Baseline Fluctuations Research Articles

Sources of variation in baseline gene expression levels from toxicogenomics study control animals across multiple laboratories

BackgroundThe use of gene expression profiling in both clinical and laboratory settings would be enhanced by better characterization of variance due to individual, environmental, and technical factors. Meta-analysis of microarray data from untreated or vehicle-treated animals within the control arm of toxicogenomics studies could yield useful information on baseline fluctuations in gene expression, although control animal data has not been available on a scale and in a form best served for data-mining.ResultsA dataset of control animal microarray expression data was assembled by a working group of the Health and Environmental Sciences Institute's Technical Committee on the Application of Genomics in Mechanism Based Risk Assessment in order to provide a public resource for assessments of variability in baseline gene expression. Data from over 500 Affymetrix microarrays from control rat liver and kidney were collected from 16 different institutions. Thirty-five biological and technical factors were obtained for each animal, describing a wide range of study characteristics, and a subset were evaluated in detail for their contribution to total variability using multivariate statistical and graphical techniques.ConclusionThe study factors that emerged as key sources of variability included gender, organ section, strain, and fasting state. These and other study factors were identified as key descriptors that should be included in the minimal information about a toxicogenomics study needed for interpretation of results by an independent source. Genes that are the most and least variable, gender-selective, or altered by fasting were also identified and functionally categorized. Better characterization of gene expression variability in control animals will aid in the design of toxicogenomics studies and in the interpretation of their results.

Comparing ape densities and habitats in northern Congo: surveys of sympatric gorillas and chimpanzees in the Odzala and Ndoki regions

The conservation status of western lowland gorillas and central chimpanzees in western equatorial Africa remains largely speculative because many remote areas have never been surveyed and the impact of emergent diseases in the region has not been well documented. In this study, we compared ape densities and habitats in the Lokoué study area in Odzala National Park and the Goualougo Triangle in Nouabalé-Ndoki National Park in northern Republic of Congo. Both of these sites have long been considered strongholds for the conservation of chimpanzees and gorillas, but supposedly differ in vegetative composition and relative ape abundance. We compared habitats between these sites using conventional ground surveys and classified Landsat-7 ETM+ satellite images. We present density estimates via both standing-crop and marked-nest methods for the first time for sympatric apes of the Congo Basin. The marked-nest method was effective in depicting chimpanzee densities, but underestimated gorilla densities at both sites. Marked-nest surveys also revealed a dramatic decline in the ape population of Lokoué which coincided with a local Ebola epidemic. Normal baseline fluctuations in ape nest encounter rates during the repeated passages of marked-nest surveys were clearly distinguishable from a 80% decline in ape nest encounter rates at Lokoué. Our results showed that ape densities, habitat composition, and population dynamics differed between these populations in northern Congo. We emphasize the importance of intensifying monitoring efforts and further refinement of ape survey methods, as our results indicated that even the largest remaining ape populations in intact and protected forests are susceptible to sudden and dramatic declines.

Seasonal Fluctuations of Bacterial Community Diversity in Agricultural Soil and Experimental Validation by Laboratory Disturbance Experiments

Natural fluctuations in soil microbial communities are poorly documented because of the inherent difficulty to perform a simultaneous analysis of the relative abundances of multiple populations over a long time period. Yet, it is important to understand the magnitudes of community composition variability as a function of natural influences (e.g., temperature, plant growth, or rainfall) because this forms the reference or baseline against which external disturbances (e.g., anthropogenic emissions) can be judged. Second, definition of baseline fluctuations in complex microbial communities may help to understand at which point the systems become unbalanced and cannot return to their original composition. In this paper, we examined the seasonal fluctuations in the bacterial community of an agricultural soil used for regular plant crop production by using terminal restriction fragment length polymorphism profiling (T-RFLP) of the amplified 16S ribosomal ribonucleic acid (rRNA) gene diversity. Cluster and statistical analysis of T-RFLP data showed that soil bacterial communities fluctuated very little during the seasons (similarity indices between 0.835 and 0.997) with insignificant variations in 16S rRNA gene richness and diversity indices. Despite overall insignificant fluctuations, between 8 and 30% of all terminal restriction fragments changed their relative intensity in a significant manner among consecutive time samples. To determine the magnitude of community variations induced by external factors, soil samples were subjected to either inoculation with a pure bacterial culture, addition of the herbicide mecoprop, or addition of nutrients. All treatments resulted in statistically measurable changes of T-RFLP profiles of the communities. Addition of nutrients or bacteria plus mecoprop resulted in bacteria composition, which did not return to the original profile within 14 days. We propose that at less than 70% similarity in T-RFLP, the bacterial communities risk to drift apart to inherently different states.

