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Plasma propofol concentrations during orthotopic liver transplantation.

OBJECTIVE: The aim of this study was to investigate the changes in plasma concentrations of propofol in three phases (the paleohepatic, anhepatic, and neohepatic phases) during orthotopic liver transplantation (OLT) using target-controlled infusion (TCI). METHODS: Ten patients undergoing OLT without venovenous bypass were studied (age 29-53 years, weight 56-79 kg). After intubation, a non-hypnotic target concentration of propofol 0.5 microg ml(-1) using a Diprifusor pump (Zeneca Pharmaceuticals, Macclesfield, UK) was administered as a supplement anesthesia throughout the procedure. Plasma samples were obtained in each phase for propofol assay, respectively. Performance parameters for the Diprifusor system in each phase, the percentage median performance error (MDPE), the percentage median absolute performance error (MDAPE), and the percentage median absolute constancy error (MDACE) were evaluated. RESULTS: In all patients, measured plasma propofol concentrations were several times higher than Diprifusor values in each phase during the procedure. In nine patients, propofol concentrations in the anhepatic phase were higher than those in the paleohepatic or neohepatic phase (P < 0.05). There were no significant differences between the paleohepatic and neohepatic phases. Interindividual variation of the plasma propofol concentrations was significant (P < 0.05). Percentage median performance error of Diprifusor in each phase, as well as MDAPE, was large (>300%) and was significantly higher in the anhepatic phase (P < 0.01), whereas MDACE was relatively small and there was no significant difference between phases. CONCLUSIONS: Models used by Diprifusor are not suitable for liver transplantation patients. A further study should be performed in order to determine all pharmacokinetic parameters of propofol in these patients.

Adult↗

Evidence for functionally distinct pili expressed by Neisseria meningitidis.

In order to investigate possible functional consequences of phase and antigenic variation of meningococci, the attachment of 15 strains of Neisseria meningitidis to human erythrocytes was studied by a nitrocellulose hemadsorption assay. This assay allows the study of individual meningococcal colonies with respect to erythrocyte attachment. Of the 15 strains studied, 7 demonstrated binding of human erythrocytes (HA+). Among these seven strains, the percentage of colonies that were HA+ ranged from 0.2 to 97%. Meningococcal colonies that did not produce pilin (the major structural subunit of pili) did not demonstrate erythrocyte binding (HA-). The HA+ colony phenotype was correlated with assembly of pilin into pili and expression of pili on the meningococcal surface. However, only some piliated colonies bound human erythrocytes. This could not be explained by differences between piliated HA+ and HA- colonies in the amount of pilin produced or by differences in number of pili expressed per diplococcus. Pili of five of the meningococcal strains with HA+ colonies were antigenically related to gonococcal pili (class I meningococcal pili), but HA+ colonies were also seen in two meningococcal strains expressing class II meningococcal pili. Changes from HA+ to HA- and from HA- to HA+, in the presence of continuing pilin production and pilus assembly, occurred at frequencies of up to 10(-2)/CFU per generation. Such frequencies resemble those of phase and antigenic variation described previously for Neisseria species pilin. These studies indicate that phase variation influences the ability of meningococci to attach to human cells and suggest that meningococci may express functionally different pili.

Antigens, Bacterial↗

Rapid sensitivity changes on flickering backgrounds: tests of models of light adaptation.

