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Biomedical subjects

S Tu

Publications and source records attributed to S Tu.

At least 19 recordsLinked to original sources

Health-related issues in individuals with agenesis of the corpus callosum.

OBJECTIVES: To explore and compare the prevalence and expression of specific health-related variables in a large survey sample of persons with agenesis of the corpus callosum (ACC) and their siblings. METHODS: Caregiver surveys of individuals with ACC (n=189) and their siblings (n=189) provided data regarding diagnoses, physical features, neurological and sensory information, feeding, elimination and sleep concerns, and some behavioural features. RESULTS: Compared with their siblings, individuals with ACC had more concurrent conditions and were more likely to have altered pain perception and sensitivity to touch. In addition, individuals with ACC had more sensory deficits and abnormalities as well as altered patterns of feeding/eating, elimination and sleep. CONCLUSIONS: These data raise important questions for future research and suggest the need for increased vigilance by caregivers and health-care professionals of individuals with callosal disorders. Early detection and intervention may help prevent or ameliorate health problems in this population.

Adolescent↗

Decision support, knowledge representation and management in medicine.

OBJECTIVES: Clinical decision-support systems (CDSSs) are being recognized as important tools for improving quality of care. In this paper, we review the literature to find trends in CDSSs that were developed over the last few decades and give some indication of future directions in developing successful, usable clinical decision-support systems. METHODS: We searched PubMed for papers that were published during the past five years with the words Decision Support Systems appearing in the title and used our own knowledge of the field for earlier work. RESULTS: The goals of developers of modern CDSSs are to develop systems that deliver needed information and could be integrated with the healthcare's organizational dynamics. Such CDSSs form part of knowledge-management activities that healthcare organizations employ in order to excel. During the past few decades, we have witnessed a gradual maturation of knowledge representation formalisms and the needed infrastructure for developing integrated CDSSs, including electronic health record systems (EHR), standard terminologies, and messaging standards for exchange of clinical data. The demand for CDSSs that are effective and that will evolve as circumstances change gave rise to methodologies that guide developers on the construction and evaluation of CDSSs. CONCLUSION: Although there exist many approaches for representing, managing and delivering clinical knowledge, the design and implementation of good and useful systems that will last and evolve are still active areas of research. The gradual maturation of EHR and infrastructure standards should make it possible for CDSSs implementers to make major contributions to the delivery of healthcare.

Decision Making, Computer-Assisted↗

Phytoremediation of arsenic-contaminated groundwater by the arsenic hyperaccumulating fern Pteris vittata L.

Arsenic concentrations in a much larger fraction of U.S. groundwater sources will exceed the maximum contaminant limit when the new 10 microg L(-1) EPA standard for drinking water takes effect in 2006. Thus, it is important to develop remediation technologies that can meet this new standard. Phytoremediation of arsenic-contaminated groundwater is a relatively new idea. In this research, an arsenic-hyperaccumulating fern, commonly known as Chinese Brake fern (Pteris vittata L.), was grown hydroponically to examine its effectiveness in arsenic removal from what is believed to be herbicide-contaminated groundwater. One plant grown in 600 mL of groundwater effectively reduced the arsenic concentration from 46 to less than 10 microg L(-1) in 3 days. Re-used plants continued to take up arsenic from the groundwater, albeit at a slower rate (from 46 to 20 microg L(-1) during the same time). Young fern plants were more efficient in removing arsenic than were older fern plants of similar size. The addition of a supplement of phosphate-free Hoagland nutrition to the groundwater had little effect on arsenic removal, but the addition of phosphate nutrition significantly reduced its arsenic affinity and, thus, inhibited the arsenic removal. This study suggested that Chinese Brake has some potential to remove arsenic from groundwater.

Arsenic↗

Cdc42 is a substrate for caspases and influences Fas-induced apoptosis.