Mapping correlated membrane pulsations and fluctuations in human cells

The cell membrane and cytoskeleton are dynamic structures that are strongly influenced by the thermo-mechanical background in addition to biologically driven mechanical processes. We used atomic force microscopy (AFM) to measure the local membrane motion of human foreskin fibroblasts (HFFs) which were found to be governed by random and non-random correlated mechanical processes. Interphase cells displayed distinct membrane pulsations in which the membrane was observed to slowly contract upwards followed by a recovery to its initial position. These pulsations occurred one to three times per minute with variable amplitudes (20-100 pN) separated by periods of random baseline fluctuations with amplitudes of <20 pN. Cells were exposed to actin and microtubule (MT) destabilizing drugs and induced into early apoptosis. Mechanical pulsations (20-80 pN) were not prevented by actin or MT depolymerization but were prevented in early apoptotic cells which only displayed small amplitude baseline fluctuations (<20 pN). Correlation analysis revealed that the cell membrane motion is largely random; however several non-random processes, with time constants varying between approximately 2 and 35 s are present. Results were compared to measured cardiomyocyte motion which was well defined and highly correlated. Employing automated positioning of the AFM tip, interphase HFF correlation time constants were also mapped over a 10 microm2 area above the nucleus providing some insights into the spatial variability of membrane correlations. Here, we are able to show that membrane pulsations and fluctuations can be linked to physiological state and cytoskeletal dynamics through distinct sets of correlation time constants in human cells.

Biochemical Measurement of Muscle Injury Created by Lumbar Surgery

1. To determine whether lumbar disc surgery (LS) provides a sufficiently detectable rise in serum creatine kinase (CK) concentration to serve as a model to study biochemical measurement of muscle injury, and 2. To use the model to examine the consistency of the time course of CK concentration changes. The study used a repeated measures design. Six women and six men scheduled for LS were recruited. Blood samples were taken in the pre-operative waiting areas, immediately after surgery, at 6 hour intervals until discharge, and at 2, 4, and 6 to 7 days following surgery. Total serum CK was quantified using the Roche Modular to detect enzyme concentration. Following LS, mean Total CK increased from a baseline 50 U/L (SD = 53) to a peak 114 U/L (SD = 32) in women (P < 0.001) and from 183 U/L (SD = 69) to a peak 454 U/L (SD = 173) in men (P < 0.05). Baseline to peak changes in CK exceeded subjects' own baseline fluctuations in all 6 women and all 6 men, and amounted to a mean 6 fold (SD = 4) increase in women and 16 fold (SD = 31) increase in men. While CK concentrations returned to baseline over the observation period in all subjects, time to peak ranged between 9 to 47 hours. The LS model produced a consistently detectable CK response in both genders. Time to peak is variable indicating a need for multiple serial measures to capture this biochemical injury response.

Automatic detection of microvolt T-wave alternans in Holter recordings: Effect of baseline wandering

ECG deviations from the isoelectric line (baseline wandering) may affect a reliable detection of T-wave alternans (TWA), a phenomenon associated with increased risk of death. The present study was designed to demonstrate, making use of simulated ECG time series, that baseline wandering might cause erroneous TWA detection from TWA-free ECG tracings, or prevent correct TWA detection whenever TWA was present. Our simulated time series were obtained from a real ECG complex (0.75 s recording, sampled at 200 Hz) repeated 170 times. TWA was simulated by varying T-wave amplitude (10, 50, 100 and 500 μV) in a time window of 160 ms centered around the T-wave apex. TWA fundamental frequency was 0.67 Hz. Baseline fluctuations were simulated by sinusoidal waves of 0.1 mV amplitude and frequency of 0.30, 0.67 and 1.50 Hz, respectively. The presence of baseline oscillations at lower (0.30 Hz) and higher (1.50 Hz) frequency than TWA own frequency prevented TWA detection when TWA amplitude was lower or equal to that of baseline oscillations. TWA detection improved after removal of baseline oscillations by application of a third-order spline interpolation, only for frequencies lower than TWA frequency. For baseline oscillations at greater frequency than heart rate, however, spline interpolation became harmful. An improvement over the spline interpolation was obtained by a new heart-rate adapting match filter with a narrow bandwidth around TWA frequency, which allowed detection of TWA almost independently of baseline frequency components when these were different from TWA own frequency.