To investigate mechanisms underlying sensitivity changes that are capable of following rapid variations in intensity of the background field, we measured the threshold radiance needed to detect a 2-ms probe flash presented at various phases relative to a sinusoidally flickering background. The temporal frequency, mean luminance, and modulation of the background were systematically varied. The sensitivity change consisted of two components: a phase-insensitive increase in threshold that occurs at all the phases of the background field (a change in the dc level of the threshold), and a phase-dependent variation in threshold. Both components can reliably be measured at temporal frequencies up to approximately 50 Hz. On a 30-Hz background, the threshold varied with phase over roughly 0.5 log unit within a half-cycle (17 ms). For background flicker rates of 20-40 Hz the probe threshold increased with increasing instantaneous background radiance, following a typical threshold-versus-radiance template, and approaching Weber-law behavior during the peak of the background flicker. This pattern of threshold elevation was measured at mean background illuminances from 580 to 9100 Td (trolands), with the dimmer backgrounds being slightly less effective in producing threshold elevations. The measured increase in the dc level commenced as soon as the modulation of the background flicker began, and the amount of threshold elevation followed the envelope of the background flicker, ruling out modulation gain control explanations for the change in sensitivity on flickering backgrounds. The threshold elevations measured on a 30-Hz, 25% modulation background were lower than those measured on a 30-Hz, 100% modulation background at all phases. The measured changes in threshold with changes in background modulation rule out all adaptation models consisting of a multiplicative and a subtractive adaptation processes followed by a single, late, static nonlinearity.

Adaptation, Ocular↗

Microbial spheres: a novel cyanobacterial-diatom symbiosis.

Cyanobacteria, algae and bacteria are widespread inhabitants of North Sea microbial mats. Our studies of these populations showed uncommon modes of living and extraordinary structures, which have not been described before. The structures are spherical objects covering a community of cyanobacteria, diatoms and bacteria. The cultivation of these communities in the laboratory and intensive observations of their exceptional movement has led to some spectacular findings. The sphere formations go through different phases with variation in the dominance of different microorganisms. The role of the bacteria is the most important in the first phase, and can be increased by the addition of signal substances. Spheres surrounded by envelopes of unknown composition and permeability appear, with numerous bacteria and sporadic diatoms inside. Then the cyanobacteria penetrate the spheres and arrange themselves at the surface. The communities proliferate over some weeks and are finally released. Laboratory expositions of the microbial communities to different parameters pinpoint the limits of sphere formation. The metabolic products of the sphere communities are concentrated in the spheres and lead to a different kind of compound compared with the surrounding environment. In this way, the microbial communities strongly influence the structure of the sediments. Uncommon circular structures, which develop into spheres between 0.08 and 3 mm in size were found in subcultures of non-axenic filamentous cyanobacteria enrichments from North Sea microbial mats. These filamentous cyanobacteria ( Phormidium sp.) together with associated benthic diatoms of the genus Navicula and associated heterotrophic bacteria were held as reproducible synergistic cultures. Phormidium sp. filaments tightly intertwined with each other, formed the surface of the spheres, trapping diatoms inside. The formation of "spheres" was the result of radial and synchronous movements of the cyanobacteria. In old cultures, the direction of the cyanobacterial movement has turned in the opposite direction, away from the sphere. The integrity of large "spheres" was influenced by chemotactic phenomena and maintained by some type of trichome-trichome interaction. This suggests the presence of metabolic secondary products, which attract cyanobacteria and influence their movement in a form of chemotactic response.

Cyanobacteria↗

Bone vibrator placement and the cancellation technique.

An issue in the measurement of bone conduction sensitivity is the placement of the bone vibrator. The effect of bone vibrator position on the amplitude and phase of the received signal was investigated using a cancellation technique. This technique involves cancelling the signal delivered by the bone vibrator with a signal delivered acoustically via an earphone. At cancellation, the acoustic signal is equal in amplitude but opposite in phase to the bone-conducted signal. Results showed that the amplitude of the received signal did not vary significantly with bone vibrator position close to the center of the forehead whereas the phase of the received signal was critically dependent on bone vibrator position. Substantial intersubject differences were observed in the variation of phase with bone vibrator position. The precision of measurement using the cancellation technique was found to be high.

Acoustics↗

[Evaluation of the postoperative "state of health" using the example of the body core temperature rhythms of sheep].

