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PubMed2002

NIDDK encourages technology research in diabetes.

The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) actively supports technology-related research directed at development of new therapies for prevention and treatment of diabetes and its complications. Identification of the genetic and environmental contributors to diabetes and the molecular mechanisms through which they act will yield new targets for therapeutic development. Major efforts are also directed at development of beta-cell replacement therapy; improved methods for sensing glucose and delivering insulin; imaging technologies and other surrogate markers to detect disease progression; improved animal models for study of diabetes and its complications; and clinical trials to evaluate the safety and efficacy of new therapies. Application of genomic, proteomic and other new technologies to diabetes research, collaborations between diabetes researchers and researchers with technologies relevant to diabetes, and bench to bedside translational research are particularly encouraged. A variety of funding mechanisms are available to prospective researchers.

Diabetes Mellitus↗
PubMed2002

Diabetes disease management program for an indigent population empowered by telemedicine technology.

Mercy Health Center in Laredo, Texas implemented a Telemedicine Diabetes Disease Management Program to determine the impact of a web-based patient interface technology as part of a diabetes disease management program. The program featured the use of the Health Hero iCare Desktop and the Health Buddy appliance. The Mercy Health Center outcomes study aimed to assess the effect of telemedicine technology on the health of indigent border residents with diabetes. The study was conducted in calendar year 2000-2001 using comparative cohort data from calendar year 1999. Using the technology, patients were monitored daily at home, and to ensure early intervention, nurses were alerted if patients reported abnormalities. The goals of the program were to decrease hospital-based resource utilization, improve patient compliance with treatment plans, improve the level of patient satisfaction with healthcare services, and improve patients' perceived quality of life. Objective outcomes, including inpatient admissions, emergency room visits, postdischarge care visits, and outpatient visits, as well as charges for healthcare services, were all measured on a per patient per year basis. Subjective outcomes, including quality of life and patient satisfaction, were estimated from surveys conducted before, quarterly for two quarters within the program, and at the end of the study period. For each measure except for quality of life, comparisons were made between the year just prior to and the year of Health Buddy utilization. Quality of life was compared for the year just prior to Health Buddy utilization and at the end of the second quarter. After 1 year, reductions in overall utilization and charges, as well as improvements in quality of life, were demonstrated. Patients in the program showed reduced overall charges of 747 dollars per patient per year. Inpatient admissions were reduced 32% (p < 0.07), emergency room encounters were reduced 34% (p < 0.06), postdischarge care visits were reduced 44% (p < 0.28), and outpatient visits were reduced 49% (p < 0.001). Quality of life was assessed using the Medical Outcomes Study 12-item Short Form health survey. The mean improvement in the mental component after 6 months in the program was 2.8, from 45.1 preprogram to 47.9 within the program (p < 0.0264). The mean improvement in the physical component after 6 months in the program was 2.1, from 41.7 preprogram to 43.8 within the program (p < 0.0518). The reductions in utilization and improvement in quality of life can likely be attributed to the patient's enhanced self-management behaviors and the nurse's ability to intervene in a timely manner when warranted. Without technology and daily remote monitoring, standard patient care is based on episodic encounters between patients and their care providers, which does not allow for prevention, education, or early intervention. This program bridged the gap between office visits for the patients. The early intervention ultimately reduced the cost of care.

Diabetes Mellitus↗
PubMed1999

Issues and implications in the selection of blood glucose monitoring technologies.

Over the last 2 decades assay technology originating in the laboratory has been adapted for the special situation of in vitro blood glucose monitoring in the home, at work or play, or at the bedside. The availability of blood glucose monitoring devices has had a significant impact on the treatment of diabetes, especially with respect to involving the patients in their treatment. The unique requirements of this type of testing have led to novel developments in sample acquisition techniques, analyte detection, measurement techniques, and error detection. The performance of these in vitro devices in terms of accuracy and imprecision is largely dependent on factors that contribute to variation in response that are related to testing with blood samples outside of the laboratory. These factors include, for example, variations in environmental conditions, the variability of hematocrit and oxygen concentrations of the blood, and the fact that the blood is used undiluted. Therefore, the technologies used have been selected, developed, optimized, and calibrated to minimize the impact of these factors. The technologies also must be capable of providing accurate, reproducible results over the large range of clinical interest from the hypoglycemic range to glucose concentrations 10 to 15 to 20 times greater. However, when selecting a technology there are invariably some trade-offs to consider. Thus, the products must be optimized to balance performance, reliability, and cost. Examples are discussed.