Temporal features in observed and simulated meteorology and air quality over the Eastern United States

Over the next several years, grid-based photochemical models such as the community multiscale air quality (CMAQ) model, the regional modeling system for aerosols and deposition (REMSAD), the comprehensive air quality model with extensions (CAMx), and other regional models will be used by regulatory agencies in the United States for designing emission control strategies to meet and maintain the National Ambient Air Quality Standards (NAAQS) for O 3, PM 2.5, and regional haze. In this study, temporal scale analysis is applied as a technique to evaluate an annual simulation of meteorology, O 3, and PM 2.5 and its chemical components over the continental US utilizing two modeling systems. The spectral decomposition of total PM 2.5 mass from hourly observations and CMAQ and REMSAD model predictions revealed that days of high PM 2.5 concentrations are generally characterized by positive forcing from fluctuations having periods equal to or greater than a day (i.e., the diurnal, synoptic, and longer-term components) while the magnitude of intra-day fluctuations showed only small differences between average and episodic conditions. Both modeling systems did not capture most of the variability of the high-frequency, intra-day component for all variables for which hourly measurements were available. Furthermore, it is illustrated that correlations were insignificant on the intra-day time scale for all variables, suggesting that these models in the setup used for this study were not skillful in simulating the higher-frequency variations in meteorological variables and the levels of all pollutants. The models exhibited greatest skills at capturing longer-term (seasonal) fluctuations for temperature, wind speed, O 3, sulfate and nitrate. Correlations for total PM 2.5, ammonium, elemental carbon (EC), organic carbon (OC) and crustal PM 2.5 correlations were highest for the synoptic time scale implying problems with factors other than meteorology, such as emissions or lateral chemical boundary conditions, in capturing the baseline fluctuations.

On the Use of Band-Target Entropy Minimization to Simplify the Interpretation of Two-Dimensional Correlation Spectroscopy

Two-dimensional (2D) correlation spectroscopy has been extensively applied to analyze various vibrational spectroscopic data, especially infrared and Raman. However, when it is applied to real-world experimental data, which often contains various imperfections (such as noise interference, baseline fluctuations, and band-shifting) and highly overlapping bands, many artifacts and misleading features in synchronous and asynchronous maps will emerge, and this will lead to difficulties with interpretation. Therefore, an approach that counters many artifacts and therefore leads to simplified interpretation of 2D correlation analysis is certainly useful. In the present contribution, band-target entropy minimization (BTEM) is employed as a spectral pretreatment to handle many of the artifact problems before the application of 2D correlation analysis. BTEM is employed to elucidate the pure component spectra of mixtures and their corresponding concentration profiles. Two alternate forms of analysis result. In the first, the normally vxv problem is converted to an equivalent nvxnv problem, where n represents the number of species present. In the second, the pure component spectra are transformed into simple distributions, and an equivalent and less computationally intensive nv'xnv' problem results (v'<v). In both cases, the separation of spectral contributions greatly simplifies interpretation of the 2D plots. This new approach is successfully applied to a solvent evaporation study where in situ Fourier transform infrared (FT-IR) spectroscopy is used as the analytical tool.

Examination of the oxygenation state of hemoglobin in a phantom and in-vivo tissue applying absorption balancing with two and three laser wavelengths

Two-dimensional absorption measurements of hemoglobin in (i) a phantom, imitating the optical properties of tissue, and (ii) in-vivo breast tissue are reported. The method is based on quasi-simultaneous balanced absorption measurements of hemoglobin and oxygenated hemoglobin at selected wavelengths in order to minimize baseline fluctuations during spatial scanning of the sample. The method allows the detection of 0.8 cm-diameter inclusions of oxygenated hemoglobin differing by about 30% in its oxygenation state from the surrounding hemoglobin if two-wavelengths balancing is applied. However, small wavelength detunings from the optimum wavelength positions cause considerable fluctuations of the signal baseline and deteriorate the detection sensitivity, if there is an inhomogeneous distribution of another weak wavelength dependent absorber in the sample. Although the optical absorption of water is relatively small for the wavelengths applied, a considerable influence of the water on the signal baseline was observed in in-vivo measurements of the hemoglobin status in healthy breast tissue. For better compensation of interfering water absorption, a third laser wavelength was applied in order to balance the water absorption. The prospects of this new optical technique for screening of breast tumors are discussed.