A postoperative (p.op.) estimation of "healthiness"--especially an estimation of duration of possible existing changes, caused by surgical treatment--is important not only for the ongoing of the healing up process. A re-activation of treated farm or laboratory animals which is set up too early might produce reduction of efficiency or falsification of experimental results. Investigations on p.op. de-synchronisation have proved that "healthiness" means--besides the absence of clinical symptoms--also stable relations among the circadian rhythms. As the ultradian rhythms (wavelength less than 24 h) which exist beside the circadian ones depend on endogenic and exogenic factors much more than the circadian rhythms do, the aim of this study was to investigate strength and especially duration of changes p.op. in using core temperature rhythms of sheep as example, by setting great value on investigating ultradian rhythms. The core temperatures of 5 Merino-mixed sheep were permanently measured for 4 weeks p.op. by special radiotelemetric equipment, under controlled circumstances. All recorded data have been expertised "macroscopically" and Fourier-analysis was employed for judging phase shift and intensity of existing rhythms. Though no signs for systemic disturbances could be found and the recorded temperature always was in between the physiological range, important shifts of phases and variations in intensities in the ultradian scope as well as in the circadian one occurred. The "normal" or final phase relations and the constant daily pattern of intensities in sheep were reached 16 days p.op. earliest.

Animals↗

[Daily variations in S-adenosylmethionine content and oxyindole-O-methyltransferase activity in rat epiphysis].

Rat epiphysis was found to contain a relatively high amount of S-adenosylmethionine (SAM), which undergoes daily variations with a maximum in the middle of the daytime period and a minimum at the night-time phase. The variations are of endogenous type and are persistent in blinded animals. On the contrast, upon continuous illumination the SAM level in rat epiphysis is decreased and impaired. The activity of oxyindole-O-methyltransferase, the terminal enzyme of epiphysial melatonin biosynthesis which consumes methyl groups of SAM, is not subjected to daily variations. It is demonstrated that the artefact of the previously observed daily variations in the oxyindole-O-methyltransferase activity is due to day-to-night changes in SAM content.

Acetylserotonin O-Methyltransferase↗

Phase relationships between segmentally organized oscillators in the leech heartbeat pattern generating network.

Motor pattern generating networks that produce segmentally distributed motor outflow are often portrayed as a series of coupled segmental oscillators that produce a regular progression (constant phase differences) in their rhythmic activity. The leech heartbeat central pattern generator is paced by a core timing network, which consists of two coupled segmental oscillators in segmental ganglia 3 and 4. The segmental oscillators comprise paired mutually inhibitory oscillator interneurons and the processes of intersegmental coordinating interneurons. As a first step in understanding the coordination of segmental motor outflow by this pattern generator, we describe the functional synaptic interactions, and activity and phase relationships of the heart interneurons of the timing network, in isolated nerve cord preparations. In the timing network, most (approximately 75%) of the coordinating interneuron action potentials were generated at a primary spike initiation site located in ganglion 4 (G4). A secondary spike initiation site in ganglion 3 (G3) became active in the absence of activity at the primary site. Generally, the secondary site was characterized by a reluctance to burst and a lower spike frequency, when compared with the primary site. Oscillator interneurons in G3 inhibited spike activity at both initiation sites, whereas oscillator interneurons in G4 inhibited spike activity only at the primary initiation site. This asymmetry in the control of spike activity in the coordinating interneurons may account for the observation that the phase of the coordinating interneurons is more tightly linked to the G3 than G4 oscillator interneurons. The cycle period of the timing network and the phase difference between the ipsilateral G3 and G4 oscillator interneurons were regular within individual preparations, but varied among preparations. This variation in phase differences observed across preparations implies that modulated intrinsic membrane and synaptic properties, rather than the pattern of synaptic connections, are instrumental in determining phase within the timing network.

Action Potentials↗

Early stages of LDL oxidation: apolipoprotein B structural changes monitored by infrared spectroscopy.

