolic model.

The transmissible spongiform encephalopathies (TSE) are known to affect humans and various animals. The bovine spongiform encephalopathy (BSE) and the human Creutzfeldt-Jacob disease (CJD) are among the most notable degenerative disorders caused by prions. Considering the BSE epidemic and the description of a new variant of Creutzfeldt-Jacob disease (nvCJD), which is probably related to bovine spongiform encephalopathy, TSE have recently gained a lot of public attention. Although the causative factors (prions, viruses) are still under discussion, none of the present concepts are explanatory for all aspects of the human CJD. CJD may present as a sporadic, genetic, or infectious illness and there is now considerable concern that bovine prions may have been passed to humans. To exclude transmission of CJD via medical products and instruments, the effectiveness of cleaning, disinfection and sterilization procedures must be firmly established. This manuscript presents an overview to anaesthesiology and intensive care medicine of recommended inactivation procedures and assessed these procedures in the light of the inactivation of prions.

Monocytes play an important role in humoral as well as in cell-mediated immunity. In the present study, the influences of the anti-migraine preparations metoprolol, propranolol, metoclopramide, acetylsalicylic acid, dihydro-ergotamine and sumatriptan on monocyte chemotaxis were examined in vitro. First, mononuclear cells were isolated by centrifugation from venous blood samples obtained from 10 healthy male volunteers. Chemotaxis was determined using a microchemotaxis chamber. While metoprolol, metoclopramide, dihydroergotamine and sumatriptan did not influence monocyte chemotaxis, high doses of propranolol and acetylsalicylic acid caused a significant (por = 0.001) inhibition of this important cellular function. Therefore, it is quite possible that both drugs produce adverse immunological effects in vivo in cases of high dosage or obstruction of elimination.

Polymorphonuclear neutrophile leucocytes (PMNL) play an important role in the defence against bacterial infections. It is known that some anaesthetics are able to disturb PMNL functions. We examined the influence of midazolam and flunitrazepam on the activity of the bactericidal enzymes lysozyme and beta-glucuronidase released from PMNL in vitro.As described before [4], PMNL were isolated from venous blood samples obtained from 10 healthy male volunteers. PMNL stimulation and measurement of lysozyme and beta-glucuronidase activities were conducted according to the description by Metcalf et al. [5]. The BIOMED-system [8] was used for statistical evaluation.Neither midazolam nor flunitrazepam caused any statistically important alteration of lysozyme activity. However, clinically relevant concentrations of both benzodiazepines significantly enhanced beta-glucuronidase activity. The additives of flunitrazepam did not play any role.Surprisingly enough, midazolam and flunitrazepam increased the activity of beta-glucuronidase released from PMNL in vitro. At present, this result can neither be explained nor can its importance be estimated. On the other hand, the benzodiazepines did not relevantly influence lysozyme activity.

Polymorphonuclear eosinophilic leucocytes (PME) participate in wound healing processes, the inflammatory response, bronchial asthma, allergies and defence against invading parasites. We have examined the effects of thiopental, methohexital, propofol, etomidate and ketamine on PME chemotaxis in vitro. PME were isolated from venous blood samples of 10 healthy volunteers using multi-stage Percoll gradient centrifugation. Eosinophilic chemotaxis was determined using a 48-well microchemotaxis chamber. Thiopental 150 micrograms ml-1 and etomidate 0.32 microgram ml-1 caused significant (Por = 0.05) inhibition of PME chemotaxis. We conclude that thiopental and etomidate may have an adverse influence on wound healing processes and parasitic diseases. Further studies are recommended.

Polymorphonuclear leucocytes (PMNL) are an essential contribution to protection from bacterial infection. We have examined the effects of thiopentone, etomidate, ketamine and flunitrazepam on phagocytosis and killing of Staphylococcus aureus and Escherichia coli by PMNL in vitro with fluorescence microscopy. All anaesthetic agents significantly inhibited both phagocytosis and bactericidal activity. The additives in the commercial preparations may have contributed to the suppression.

Polymorphonuclear leucocytes (PMNL) are an essential component of the defence system against invading bacteria. There is evidence that some anaesthetics are able to suppress PMNL functions, promoting, perhaps, perioperative infection. We studied the effects of thiopentone, etomidate, ketamine, and midazolam on the generation of bactericidal agents (superoxide anion, hydrogen peroxide, and myeloperoxidase) by PMNL in vitro. Thiopentone inhibited superoxide anion (Por = 0.01) as well as hydrogen peroxide production (Por = 0.001). However, there was no statistically significant effect on myeloperoxidase release. Neither etomidate nor ketamine influenced the PMNL functions tested to any extent. Midazolam suppressed superoxide anion generation (Por = 0.01) but only if a concentration far beyond clinical relevance was used.