Near-infrared spectroscopy to define cognitive frontal lobe functions

Near-infrared spectroscopy (NIRS) monitors changes in the regional cerebral oxygenation (rSO 2 ) and has been used to study cerebral physiologic functions in normal states and during epileptic seizures. Yet, the limitations and pitfalls of the technique are not fully understood. The authors evaluated NIRS changes over the frontal lobes during language tasks known to be associated with the integrity of the dominant frontal lobe in 17 normal adults (handedness: 14 right, 3 left). Recording protocol involved a baseline (3 minutes) with the subject relaxed and thinking of a blue sky and a second baseline during voluntary mouth movements mimicking speech. Two standardized neuropsychological word-generation tasks (controlled word-association tests: CFL and Animals) were then administered (4 minutes total) followed again by the two baseline procedures. Mouth movement without verbalization increased rSO 2 values in excess of 2 SD of baseline fluctuations in 70% of the subjects. A t-test comparison of these baseline measurements was statistically significant (P < 0.0001). A general linear model repeated-measures procedure was then used to statistically examine NIRS increments during the cognitive tasks above and beyond the contribution produced by mouth movements during the second baseline. Compared to the second baseline, rSO 2 further increased significantly during the word generation tasks (left frontal F value = 21.4, P < 0.0001; right frontal F value = 15.2, P < 0.001), confirming the utility of the technique. There was no apparent difference related to handedness. These findings corroborate the usefulness of NIRS to demonstrate focal cerebral activation during an executive language task. However, interpretation of changes can be confounded by extracerebral factors such as mouth movement, a finding of particular relevance in NIRS clinical applications.

Right-left correlation of the sympathetically induced fluctuations of photoplethysmographic signal in diabetic and non-diabetic subjects

Photoplethysmography (PPG) records the cardiac-induced changes in tissue blood volume by light-transmission measurements. The baseline and amplitude of the PPG signal show very low-frequency (VLF) spontaneous fluctuations, which are mediated by the sympathetic nervous system, and high correlation between right and left extremities of healthy subjects. As sympathetic neuropathy is one of the diabetic complications, the right-left correlation of the PPG fluctuations was examined in diabetic patients. The PPG signal was simultaneously measured in the two index fingers and the two second toes of 35 diabetic patients and 33 non-diabetic subjects. For each PPG pulse, the baseline and amplitude were determined, and the right-left correlation coefficients of the VLF fluctuations in the baseline and amplitude were derived. The VLF fluctuations in the baseline showed high right-left correlation, both for fingers (0.93 +/- 0.05) and toes (0.93 +/- 0.06), for the non-diabetic subjects, and significantly lower correlation (0.78 +/- 0.22 and 0.84 +/- 0.17, respectively) for the diabetic patients. Similar results were obtained for the amplitude VLF fluctuations. The right-left correlation coefficients for diabetic patients decreased with the disease duration for the toe baseline and toe amplitude fluctuations and correlated with heart rate response to deep breathing for the finger baseline and toe amplitude fluctuations. The right-left correlation coefficients of the PPG fluctuations provide a simple and convenient means for assessing the adequacy of the sympathetic nervous system function.

New Reference Galaxy Standards for HiEmission Observations

We have taken advantage of the improved baselines and higher sensitivity available with the upgraded Arecibo 305 m telescope to create a new H I spectral line catalog of disk galaxies that can be used as a reference catalog for anyone interested in 21 cm spectral line work. In all 108 galaxies were observed, covering 24 hr of the sky at declinations between 0° and 36° and velocities between 0 and 25,000 km s-1. The majority of the galaxies were observed at least two times on different nights to avoid problems with radio frequency interference, baseline fluctuations, etc. Comparing our measured values with all those available in the literature shows that although large individual variations may exist, the average difference between the measurements is zero. In all we have considerable confidence in our measurements, and the resulting catalog should be extremely useful as a well-defined reference catalog for anyone interested in 21 cm spectral line work.

Sympathetically induced spontaneous fluctuations of the photoplethysmographic signal.