Fas-mediated apoptosis results in the activation of caspases, which subsequently cleave cellular substrates that are essential for normal cell viability. In the present study, we show that the Ras-related GTP-binding protein Cdc42 is susceptible to caspase-catalyzed proteolysis in a number of cell lines, including NIH3T3 fibroblasts, human breast cancer cells (e.g. T47D), and COS-7 cells. Both caspase-3 and caspase-7 were able to catalyze the cleavage of Cdc42, whereas caspase-6 and caspase-8 were without effect. The susceptibility to the caspase-stimulated degradation is specific; although Rac can also serve as a caspase substrate, neither Rho nor Ras is degraded. Caspase sensitivity is conferred by a consensus sequence (DXXD) that lies immediately upstream of the Rho insert regions (residues 122-134) of Cdc42 and Rac. The removal of a stretch of residues (120) that includes the insert region or site-directed mutagenesis of either aspartic acid 118 or 121 within a constitutively active background (i.e. Cdc42(F28L)) as well as a wild-type Cdc42 background yields Cdc42 molecules that provide a marked protection against Fas ligand-induced apoptosis. Overall, these results are consistent with a model in which Cdc42 acts downstream of Fas, perhaps to influence the rate of apoptosis, with the ultimate caspase-mediated degradation of Cdc42 then allowing for a maximal apoptotic response.

3T3 Cells↗

What is the value added by human intervention in protein structure prediction?

This article presents results of blind predictions submitted to the CASP4 protein structure prediction experiment. We made two sets of predictions: one using the fully automated SAM-T99 server and one using the improved SAM-T2K method with human intervention. Both methods use iterative hidden Markov model-based methods for constructing protein family profiles, using only sequence information. Although the SAM-T99 method is purely sequence based, the SAM-T2K method uses the predicted secondary structure of the target sequence and the known secondary structure of the templates to improve fold recognition and alignment. In this article, we try to determine what aspects of the SAM-T2K method were responsible for its significantly better performance in the CASP4 experiment in the hopes of producing a better automatic prediction server. The use of secondary structure prediction seems to be the most valuable single improvement, though the combined total of various human interventions is probably at least as important.

Adenosine Triphosphatases↗

Sharable representation of clinical guidelines in GLIF: relationship to the Arden Syntax.

Clinical guidelines are intended to improve the quality and cost effectiveness of patient care. Integration of guidelines into electronic medical records and order-entry systems, in a way that enables delivery of patient-specific advice at the point of care, is likely to encourage guidelines acceptance and effectiveness. Among the methodologies for modeling guidelines and medical decision rules, the Arden Syntax for Medical Logic Modules and the GuideLine Interchange Format version 3 (GLIF3) emphasize the importance of sharing encoded logic across different medical institutions and implementation platforms. These two methodologies have similarities and differences; in this paper we clarify their roles. Both methods can be used to support sharing of medical knowledge, but they do so in complementary situations. The Arden Syntax is suitable for representing individual decision rules in self-contained units called Medical Logic Modules (MLMs), which are usually implemented as event-driven alerts or reminders. In contrast, GLIF3 is designed for encoding complex multistep guidelines that unfold over time. As a consequence, GLIF3 has several mechanisms for complexity management and additional constructs that may require overhead unnecessary for expressing simple alerts and reminders. Unlike the Arden Syntax, GLIF3 encourages a top-down process of guideline modeling consisting of three levels that are created in order: Level 1 comprises a human-readable flowchart of clinical decisions and actions. Level 2 comprises a computable specification that can be verified for logical consistency and completeness; and Level 3 comprises an implementable specification that includes information required for local adaptation of guideline logic as well as for mapping guideline variables onto institutional medical records. A major emphasis of the current GLIF3 development process has been to create the computable specification that formally represents medical decision and eligibility criteria. We based GLIF3's formal expression language on the Arden Syntax's logic grammar, making the necessary extensions to the Arden Syntax's data structures and operators to support GLIF3's object-oriented data model. We discuss why the process of generating a set of MLMs from a GLIF-encoded guideline cannot be automated, why it can result in information loss, and why simple medical rules are best represented as individual MLMs. We thus show that the Arden Syntax and GLIF3 play complementary roles in representing medical knowledge for clinical decision support.

Computer Simulation↗

Toward a representation format for sharable clinical guidelines.