Polymorphonuclear leukocytes (PMNL) play a vital role in the defence against invading bacteria. It is known that some anaesthetics inhibit PMNL function and, thus, possibly enhance perioperative infection. We investigated the effect of methohexitone, flunitrazepam, and droperidol on three bactericidal PMNL functions, i.e., superoxide anion production, hydrogen peroxide generation, and activity of released myeloperoxidase, in vitro. Approved photometrical assays were used. Superoxide anion was measured by the reduction of cytochrome C, hydrogen peroxide by the horse radish peroxidase catalysed oxidation of phenol red, and myeloperoxidase by the turnover of 2,2'-azino-di(3-ethylbenzthiazoline) sulfonic acid. Methohexitone (P < or = 0.001) and flunitrazepam (P < or = 0.01) inhibited superoxide anion production, and methohexitone (P < or = 0.01) reduced hydrogen peroxide generation but only at concentrations beyond clinical relevance. Droperidol did not cause any alteration of the PMNL functions tested. Consequently, it seems unlikely that the usual doses of methohexitone, flunitrazepam, or droperidol promote bacterial infections in vivo by impairing the activity of myeloperoxidase or by inhibiting the generation of superoxide anion or hydrogen peroxide.

Infection remains a major cause of morbidity and mortality in intensive care medicine. The increased susceptibility of the severely injured patient to sepsis and consecutive multiorgan failure has been attributed to abnormalities in cell-mediated immunity. The purpose of our study was to determine changes in the pattern of lymphocyte subpopulations in severely injured patients and to relate these changes to any development of sepsis and to outcome (indirect immunofluorescence with monoclonal antibodies). During 14 months we investigated 28 patients (ages 15-65 years) suffering from severe multisystem trauma (22 cases) or diffuse peritonitis (6 cases), 6 of whom (21.4%) developed sepsis and multiorgan failure; 4 of these 6 septic patients died. According to the clinical data, patients developed sepsis between the 3rd and 6th days after trauma. We therefore defined days 1-3 as the preseptic phase, days 3-6 as the phase of sepsis development, and days 4-10 as the phase of septic disease. In the preseptic phase there was no statistically significant difference in the pattern of the eight lymphocyte subpopulations measured between patients who later developed sepsis and those who did not. During the phase of sepsis development, however, the patients who did develop sepsis showed significantly reduced numbers of CD2-, CD8-, and CD20-positive cells (P = 0.0003; P = 0.009; P = 0.012). The number of helper cells (CD4) was also decreased, but the difference between the two groups failed to reach statistical significance (P = 0.08).(ABSTRACT TRUNCATED AT 250 WORDS)

Knowledge of the actual concentrations of local anesthetic administered by various techniques is essential requisite when undesirable side effects and possible toxicity of a substance are to be evaluated. Therefore, numerous studies of plasma concentrations have been presented, which were carried out with the additional purpose of analyzing the kinetics of different local anesthetics with respect to limiting-value concentrations in the organism. Despite a sufficient degree of precision in the analysis of amide local anesthetics, it is uncertain whether the results of the different studies are comparable, because blood samples have been taken variously from peripheral veins, central veins or arteries. In the present study changes in bupivacaine concentrations were monitored by means of a standardized method consisting in simultaneous sampling of blood in peripheral veins, central veins and arteries. METHODS. Each of 12 patients undergoing orthopedic hip surgery received average 17 ml bupivacaine (0.75%) via peridural lumbar catheter. After the administration of bupivacaine, blood samples were taken simultaneously from peripheral veins, central veins and arteries at 1, 3, 5, 10, 15, 30, 45, 60, and 90 min after injection. Placement of an arterial cannula and central venous catheter was indicated in all patients (hip-joint revision arthroplasty). Quantitative analysis of bupivacaine concentration was carried out by means of high-pressure liquid chromatography (HPLC). All patients had given their informed consent. RESULTS. All patients showed a rapid increase in bupivacaine concentration in the central venous blood within the first few minutes after administration, the maximum being reached between 3 and 10 min after. A similar course was observed with arterial plasma concentrations; absolute values, however, were an average of 10-20% lower at 15 min following administration. Bupivacaine concentrations in peripheral veins rose more slowly and reached a maximum between 15 and 30 min. At 30 min after peridural application the concentration curves in blood from all three sites were similar. DISCUSSION. In earlier studies the influence of the site of blood sampling has often been underestimated. According to our results, central venous and arterial plasma concentrations correspond closely at all times following peridural application. The observed uniform differences in concentrations at the various sites of sampling can be explained by the fact that pulmonary uptake of local anesthetics causes the lower arterial levels. Especially in the early phase of resorption after administration of local anesthetics, the concentration in peripheral blood does not seem to be representative, because an equilibrium is not established between arterial and central venous blood until 30 min after administration at the earliest. In our opinion the peripheral venous concentrations are unreliable, particularly in the early phases, for the evaluation of unwanted effects or toxicity of local anesthetics, because the initial low values and the delayed increase in these could lead to a false sense of security.

