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PubMed2004

An evaluation of new criteria for CpG islands in the human genome as gene markers.

MOTIVATION: Recently, more stringent criteria for CpG islands have been introduced to exclude Alu repeats, thereby enabling a higher proportion of CpG islands associating with genes to be identified. Using these new criteria, several types of associations between CpG islands and genes were investigated to further establish the importance of CpG islands as gene markers. RESULTS: The CpG islands were searched by CpGIE, a java software program developed for CpG island identification. CpGIE was advanced in identification accuracy compared with other tools. According to our results, about 70% of the identified CpG islands were associating with the human genes and over half of them are in the promoters. Furthermore, the investigation of genes in the confirmed gene model showed that 56% of them had a CpG island overlapping the transcription start sites. In comparison, the new criteria were found capable of filtering a large fraction of Alu repeats that was identified as CpG islands by the generally accepted criteria within the genes, but very few CpG islands associating with the promoters were affected. The genes in the predicted gene model were not obviously associated with CpG islands, suggesting that CpG islands can be used to evaluate the accuracy of gene annotation. AVAILABILITY: http://bioinfo.hku.hk/cpgieintro

Algorithms↗

PubMed1989

Computerized quantitative analysis of coomassie-blue-stained serum proteins separated by two-dimensional electrophoresis.

Two-dimensional electrophoresis in combination with Coomassie Blue staining was refined for use as a quantitative method. Microcomputer software was developed for use with the IBM AT and compatible computers for analyzing the gels. To test the refined method to determine its usefulness in simultaneous measurements of 28 human serum proteins, we measured each protein relative to a single standard (bovine serum albumin) polymerized at different concentrations in a calibration scale, rather than using 28 individual standards. All samples were analyzed in triplicate. We evaluated calibration, linearity of response, recoveries, units, within-run CV, and between-run CV. The five isoforms of apolipoprotein A-I were analyzed in samples from 16 healthy donors and the isoform ratios determined. The method as presented here should prove useful for diagnosis of non-urgent disease states and for analysis for protein isoforms in relation to disease; it should also be applicable to assays of proteins in other fluids and tissues.

Analysis of Variance↗

PubMed2005

Registration of MR and CT images of the liver: comparison of voxel similarity and surface based registration algorithms.

The purpose of this work was to determine the feasibility and efficacy of retrospective registration of MR and CT images of the liver. The open-source ITK Insight Software package developed by the National Library of Medicine (USA) contains a multi-resolution, voxel-similarity-based registration algorithm which we selected as our baseline registration method. For comparison we implemented a multi-scale surface fitting technique based on the head-and-hat algorithm. Registration accuracy was assessed using the mean displacement of automatically selected point landmarks. The ITK voxel-similarity-based registration algorithm performed better than the surface-based approach with mean misregistration in the range of 7.7-8.4 mm for CT-CT registration, 8.2 mm for MR-MR registration, and 14.0-18.9 mm for MR-CT registration compared to mean misregistration from the surface-based technique in the range of 9.6-11.1 mm for CT-CT registration, 9.2-12.4 mm for MR-MR registration, and 15.2-19.0 mm for MR-CT registration.

Algorithms↗

PubMed2004

Large field-of-view real-time MRI with a 32-channel system.

The emergence of parallel MRI techniques and new applications for real-time interactive MRI underscores the need to evaluate performance gained by increasing the capability of MRI phased-array systems beyond the standard four to eight high-bandwidth channels. Therefore, to explore the advantages of highly parallel MRI a 32-channel 1.5 T MRI system and 32-element torso phased arrays were designed and constructed for real-time interactive MRI. The system was assembled from multiple synchronized scanner-receiver subsystems. Software was developed to coordinate across subsystems the real-time acquisition, reconstruction, and display of 32-channel images. Real-time, large field-of-view (FOV) body-survey imaging was performed using interleaved echo-planar and single-shot fast-spin-echo pulse sequences. A new method is demonstrated for augmenting parallel image acquisition by independently offsetting the frequency of different array elements (FASSET) to variably shift their FOV. When combined with conventional parallel imaging techniques, image acceleration factors of up to 4 were investigated. The use of a large number of coils allowed the FOV to be doubled in two dimensions during rapid imaging, with no degradation of imaging time or spatial resolution. The system provides a platform for evaluating the applications of many-channel real-time MRI, and for understanding the factors that optimize the choice of array size.

