Evaluation of artificial time series microarray data for dynamic gene regulatory network inference.

High-throughput technology like microarrays is widely used in the inference of gene regulatory networks (GRNs). We focused on time series data since we are interested in the dynamics of GRNs and the identification of dynamic networks. We evaluated the amount of information that exists in artificial time series microarray data and the ability of an inference process to produce accurate models based on them. We used dynamic artificial gene regulatory networks in order to create artificial microarray data. Key features that characterize microarray data such as the time separation of directly triggered genes, the percentage of directly triggered genes and the triggering function type were altered in order to reveal the limits that are imposed by the nature of microarray data on the inference process. We examined the effect of various factors on the inference performance such as the network size, the presence of noise in microarray data, and the network sparseness. We used a system theory approach and examined the relationship between the pole placement of the inferred system and the inference performance. We examined the relationship between the inference performance in the time domain and the true system parameter identification. Simulation results indicated that time separation and the percentage of directly triggered genes are crucial factors. Also, network sparseness, the triggering function type and noise in input data affect the inference performance. When two factors were simultaneously varied, it was found that variation of one parameter significantly affects the dynamic response of the other. Crucial factors were also examined using a real GRN and acquired results confirmed simulation findings with artificial data. Different initial conditions were also used as an alternative triggering approach. Relevant results confirmed that the number of datasets constitutes the most significant parameter with regard to the inference performance.

MEG evaluation of pico-Tesla external TMS on multiple sclerosis patients.

Magnetoencephalographic (MEG) recordings of 10 multiple sclerosis (MS) patients (2 men, 8 women, mean 41.3±9.5 years, mean disease duration 12.7±7.2 years) were obtained using a whole-head 122 - channel MEG system in a magnetically shielded room of low magnetic noise. Our experimental design was double-blind in order to look for possible effect of external pico - Tesla Transcranial Magnetic Stimulation (pT-TMS). The external pT-TMS was applied on the MS patients with proper field characteristics (magnetic field amplitude: 1-7.5pT, frequency: the alpha-rhythm of the patient 8-13Hz) which were obtained prior to the application of pT-TMS. Each MS patient had two separate recording sessions consisting of 3 runs in between where were given real or sham pT-TMS. It was then tried to predict the real and sham stimulation sessions based on the changes in the mean peak frequency difference (MPFD) observed in the brain of the patients in the 2-7Hz frequency band. After unblinding it was found a significant effect of an increase of frequencies in the range of 2-7Hz across the subjects followed by an improvement and normalization of the MEG.

Biomagnetic activity and non linear analysis in obstetrics and gynecology in a Greek population.

This article reports the application of non-linear analysis to biomagnetic signals recorded from fetal growth restriction, fetal brain activity, ovarian lesions, breast lesions, umbilical arteries, uterine myomas, and uterine arteries in a Greek population. The results were correlated with clinical findings. The biomagnetic measurements and the application of non-linear analysis are promising procedures in Obstetrics and Gynecology.

MEG localization of spike sources in human patients with brain tumors.

The purpose of this study was to use magnetoencephalography (MEG) to identify epileptic zones in patients with brain tumors before undergoing tumor surgery. The MEG data were recorded with a 122-channel biomagnetometer. Equivalent current dipoles (ECD) were calculated for epileptic spikes on MEG recordings according to the single dipole model. Eight patients (five males and three females) within the age range (43-73 years; mean ± SD = 55.12 ± 9.77) were examined by MEG before neurosurgery operation. Four patients had meningioma grade I, three had glioblastoma grade IV and one had astrocytoma grade II. All the patients showed ECD at their MEG's before surgical operation except a female one with meningioma who showed no ECD. Tumors observed in the frontal areas show posteriorly located ECD. We conclude that the MEG is a valuable clinical tool for the localization of epileptic foci in patients with brain tumors before surgical tumor operation.

A study on the age dependency of gustatory states: low-frequency spectral component in the resting-state MEG.

