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PubMed1994

Computerized quantitation of synergism and antagonism of taxol, topotecan, and cisplatin against human teratocarcinoma cell growth: a rational approach to clinical protocol design.

BACKGROUND: Cisplatin-based induction chemotherapy may achieve a complete response (i.e., no sign of tumor following treatment) in 70%-80% of patients with germ cell tumors. However, only a minority of patients in whom the firstline regimens fail are cured with the salvage regimens. PURPOSE: The aim of these studies was to identify new agents or new regimens for the treatment of germ cell tumors by carrying out quantitative assessment in vitro of two promising new antitumor agents (paclitaxel [Taxol] and topotecan) and three more established agents (cisplatin, vincristine, and etoposide). These agents were used singly or in two- and three-drug combinations and were selected because they represent five distinct categories of antineoplastic mechanisms. METHODS: The combination index-isobologram method, which is based on the median-effect principle developed by Chou and Talalay, was used for computerized data analysis. This method was selected because it takes into account both the potencies of each drug and combinations of these drugs and the shapes of their dose-effect curves. RESULTS: Synergism against the growth of teratocarcinoma cells resistant to cisplatin (833K/64CP10 cells) was greater than against the growth of parent 833K cells. The degrees of synergism were in the following order: cisplatin + topotecan > or = paclitaxel + cisplatin + topotecan > paclitaxel + topotecan > or = paclitaxel + etoposide > paclitaxel + cisplatin + etoposide > paclitaxel + cisplatin. All other combinations showed nearly additive effects or moderate antagonism. The degrees of antagonism were as follows: cisplatin + etoposide > or = paclitaxel + vincristine > paclitaxel + cisplatin + vincristine > cisplastin + vincristine. The combination of paclitaxel and cisplatin was synergistic against 833K/64CP10 cells and moderately antagonistic against 833K cells. Since the combination of paclitaxel, cisplatin, and topotecan and the two-component combinations of these drugs (cisplatin + topotecan and paclitaxel + topotecan) showed synergism stronger than that of other combinations, these three drugs were selected for illustrating detailed data analysis, using a computer software program developed in this institute. CONCLUSIONS AND IMPLICATIONS: Our findings suggest that, as a result of synergy, the doses of these agents needed to achieve an antitumor effect may be reduced by twofold to eightfold when these agents are given in combination. The present quantitative data analyses for synergism or antagonism provide a basis for a rational design of clinical protocols for combination chemotherapy in patients with advanced germ cell tumors.

Antineoplastic Agents↗

PubMed1999

Three-dimensional video analysis of facial movements: a new method to assess the quantity and quality of the smile.

The results of neuromuscular reconstructions of the paralyzed face are difficult to assess. Very sophisticated methods are necessary to measure the motor deficits of facial paralysis or the functional recovery in the face. The aim of this development was a relatively simple system for data acquisition, which is easy to handle and which makes it relatively cheap to delegate data acquisition to centers all over the world, which will not be able to derive a data analysis on their own, but will send their data to a center with specialized equipment. A complex mirror system was developed to get three different views of the face at the same time on the video screen. At each investigation, a digital video is taken from a calibration grid and from standardized facial movements of the patient. Secondary analysis of the digital videofilm is made possible at any time later on by the support of a computer program, which calculates distances and movements three-dimensionally from the frontal image and the right and left mirror images. Pathologies of the mimic movements can be identified as well as improvements after surgical procedures by this system. The significant advantage is the possibility to watch the same movement on the video which is under study and to apply any kind of study later on. Taking the video needs only a few minutes, and fatigue of the patient's mimic system is prevented. Measurements usually at the endpoints of the movements give excellent information on the quantity of the movement or the degree of the facial palsy, whereas the video itself is very informative regarding the quality of the smile. Specific computer software was developed for standardized three-dimensional analysis of the video-documented facial movements and for data presentation. There are options like two-dimensional graphs of single moving points in the face or three-dimensional graphs of the movements of all measured points at the same time during a standardized facial movement. By a comparison of the right- and left-sided alterations of specific distances between two points during the facial movements, the degree of normal symmetry or pathologic asymmetry is quantified. This system is more suitable for detailed scientific multicenter studies than any other system previously established. A very sensitive instrument for exact evaluation of mimic function is now available.