Somatosensory evoked potentials (SEP) after median nerve stimulation were recorded in 40 patients during infusion of either 15 mg/kg bw thiopentone or 1 mg/kg bw etomidate (n = 10) within 15 min and after 0.3 mg/kg bw etomidate (n = 20). Marked alterations of SEP waveforms and changes in latencies were observed in all patients. Central conduction time (CCT) was significantly correlated to plasma thiopentone concentration. Infusion of high doses of thiopentone and etomidate was followed by a complete loss of middle and long latency components. Amplitude of the primary cortical SEP N20 was found to be unchanged after thiopentone and to be increased after etomidate, indicating the synchronizing properties of this drug. A pronounced increase in SEP latencies and CCT and waveform alterations have to be considered during hypnotic drug administration in intensive care medicine and intraoperatively.

44 malades de chirurgie gynecologique recoivent soit neuroleptanalgesie+halothane soit une association de neuroleptanalgesie+anesthesie extradurale

The influence of clinically relevant concentrations of thiopentone sodium, methohexitone, and etomidate on polymorphonuclear neutrophilic granulocyte (PMN) adherence was investigated in vitro by using nylon fibre columns. The three induction agents produced dose-dependently a significant (p less than 0.01) reduction in adherence. This effect is possibly related to increased risk of postoperative bacterial infection. Further studies on this problem are recommended.

44 patients undergoing comparable gynaecological operations received either halothane- modified neuroleptanaesthesia or a combination of epidural and NLA. Monoclonal antibodies were used to determine 8 different lymphocyte subpopulations in blood samples drawn before and after anaesthesia and on the first postoperative day. Cell populations were counted by fluorescent microscopy. Halothane anaesthesia produced both a depression of T-cells (72.67% preoperatively to 52.79% postoperatively) and of the helper/suppressor ratio (1.46 to 1.10); meanwhile activated T-cells increased from 2.33% to 6.83%. After neuroleptanaesthesia as well as after halothane the HLA-DR positive cells decreased (21.05% to 19.29%; 25.22% to 20.29%). The B-cell fraction was elevated from 2.33% to 6.83% following combined anaesthesia. The potential of the anaesthetics to produce subsequent alterations in host defense is discussed.

In patients with cancer pain treated by continuous epidural opiate infusion (4.5-24 mg morphine per day) via implanted or portable pumps (n = 40) plasma levels of morphine were determined during the postoperative period and during regular refill of the pump systems. Concentrations were between 2.6 and 18.8 ng/ml depending on daily dosage and body weight. There were no signs of accumulation. Concentrations in lumbar CSF measured in some of the patients were 15-20 higher but decreased by 10-20% (in relation to daily dosage) in the course of long-term treatment. This may be induced by reduction in permeability of the dura due to fibrosis within the epidural space after chronicle catheterization. Cervical CSF concentrations (during chordotomy) were about 1/6 to 1/7 of the corresponding lumbar CSF levels. It may be assumed that epidural opiate infusion in spite of low blood levels is accompanied by relevant cerebral opiate actions.

The prosthetic supply of the hip-joint may be accompanied by the problem of venous air embolism. By including 53 orthopaedic patients having undergone total hip replacement, the influence of bone-cement as well as of the different anaesthetic techniques on the frequency of embolic phenomenons was investigated. Embolism was determined as an abrupt decrease (greater than 5 mmHg) in the end-tidal pCO2. Venous embolism often occurred with cemented endoprostheses in contrast to non-cement implantations. Patients with general anaesthesia presented more often with venous air embolism than patients with epidural anaesthesia. This might be explained by an expanding effect of nitrous oxide on air bubbles entering the vascular bed under the implantation of the shaft-prostheses. Our data stress the importance of continuous monitoring of end-tidal pCO2 for early discovery of lung embolism.

After injection of etomidate during surgery for herniation of an intervertebral disk an anaphylactoid reaction occurred. Generalized erythema, severe urticaria, and rise in heart rate and blood pressure drop were observed. After treatment with an antihistaminic and a corticosteroid the phenomenons completely disappeared within 45 minutes.