Magnetoencephalography (MEG) recordings were evaluated for 25 healthy female volunteers, in five different gustatory states: normal, sweet, bitter, sour and salty. The study population was divided in two groups according to age: group A (10-19 years old) and group B (20-30 years old). There was a higher count of low frequencies (2 Hz) and a lower count of high frequencies (7 Hz) with increasing age, in all studied states. We compared each state for the frequencies of 2 Hz and 7 Hz between the two groups. Statistically significant differences were found in the normal and sweet states for the frequencies of 2 Hz and 7 Hz and in the salty taste in the frequency of 7 Hz. We also intra-compared the five states in group A and the five states in group B for the 2 Hz and 7 Hz frequencies. The results were not statistically significant. A differentiation in the distribution of the frequencies with increasing age may provide new insights into the age-dependence of taste quality brain centers.

Gastrointestinal bleeding as initial presentation of melanoma of unknown primary origin: report of a case and review of the literature.

The case of an 81-year-old patient, initially presenting with gastrointestinal (GI) bleeding, including melena and hematemesis is reported. Endoscopy revealed an ulcerated mass of the stomach corpus with immunohistochemistry stains consistent with metastatic melanoma. The thorough physical and paraclinical examination did not reveal any lesions or nodules as a primary site of the disease. The literature concerning this rare presentation of melanoma is also reviewed.

Diagnostic value of rapid urease test and urea breath test for Helicobacter pylori detection in patients with Billroth II gastrectomy: a prospective controlled trial.

AIM: The aim of this work was to assess the reliability of rapid urease test (RUT) and urea breath test (UBT) for detecting Helicobacter pylori (H. pylori) in patients with Billroth II (BII) gastrectomy, using histology as reference. METHODS: In this prospective controlled study, 31 consecutive patients with BII gastrectomy and 73 controls who had an indication for endoscopy were included. Their H. pylori status was assessed with biopsies for histology, RUT and UBT. Histology served as the gold standard. Only the biopsies from the gastric fundus were evaluated. Specificity, sensitivity, positive and negative predictive value, degree of agreement and k-statistics were used. RESULTS: RUT and UBT for detecting H. pylori in the control group had excellent agreement [97%, kappa (k)=0.94 and 99%, k=0.97 respectively] with biopsies. In BII patients, RUT from fundic biopsies had very good agreement (87%, k=0.74) compared to histology from fundic biopsies, whereas the UBT was unreliable (agreement: 71%, k=0.41) compared to histology. CONCLUSION: The RUT from fundic biopsies in BII patients is a reliable test for H. pylori detection, whereas the UBT is unreliable.

Meg recordings of patients with CNS disorders before and after external magnetic stimulation.

Magnetoencephalographic (MEG) recordings of patients with CNS disorders were obtained using a whole-head 122-channel magnetometer SQUID and analyzed using Fourier statistical analysis. External transcranial magnetic stimulation in the order of pico Tesla (pTMS) was applied to the above patients with proper characteristics (magnetic intensity 1-7.5 pT; frequency: 8-13 Hz) which were obtained with MEG recordings prior to pTMS. The MEG recordings after the application of pTMS showed a rapid attenuation of the high abnormal activity followed by an increase in the number of the low frequency components toward the patients alpha-rhythm. The possible mechanisms of the effects of external magnetic stimulation on the pineal gland in the brain are presented.

Do we present abstracts on ethical, legal, cost-effectiveness and patient care issues at major gastroenterology congresses?

INTRODUCTION: In the era of the new millennium, a lot of preclinical and clinical research is published. However, ethico-legal, cost-effectiveness and patient care issues are not addressed equally. AIM: To investigate whether abstracts presented at major international gastroenterology congresses refer to issues relevant to doctor-patient relationship, cost-effectiveness and care. METHODS: We reviewed the abstracts on disk CD-ROMs of the United European Gastroenterology Week (UEGW) and the Digestive Disease Week (DDW), for the years 1998-2006. We used the following keywords: ethical/ethically, legal, consent, cost-effective/effectiveness, care, quality and tolerable/tolerability. RESULTS: Over the study period, 1,612/20,018 (8.05%) and 764/45,628 (1.67%) abstracts including the above keywords were presented at UEGW and DDW congresses (p = 0.013), respectively. Statistically significant more abstracts containing separately any of the key words (apart from 'legal') were presented at the UEGW than at the DDW congress. There was a significant trend of increased referring to these key words over the study period for UEGW (p < 0.041) but not for DDW congresses (p = 0.70). CONCLUSION: The abstracts presented at the UEGW refer to ethico-legal, cost-effectiveness and patient care issues more frequently than those presented at the DDW. There is a trend of increased referring to these subjects at the UEGW but not at the DDW.