Calibration↗

PubMed1995

Cost-effective health information systems: user-driven internal development at the University of Iowa.

GOALS: The Information Network For Online Retrieval & Medical Management (INFORMM), health information system (HIS) for the University of Iowa Hospitals and Clinics (UIHC), was analyzed with regard to development of a Computer-Based Patient Record (CBPR) in a cost-effective manner. The analysis: i) profiles INFORMM system functionality; ii) displays INFORMM use and satisfaction among physicians, nurses, and other hospital employees; iii) characterizes dynamics affecting INFORMM growth; and iv) evaluates the cost of a system of internal-development of software. DATA SOURCES: INFORMM utilization for 1989, 1994, and 1995; service requests from users for the years 1985, 1990, and 1994; 1994 MECON-PEERx data; gap analysis user survey conducted by an independent consulting firm. MAIN RESULTS: 1) Physician use has been dominated by a single function: retrieval of laboratory results. 2) Nurse use of the system was more diverse. A recent surge of nurse and physician use resulted from the introduction of online documentation of nursing care. 3) Overall use has been predominantly by non-clinician users, no one function dominating their pattern of use. 4) User service requests were predominantly from the non-clinician group of users. Requests from non-physician groups have been coordinated by a limited number of representatives of those groups, unlike requests from physicians. 5) The UIHC HIS ranked high in user satisfaction. 6) The overall cost of the UIHC HIS system is relatively low as a percentage of the gross operating budget or as a ratio to the volume of patient activities in this medical center. CONCLUSIONS: Internal development of INFORMM has been a cost-effective solution to the information demands of nursing staff and other users. INFORMM system composition reflects the quantity and organization of user requests. Satisfying the needs of physicians requires a change in the manner in which physician needs are assessed.

Attitude to Computers↗

PubMed2003

Expression profiling of the schizont and trophozoite stages of Plasmodium falciparum with a long-oligonucleotide microarray.

BACKGROUND: The worldwide persistence of drug-resistant Plasmodium falciparum, the most lethal variety of human malaria, is a global health concern. The P. falciparum sequencing project has brought new opportunities for identifying molecular targets for antimalarial drug and vaccine development. RESULTS: We developed a software package, ArrayOligoSelector, to design an open reading frame (ORF)-specific DNA microarray using the publicly available P. falciparum genome sequence. Each gene was represented by one or more long 70 mer oligonucleotides selected on the basis of uniqueness within the genome, exclusion of low-complexity sequence, balanced base composition and proximity to the 3' end. A first-generation microarray representing approximately 6,000 ORFs of the P. falciparum genome was constructed. Array performance was evaluated through the use of control oligonucleotide sets with increasing levels of introduced mutations, as well as traditional northern blotting. Using this array, we extensively characterized the gene-expression profile of the intraerythrocytic trophozoite and schizont stages of P. falciparum. The results revealed extensive transcriptional regulation of genes specialized for processes specific to these two stages. CONCLUSIONS: DNA microarrays based on long oligonucleotides are powerful tools for the functional annotation and exploration of the P. falciparum genome. Expression profiling of trophozoites and schizonts revealed genes associated with stage-specific processes and may serve as the basis for future drug targets and vaccine development.

Animals↗

PubMed2003

[Modified methods of percutaneous electrogastroenterography].

