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PubMed2001

Genomics: implications for health systems.

In anticipation of and following the announcement of the completion of the mapping of the human genome, numerous articles have appeared in scientific, industry, and consumer journals and magazines on the topic of genomics. Building off the excitement surrounding this scientific milestone, many of these articles--irrespective of the audience--look to the future and anticipate how this knowledge breakthrough will change the way classes of diseases are diagnosed, treated, and even prevented over the next several generations. However, literature that explores the potential effect of genomics on health system care delivery is virtually nonexistent. As such, this article begins to prepare health system executives for the future by speculating how genomics may affect their organizations and suggesting strategies for future success.

Delivery of Health Care↗
PubMed2004

Relationship between small group problem-solving activity and lectures in health science curricula.

Components of problem-based education, such as small group teaching, are being implemented in diverse health curricula. Implementation, however, is often motivated by the intuitive appeal of many problem-based learning components, when what is needed is the detailed examination of how these components support students' integration of knowledge as well as continuity of their learning experiences. This study presents an investigation of the relationship between lecture and small group teaching (SGT) in a medical curriculum. Four problem-oriented SGT sessions representing diverse topics in the first-year curriculum and their corresponding lectures were videotaped and analyzed using techniques of concept mapping, where the broad concepts from the lectures were identified and matched to the case-specific concepts in the small group sessions. The results show that lectures function as an anchor for the students' discussion of issues relevant to clinical problem-solving and interventions in small group sessions. These discussions extended to contextual aspects of clinical practice that were not dealt with in the lectures, such as ethical/cultural issues around the treatment of patients. Furthermore, small group environments were found to promote discussions that allowed the integration of information from different sources and encompassed concepts across a number of disciplines. These results suggest that carefully designed small group sessions serve the purposes of 1) illustrating broader concepts in lectures to case-specific, clinically relevant problem-solving and 2) promoting knowledge integration from diverse sources of information. The implications of these results for learning and reasoning in health science curricula are discussed.

Cardiology↗
PubMed1997

Extending the standard architecture for healthcare units: the guideline server.

The main topic of our research is health care unit (HCU) reengineering. To this aim, a guideline oriented conceptual model of HCUs was developed. In order to map this conceptual model into an information system with a client-server architecture, a guideline server is needed. The guideline concept and its life cycle are introduced and the main functions of the guideline server are presented.

Case Management↗
PubMed2004

fMRI activation maps based on the NN-ARx model.

The most significant progresses in the understanding of human brain functions have been possible due to the use of functional magnetic resonance imaging (fMRI), which when used in combination with other standard neuroimaging techniques (i.e., EEG) provides researchers with a potential tool to elucidate many biophysical principles, established previously by animal comparative studies. However, to date, most of the methods proposed in the literature seeking fMRI signs have been limited to the use of a top-down data analysis approach, thus ignoring a pool of physiological facts. In spite of the important contributions achieved by applying these methods to actual data, there is a disproportionate gap between theoretical models and data-analysis strategies while trying to focus on several new prospects, like for example fMRI/EEG data fusion, causality/connectivity patterns, and nonlinear BOLD signal dynamics. In this paper, we propose a new approach which will allow many of the abovementioned hot topics to be addressed in the near future with an underlying interpretability based on bottom-up modeling. In particular, the theta-MAP presented in the paper to test brain activation corresponds very well with the standardized t test of the SPM99 toolbox. Additionally, a new Impulse Response Function (IRF) has been formulated, directly related to the well-established concept of the hemodynamics response function (HRF). The model uses not only the information contained in the signal but also that in the structure of the background noise to simultaneously estimate the IRF and the autocorrelation function (ACF) by using an autoregressive (AR) model with a filtered Poisson process driving the dynamics. The short-range contributions of voxels within the near-neighborhood are also included, and the potential drift was characterized by a polynomial series. Since our model originated from an immediate extension of the hemodynamics approach [Friston, K.J., Mechelli, A., Turner, R., Price C.J. (2000a). Nonlinear responses in fMRI: the balloon model, volterra kernels, and other hemodynamics. NeuroImage 12, 466-477.], a natural interpretability of the results is feasible.

Algorithms↗
PubMed2006

Kinase inhibitors and airway inflammation.

Kinases are believed to play a crucial role in the expression and activation of inflammatory mediators in the airway, in T-cell function and airway remodelling. Important kinases such as Inhibitor of kappaB kinase (IKK)2, mitogen activated protein (MAP) kinases and phsopho-inositol (PI)3 kinase regulate inflammation either through activation of pro-inflammatory transcription factors such as activating protein-1 (AP-1) and nuclear factor kappaB (NF-kappaB), which are activated in airway disease, or through regulation of mRNA half-life. Selective kinase inhibitors have been developed which reduce inflammation and some characteristics of disease in animal models. Targeting specific kinases that are overexpressed or over active in disease should allow for selective treatment of respiratory diseases. Interest in this area has intensified due to the success of the specific Abelson murine leukaemia viral oncogene (Abl) kinase inhibitor imatinib mesylate (Gleevec) in the treatment of chronic myelogenous leukaemia. Encouraging data from animal models and primary cells and early Phase I and II studies in other diseases suggest that inhibitors of p38 MAP kinase and IKK2 may prove to be useful novel therapies in the treatment of severe asthma, chronic obstructive pulmonary disease (COPD), cystic fibrosis and other inflammatory airway diseases.