Clinical guidelines are being developed for the purpose of reducing medical errors and unjustified variations in medical practice, and for basing medical practice on evidence. Encoding guidelines in a computer-interpretable format and integrating them with the electronic medical record can enable delivery of patient-specific recommendations when and where needed. Since great effort must be expended in developing high-quality guidelines, and in making them computer-interpretable, it is highly desirable to be able to share computer-interpretable guidelines (CIGs) among institutions. Adoption of a common format for representing CIGs is one approach to sharing. Factors that need to be considered in creating a format for sharable CIGs include (i) the scope of guidelines and their intended applications, (ii) the method of delivery of the recommendations, and (iii) the environment, consisting of the practice setting and the information system in which the guidelines will be applied. Several investigators have proposed solutions that improve the sharability of CIGs and, more generally, of medical knowledge. These approaches can be useful in the development of a format for sharable CIGs. Challenges in sharing CIGs also include the need to extend the traditional framework for disseminating guidelines to enable them to be integrated into practice. These extensions include processes for (i) local adaptation of recommendations encoded in shared generic guidelines and (ii) integration of guidelines into the institutional information systems.

Computer Simulation↗

A randomized, controlled, single-blind trial of leflunomide in the treatment of rheumatoid arthritis.

The efficacy and safety of leflunomide (LEF) in the treatment of rheumatoid arthritis (RA) were evaluated and the comparison with methotrexate's (MTX's) was performed in a 12-week, single-blind, randomized, parallel trial for treating 81 patients with RA. There were 56 cases in LEF group and 25 cases in MTX group. The dose of LEF was 20 mg per day and MTX 15 mg per week. All patients took oxaproxin simultaneously at the 4th to 6th week after the trail. The results showed that the general effective rate and notable effective rate were 94.64% and 73.21% in LEF group, 72% and 44% in MTX group, respectively, with the differences being statistically significant between the two groups (P < 0.05). LEF and oxaprozin could obviously improve the symptoms, signs and joint functions. The incidence of side reactions was lower in LEF group (17.86%) than in MTX group (40.00%, P < 0.05). LEF had a good therapeutic effect for RA, especially for refractory RA and had slight side reactions, and could be regarded as a superior immunosuppressive agent used in the treatment of RA and other connective tissue diseases.

Adolescent↗

Estramustine-related hypocalcemia in patients with prostate carcinoma and osteoblastic metastases.

We describe a patient with androgen-independent prostate cancer in whom hypocalcemia developed during treatment with estramustine. The patient's total serum calcium level before and after the initiation of estramustine was 8.3 and 4.3 mg/dL, respectively (normal range 8.4 to 10.2). This finding prompted us to review the calcium levels in 135 consecutive patients who were also undergoing treatment with a similar estramustine-containing regimen. We found that hypocalcemia had developed in 20% of these patients during treatment. We speculate that estramustine may cause hypocalcemia by inhibiting the mobilization of calcium and the action of the parathyroid hormone in the skeleton.

Adenocarcinoma↗

Effects and mechanisms of somatostatin analogs on apoptosis of pancreatic acinar cells in acute pancreatitis in mice.

AIM: To investigate the effects of somatostatin analogs (SSa) on apoptosis of pancreatic acinar cells and apoptosis-regulated gene bax, and p53 in treating acute pancreatitis in mice. METHODS: In cerulein-induced pancreatitis, with or without treatment of somatostatin, analogs (Octreotide) in CD-1 (BALB/c x DBetaAlpha/1) mice, apoptosis of pancreatic acinar cells was detected by using the TdT-mediated dUTP nick-end labeling (TUNEL) method, and the expression of apoptosis-regulated gene bax and p53 was determined by using the streptavidin-peroxidase immunohistochemical technique and the RT-PCR method, respectively. RESULTS: On HE staining, acinar cells in the pancreas showed pyknotic nuclei and the formation of apoptotic bodies, which are the typical morphological features of apoptosis. Regarding TUNEL use, the apoptotic index of pancreatic acinar cells in the non-treated group at 5 and 14 h after induction of acute pancreatitis was significantly lower than those of the SSa-treated group, respectively (P < 0.01). On immunohistochemistry and RT-PCR, there was an expression of neither bax nor p53 in normal pancreatic tissues. The expression of bax in the SSa-treated group at 5 and 14 h after treatment of SSa was markedly higher than those of the non-treated group, respectively (P < 0.01), but there was no significant difference in the expression of p53 between the SSa-treated group and the non-treated group. CONCLUSIONS: The induction of apoptosis in pancreatic acinar cells injury to reduce inflammatory reaction might be one of the mechanisms of SSa in treating acute pancreatitis in mice, and the mechanisms of apoptosis probably correlated with the expression of apoptosis-regulated gene bax, but have no relationship with the expression of p53.