In 62 normal males and females gastrointestinal (GI) electrical activity was evaluated before and after standard breakfast with the method of epicutaneous electrogastroenterography (EGEG) with the use of AgCl electrodes and original hard- and software "Gastroenterograph" developed by the authors. Spectral analysis (SA) of GI electrical potentials enabled quantification of the electrical activity of the stomach, duodenum, jejunum, ileum and the whole of the small intestine. The stomach and the small intestine were main contributors to the total GI electrical activity during fasting. Changes in the functional activity of the digestive system after the meal were characterized by increases in selected SA parameters (length of the spectral curve and area underneath), dissociation between their values and redistribution of ratios in different GI segments.

Action Potentials↗

PubMedDate not supplied

Topographic predicted corneal acuity with intrastromal corneal ring segments.

PURPOSE: To evaluate predicted optical quality of the central anterior corneal surface before and after the intrastromal corneal ring segment (ICRS) refractive procedure using a clinical videokeratoscope and software index developed for that purpose. METHODS: Predicted corneal acuity, a topographically derived index provided with the EyeSys System 2000 videokeratscope, representing potential optical quality of the cornea, was assessed preoperatively and at postoperative month 3 in 94 eyes that received an ICRS to treat -1.00 to -6.00 D of myopia. Predicted corneal acuity was calculated by determining the difference between a measured cornea and its best-fit ellipses for reflected ring circumferences within the central 3 mm diameter zone. RESULTS: Preoperative predicted corneal acuity was 20/10 in 92 of 94 eyes (98%). At month 3 after the ICRS procedure, 48 (51%) of moderately myopic eyes were corrected to 20/20 or better, 96% (90 eyes) were corrected to 20/40 or better, and 98% of eyes (92 eyes) had a predicted corneal acuity of 20/10. For the eyes with a predicted corneal acuity of 20/10, spectacle-corrected visual acuity was normally distributed between 20/10 and 20/25. CONCLUSION: Predicted corneal acuity did not change significantly from baseline in eyes with an ICRS. This suggests that topographic irregularities in the central 3 mm of the cornea detectable by predicted corneal acuity software were not induced in the central cornea with the ICRS.

Corneal Stroma↗

PubMed2005

A path planning approach for computing large-amplitude motions of flexible molecules.

MOTIVATION: Motion is inherent in molecular interactions. Molecular flexibility must be taken into account in order to develop accurate computational techniques for predicting interactions. Energy-based methods currently used in molecular modeling (i.e. molecular dynamics, Monte Carlo algorithms) are, in practice, only able to compute local motions while accounting for molecular flexibility. However, large-amplitude motions often occur in biological processes. We investigate the application of geometric path planning algorithms to compute such large motions in flexible molecular models. Our purpose is to exploit the efficacy of a geometric conformational search as a filtering stage before subsequent energy refinements. RESULTS: In this paper two kinds of large-amplitude motion are treated: protein loop conformational changes (involving protein backbone flexibility) and ligand trajectories to deep active sites in proteins (involving ligand and protein side-chain flexibility). First studies performed using our two-stage approach (geometric search followed by energy refinements) show that, compared to classical molecular modeling methods, quite similar results can be obtained with a performance gain of several orders of magnitude. Furthermore, our results also indicate that the geometric stage can provide highly valuable information to biologists. AVAILABILITY: The algorithms have been implemented in the general-purpose motion planning software Move3D, developed at LAAS-CNRS. We are currently working on an optimized stand-alone library that will be available to the scientific community.

Algorithms↗

PubMed2006

Design of a sampling plan to detect ochratoxin A in green coffee.