Nonlinear analysis of brain magnetoencephalographic activity in Alzheimer disease patients.

OBJECTIVES: Non-linear analysis was applied on MEG signals of Alzheimer Disease (AD) patients in order to investigate the underlying complexity of the brain dynamics. MATERIALS AND METHODS: A Single channel SQUID was used to record the MEG signals in 9 AD patients and 5 normal individuals. The magnetic activity, for each patient, was recorded from a total of 64 points of the skull (32 points from each temporal lobe). Nonlinear analysis was applied in the abnormal MEG points of the brain. RESULTS: In AD patients some recorded points were found with high amplitudes and low frequencies in magnetic activity. By applying nonlinear analysis in these records low values in the correlation dimension D of the reconstructed phase space were found. CONCLUSIONS: SQUID obtained MEG signaling from brains of AD patients showed a lower complexity compared to the brain of normal subjects.

MEG evaluation of Parkinson's diseased patients after external magnetic stimulation.

Magnetoencephalographic (MEG) recordings of Parkinson's diseased (PD) patients were obtained using a whole-head 122-channel magnetometer and analyzed with Fourier statistical analysis. External transcranial magnetic stimulation (TMS) in the order of pico Tesla was applied on the above patients with proper field characteristics (magnetic amplitude : 1-7.5 pT, frequency : the alpha-rhythm of the patient: 8-13 Hz) which were obtained prior to TMS. The MEG recordings after the application of TMS showed a rapid attenuation of the high abnormal activity followed by an increase of the low frequency components toward the patients' alpha-rhythm. The patients responded to the TMS with a feeling of relaxation and partial or complete disappearance of tremor, muscular ache and levodopa induced dyskinesias as well as rapid reversed visuospatial impairment, which were followed by a corresponding improvement and normalization of the MEG.

Identification of taste quality with the use of meg.

We investigated the localization of current sources for spontaneous magnetoencephalographic (MEG) data in the frequency domain. MEGs were evaluated in three different states: (i) physiological condition; (ii) sweet taste, and (iii) salt taste. Low frequencies can be seen in the maps obtained with the sweet taste, whereas in the physiological and salt taste, the maps show higher frequencies in the majority of channels. A differentiation in the spatial distribution of the frequencies provides novel insights into the identification of taste quality with the MEG systems.

Low-frequency MEG activity and MRI evaluation in Parkinson's disease.

BACKGROUND: Low - frequency activity has been reported in Parkinson disease (PD). We investigated the magnetoencephalographic (MEG) recordings from PD patients and healthy volunteers in the frequency domain. METHODS: The MEG recordings were carried out in a magnetically shielded room with a whole-head 122-channel gradiometer. Nine patients suffering from PD and 9 age and gender matched healthy subjects were included in the study. MRI with T1-w and T2-w images, was available in patients' records. RESULTS: Frequency analysis may be usefully combined in the analysis of data sets, which contain oscillatory components. Prominent low frequencies can be seen in the spectrum obtained from the PD patients whereas in the control group the frequency range was 6Hz in the majority of channels. MRI did not disclose specific findings in any case. CONCLUSIONS: It is suggested that the MEG could be a complementary method in the diagnostic evaluation of PD using spatial distribution of the raw data in the frequency domain.

Bleeding duodenal ulcer: comparison between Helicobacter pylori positive and Helicobacter pylori negative bleeders.

BACKGROUND AND AIMS: To provide a direct comparison of Helicobacter pylori-positive subjects bleeding from duodenal ulcer with H. pylori-negative ones, in terms of severity of bleeding and outcome. PATIENTS AND METHODS: A case-control study was prospectively conducted in 105 H. pylori-negative duodenal ulcer bleeders and same number of sex- and age-matched H. pylori-positive ones. RESULTS: NSAID consumption was more common among H. pylori-negative subjects (81%) compared to their H. pylori-positive counterparts (58.1%, P < 0.001). H. pylori-negative bleeders were found to need more often haemostasis (55.2% versus 31.4%, P < 0.001) or surgical intervention (15.2% versus 4.8%, P = 0.011) and to have a greater proportion of rebleeding (32.4% versus 13.3%, P = 0.001), a more prolonged hospitalisation (11.6 +/- 4.1 versus 6.2 +/- 1.5 days, P < 0.001) and a higher rate of in-hospital mortality (15.2% versus 3.8%, P = 0.005). In the overall population (N = 210), H. pylori negativity, among other known risk factors, emerged as independent predictor (odds ratio: 3.2; 95% CI: 1.5, 11.2; P = 0.004) of an unfavourable outcome (surgery or death). CONCLUSIONS: Duodenal ulcer bleeding in H. pylori-negative subjects appears to be more severe, to have a higher rate of rebleeding, and to lead more often to surgery or fatality compared to the vast majority of H. pylori-positive duodenal ulcer bleeders.