Abdomen↗

PubMed2003

[Design of an impedance plethysmograph for reactive hyperemia evaluation in the forearm].

Impedance pletismography is based on the evaluation of the voltage change that occur as a consequence of blood flow variations in a particular tissue section. Current applied for the procedure should be alternating, weak and of high frequency to avoid electrically excitable cells stimulation, such as muscles and nerves. Blood volume changes can be measured by this method and has been applied in the diagnosis of deep venous thrombosis of limbs. An impedance meter was designed and built to be used in the forearm of patients. It consists of a voltage stabilizer TPS 76150 with simultaneous ECG recording (DII lead). Injected signal had 50 KHz (Wien's bridge) and registered through two operational amplifiers LM 3080 (1 mA). Signal was demodulated and amplified. Electrodes used were made of silver strips with conductance improved by conductivity gel, fixed by elastic rubber strips. Circuit wiring and equisition software was developed at the Bioengineering Department of Simón Bolívar University. Fifteen healthy subjects, age range 18-30 years old, were submitted to noninvasive forearm blood flow evaluation with the already described electronic device. Brachial artery occlusions were made with a cuff at subdiastolic, supradiastolic and suprasystolic blood pressures, for 60 and 90 seconds and then this occlusion was abruptly released. The curve was displayed and recorded in a portable PC (laptop). During suprasystolic occlusion the impedance observed curve showed a progressive increased until stabilization. When occlusion was released a sudden peak appeared which corresponds to reactive hyperemia of the forearm. This peak has been associated to the secretion of endothelial vasodilatory substances. In conclusion, this device is suitable to be used in clinical settings for the evaluation of reactive hyperemia and potentially useful in diagnosis of deep veins occlusions.

Adult↗

PubMed2004

Computer-navigated ACL reconstruction with the OrthoPilot.

Within the minimally invasive-operation techniques, small approaches are desirable in many fields of the surgery to reduce soft-tissue trauma; however, the risk exists that the surgeon will lose the general view of the topographic structures. The remedy lies in computer navigation with the OrthoPilot. This navigation system has already been used successfully for knee endoprosthesis. A special software was developed for use of the navigation-system, OrthoPilot, for ACL reconstruction. This system is capable of determining the exact optimum position of tunnel replacement by computer navigation. This determination is made by a high-precisive infra-red camera and rigid bodies fixed onto the patient. The experience gained in performing 150 ACL reconstructions to date demonstrates the ease of handling, reduction in extra operation time to a minimum of 10-15 minutes, and only minimal trauma by fixing the rigid bodies. In all cases, an optimum position was documented for the tunnel replacement. Furthermore, no expensive pre-operation x-rays (CT scan, nuclear spin) are needed. Use of the computer-assisted navigation system demonstrated that femoral and tibial tunnel replacement can be positioned precisely. Thus, a false position of the tunnel replacement, the main cause of' transplant-failure, can be avoided. The OrthoPilot is an important support system for both less-experienced and experienced surgeons when performing surgical ACL revisions.

Anterior Cruciate Ligament↗

PubMed2002

ARROGANT: an application to manipulate large gene collections.

ARROGANT (ARRay OrGANizing Tool) is a software tool developed to facilitate the identification, annotation and comparison of large collections of genes or clones. The objective is to enable users to compile gene/clone collections from different databases, allowing them to design experiments and analyze the collections as well as associated experimental data efficiently. ARROGANT can relate different sequence identifiers to their common reference sequence using the UniGene database, allowing for the comparison of data from two different microarray experiments. ARROGANT has been successfully used to analyze microarray expression data for colon cancer, to compile genes potentially related to cardiac diseases for subsequent resequencing (to identify single nucleotide polymorphisms, SNPs), to design a new comprehensive human cDNA microarray for cancer, to combine and compare expression data generated by different microarrays and to provide annotation for genes on custom and Affymetrix chips.