The establishment of maximum limits for ochratoxin A (OTA) in coffee by importing countries requires that coffee-producing countries develop scientifically based sampling plans to assess OTA contents in lots of green coffee before coffee enters the market thus reducing consumer exposure to OTA, minimizing the number of lots rejected, and reducing financial loss for producing countries. A study was carried out to design an official sampling plan to determine OTA in green coffee produced in Brazil. Twenty-five lots of green coffee (type 7 - approximately 160 defects) were sampled according to an experimental protocol where 16 test samples were taken from each lot (total of 16 kg) resulting in a total of 800 OTA analyses. The total, sampling, sample preparation, and analytical variances were 10.75 (CV = 65.6%), 7.80 (CV = 55.8%), 2.84 (CV = 33.7%), and 0.11 (CV = 6.6%), respectively, assuming a regulatory limit of 5 microg kg(-1) OTA and using a 1 kg sample, Romer RAS mill, 25 g sub-samples, and high performance liquid chromatography. The observed OTA distribution among the 16 OTA sample results was compared to several theoretical distributions. The 2 parameter-log normal distribution was selected to model OTA test results for green coffee as it gave the best fit across all 25 lot distributions. Specific computer software was developed using the variance and distribution information to predict the probability of accepting or rejecting coffee lots at specific OTA concentrations. The acceptation probability was used to compute an operating characteristic (OC) curve specific to a sampling plan design. The OC curve was used to predict the rejection of good lots (sellers' or exporters' risk) and the acceptance of bad lots (buyers' or importers' risk).

Coffee↗

PubMed2004

SNPbox: a modular software package for large-scale primer design.

UNLABELLED: We developed a modular software package SNPbox that automates and standardizes the generation of PCR primers and is used in the strategy for constructing single nucleotide polymorphisms (SNPs) maps. In this strategy, the focus of primer design can be either on the validation of annotated public SNPs or on the SNP discovery in exon regions or extended genomic regions, both by resequencing. SNPbox relies on Primer3 for the primer design and combines this program with other publicly available software tools such as BLAST, Spidey and RepeatMasker, and newly developed algorithms. Primer conditions were chosen such that PCR amplifications are uniform for each PCR amplicon facilitating the use of high-throughput genetic platforms. SNPbox can also be used for the design of primer sets for mutation analysis, STR marker genotyping and microarray oligo design. Of the 2500 primer sets designed by SNPbox, 95% successfully amplified genomic DNA under uniform PCR conditions. AVAILABILITY: The software is available from the authors upon request. SUPPLEMENTARY INFORMATION: SNPbox_supplement.

Algorithms↗

PubMed1995

Prevention of AIDS and living together with an HIV-infected patient.

In Brazil, approximately 45 thousand cases had been reported until the end of 1993, with an estimated 50% underreport. According to the Ministry of Health, until the year 2,000 from 2 to 8 million Brazilians citizens will be infected with HIV. The basic aspect of the educational campaigns regarding AIDS does not refer only to information on forms of transmission and prevention measures, but also attempts to fight against the mystification and the enormous resistance of the public to definitely accept the fact that transmission does not occur by simple means such as having a drink from the same glass, independently of its socioeconomic and cultural level. In addition to the lack of information, prejudice and discrimination appear strongly rooted in the population to the point of a tendency of social and effective rejection of the HIV-infected patient. Fighting against prejudice, against which there is also no vaccine, is a task as gigantic as fighting against the virus. For both, investments in education of and information to the population in general, is very important. Development of a software which would fulfill the function of explaining, and providing the correct information about AIDS, would be extremely valuable for any part of the society and could also be used as a complementary element by health professionals. The objective was to develop an interactive software in order to demonstrate prevention measures and universal precaution in AIDS; to inform about the necessary care to people that are living together an HIV-infected patient. To develop this software with animation and elucidating text regarding AIDS for the general population, we are using the Storyboard live to be run in Windows environment.

Acquired Immunodeficiency Syndrome↗

PubMed1995

Software compensation for lung volume in assessment of inspiratory muscle strength and endurance.

BACKGROUND: To increase the sensitivity of measurements of maximal inspiratory pressure (MIP) as a test of inspiratory muscle strength and endurance, software was developed to correct for variation in lung volume. METHODS: Using a body plethysmograph to determine absolute lung volume during each manoeuvre, values for MIP were expressed as a percentage of the pressure "expected" from the unfatigued MIP/lung volume relation in each subject. RESULTS: The method reduced the variance in peak and average pressure during a series of 18 MIP manoeuvres of 10 seconds duration separated by rest intervals of 10 seconds. CONCLUSIONS: The correlation between average pressure and contraction number was improved significantly by the MIP/lung volume correction. This simple correction has many applications in measurements of the MIP.