Pharmacokinetics of mezlocillin (70 mg/kg as an infusion) were investigated in 8 patients with multiorgan failure undergoing continuous veno-venous haemofiltration (CVVH) due to acute renal failure (HF-group) in comparison to 8 intensive care patients with an uneffected renal system (control group). Mezlocillin concentration were studied in blood, ultrafiltrate and urine (control group). Elimination of mezlocillin was prolonged in the HF-group with a t1/2 of 170 min in comparison to 109 min in the control patients. No relevant absorption at the haemofilter membrane could be observed. With regard to our results a dose reduction and intermittend application of mezlocillin is suggested; in addition, monitoring of drug levels in critically ill patients becomes of increasing interest, especially during haemofiltration.

The influence of clinically relevant concentrations of fentanyl, alfentanil, morphine, pethidine, and buprenorphine on polymorphonuclear neutrophilic granulocyte (PMN) adherence was investigated in vitro by using nylon fibre columns. Since none of the drugs produced any significant (p less than 0.05) change of adherence, no evidence of opioid mediated increased risk of postoperative bacterial infection could be found.

Spectral analysis with the compressed spectral array display (CSA) and calculation of spectral edge frequency (SEF) was performed in 43 cases undergoing endarterectomy of the carotid bifurcation. New neurologic deficit appeared in 2 patients (= 4.6%). One of them died postoperatively (= 2.3%), the other suffered from permanent paralysis of the hand. Another 9 patients showed loss of high frequency activity (= decrease in SEF) without a new deficit in the postoperative period. A significant EEG event was defined as a decrease in SEF after carotid cross clamping for at least 5 min. Fisher's exact probability test revealed a close correlation between these EEG events and neurologic outcome. The sensitivity of the test, which was calculated on true positive and false negative events, was 100%, the specificity, based on true negative and false positive events, was 76%. The predictability of the test, based on all EEG events, was 18%; respectively 40% when calculated on significant events.

Alfentanil mask anaesthesia was performed in 63 patients undergoing termination of pregnancy or curettage. Three different types of premedication were used: a) pethidine, promethazine, and atropine; b) diazepam and atropine; c) atropine. The patients were ventilated either with nitrous oxide and oxygen or with halothane and oxygen. Halothane reduced the frequency of muscular rigidity (32%; N2O 75%), postoperative sickness, and vomiting (23%; N2O 50%). On the other hand, patients regained consciousness earlier if nitrous oxide was used. Premedication a) also reduced the frequency of nausea and emesis (21%; other premedications 63%).-Alfentanil intubation anaesthesia was performed in 52 patients undergoing laparoscopy. Premedication and inhalation anaesthetic varied as described above in the group with mask anaesthesia. Muscular rigidity did not occur, and nausea/emesis were rare events (8%). Halothane prolonged the recovery phase of consciousness and respiration. Premedication a) also resulted in respiratory depression.

Risk factors related to increased mortality were determined on the basis of 329 aortocoronary bypass operations. They were: (1) emergency surgery, (2) poor left ventricular function, (3) reoperation, and (4) pulmonary hypertension. Angina pectoris, recent myocardial infarction, age over 65 years, obesity, significant systemic disturbances, smoking, arterial hypertension, and sex were without effect.

A demand-controlled alfentanil bolus technique, which proved to be a safe and easy-to-handle method in 22 neurosurgical operations of mean and longer duration, is described. In the case of these not very painful procedures the use of more complicated time-controlled bolus or infusion techniques does not seem to be necessary.

The general opinion on epidural anesthesia in obstetrics may be adversely affected by recent public controversies about the mother's situation during childbirth in hospital, which nowadays is often considered to be a highly technological, impersonal, or "unnatural" procedure. This assumption led us to conduct an inquiry on maternal assessment of obstetric epidural anesthesia and its relation to the clinical and social history. The study included 113 parturients, who received epidural anesthesia (on-demand epidural injections of bupivacaine 0.25%) for vaginal delivery. Mothers were asked to answer certain questions about this regimen (e.g. analgetic efficacy; difficulties in deciding on this method; recommendations to other parturients; opinion of the role of epidural anesthesia in obstetrics; choice of analgesic regimen for future childbirth) 1 day after delivery and 2 months later. Additional social and historical factors (e.g. education; profession; family status; preceding pregnancy, childbirth or abortion; complications during pregnancy or childbirth; duration of parturition) were used to reveal relevant statistical correlations. Sixty-five percent of the patients considered pain relief by epidural anesthesia as "good" or even "very good" during the first inquiry immediately after childbirth. Women who had undergone prior interruptions of pregnancy were less satisfied, probably because of their rather ambiguous attitude towards motherhood. With regard to the choice of analgesic regimen for future childbirth (50% of the patients had made a definite decision to have epidural anesthesia under this condition), those women were especially reserved who had suffered from complications during pregnancy and disapproved of it in the future.(ABSTRACT TRUNCATED AT 250 WORDS)