Changes in the conformation of apoliprotein B-100 in the early stages of copper-mediated low density lipoprotein oxidation have been monitored by infrared spectroscopy. During the lag phase no variation in structure is observed, indicating that copper binding to the protein does not significantly affect its structure. In the propagation phase, while hydroperoxides are formed but the protein is not modified, no changes in secondary structure are observed, but the thermal profile of the band corresponding to alpha-helix is displaced in frequency, indicating changes in tertiary structure associated with this conformation but not with beta-sheet components. When aldehyde formation starts, a decrease of approximately 3% in the area of bands corresponding to alpha-helix and beta-sheet is produced, concomitantly with an increase in beta-turns and unordered structure. The two bands corresponding to beta-turns vary as well under these conditions, indicating changes in these structures. Also at this stage the thermal profile shows variations in frequency for the bands corresponding to both alpha-helix and beta-sheet. The results are consistent with the hypothesis that as soon as the polyunsaturated fatty acids from the particle core are modified, this change is reflected at the surface, in the alpha-helical components contacting the monolayer.

Apolipoproteins B↗

The role of direct oligonucleotide repeats in gonococcal pilin gene variation.

Previous studies indicate that gonococcal pilin phase and antigenic variation occur by intragenomic pilin gene recombination, the outcome of which resembles that of gene conversion. During such transitions, the expressed complete pilin gene (pilE) acquires a novel sequence corresponding to that of a silent pilin gene (pilS). In the present study, we find that internal deletions of pilE can produce pilus-/pilus+ phase transitions: direct oligonucleotide repeats in the pilin-encoding portion of pilE bracket the deleted segments. A novel, orthodox pilE is formed upon repair of the internal deletions, with pilS sequence probably acting as a template for repair. Such deletion/repair of pilE is suggested as a principal mechanism underlying gonococcal pilus variation.

Bacterial Outer Membrane Proteins↗

NMR spectral quantitation by principal-component analysis. II. Determination of frequency and phase shifts.

This paper extends the use of principal-component analysis in spectral quantification to the estimation of frequency and phase shifts in a single resonant peak across a series of spectra. The estimated parameters can be used to correct the spectra accordingly, resulting in more accurate peak-area estimation. Further, the removal of the variations in phase and frequency cause by instrumental and experimental fluctuations makes it possible to determine more accurately the remaining variations, which bear biological significance. The procedure is demonstrated on simulated data, a 3D chemical-shift-imaging dataset acquired from a cylinder of inorganic phosphate (Pi), and a set of 736 31P NMR in vivo spectra taken from a kinetic study of rate muscle energetics. In all cases, the procedure rapidly and automatically identifies the frequency and phase shifts present in the individual spectra. In the kinetic study, the procedure is used twice, first to adjust the phase and frequency of a reference peak (phosphocreatine) and then to determine the individual frequencies of the Pi peak in each of the spectra which further can be used for estimation of pH changes during the experiment.

Computer Simulation↗

Variation in Cobb angle measurements in scoliosis.

In order to determine the reliability of the Cobb angle measurement as it is used in the clinical management of scoliosis, a methodological survey was carried out. In the measurement of a Cobb angle two phases can be distinguished: (a) the production of a spinal radiograph and (b) the measurement of the angle itself. In respect of the first phase, the variation in production of the radiographs was calculated on Cobb angle measurements made by one investigator on serial radiographs of patients who underwent spinal fusion for scoliosis and therefore had a fixed spinal curvature. For the second phase, the accuracy of Cobb angle measurement was investigated by comparing measurements on the same radiographs of 46 scoliosis patients obtained by three investigators, namely two orthopaedic surgeons and an orthopaedic fellow who was assigned to a school screening project. Results were expressed as a Spearman correlation coefficient and a standard deviation of the differences. The Spearman correlation coefficient was 0.98 for the repeated radiographs (production variation) and also 0.98 for the repeated measurements on one radiograph (interobserver measurement variation). The standard deviation of the differences in Cobb angle for the repeated radiographs amounted to 3.2 degrees and for the repeated measurements on one radiograph it was 2.0 degrees. Although there is a good reproducibility of the Cobb angle measurement between different investigators, the variation in production of a spinal radiograph is an important source of error. This should be taken into account when making decisions in scoliosis management.