The photoplethysmographic signal shows very low-frequency (VLF) spontaneous fluctuations that have been shown to be mediated by the sympathetic nervous system. In the current study, the photoplethysmographic signal was simultaneously measured in the two index fingers and the two second toes of 54 healthy male subjects. For each photoplethysmographic pulse, two parameters were derived: the pulse amplitude and its baseline, which are related to the arterial wall compliance and to the arterial blood volume, respectively. The baseline and the amplitude VLF fluctuations showed high right-left correlation both for hands (mean +/- SD 0.94 +/- 0.05 and 0.92 +/- 0.07, respectively) and for feet (0.90 +/- 0.08 and 0.89 +/- 0.07, respectively) that only slightly depended on the subject's age. Lower correlation was found between the hand and the foot (0.73 +/- 0.12 and 0.72 +/- 0.12 for the baseline and the amplitude, respectively). For each hand and foot the baseline and the amplitude VLF fluctuations were also correlated, with the baseline fluctuations lagging the amplitude fluctuations by 3-20 pulses. The amplitude-baseline correlation and the standard deviation of the amplitude or the baseline divided by its mean significantly decreased with age. The VLF fluctuations of the photoplethysmographic parameters and the correlation coefficients between them provide better understanding of the autonomic nervous regulation of the blood circulation.

A universal denoising and peak picking algorithm for LC-MS based on matched filtration in the chromatographic time domain.

A new denoising and peak picking algorithm (MEND, matched filtration with experimental noise determination) for analysis of LC-MS data is described. The algorithm minimizes both random and chemical noise in order to determine MS peaks corresponding to sample components. Noise characteristics in the data set are experimentally determined and used for efficient denoising. MEND is shown to enable low-intensity peaks to be detected, thus providing additional useful information for sample analysis. The process of denoising, performed in the chromatographic time domain, does not distort peak shapes in the m/z domain, allowing accurate determination of MS peak centroids, including low-intensity peaks. MEND has been applied to denoising of LC-MALDI-TOF-MS and LC-ESI-TOF-MS data for tryptic digests of protein mixtures. MEND is shown to suppress chemical and random noise and baseline fluctuations, as well as filter out false peaks originating from the matrix (MALDI) or mobile phase (ESI). In addition, MEND is shown to be effective for protein expression analysis by allowing selection of a large number of differentially expressed ICAT pairs, due to increased signal-to-noise ratio and mass accuracy.

A new general-purpose isothermal microcalorimeter for use at temperatures up to 200 °C

The design and some properties of a new general-purpose isothermal microcalorimeter are reported. The instrument is a twin thermopile heat conduction calorimeter, which is designed for use up to 200 °C. The calorimetric units and surrounding heat sink are suspended inside a hollow aluminium construction, which is thermostated. Above that unit a second thermostated block is positioned and the whole assembly is suspended inside a Dewar vessel. When the instrument is used at room temperature and below, the thermostated units are cooled by use of an insertion Peltier effect cooler. The instrument can be used with a wide range of different reaction vessels (diameter 14 mm). Baseline experiments have been conducted in the temperature range 15–200 °C. Typical values obtained during 10 h periods at 200 °C are ±3 and ±10 nW for the baseline drift and baseline fluctuations, respectively. The heat detection limit, determined by release of electrical energy, is about 2 μJ. Preliminary stability measurements have been conducted at 100 °C on samples of stabilised and non-stabilised polyamide film.

Weakly Modulated Spike Trains: Significance, Precision, and Correction for Sample Size

Many single-unit electrophysiological studies of visual cortex have investigated strong evoked responses to simple stimuli such as oriented gratings. Experiments involving other types of stimuli, such as natural scenes, higher-order features, and surface brightness, produce single-unit responses that are more difficult to interpret. Experiments with brightness, in particular, evoke single-unit responses that are typically weakly modulated. When the brightness is generated by a visual illusion such as the Cornsweet illusion, statistical tests are often necessary to distinguish true responses from baseline fluctuations. Here, using data collected from cat Areas 17 and 18 in response to real and illusory brightness stimuli, we provide a method for detecting and quantifying weak but significant periodic responses. By randomizing spike trains (via bootstrap methods), we provide confidence levels for response significance, permitting the evaluation of both weak and strong responses. We show that because of a strong dependence on total spike number, response significance can only be appropriately determined with randomized spike trains of similar spike number. Such randomizations can be performed for both stimulus-elicited and spontaneously occurring spike trains. By developing a method for generating randomized modulated spike trains (phase-restricted randomization) from actual recordings, we calculate upper and lower confidence limits of modulated spike trains and describe how measurement precision varies as a function of total spike count. Finally, using this randomization method, we describe how a correction function can be determined to correct for measurement bias introduced at low spike counts. These methods may also be useful in the study of small but potentially significant responses in other systems.