Animals↗
PubMed2003

Unmatched masses in peptide mass fingerprints caused by cross-contamination: an updated statistical result.

Unmatched masses are often observed in the experimental peptide mass spectra when database searching is performed with the ProFound program. Comparison between theoretical and experimental mass spectra of standard proteins shows that contamination accounts for most of the unmatched masses. In this retrospective analysis, the top 100 most probable contaminating masses, as listed in order of their probability, are statistically filtered out from 118 different experimental peptide mass fingerprinting (PMF) maps. Most of the interfering masses originate from trypsin autolysis and human keratins. Subtraction of known contaminants from raw data and using cleaner masses for searching can enhance protein identification by PMF.

Animals↗
PubMed1994

Sensitization of insensitive branches of C nociceptors in human skin.

1. Eighteen cutaneous mechanosensitive C nociceptors were recorded from the peroneal nerves of healthy human subjects. Their identity was continuously monitored by intracutaneous electrical stimulation, and their activation by mechanical or transcutaneous electrical stimulation was detected by slowing of conduction velocity during the relative refractory period. 2. Mechanoreceptive fields (mRFs) mapped with suprathreshold von Frey hair stimuli covered an area of 99 +/- 21 mm2 (mean +/- S.E.M.). Two of the units had separate mRFs, with borders about 0.5-1.5 cm apart from each other and the largest of these units had a maximal diameter of 4.5 cm. 3. Successive topical application of mustard oil and capsaicin induced expansions of mRFs by 57 +/- 14 mm2 in eight of fifteen units. 4. In twelve units transcutaneous electrical stimulation delivered through a pointed electrode was used for mapping the electroreceptive fields (eRFs). The borders of the eRFs and the mRFs were identical for two of twelve units only. In the other ten units additional mechano-insensitive areas (55 +/- 22 mm2) were detected from which transcutaneous electrical stimuli could activate the respective unit. 5. Application of mustard oil and capsaicin to these mechano-insensitive areas sensitized five of eight units to mechanical stimuli. In these cases the mRF after sensitization exactly corresponded to the eRF. 6. It is concluded that there are insensitive branches in human mechanosensitive cutaneous C nociceptors that can be detected by transcutaneous electrical stimulation and sensitized by topical application of chemical irritants. Activation of those branches in the course of inflammatory processes may contribute to spatial summation at central synapses and hence to hyperalgesia.

Adult↗
PubMed2005

Genomics, genetic epidemiology, and genomic medicine.

Medical science is on the threshold of unparalleled progress as a result of the advent of genomics and related disciplines. Human genomics, the study of structure, function, and interactions of all genes in the human genome, promises to improve the diagnosis, treatment, and prevention of disease. This opportunity is the result of the recent completion of the Human Genome Project. It is anticipated that genomics will bring to physicians a powerful means to discover hereditary elements that interact with environmental factors leading to disease. However, the expected transformation toward genomics-based medicine will occur over decades. It will require efforts of many scientists and physicians to begin now to sort out the vast amounts of information in the human genome and translate it to meaningful applications in clinical practice. Meanwhile, practicing physicians and health professionals need to be trained in the principles, applications, and limitations of genomics and genomic medicine. Only then will we be in a position to benefit patients, which is the ultimate goal of accelerating scientific progress in medicine. In this inaugural article, we introduce and discuss concepts, facts, and methods of genomics and genetic epidemiology that will be drawn on in the forthcoming topics of the clinical genomics series.

Chromosome Mapping↗
PubMed2000

The three faces of Occupational Medicine: printed paper, problems in practice, and professional purpose.

The 50-year run of the journal Occupational Medicine and its forbears demonstrates the ways in which UK occupational medical practice has developed and changed since 1950. This has been in response to changes in society, technology and medicine. The journal has played an important part in education and professional development. It has also been the voice for the aspirations and concerns of its readers. Two aspects stand out: the development of occupational medicine as a specialty, and the way in which a medical model for occupational health service provision has been championed. A distinguished line of journal editors has been central to the crystallization of ideas within occupational medicine and their editorials map out professional successes and challenges over the years.

Chronology as Topic↗
PubMed1993

Peptide mapping using EOF-driven capillary isoelectric focusing.

Capillary isoelectric focusing (CIEF) in uncoated and commercially available coated capillaries was applied to the separation of tryptic peptides from bovine and chicken cytochrome c. This is the first report of peptide mapping by CIEF. Before separation, the pIs of individual peptides expected to be formed during the digest were calculated, and then the separation pattern obtained was correlated with the calculated pIs. This correlation was reasonably good for some peptides, but not as good for others. However, differentiation of the two species digests was easily achieved based on the CIEF map. The major limitation of the method is the fact that uv detection at 280 nm must be employed, meaning that only tryptophan and tyrosine containing peptides will be detected, since the ampholytes used to generate the pH gradient absorb below 280 nm. Post-column derivatization of the peptides is one solution to this problem. Migration time reproducibility was on the order of 2%, and run times were less than 20 min for the entire pH gradient range in the uncoated capillary. In the coated capillary, superior resolution was obtained at the expense of longer run times.