Biosensing Techniques↗
PubMed2002

Enzyme fragment complementation: a flexible high throughput screening assay technology.

High-affinity complementation of a small fragment of beta-galactosidase to an inactive deletion mutant of the enzyme forms a stable heteromeric enzyme complex capable of hydrolyzing substrates to produce either chemiluminescent or fluorescent signals. This review describes a series of screening assays in which the small beta-galactosidase fragment, Enzyme Donor or ProLabel, is either chemically conjugated or recombinantly fused to small molecules or proteins, respectively. Chemical conjugation forms the basis of several HitHunter HTS assays in which competitive displacement of the ProLabel conjugate from either a binding protein (receptor or antibody) is induced by the analyte in question. In this manner, a calibration curve is generated, to measure cellular analytes including 3',5'-cyclic AMP. Changes in this second messenger, occurring due to G protein-coupled receptor (GPCR) activation, can thus be easily measured in a homogeneous assay. Similar assays have been developed for tyrosine kinases, serine threonine kinases, nuclear hormone receptors, and proteases. A second form of assay technology involves measurement of cellular protein expression, in which the protein is fused to ProLabel. Analysis can be undertaken in crude cell lysates, or with intact cells, using beta-galactosidase complementation in a microtiter plate. This homogeneous technology is highly sensitive and has been developed to measure protein expression changes occurring in response to pathway activation by targets such as GPCRs, tyrosine kinase receptors, and proteases. In summary, the DiscoveRx technology using beta-galactosidase complementation provides a robust and flexible assay technology for use in cell-free and cell-based HTS.

Animals↗
PubMed1999

Advances in metered dose inhaler technology with the development of a chlorofluorocarbon-free drug delivery system.

The impending phaseout of chlorofluorocarbon (CFC)-containing metered dose inhalers (MDIs) has challenged the pharmaceutical industry to rethink and redesign many components of the technology involved in delivering asthma medication to the lungs. Along with the emergence of the first formulation using the nonozone-depleting propellant, hydrofluoroalkane (HFA) 134a to replace CFC propellants, advances in drug delivery technology have improved the performance characteristics of the MDI itself. Although MDIs have remained the mainstay of asthma therapy for 40 years, MDI technology still presents challenges. Some of the shortcomings of existing CFC MDIs affect the reliability of dosing. These challenges have been addressed in the development of the first CFC-free beta-agonist for the treatment of asthma. Airomir CFC-free (salbutamol sulfate; 3M Pharmaceuticals, St. Paul, MN), which is currently available in over 30 countries and was recently approved in the United States (Proventil HFA; Schering-Plough, Madison, NJ), incorporates numerous design and technological improvements which together with the introduction of CFC-free propellants mark the beginning of the next generation of asthma therapy. Although the new generation of CFC-free MDIs incorporates several improvements in dose reproducibility, these changes should be virtually transparent to the patient switching from a CFC MDI to a CFC-free MDI. What may be noticeable is a "softer puff," which is the result of valve and actuator redesign. The taste of the new CFC-free product may also be a little different yet totally acceptable to users.

Administration, Inhalation↗
PubMed2006

Concept of sample in OMICS technology.

Fundamental biological processes can now be studied by applying the full range of OMICS technologies (genomics, transcriptomics, proteomics, metabolomics, and beyond) to the same biological sample. Clearly, it would be desirable if the concept of sample were shared among these technologies, especially as up until the time a biological sample is prepared for use in a specific OMICS assay, its description is inherently technology independent. Sharing a common informatic representation would encourage data sharing (rather than data replication), thereby reducing redundant data capture and the potential for error. This would result in a significant degree of harmonization across different OMICS data standardization activities, a task that is critical if we are to integrate data from these different data sources. Here, we review the current concept of sample in OMICS technologies as it is being dealt with by different OMICS standardization initiatives and discuss the special role that the newly formed Genomic Standards Consortium (GSC) might have to play in this domain.

Animals↗
PubMed2006

Antibody microarrays: current status and key technological advances.