Acute Disease↗

[Temperature distribution of tumor tissues irradiated by microwave].

This paper calculates the temperature distribution of the spherical tumor, applying the theory of electromagnetic scattering and the thermal conductivity of tissues (including normal tissues and tumor tissues). Our research work will be of some value in clinical medicine.

Body Temperature↗

Neurotrophins, but not depolarization, regulate substance P expression in the developing optic tectum.

Neurotransmitter expression can be regulated by both activity and neurotrophins in a number of in vitro systems. We examined whether either of these factors was likely to play a role in the in vivo optic nerve-dependent regulation of a substance P-like immunoreactive (SP-ir) population of cells in the developing optic tectum of the frog. In contrast to our previous results with the adult system, blocking tectal cell responses to glutamate release by retinal ganglion cells with 6-cyano-7-nitroquinoxaline-2,3 dione (CNQX) did not affect the percent of SP-ir cells in the developing tectum. Treatment with d-(-)-2-amino-5-phosphonovaleric acid (d-AP-5) was also ineffective in this regard, although both it and CNQX treatment disrupted visual map topography. Chronic treatment with brain-derived neurotrophic factor (BDNF) and neurotrophin-4/5 (NT-4/5) produced increases in SP-ir cells in the treated lobes of normal animals, which were significant in the case of NT-4/5. Both substances also prevented the decrease of SP cells that would otherwise occur in the deafferented lobe of unilaterally optic nerve-transected tadpoles. These changes in the percent of SP-ir cells occurred without any detectable changes in the overall number of tectal cells. NGF had no effect on SP expression. Nor did it affect topographic map formation, which was disrupted by treatment with either BDNF or NT-4/5. Our results demonstrate that different mechanisms regulate SP expression in the developing and adult tectum. They indicate that neurotrophin levels in the developing optic tectum may selectively regulate a specific neuropeptide-expressing population of cells.

2-Amino-5-phosphonovalerate↗

Achieving reuse of computable guideline systems.

We describe an architecture for reusing computable guidelines and the programs used to interpret them across varied legacy clinical systems. Developed for the PRODIGY 3 project, our architecture aims to support interactive, point of care use of guidelines in primary care. Legacy medical record systems in UK primary care are diverse, using different terminologies, different data models, and varying user-interface philosophies. However, our goal is to provide common guideline knowledge bases and system components, while achieving full integration with the host medical record system, and a user interface tailored to that system. In conjunction with system suppliers, we identified areas of standardization required to achieve this goal. Firstly, standardized interfaces were created for mediation with the legacy system medical record and for act management. Secondly, a standard interface was developed for communication with the User Interface for guideline interaction. Thirdly, a terminology mapping knowledge base and system component was provided. Lastly, we developed a numeric unit conversion knowledge base and system component. The standardization of this architecture was achieved by close collaboration with existing vendors of Primary Care computing systems in the UK. The work has been verified by two suppliers successfully building and deploying systems with User Interfaces which mirror their normal look and feel, communicating fully with existing medical records, while using identical Guideline Interpreter components and knowledge bases. Encouragingly further experiments in other areas of clinical decision support have not required extension of our interfaces.

Artificial Intelligence↗

Sharable computer-based clinical practice guidelines: rationale, obstacles, approaches, and prospects.

Clinical practice guideline automation at the point of care is of growing interest, yet most guidelines are authored in unstructured narrative form. Computer-based execution depends on a formal structured representation, and also faces a number of other challenges at all stages of the guideline lifecycle: modeling, authoring, dissemination, implementation, and update. This is because of the multiplicity of conceptual models, authoring tools, authoring approaches, intended applications, implementation platforms, and local interface requirements and operational constraints. Complexity and time required for development and structure are also huge obstacles. These factors argue for convergence on a common shared model for representation that can be the basis of dissemination. A common model would facilitate direct interpretation or mapping to multiple implementation environments. GLIF (GuideLine Interchange Format) is a formal representation model for guidelines, created by the InterMed Collaboratory as a proposed basis for a shared representation. GLIF currently addresses the process of authoring and dissemination; the InterMed team's major focus now is on tools to facilitate these tasks and the mapping to clinical information system environments. Because of limitations in what can be done by a single team with finite resources, however, and the variety of additional perspectives that need to be accommodated, the InterMed team has determined that further development of a shared representation would be best served as an open process in which the world community is engaged. Under the auspices of the HL7 Decision Support Technical Committee, a GLIF Special Interest Group has been established, which is intended to be a forum for collaborative refinement and extension of a standard representation that can support the needs of the guideline lifecycle. Significant areas for future work will need to include demonstrations of effective means for incorporating guide-lines at point of care, reconciliation of functional requirements of different models and identification of those most important for supporting practical implementation, im-proved means for authoring and management of complexity, and methods for automatically analyzing and validating syntax, semantics, and logical consistency of guidelines.