Adult↗

PubMed2003

A specialized plug-in software module for computer-aided quantitative measurement of medical images.

This paper presents a specialized system for quantitative measurement of medical images. Using Visual C++, we developed a computer-aided software based on Image-Pro Plus (IPP), a software development platform. When transferred to the hard disk of a computer by an MVPCI-V3A frame grabber, medical images can be automatically processed by our own IPP plug-in for immunohistochemical analysis, cytomorphological measurement and blood vessel segmentation. In 34 clinical studies, the system has shown its high stability, reliability and ease of utility.

Algorithms↗

PubMedDate not supplied

Automated multiple peptide synthesis.

A fully automated instrument for multiple simultaneous peptide synthesis was constructed to provide large numbers of peptides for immunological research. The synthesis is performed in a flow-through mode with the conventional solid supports contained in 48 individual reaction columns. The instrument is based on a commercial autosampler equipped with a motor-driven syringe for accurate delivery of reagents and a robot arm carrying a dispenser needle. Dedicated software was developed to compile overlapping peptides from a given protein sequence and to control all functions of the robot. In situ activation by BOP was chosen as the optimized chemistry protocol. The peptides are cleaved from the resin in the reactors used for synthesis, thus minimizing handling. Performance of the instrument was demonstrated by synthesis of overlapping 14-mer peptides derived from the sequence of HIV reversed transcriptase. A second mode of operation allows the synthesis to be carried out on the surface of polyethylene pins. Peptides derived from the sequence of human TNF were synthesized using this method and used to characterize antibodies raised against the intact protein.

Amino Acid Sequence↗

PubMed1994

A semiautomated test apparatus for studying partner preference behavior in the rat.

A semiautomated three-compartment box (3CB) for studying partner preference behavior of rats is described. This apparatus automatically records the rat's time spent in each compartment, as well as the locomotor activity (i.e., the number of visits an animal pays to each compartment). Software was developed for calculating partner preference scores. Behavioral testing in the semiautomated 3CB, which is a modification of an earlier version, is less time consuming and less laborious. Three 3CBs can be observed simultaneously by two trained observers, and the behavioral interactions of three experimental animals with the stimulus animals can be observed and scored by hand. The use of the new apparatus was validated by studying adult partner preference behavior of neonatally ATD-treated male rats. The collected data fully corroborate previous results, obtained in the earlier version of the 3CB, again revealing the behavioral bisexual nature of these ATD males. A new finding was the much higher locomotor activity of the ATD males compared to controls.

Androstatrienes↗

PubMed2006

The hyoid bone in malay infants with cleft lip and palate.

OBJECTIVE: To compare morphological and positional variations of the hyoid bone in unoperated infants with cleft lip and palate (CL/P) with those in noncleft infants. DESIGN: Retrospective, cross sectional. PATIENTS AND METHODS: Three-dimensional computed tomography scans were obtained from 29 unoperated CL/P infants of Malay origin aged between 0 and 12 months and from 12 noncleft infants in the same age range. Observations were made and measurements were obtained with a software package developed at the Australian Craniofacial Unit. The sizes of the hyoid bones and the position of the hyoid body and epiglottis in relation to the cervical spine were measured. Anatomical anomalies of the hyoid and prevalence of aspiration pneumonia were also documented. RESULTS: The hyoid bones and epiglottis were found to be located more inferiorly in CL/P infants compared with the noncleft infants. Also, 17% (5/29) of the CL/P infants had nonossified hyoid bodies. CONCLUSION: The results suggest that there are differences in the location and genesis of the hyoid bone in infants with CL/P that warrant further investigation.

Age Distribution↗

PubMed1986

A portable data-logging system for industrial hygiene personal chlorine monitoring.