Antibody-based microarrays are among the novel classes of rapidly evolving proteomic technologies that holds great promise in biomedicine. Miniaturized microarrays (< 1 cm2) can be printed with thousands of individual antibodies carrying the desired specificities, and with biological sample (e.g., an entire proteome) added, virtually any specifically bound analytes can be detected. While consuming only minute amounts (< microL scale) of reagents, ultra- sensitive assays (zeptomol range) can readily be performed in a highly multiplexed manner. The microarray patterns generated can then be transformed into proteomic maps, or detailed molecular fingerprints, revealing the composition of the proteome. Thus, protein expression profiling and global proteome analysis using this tool will offer new opportunities for drug target and biomarker discovery, disease diagnostics, and insights into disease biology. Adopting the antibody microarray technology platform, several biomedical applications, ranging from focused assays to proteome-scale analysis will be rapidly emerging in the coming years. This review will discuss the current status of the antibody microarray technology focusing on recent technological advances and key issues in the process of evolving the methodology into a high-performing proteomic research tool.

Animals↗
PubMed1998

Accuracy of orthognathic evaluation using telemedicine technology.

OBJECTIVE: Telemedicine technology has the ability to project highly specialized medical and dental expertise anywhere in the world. This is particularly important to many small, isolated communities that do not have access to medical and dental specialists. Telemedicine also has the potential to reduce unnecessary travel, time away from work, and unneeded hospital admissions. For this technology to be successful, however, clinicians need to have confidence in its capabilities. This study was conducted to determine the accuracy of an orthognathic evaluation using telemedicine. MATERIALS AND METHODS: Thirteen patients were randomly selected for review by two surgeons each using telemedicine and clinical examinations. Clinically acceptable differences were established, and the results of the two examination methods were compared. RESULTS: A main effect of the examination method was observed in 7 of the 18 continuous measurements taken. Examination of the absolute value of the within-subject difference between the two examination methods demonstrated that the mean absolute difference was statistically different from zero for 13 of 18 measurements taken. CONCLUSIONS: These data demonstrate that a relatively accurate orthognathic examination can be performed with this technology. With this in mind, clinicians may feel comfortable using this technology for other clinical applications.

Adult↗
PubMed1999

The cost-effectiveness of the cytology laboratory and new cytology technologies in cervical cancer prevention.

The effect of changes in cytology laboratory costs, including the costs of new technologies, on the cost-effectiveness of cervical cancer prevention has not been studied. Using University of Iowa laboratory detection rates and costs, a decision model determined the cost-effectiveness of the laboratory with and without new technologies. Compared with not performing a cervicovaginal smear, the cost to increase the discounted life expectancy per patient by 1 year was $2,805 for the laboratory component alone and $19,655 for the entire cervical cancer prevention strategy. In moderate- to high-risk women, cervical cancer screening was cost-effective even at high cytology laboratory costs (eg, $75 per smear). New technologies were cost-effective only if they resulted in a substantial increase in the detection of high-grade squamous intraepithelial lesions (eg, an additional 236 high-grade squamous intraepithelial lesions per 10,000 women). New technologies have not demonstrated these increased detection rates.

Cost-Benefit Analysis↗
PubMed2003

Genome analysis technologies: towards species identification by genotype.

Traditional identification of species has been based on phenotypic traits, although it is clear that, theoretically, genotype-based classification is more accurate. This is especially the case for microorganisms which possess less identifiable traits and are more easily influenced by environment. Therefore, technology that allows identification of species based on genotype is highly desirable. Whole genome sequencing can provide a sufficient amount of information and can be determinative for this purpose but is very impractical for routine use. Thus, a competent technology is needed that allows a reproducible reduction in the amount of information required about a whole genome, while still providing sufficiently accurate identification. It is almost imperative for such a technology to be of a high cost-performance and of easy handling. Universality and portability are also strongly desired. Based on these criteria, the current state of genome analysis technologies are reviewed. Among various methodologies discussed here, amplified fragment length polymorphism (AFLP), genome profiling (GP) and microarrays are the subject of particular attention. As species identification is a base for most fields of biology including microbiology, ecology, epidemiology and for various biotechnologies, it is of paramount importance to establish a more efficient, easily handled and more objective methodology, in parallel with conventional phenotype-based methodologies. GP is currently considered to have the most optimal nature for identification of species since it can reproducibly reduce a huge amount of genome information to a manageable size by way of random polymerase chain reaction and can extract a sufficient amount of information for species identification from the DNA fragments thus profiled by temperature gradient gel electrophoresis. The potential ability of DNA microarrays for this purpose is also discussed and promises much for the future.