Amino Acid Sequence↗
PubMed2000

Detection of BCR/ABL gene rearrangement and the elimination of rearranged clone in chronic myelocytic leukemia patients.

Cytogenetic and molecular studies were performed on 20 interferon-alpha receiving Turkish chronic myelocytic leukemia patients. Four different restriction endonucleases and bcr-G probe were used for southern blot analysis to detect rearrangements of the bcr gene. The RT-PCR method was also applied to detect chimeric bcr/abl mRNA. Seventeen patients showed a chromosomal break within the 5.8 kb M-bcr region by southern blot analysis while three cases out of 20 have not shown any rearrangement. These three cases were further analysed by RT-PCR and they were also found to be carrying the Philadelphia translocation (Ph). However, in four years of follow-up this RT-PCR positivity has disappeared, which suggests an elimination of Ph clone with prolonged interferon-alpha treatment.

Adult↗
PubMed1997

Spatial organization of facial vibrissae and cortical barrels in the guinea pig and golden hamster.

The arrangements of vibrissae in guinea pigs and golden hamsters were previously reported to be different from those in mice and rats. Whereas the mystacial pads in mice and rats include four straddlers and five rows of vibrissae, guinea pigs were described to possess six rows of irregularly aligned mystacial vibrissae and no straddlers, and golden hamsters to include seven vibrissal rows and also no straddlers. We found that all of these four species possess similar vibrissal arrangements within the mystacial pad. To demonstrate this similarity, we developed a new method of sinus hair visualization in flattened and cleared preparations of the mystacial pad. Intrinsic muscles of the mystacial pad that were revealed in thick histological preparations showed clearly the structural and functional relationships between straddlers and vibrissal rows. To verify this finding, and to extend the knowledge of vibrissal cortical representations in guinea pigs and golden hamsters, we have investigated the spatial organization and the functional vibrissal representations of barrels in the posteromedial barrel subfield (PMBSF) of these rodents. The barrel morphology was clearly preserved in Nissl-stained sections and sections processed for cytochrome oxidase of flattened cerebral cortices. We demonstrate that the vibrissal arrangement in the mystacial pad is replicated in the PMBSF of guinea pigs and golden hamsters and that this arrangement is similar to that found in mice and rats. To facilitate comparative studies, these findings strongly recommend the use, in guinea pigs and golden hamsters, of the same classifications and nomenclatures that are used in mice and rats to describe mystacial vibrissae and cortical barrels.

Animals↗
PubMed2005

Cross-cultural effect on the brain revisited: universal structures plus writing system variation.

Recognizing printed words requires the mapping of graphic forms, which vary with writing systems, to linguistic forms, which vary with languages. Using a newly developed meta-analytic approach, aggregated Gaussian-estimated sources (AGES; Chein et al. [2002]: Psychol Behav 77:635-639), we examined the neuroimaging results for word reading within and across writing systems and languages. To find commonalities, we compiled 25 studies in English and other Western European languages that use an alphabetic writing system, 9 studies of native Chinese reading, 5 studies of Japanese Kana (syllabic) reading, and 4 studies of Kanji (morpho-syllabic) reading. Using the AGES approach, we created meta-images within each writing system, isolated reliable foci of activation, and compared findings across writing systems and languages. The results suggest that these writing systems utilize a common network of regions in word processing. Writing systems engage largely the same systems in terms of gross cortical regions, but localization within those regions suggests differences across writing systems. In particular, the region known as the visual word form area (VWFA) shows strikingly consistent localization across tasks and across writing systems. This region in the left mid-fusiform gyrus is critical to word recognition across writing systems and languages.

Brain↗
PubMed2005

Stuttered and fluent speech production: an ALE meta-analysis of functional neuroimaging studies.

This study reports an activation likelihood estimation (ALE) meta-analysis of imaging studies of chronic developmental stuttering in adults. Two parallel meta-analyses were carried out: (1) stuttered production in the stutterers; (2) fluent production in the control subjects. The control subjects' data replicated previous analyses of single-word reading, identifying activation in primary motor cortex, premotor cortex, supplementary motor area, Rolandic operculum, lateral cerebellum, and auditory areas, among others. The stuttering subjects' analysis showed that similar brain areas are involved in stuttered speech as in fluent speech, but with some important differences. Motor areas were over-activated in stuttering, including primary motor cortex, supplementary motor area, cingulate motor area, and cerebellar vermis. Frontal operculum, Rolandic operculum, and anterior insula showed anomalous right-laterality in stutterers. Auditory activations, due to hearing one's own speech, were essentially undetectable in stutterers. The phenomenon of efference copy is proposed as a unifying account of the pattern activation revealed within this ALE meta-analysis. This provides the basis for a stuttering system model that is testable and should help to advance the understanding and treatment of this disorder.

Brain↗