Base Sequence↗

PubMed2006

Changes in electroencephalographic bicoherence during sevoflurane anesthesia combined with intravenous fentanyl.

With the introduction of bispectral index (BIS) as a measure of a patient's sedation during general anesthesia, attention has been directed toward bispectral analysis of electroencephalography (EEG). In the present study we evaluated the relationship between EEG bicoherence and sevoflurane concentration. Sixteen ASA physical status I-II patients scheduled for elective abdominal surgery were enrolled in the study. Anesthesia was induced with 5% sevoflurane and maintained with sevoflurane and oxygen (50%). Just before surgery, IV fentanyl (2 microg/kg) was given and then continuously infused (2 microg x kg(-1) x h(-1)). Using software we developed, EEG bicoherence, BIS, and 95% spectral edge frequency (SEF95) were recorded at end-tidal sevoflurane concentrations of 0.5%, 0.8%, 1.1%, 1.4%, 1.7%, 2.0%, and 2.3%. Under light anesthesia, EEG bicoherence values were low. With increasing sevoflurane concentrations, 2 peaks of bicoherence emerged along the diagonal line (f1 = f2). Both the first (at around 4 Hz) and second (at around 10 Hz) grew higher (37.7% +/- 7.5% and 35.1% +/- 9.0%, respectively) as the sevoflurane concentration increased to 1.4%. However, the first peak leveled off whereas the second tended to decrease slightly with further increases in sevoflurane concentration. The BIS value decreased as the sevoflurane concentration increased and leveled off at 1.4% and higher concentrations of sevoflurane. The SEF 95 also decreased as the sevoflurane concentration increased up to 2.3%. Thus the distribution pattern of the two bicoherence peaks is likely to be better than BIS of the anesthetic effect of sevoflurane during surgery.

Adult↗

PubMed2002

Dynamic ventilation (3)He-magnetic resonance imaging with lung motion correction: gas flow distribution analysis.

RATIONALE AND OBJECTIVES: Software was developed to correct for lung motion to improve the description of hyperpolarized (3)He gas distribution in the lung. METHODS: Five volunteers were studied by dynamic ventilation (3)He-MRI using an ultrafast FLASH 2D sequence with a temporal resolution of 128 milliseconds. Signal kinetics were evaluated in the trachea and seven parenchymal Regions of Interest. Reference ranges for healthy subjects were defined for motion-corrected and uncorrected images. RESULTS: Motion correction was successfully performed. Reference ranges were 0.11-1.21 seconds for tracheal transit time, 0-0.02 seconds for trachea-alveolar interval, 0.22-0.62 seconds for alveolar rise time and 0-76.6 arbitrary units for alveolar amplitude for motion corrected images, and 0-1.09 seconds, 0-0.11 seconds, 0.26-0.85 seconds, 46.4-99.8 arbitrary units for uncorrected images. CONCLUSIONS: Evaluation of (3)He-distribution in the lung using motion correction of dynamic (3)He-ventilation imaging is feasible and gives more narrow reference ranges.

Adult↗

PubMed1989

Six-microtransducer catheter connected to computer in evaluation of urethral closure function of women.

A new instrument consisting of a six-transducer catheter, one transducer for the bladder and five transducers for urethral pressure recordings, and a computer with specific software was developed for urodynamic investigation of women. Twenty-six patients with stress urinary incontinence (SUI) and 10 continent female patients were evaluated during the single cough, the first and the fourth ones of the forced coughings in supine and standing positions. The results were compared with those obtained with the conventional two-transducer method. Negative urethral closure pressure (UCP) at stress, indicative of SUI, was present in 88 percent of the cases with the six-transducer method, and in 77 percent with the two-transducer method. The fourth cough in the standing position with the six-transducer method was most diagnostic. In SUI, the six-transducer method indicated exactly, e.g., the minimum bladder pressure needed for negative UCP and the duration of negative UCP. Patients with SUI had significantly lower UCP at rest, UCP at stress, and pressure transmission ratio (PTR) than continent women. Findings, that UCP at stress decreased and duration of negative UCP at stress increased but PTR did not change when the fourth cough was compared with the first one in SUI, suggest that factors which are responsible for the altered urodynamics during prolonged stress are anatomic rather than functional.