Magnelic stimulation can modulate seizures in epileptic patients.

OBJECTIVE: The aim of this study is to investigate the influence of external magnetic stimulation (EMS) in epileptic patients using magnetoencephalographic (MEG) measurements and non-linear analytic techniques. METHODS: The examined group consisted of 15 men aged 19-56 years (mean: 39.5 +/- 11.3) and 15 women aged 15-53 years (mean: 36.7 +/- 11.4). For each one the magnetic activity was recorded from 32 points for each temporal lobe. External magnetic stimulation (EMS) with proper field characteristics (intensity: 1-7.5 pT, frequency: the alpha-rhythm of the patient (8-13 Hz)) was applied in the frontal, occipital and temporal lobes for 2 to 6 minutes and the emitted brain magnetic activity was recorded again. In order to investigate if there is any alteration in the MEG complexity underlying the neural dynamics characterizing the pathologic brain before and after the EMS, chaotic analysis approach was applied for the estimation of the dimensional analysis of the existing strange attractors. RESULTS: The application of EMS resulted in rapid attenuation of the MEG activity of epileptic patients. The obtained results of the dimensionality calculation provide a shift from lower to higher dimensional values. Such a shift is an indication that we are dealing with a chaotic system similar with the one characterizing normal subjects. CONCLUSIONS: The increased values of the dimensional complexity and the lower activity of the MEG after the application of EMS strongly supports the beneficial effects of EMS in epileptic patients.

Chaotic analysis approach in neonatal magneto-encephalography.

The aim of this study was to investigate the presence of any non-linearity in the magneto-encephalographic recordings (MEG) in neonates born to pre-eclamptic mothers in comparison with the ones born to mothers having uncomplicated pregnancies, in order to find out differences in the mechanisms underlying their brain waves. Our study population consisted of 40 term neonates who were delivered normally, without any clinical signs of brain damage. Thirty of them had a normal pregnancy and labour with normal Apgar scores, umbilical cord pH, and birth weight, while 10 neonates had suffered a pre-eclamptic pregnancy. The above analysis of the MEG in the neonatal pre-eclamptic brain showed a lower dimension complexity as compared with the normal neonatal brain and a lower first Lyapunov exponent which means lower information processing. The non-linear analysis of the MEG activities in neonates may offer important perspectives to understand significant features of their brain function.

Chaotic and periodic analysis of fetal magnetocardiogram recordings in growth restriction.

OBJECTIVE: We studied how chaotic and periodic heart rate dynamics differ between normal fetuses (n = 19) and intrauterine growth restricted fetuses (n = 11) at 34 to 37 weeks of gestation. We quantified the chaotic dynamics of each heart rate time series obtained by fetal magnetocardiography (FMCG) using correlation dimension. METHODS: The FMCG was recorded digitally by a single-channel biomagnetometer in an electrically shielded room of low magnetic noise. The position of the fetal heart was determined using ultrasonography. RESULTS: The correlation dimension was significantly lower in IUGR than in normal fetuses (p < 0.001, t-test). The periodic dynamics were also obtained by FMCG and measured by power spectrum. The low-frequency components and therefore the periodicity of the low-frequency range were significantly higher in IUGR than in normal fetuses (p < 0.001, t-test). CONCLUSIONS: The analysis of FMCG recordings may offer important perspectives to understand significant features of the heart function of the fetuses. This technique improves the recognition of IUGR fetuses over healthy ones and may help improve perinatal morbidity and mortality.

Pre- and postsurgical biomagnetic activity in malt-type gastric lesions. A case report.