Humans↗

[Variations of beta-cell early-phase insulin secretion in type 2 diabetic patients in different stages].

OBJECTIVE: To explore the variations of early-phase insulin secretion in Type 2 diabetic patients in different stages. METHODS: L-arginine stimulative test, fast blood glucose and body mass index (BMI) were evaluated in 40 nomal controls (NC) and 101 Type 2 diabetic patients. The diabetic patients were divided into three groups: newly diagnosed group (n = 35), effectively treated by sulfonylureas group (n = 32) , and secondary failure of sulfonylureas group (n = 34). The indexs of insulin resistance of homeostasis model assessment (HOMA-IR), beta-cell insulin secretion of homeostasis model assessment (HOMA-IS), and the acute insulin response (AIRARG) index were calculated. Some statistical comparisons were done among the 4 groups. RESULTS: The indexs of HOMA-IR in each group of Type 2 diabetic patients were all higher than those in NC group (P < 0.01). The AIRARG indexs were obviously lower in Type 2 diabetic patients in different stages than those in NC group (P < 0.01), and the subsequence from the highest to the lowest among the groups of diabetic patients was: the newly diagnosed group, the effectively treated by sulfonylureas group, and the secondary failure of sulfonylureas group (P < 0.01). But there was no significant difference in indexs of HOMA-IS between the newly diagnosed group and the effectively treated by sulfonylureas group. CONCLUSION: There is severe insulin resistance in Type 2 diabetic patients in each stage. The variations of early-phase insulin secretion manifest a vary procedure of obvious deterioration by degrees from the newly diagnosed group to the secondary failure of sulfonylureas group in Type 2 diabetic patients.

Adult↗

CA-125 and placental protein 14 concentrations in plasma and peritoneal fluid of women with deeply infiltrating pelvic endometriosis.

OBJECTIVE: To investigate the plasma and peritoneal fluid (PF) concentrations of CA-125 and placental protein (PP14) in women with deeply infiltrating endometriosis. DESIGN: Plasma and PF were collected during 384 consecutive laparoscopies for pelvic pain or infertility. MAIN OUTCOME MEASURE: The presence and extent of endometriosis were carefully assessed, including the area, depth of infiltration, and volume of subtle lesions, typical lesions, and endometriomas. The day of the menstrual cycle was ascertained by endometrial biopsy and/or basal body temperature charts. RESULTS: Peritoneal fluid concentrations were some 100 and 10 times higher than plasma concentrations for CA-125 and PP14, respectively. Cyclic variations of CA-125 concentrations were only found in women with endometriosis showing increased plasma concentrations at the end of the cycle and increased PF concentrations in the early follicular phase. Cyclic variations of PP14 concentrations were found in women with and without endometriosis both in plasma and PF showing increased concentrations in the late luteal and early follicular phases. In women with endometriosis the increased plasma concentrations of PP14 and CA-125 correlated with the presence and volume of endometriomas and of deeply infiltrating endometriosis. The increased concentrations in PF correlated only with the pelvic area of subtle endometriotic lesions. The diagnostic sensitivity and specificity of CA-125 for endometriosis were 25% and 87%, respectively, and for endometriomas and/or deeply infiltrating endometriosis 36% and 87%, respectively, for a cutoff concentration of 25 U/mL. CONCLUSION: Superficial pelvic endometriosis secretes PP14 and CA-125 mainly toward the PF, whereas endometriomas and deeply infiltrating endometriosis secrete mainly toward the plasma. The increased plasma concentrations of CA-125 are most pronounced during the late luteal phase, and endometriomas and/or deeply infiltrating endometriosis can be detected with a sensitivity of 36% and a specificity of 87%.