Adult↗

PubMed2005

Digital imaging of the optic nerve head: monoscopic and stereoscopic analysis.

AIMS: To compare monoscopic and stereoscopic assessment of the optic disc using novel software for the digital stereoscopic analysis of optic disc stereopairs. METHODS: Software was developed for the stereoscopic display of digital optic disc images using an interlaced display method. Neuroretinal rim width was determined at 10 degree intervals around the optic disc using a custom (stereoscopic) cursor whose depth was adjusted to that of Elschnig's rim. Measurements were taken, first viewing the disc monoscopically and at a separate sitting, stereoscopically. RESULTS: Measurements were made in 35 eyes from 35 patients (1260 estimates for each observer) using three observers. The mean cup to disc ratio (CDR) ranged from 0.57 to 0.66 (SD 0.13-0.14) for monoscopic viewing compared with 0.64 to 0.69 (SD 0.12-0.14) for stereoscopic viewing. Stereoscopic assessments gave higher CDRs in temporal, superior, nasal, and inferior aspects of the optic disc (p<0.001, Mann-Whitney U test). Agreement between observers in estimating CDR was high for monoscopic assessment (intraclass correlation coefficient 0.74 (CI 0.72 to 0.76) increasing to 0.80 (0.78 to 0.82) for stereoscopic assessment. CONCLUSION: Digital stereoscopic optic disc assessment provides lower estimates of neuroretinal rim width and higher levels of interobserver agreement compared with monoscopic assessments.

Adult↗

PubMed2002

Assessment of normal and ischaemic myocardium by quantitative M-mode tissue Doppler imaging.

This paper presents a methodology and a software package developed to quantify M-mode tissue Doppler imaging (TDI), defining a number of quantitative parameters drawn from velocity and gradient curves obtained after segmenting the myocardial wall into anatomical layers. The independent clinical predictive value of these parameters to detect motion abnormalities in the presence of ischaemia was evaluated in a comparative study between a group of 17 healthy volunteers and 18 ischaemic patients. Factor analysis and stepwise logistic regression were used to assess the independent predictive value of these parameters in detecting abnormal contractility of the basal posterior segment. The statistical analysis performed has proved that any single parameter related to the gradient intensity, particularly the maximum gradient at the moment of the "e" wave, provides meaningful clinical information, achieving a rate of correct classification of 79.1% on the same data set used for the analysis. Adding additional parameters does not improve the diagnostic performance. Further testing with different settings (stress studies, other pathologies or segments) is warranted.

Adult↗

PubMed2003

Cardiotonic bipyridine amrinone slows myosin-induced actin filament sliding at saturating [MgATP].

Previously reported effects of amrinone on skeletal muscle function suggest that the drug reduces the rate constant of myosin cross-bridge dissociation. We have used the in vitro motility assay to further elucidate the mechanism underlying this effect and to aid these studies a new, improved, filament tracking software was developed in the Matlab environment. The experiments were carried out at 30 degrees C using heavy meromyosin from fast rabbit muscle and rhodamine-phalloidin labeled actin filaments. A slowing effect of amrinone on filament sliding velocity at 1 mM MgATP was observed at drug concentrations >0.3 mM. This effect showed signs of saturation at the highest drug concentrations (1-2 mM) that could be readily tested. The sliding velocity exhibited hyperbolic dependence on [MgATP] with a Vmax of 7.2 +/- 0.9 microm/s and a KM of 0.18 +/- 0.02 mM. Amrinone (1 mM) reduced Vmax by 32 +/- 5% (P < 0.01) and KM by 42 +/- 8% (P < 0.05; n=4). These results are accounted for in the most straightforward way by a model where amrinone acts directly on the actomyosin system and reduces the rate constant of MgADP release. Such a well-defined effect on the myosin cross-bridge cycle makes the drug a potentially useful pharmacological tool for further studies of myosin function both in vitro and in the ordered filament array of a living muscle fiber.