PURPOSE: To evaluate the biomagnetic activity of a low-grade mucosa-associated lymphoid tissue (MALT-) type gastric lymphoma, and to determine if this procedure could be an adjunct to endoscopic ultrasonography (EUS) in the assessment of the disease pre- and postsurgically. MATERIAL AND METHODS: A 47-year-old female with a 2-year clinical history of a low-grade MALT-type gastric lymphoma associated with Helicobacter pylori was examined. The disease showed no histologic remission after eradication of the H. pylori infection and subsequent treatment with chemotherapy and the patient was classified as stage II EA. A decision for surgical resection was made. Biomagnetic waveform recordings were made in the target area before and after surgery and the Fourier analysis of these recordings was performed. RESULTS: The gastric lymphoma biomagnetic waveforms showed high amplitudes (1.8 pT) before and low amplitudes (0.6 pT) after resection. The corresponding Fourier analysis demonstrated that the maximum spectral power of the presurgical measurement was elevated (mean 235 +/- 847 pT2/Hz) compared with that obtained postsurgically (mean 725 +/- 89 pT2/Hz). The difference was of statistical significance ( p < 0.0001, t-test). CONCLUSION: Biomagnetic monitoring of gastric lymphoma, which is an entirely new diagnostic modality, could be a supplement to EUS for assessing remission or persistence of disease with medical treatment during follow up.

Differential diagnosis of prostate lesions with the use of biomagnetic measurements and non-linear analysis.

The purpose of this study was to investigate the biomagnetic activity emitted from the prostate gland and to differentiate cancerous from benign prostate lesions with the use of biomagnetic measurement and non-linear analysis. Magnetic recordings were obtained from 47 patients with palpable prostate lesions. Histology revealed 24 prostate cancer patients and 23 benign prostate hyperplasia (BPH) patients. The superconducting quantum interference device (SQUID) biomagnetometer was used to measure the prostate's magnetic field by placing the SQUID detector 3 mm above the symphysis pubis. The magnetic field recorded in the 2-7 Hz frequency range was of high amplitude in most malignant lesions whereas all benign cases were of low amplitude. According to our results, the sensitivity, specificity, positive predictive value and negative predictive value were 83.33%, 100%, 100% and 85.18%, respectively. By applying the Grassberger-Procaccia algorithm to the magnetoprostatogram time series in malignant and benign prostate lesions we found clear saturation in malignant prostate lesions with m>7 whereas in the benign lesions there was not clear saturation. Prostate cancer emits higher biomagnetic activity than the BPH. This confirms a higher angiogenic activity in prostate cancer than the BPH lesions. Furthermore, the saturation value in the estimation of the correlation dimension of the attractor for the cancer lesions confirms the lower complexity of the system in comparison to the BPH, which is characterized by higher complexity.

Acute upper gastrointestinal bleeding: comparison between recent users and nonusers of nonsteroidal anti-inflammatory drugs.

BACKGROUND AND STUDY AIMS: To determine clinical, endoscopic, and outcome differences between recent users and nonusers of nonsteroidal anti-inflammatory drugs (NSAIDs) presenting with upper gastrointestinal bleeding (UGIB). PATIENTS AND METHODS: A total of 330 consecutive patients who presented with clinical manifestations of UGIB underwent urgent endoscopy after clinical assessment within 12 h of admission. The patients were divided into two groups, depending on whether there was a positive or negative history of recent NSAID use. Urgent endoscopy followed by endoscopic hemostasis and/or biopsy, as needed, was performed by the same endoscopist, who was blinded to the patients' clinical status. RESULTS: The baseline characteristics, clinically estimated severity of UGIB, and outcome did not differ between the two groups. Recent NSAID users were found to bleed from an ulcer more frequently (P=0.009) than nonusers of NSAIDs, the latter more often having a history of peptic ulcer or UGIB (P=0.02). Bleeding ulcers were mostly duodenal in the NSAID group and gastric in the non-NSAID group (P<0.001). Helicobacter pylori infection was significantly more common among NSAID users (P<0.01). The group of NSAID users included a significantly greater proportion of alcohol abusers (P=0.01), who were found to bleed mostly from erosive gastritis. CONCLUSIONS: Recent NSAID users were found to bleed from ulcers, mostly duodenal, and to have H. pylori infection more frequently than UGI bleeders with a negative history of NSAID consumption. Alcohol abuse was also more common among NSAID users. The severity of bleeding and the outcome did not differ between the two groups.