Analysis of Variance↗

Model studies on the influence of nonstationary flow on the mean flow estimate with the indicator-dilution technique.

The applicability of the indicator-dilution technique for the estimate of the mean flow under circumstances of nonstationary flow is investigated by model studies. The studies comprise experiments using a hydrodynamical model as well as calculations with a compartmental approach. The main conclusions are: (1) The influence of nonstationary flow on the mean flow estimate with the indicator-dilution technique can be described accurately by a mathematical model based on a mixing-chamber approach. (2) The relative error in the mean flow estimate by a single measurement is dependent on the system parameters (number and time constant of mixing chambers) and the flow parameters (relative amplitude and relative frequency of flow variation and the phase with respect to the variation at the moment of injection). (3) Errors due to cyclic nonstationarities of the flow can be reduced strongly by averaging over two measurements with injection at two points of time with phases pi radians apart.

Cardiac Output↗

Role of non-histones in chromosome structure. Cell cycle variations in protein synthesis.

As part of a study of the role of non-histone proteins in chromosome structure, the synthesis of non-histones associated with interphase chromatin was investigated. Synchronized suspension cultures of HeLa cells were pulse-labeled with [35S]methionine, and chromatin was prepared by mild micrococcal nuclease digestion. Two-dimensional polyacrylamide gel electrophoresis, in addition to one-dimensional electrophoresis, was used to resolve the patterns of incorporation of radioactive label. Significant variations in non-histone synthesis were seen during the cell cycle. A strong correlation was not found between DNA synthesis in mid-S phase and variations in non-histone synthesis. The non-histone proteins of purified metaphase chromosomes were also characterized by two-dimensional gel electrophoresis and compared to the proteins of interphase chromatin. The pattern of non-histones is not identical with that of interphase chromatin, although a number of major species may be shared by interphase chromatin and metaphase chromosomes. The HeLa nuclear scaffold, the framework that maintains the overall morphology of the interphase nucleus, shows relatively few proteins on two-dimensional gels. The synthesis of nuclear scaffold proteins was quantitated by excising each of 19 proteins from two-dimensional gels and determining the incorporated radioactivity by scintillation counting. Substantial variations in protein synthesis were found, with several species showing changes of about 2-fold in the percentage of incorporation.

Cell Cycle↗

Variations of neurohypophysial function in normally cycling women.

Using a neurophysin radioimmunoassay, we have studied basal neurohypophysial function in seven normal women. An increase in neurophysin blood levels has been demonstrated during the ovulatory and/or luteal phase as compared to the follicular phase; these variations are related to the changes in the circulating levels of 17beta-estradiol. The data provide additional evidence for a relationship between estrogens and neurohyprophysial function, as previously shown following exogenous administration of estriol and ethinyl estradiol in man.

Adult↗

[Two phases of the contingent negative variation in humans: connection with motor and mental functions].

The question of dependence of the contingent negative variation (CNV) on the regulating mechanisms of motor and mental functions is not sufficiently studied. The tasks of the present work were: to investigate the dependence of the CNV early and late phases on the state of motor and mental functions in patients with Parkinson's disease (PD), and to elucidate the levodopa influence on the CNV parameters. 18 healthy subjects and 56 patients with PD were studied. In PD patients, significant reductions of amplitudes and squares of two CNV phases were observed. A negative correlation of the degree of coordinating muscle relationships disturbance with amplitudes of two CNV phases was found (p < 0.01). A positive interdependence between values of the both CNV phases and the state of mental functions was established, memory in particular (p < 0.05). After levodopa administration in PD patients, the early CNV phase did not significantly change, whereas the late CNV phase significantly increased (p < 0.05). Results of the investigation suggest an important role of the structures ensuring both direct motor control and mental functions in two CNV phases formation. A more obvious levodopa influence on the late CNV phase suggest participation of the basal ganglia efferent system in generation of the late CNV phase rather than in organization of the early CNV phase.

Aged↗