Genome↗
PubMed2002

Concept and prototype of protein-ligand docking simulator with force feedback technology.

A novel concept for a protein-ligand docking simulator using Virtual Reality (VR) technologies, in particular the tactile sense technology, was designed and a prototype was developed. Most conventional docking simulators are based on numerical differential calculations of the total energy between a protein and a ligand. However, the basic concept of our method differs from that of conventional simulators. Our design utilizes the force between a ligand and a protein instead of the total energy. The most characteristic function of the system is its ability to enable the user to 'touch' and sense the electrostatic potential field of a protein molecule. The user can scan the surface of a protein using a globular probe, which is given an electrostatic charge, and is controlled by a force feedback device. The electrostatic force between the protein and the probe is calculated in real time and immediately fed back into the force feedback device. The user can easily search interactively for positions where the probe is strongly attracted to the force field. Such positions can be regarded as candidate sites where functional groups of ligands corresponding to the probe can bind to the target protein. Certain limitations remain; for example, only twenty protein atoms can be used to generate the electrostatic field. Furthermore, the system can only use globular probes, preventing drug molecules or small chemical groups from being simulated. These limitations are the result of our insufficient computer resources. However, our prototype system has the potential to become a novel application method as well as being applicable to conventional VR technologies, especially to force feedback technologies.

Computational Biology↗
PubMed2000

Age-related effects of blocked and random practice schedules on learning a new technology.

Computer technology is pervasive in today's society. Issues of training must be investigated to ensure that older individuals are capable of interacting with such technology. In the present research a simulated automatic teller machine (ATM) served as a prototypical technology for which issues of training and transfer could be investigated. The focus of the study was on the potential benefits of a random practice schedule (wherein trial types are intermixed) relative to a blocked practice schedule (wherein trial types are grouped together). Both younger and older adults benefited from random practice for the acquisition of the ability to perform transactions on an ATM. Moreover, random practice was beneficial for both age groups in the transfer of learning to novel tasks on a novel ATM. These data have general implications for theories of training and specific implications for the development of training protocols for older adults and new technologies.

Adolescent↗
PubMed2004

DNA chip technology in brain banks: confronting a degrading world.

DNA microarray technology is based on the principle of hybridization between 2 complementary strands of nucleic acids, one being fixed into a solid membrane, the other being the sample to analyze. This has resulted in a very powerful method to examine differential gene expression between samples, and has been widely used in the study of tumors. The application of DNA microarray technology to the study of the nervous system has to consider several properties of the nervous tissue: composition of various neuronal types, as well as astrocytes, oligodendrocytes, and microglia; regional and area differences; developmental and age-dependent variations; and functional and pathological status. Moreover, human samples are usually obtained postmortem following variable agonal periods and postmortem delays between death and tissue preservation, which are accompanied by variable RNA degradation. Yet human postmortem nervous tissue stored in brain banks offers a unique opportunity to facilitate material for the study of diseases of the nervous system and to gain direct understanding on the mechanisms of disease. This review analyzes the application of DNA microarray technology to current practice using brain-banked tissues in order to recognize and minimize sub-optimal processing of brain samples and to correct pitfalls due to inadequate procedures. Also discussed are RNA preservation and RNA degradation effects on expression pattern assessments, analysis of individual versus pooled samples, array normalization, types of DNA chip platforms, whole genomic analysis versus specialized chips, and microgenomics. Minimizing RNA degradation and improving detection of resistant RNA in postmortem brain has been considered in detail in order to improve the efficiency and reliability of DNA microarray technology employed in the study of human postmortem nervous tissue.

Animals↗
PubMed2001

Diversity arrays: a solid state technology for sequence information independent genotyping.

Here we present the successful application of the microarray technology platform to the analysis of DNA polymorphisms. Using the rice genome as a model, we demonstrate the potential of a high-throughput genome analysis method called Diversity Array Technology, DArT'. In the format presented here the technology is assaying for the presence (or amount) of a specific DNA fragment in a representation derived from the total genomic DNA of an organism or a population of organisms. Two different approaches are presented: the first involves contrasting two representations on a single array while the second involves contrasting a representation with a reference DNA fragment common to all elements of the array. The Diversity Panels created using this method allow genetic fingerprinting of any organism or group of organisms belonging to the gene pool from which the panel was developed. Diversity Arrays enable rapid and economical application of a highly parallel, solid-state genotyping technology to any genome or complex genomic mixtures.