Differential microcalorimeter for isothermal measurements of heat effects in two-phase systems and examples of its application

A differential heat-conducting double microcalorimeter intended for heat measurements at 300–700 K is described. Platinum resistance thermometers are applied as the heat-flux sensors. The calorimeter is a low-noise instrument with the baseline fluctuations ranging up to 0.02×10−6 V (5×10−6 W); it allows measurements of the heat effects with an error of 1%–1.5% at a recorded scale of about 1×10−2 J/cm2. The design features and the method of the heat-flux transformation to the electric signals, the calorimetric ampoules for measurements and for calibration and the calibrating device, the heat-balance equation and the equation for the temperature dependence of the calorimetric sensitivity, the results of the calibration and the verification of the calorimeter, and a number of illustrative examples of calorimetric measurements are presented. The calorimeters are applicable for studying solid–gas, solid–liquid, and liquid–gas interactions and thermophysical characteristics of solids and liquids.

Stochastic Effects in Intercellular Calcium Spiking in Hepatocytes

We carry out a Monte Carlo simulation of stochastic effects for two models of intercellular calcium wave propagation in rat hepatocytes. Both models involve gap junction diffusion by a second messenger. We find that, in general, the stochastic effects improve agreement with experiment, for a reasonable choice of model parameters. Both stochastic models exhibit baseline fluctuations and variations in the peak heights of Ca2+. In addition, we find for one model that there is a distribution of latency times, rather than a single latency time, with a distribution width which is comparable to the experimental observation of spike widths. We also find for the other model with low gap junction diffusion that it is possible for cell multiplets to oscillate independently initially, but to subsequently become synchronized.

Improvement in signal reliability when measuring l-glutamate released from cultured cells using multi-channel microfabricated sensors

We used a micromachining technique to fabricate a very reliable amperometric glutamate sensor consisting of dual channel thin layer flow cells for the highly selective measurement of glutamate released from cultured nerve cells. Our microfabricated sensor has two carbon film electrodes separated by a separator in the thin layer channel flow cells. We modified one carbon electrode with a bilayer of Os-gel-HRP/BSA film containing GluOx, and the other with a bilayer of Os-gel-HRP/BSA film without GluOx. Therefore, any difference between the currents at the dual electrodes should be due to the oxidation of glutamate by GluOx. This dual mode measurement technique can eliminate current changes caused by the change in the double layer capacitance when KCl solution is added to stimulate the cells or by baseline fluctuations resulting from pumping noise. As a result, we were able to monitor the transient peak caused by the glutamate release from cultured rat cortex cells with high selectivity by stimulating the cells with 100 mM of KCl solution. The specificity of the GluOx for glutamate was improved when the sensor was pre-treated with 6-diazo-5-oxo- l-norleucine (DON), which is known to be a glutaminase inhibitor. The signal we obtained at the DON-treated sensor when we measured the extracellular solution was lower than that at an untreated sensor. This result shows that the current caused by extracellular glutamine was eliminated by the DON treatment. Moreover, the extracellular glutamate concentration measured with the DON pre-treated sensor was consistent with that obtained by HPLC.

CEA, CA 50 and CA 242 in patients surviving colorectal cancer without recurrent disease

Aims To establish a baseline and intraindividual fluctuations of the tumour markers CEA, CA 50 and CA 242 in patients cured from colorectal cancer, and to test the hypothesis that serum concentrations and intraindividual fluctuations do not differ from the concentrations in cancer-free individuals. Patients and methods Ninety patients with colorectal cancer, who had undergone surgery with curative intent, were still alive at least 5 years after surgery with no signs of recurrent disease. Serum levels of tumour markers CEA, CA 50 and CA 242 before and up to 2 years after surgery were analysed after the prospective study was terminated. Results The pre-operative serum levels of CEA, CA 50 and CEA 242 were elevated in 36%, 16% and 20% of the patients. They were lowered after curative surgery. A small increase of CEA levels was found after the initial post-operative decrease. The intraindividual fluctuations for CA 50 and CA 242 did not exceed 15% but in 24% of the patients the serum levels of CA 50 were high and oscillating. The patients cured from Dukes» C cancer had higher serum concentrations of CEA than patients who had a Dukes» B cancer, which were higher than in patients who had Dukes» A cancer. Concentrations of CA 242 were higher in patients cured from Dukes» A than patients cured from Dukes» B or C cancers. Conclusions During the first 2 years after curative surgery for colorectal cancer the serum levels of CEA did not differ from those levels in normal cancer-free subjects. The serum levels of CEA were related to Dukes» staging whereas the levels of CA 242 were inversely related to Dukes» staging.