Actin Cytoskeleton↗

PubMed2005

Automated acquisition of cryo-electron micrographs for single particle reconstruction on an FEI Tecnai electron microscope.

AutoEM is a software package developed by Zhang et al. [J. Struct. Biol. 1356, 251] for semi-automated acquisition of cryo-electron micrographs from Tecnai series electron microscopes and is used frequently at the lowest level of automation. We report here on the new progress that we have made based on their preliminary work. A fourth low-dose state is created where the system can pre-select all the good holes in a grid square from a single CCD image taken at low magnification, making the system operative at much higher levels of automation. An additional control interface enables the operator to monitor the status of the program and the quality of the data, interact with the program, and direct the execution process according to intermediate results. When data acquisition is in progress, all useful information is automatically saved in certain text files which are easily accessible by a database. More detailed improvements and general advantages are illustrated and discussed. We have started to use the program to perform routine data collection. A number of applications show that the performance of the program is satisfactory and the quality of the micrographs and their power spectra acquired by the program is comparable to those manually collected under the same conditions.

Cryoelectron Microscopy↗

PubMed2001

Color Doppler velocity profile assessment of portal hemodynamics in cirrhotic patients with portal hypertension: correlation with esophageal variceal bleeding.

PURPOSE: Using the color Doppler velocity profile (CDVP), we investigated portal hemodynamics and their relationship with esophageal variceal bleeding (EVB) in patients with cirrhosis and portal hypertension. METHODS: The hemodynamics of the portal trunk, right anterior portal branch, and splenic vein were evaluated in 69 cirrhotic patients with portal hypertension and 46 healthy volunteers. The CDVP, a recently developed Doppler software, was used to measure blood flow velocity and flow volume; evaluate the spatial distribution of flow velocities in the cross-section of a vessel (velocity profile), as reflected by the profile parameter (n); and assess changes in flow volume over time (flow profile). The congestion index was calculated by dividing the cross-sectional area by the maximum cross-sectional velocity (CSVmax). The hemodynamic features were compared between patients without a history of EVB [EVB(-)] and those with a history of EVB [EVB(+)], and a logistic regression model was employed to identify factors associated with EVB. RESULTS: Compared with the healthy group, the cirrhotic group had a significantly lower mean CSVmax in the portal trunk and right anterior portal branch (both p < 0.01), a significantly elevated mean flow volume in the splenic vein and portal trunk (both p < 0.01), a significantly elevated mean ratio of splenic vein flow volume to portal trunk flow volume (SV/PT) (p < 0.001), and a significantly greater mean congestion index in the portal trunk, right anterior portal branch, and splenic vein (all p < 0.01). In the cirrhotic group, there was a significantly higher incidence of a flat flow pattern in the right anterior portal branch and a phasic flow pattern in the splenic vein than in the healthy group (both p < 0.01). Among cirrhotic patients, the EVB(+) group had a significantly greater mean flow volume in the splenic vein (p < 0.01), greater mean SV/PT (p < 0.01), greater mean spleen size (p < 0.05), and lower mean portal trunk n value (p < 0.05) compared with the EVB(-) group. Logistic regression analysis revealed that the SV/PT and portal trunk n value were independent EVB-related factors. CONCLUSIONS: The results suggest that portal hemodynamics in cirrhotic patients are characterized by passive congestion and increased blood flow. However, these 2 features had different preponderances in different parts of the portal venous system. Increased flow in the splenic vein may be the primary source of increased portal flow and may play a role in the development of EVB. The SV/PT and portal trunk n value may be valuable factors for predicting EVB.

Adolescent↗

PubMed2004

Decreases in ventricular volume correlate with decreases in ventricular pressure in idiopathic normal pressure hydrocephalus patients who experienced clinical improvement after implantation with adjustable valve shunts.