The combination of suitable portable sensors or instruments with small microprocessor-based data-logger units has made it possible to obtain detailed monitoring data for many health and environmental applications. Following data acquisition in field use, the logged data may be transferred to a desk-top personal computer for complete flexibility in manipulation of data and formating of results. A system has been assembled from commercial components and demonstrated for chlorine personal monitoring applications. The system consists of personal chlorine sensors, a Metrosonics data-logger and reader unit, and an Apple II Plus personal computer. The computer software was developed to handle sensor calibration, data evaluation and reduction, report formating and long-term storage of raw data on a disk. This system makes it possible to generate time-concentration profiles, evaluate dose above a threshold, quantitate short-term excursions and summarize time-weighted average (TWA) results. Field data from plant trials demonstrated feasibility of use, ruggedness and reliability. No significant differences were found between the time-weighted average chlorine concentrations determined by the sensor/logger system and two other methods: the sulfamic acid bubbler reference method and the 3M Poroplastic diffusional dosimeter. The sensor/data-logger system, however, provided far more information than the other two methods in terms of peak excursions, TWAs and exposure doses. For industrial hygiene applications, the system allows better definition of employee exposures, particularly for chemicals with acute as well as chronic health effects.(ABSTRACT TRUNCATED AT 250 WORDS)

Air Pollutants, Occupational↗

PubMed2006

AccuTyping: new algorithms for automated analysis of data from high-throughput genotyping with oligonucleotide microarrays.

Microarray-based analysis of single nucleotide polymorphisms (SNPs) has many applications in large-scale genetic studies. To minimize the influence of experimental variation, microarray data usually need to be processed in different aspects including background subtraction, normalization and low-signal filtering before genotype determination. Although many algorithms are sophisticated for these purposes, biases are still present. In the present paper, new algorithms for SNP microarray data analysis and the software, AccuTyping, developed based on these algorithms are described. The algorithms take advantage of a large number of SNPs included in each assay, and the fact that the top and bottom 20% of SNPs can be safely treated as homozygous after sorting based on their ratios between the signal intensities. These SNPs are then used as controls for color channel normalization and background subtraction. Genotype calls are made based on the logarithms of signal intensity ratios using two cutoff values, which were determined after training the program with a dataset of approximately 160,000 genotypes and validated by non-microarray methods. AccuTyping was used to determine >300,000 genotypes of DNA and sperm samples. The accuracy was shown to be >99%. AccuTyping can be downloaded from http://www2.umdnj.edu/lilabweb/publications/AccuTyping.html.

Algorithms↗

PubMed1991

Osteoclast cytomorphometry demonstrates an abnormal population in B cell malignancies but not in multiple myeloma.

Increased bone resorption in the vicinity of myeloma cells is mediated by local stimulating factors. Other malignancies of the B cell lineage are also able to produce resorbing factors responsible for increased bone resorption. We have studied three groups of subjects: 10 patients with overt multiple myeloma, 10 patients with a B cell malignancy, and 10 healthy human subjects as controls. Patients were studied at the time of diagnosis and had a transiliac bone biopsy. Osteoclasts were evident on histological sections by their acid phosphatase activity. A software was developed on an automatic image analyzer (Leitz TAS+) for measuring the maximal Feret's diameter (Oc.Le) of each osteoclast (corresponding to the osteoclast length). The histogram of Oc.Le frequency distribution was supplied in each group. In myeloma patients, the Oc.Le frequency distribution was similar to that in normal subjects and showed the histogram to be asymetric with a positive skew (maximum peak at 20-25 microns). With a graphical analysis, this distribution was shown to follow a lognormal distribution corresponding to a homogeneous osteoclast population. In other B cell malignancies, Oc.Le displayed a bimodal distribution with a peak at 20-25 microns and a lower peak at 10-15 microns. The graphical analysis showed that small (mononucleated?) osteoclasts are present in B cell malignancies with normal osteoclasts. This might reflect the secretion of different soluble factors by malignant cells of the B lymphocyte lineage.

Acid Phosphatase↗