Blotting, Southern↗
PubMed2006

In vitro display technologies reveal novel biopharmaceutics.

Display technologies are fundamental to the isolation of specific high-affinity binding proteins for diagnostic and therapeutic applications in cancer, neurodegenerative, and infectious diseases as well as autoimmune and inflammatory disorders. Applications extend into the broad field of antibody (Ab) engineering, synthetic enzymes, proteomics, and cell-free protein synthesis. Recently, in vitro display technologies have come to prominence due to the isolation of high-affinity human antibodies by phage display, the development of novel scaffolds for ribosome display, and the discovery of novel protein-protein interactions. In vitro display represents an emerging and innovative technology for the rapid isolation and evolution of high-affinity peptides and proteins. So far, only one clinical drug candidate produced by in vitro display technology has been approved by the FDA for use in humans, but several are in clinical or preclinical testing. This review highlights recent advances in various engineered biopharmaceutical products isolated by in vitro display with a focus on the commercial developments.

Biopharmaceutics↗
PubMed2003

Effect of repeated assisted reproductive technology on ovarian response.

PURPOSE OF REVIEW: Based on current rates of success, many infertile couples who desire pregnancy have to undergo repeated cycles of assisted reproductive technology. Concern has been raised that repeated cycles of assisted reproductive technology may have a detrimental effect on future ovarian response and function, as well as pregnancy. This review summarizes current knowledge of the effects of repeated assisted reproductive technology, highlighting recent publications. RECENT FINDINGS: The available published evidence so far indicates that the follicular response and the number of oocytes retrieved appears to be maintained with repeated treatment and the only significant decline in ovarian response is because of an increase in female age. Similarly pregnancy and live birth rates decline to a small degree only up to cycle 3 or 4, with increasing female age again being the prime determinant. Encouraging patients to undertake repeated treatment without undue delay leads to improved cumulative rates of pregnancy and live birth. Current evidence does not indicate that ovarian stimulation leads to an increased risk of ovarian malignancy. SUMMARY: Couples should be counselled from the outset that assisted reproductive technology treatment is a continuum and a number of treatment cycles may be necessary. At present, there is little indication that repeated cycles have a detrimental effect on ovarian function, although the outcome of further research is awaited.

Female↗
PubMed1997

Introducing information technologies into medical education: activities of the AAMC.

Previous articles in this column have discussed how new information technologies are revolutionizing medical education. In this article, two staff members from the Association of American Medical College's Division of Medical Education discuss how the Association (the AAMC) is working both to support the introduction of new technologies into medical education and to facilitate dialogue on information technology and curriculum issues among AAMC constituents and staff. The authors describe six AAMC initiatives related to computing in medical education: the Medical School Objectives Project, the National Curriculum Database Project, the Information Technology and Medical Education Project, a professional development program for chief information officers, the AAMC ACCESS Data Collection and Dissemination System, and the internal Staff Interest Group on Medical Informatics and Medical Education.

Curriculum↗
PubMed2003

New molecular research technologies in the study of muscle disease.

PURPOSE OF REVIEW: To describe the current technologies and progress in DNA polymorphism association studies, mRNA expression profiling (microarrays), and proteomics with respect to muscle disease, and the increasing impact of public-access databases of genome-wide information. RECENT FINDINGS: mRNA expression profiling is becoming the most mature of the highly parallel molecular technologies, with microarrays now able to query the large majority of all genes using 1 million oligonucleotide probes built on 1.2-cm2 glass substrates. Applications of microarrays to normal muscle physiology and muscle disease are discussed. Single nucleotide polymorphism association studies promise to determine the predisposition of individuals to acquired muscle disease, including sarcopenia and atrophy, although such studies are in their infancy. Proteomics technologies do not enjoy the sensitivity and specificity of hybridization, and must instead rely on mass spectrometers. Mass spectrometry technology is advancing rapidly, although the sensitivity and throughput is far behind that of mRNA expression profiling. SUMMARY: As the gene mutations responsible for many types of muscular dystrophy and myopathy have been discovered, protein and gene testing has been integrated into the standard patient diagnostic workup. Future developments will include simpler and less expensive molecular diagnostics, advances in the understanding of downstream consequences of these defects, and the genetic predispositions underlying acquired muscle disease.

Female↗