OBJECTIVE: This retrospective study examined whether changes in ventricular volume correspond with changes in adjustable valve pressure settings in a cohort of patients who received shunts to treat idiopathic normal pressure hydrocephalus. We also examined whether these pressure-volume curves and other patient variables would co-occur with a positive clinical response to shunting. METHODS: We selected 51 patients diagnosed with idiopathic normal pressure hydrocephalus who had undergone implantation of a Codman Hakim programmable valve (Medos S.A., Le Locle, Switzerland). Clinical data were gathered from the patients' records and clinical notes by an investigator blinded to patients' ventricular volumes. Ventricular volume was measured using 3D Slicer, an image analysis and interactive visualization software package developed and maintained at the Surgical Planning Laboratory at Brigham and Women's Hospital. RESULTS: Eighty-six percent of patients with gait disturbance at presentation showed improvement of this symptom, 70% experienced improvement in incontinence, and 69% experienced improvement in dementia. For the group showing 100% clinical improvement, the correlation coefficient of average changes in valve pressure over time (delta P/delta T) and average changes in ventricular volume over time (delta V/delta T) were high at 0.843 (P < 0.05). For the group experiencing no or only partial improvement, the correlation coefficient was 0.257 (P = 0.32), indicating no correlation between average delta V/delta T and average delta P/delta T for each patient. CONCLUSION: This was a carefully analyzed modeling study of idiopathic normal pressure hydrocephalus treatment made possible only by adjustable valve technology. With careful volumetric analysis, we found that changes in ventricular volume correlated with adjustments in valve pressure settings for those patients who improved clinically after shunting. This suggests that positive clinical responders retained parenchymal elasticity, emphasizing the importance of dynamic changes in this cohort.

Adolescent↗

PubMed1992

Computer-aided individual prognoses of squamous cell carcinomas of the lips, oral cavity and oropharynx.

Computer-aided individual prognoses (CIP) is a software-package developed on the basis of an empirical study and can be installed on any IBM-compatible personal computer. The project which went into the making of CIP was called "Prospective DOSAK-study on squamous cell carcinomas of the lips, oral cavity and oropharynx". In the course of the study 1485 patients were treated between 1977 and 1982, and followed up through 1985. CIP facilitates individual prognoses and comparisons of independent patient groups with parallel groups from the data of the above-mentioned study. In practical clinical work individual prognoses allow exact and reliable judgements on individual patients. In clinical cancer research it provides the information about prognostic factors required for controlled clinical studies. The comparison of independent patient populations allows for an ongoing qualitative control of the patients in each clinical institution. In clinical cancer research such a comparison means that certain characteristics of the patient, the tumor and of the disease can be given higher prognostic value. The same is true of the clinical testing of therapeutic measures which is typically carried out during phase-II-studies. Due to its menu-based organization CIP does not presuppose any specialist knowledge on the part of its users and can be regarded as particularly user-friendly.

Austria↗

PubMed2004

[Clinical use of digital retrospective image fusion of CT, MRI, FDG-PET and SPECT -- fields of indications and results].

PURPOSE: To evaluate the feasibility and the clinical benefits of retrospective digital image fusion (PET, SPECT, CT and MRI). MATERIALS AND METHODS: In a prospective study, a total of 273 image fusions were performed and evaluated. The underlying image acquisitions (CT, MRI, SPECT and PET) were performed in a way appropriate for the respective clinical question and anatomical region. Image fusion was executed with a software program developed during this study. The results of the image fusion procedure were evaluated in terms of technical feasibility, clinical objective, and therapeutic impact. RESULTS: The most frequent combinations of modalities were CT/PET (n = 156) and MRI/PET (n = 59), followed by MRI/SPECT (n = 28), CT/SPECT (n = 22) and CT/MRI (n = 8). The clinical questions included following regions (more than one region per case possible): neurocranium (n = 42), neck (n = 13), lung and mediastinum (n = 24), abdomen (n = 181), and pelvis (n = 65). In 92.6 % of all cases (n = 253), image fusion was technically successful. Image fusion was able to improve sensitivity and specificity of the single modality, or to add important diagnostic information. Image fusion was problematic in cases of different body positions between the two imaging modalities or different positions of mobile organs. In 37.9 % of the cases, image fusion added clinically relevant information compared to the single modality. CONCLUSION: For clinical questions concerning liver, pancreas, rectum, neck, or neurocranium, image fusion is a reliable method suitable for routine clinical application. Organ motion still limits its feasibility and routine use in other areas (e. g., thorax).

Adolescent↗