Artificial Intelligence↗

Handling expressiveness and comprehensibility requirements in GLIF3.

Clinical guidelines are aimed at standardizing patient care and improving its quality and cost effectiveness. Guidelines represented in a computer-interpretable (CI) format can be used to provide automatic decision support applied to individual patients during the clinical encounter. The process of creating computer-interpretable guidelines (CIG) re-moves ambiguities contained in paper-based guidelines, thus making the guideline more comprehensible. For these reasons, CIGs may have a larger impact on clinician behavior than paper-based guidelines. Since much effort goes into creating guidelines in a CI format, it is desirable that different institutions and software systems share them. In a guideline representation workshop hosted by the InterMed Collaboratory in March 2000, the need for a standard representation format for sharable CIGs was recognized. As a first step towards achieving this goal, we proposed a set of functional requirements for sharable CIGs. The requirements encompass the entire life cycle of a CIG: development, implementation, use and maintenance. In this paper we discuss requirements that are important during the development stage of a CIG. We have abstracted the requirements into two groups: expressiveness--the ability to ex-press the knowledge content of different types of guidelines--and comprehensibility--the ability to manage complexity, facilitate coherence, and visualize a guideline model to aid in human comprehension. The Guideline Interchange For-mat version 3 (GLIF3) is a language for structured representation of CIGs. It is under development to facilitate sharing CIGs among different institutions and systems. We illustrate how GLIF3 meets the specified development requirements.

Decision Making, Computer-Assisted↗

[Clinic intervention study on urogenital mycoplasma infection of pregnant women].

OBJECTIVE: To explore the hypothesis of pathogenic relationship between urogenital mycoplasma infection and adverse perinatal outcomes. METHODS: Four hundred and eighty-eight mycoplasma-positive pregnant women detected by culture method were randomly divided into erythromycine-intervention group and non-intervention group. Comparison was made on rate of reverse sero-conversion, of vertical transmission to mycoplasma and adverse perinatal outcomes incidence between groups. RESULTS: Ureaplasma urealyticum sero-conversion rate and rate of vertical-transmission in intervention group were significantly lower than in non-intervention group (P < 0.05). The incidences rates of preturm labor, post partum fever, puerperal infection and neonate pneumonia in intervention group were significantly lower than in non-intervention group (P < 0.05). CONCLUSION: Erythromycin is effective in control of ureaplasma urealyticum infection among pregnant women through cutting off vertical transmission passway and lowering adverse perinatal outcomes against ureaplasma urealyticum.

Anti-Bacterial Agents↗

Using features of Arden Syntax with object-oriented medical data models for guideline modeling.

Computer-interpretable guidelines (CIGs) can deliver patient-specific decision support at the point of care. CIGs base their recommendations on eligibility and decision criteria that relate medical concepts to patient data. CIG models use expression languages for specifying these criteria, and define models for medical data to which the expressions can refer. In developing version 3 of the GuideLine Interchange Format (GLIF3), we used existing standards as the medical data model and expression language. We investigated the object-oriented HL7 Reference Information Model (RIM) as a default data model. We developed an expression language, called GEL, based on Arden Syntax's logic grammar. Together with other GLIF constructs, GEL reconciles incompatibilities between the data models of Arden Syntax and the HL7 RIM. These incompatibilities include Arden's lack of support for complex data types and time intervals, and the mismatch between Arden's single primary time and multiple time attributes of the HL7 RIM.

Decision Making, Computer-Assisted↗

Activity-dependent regulation of substance P expression and topographic map maintenance by a cholinergic pathway.

We have assessed the role of activity in the adult frog visual system in modulating two aspects of neuronal plasticity: neurotransmitter expression and topographic map maintenance. Chronic treatment of one tectal lobe with the non-NMDA receptor antagonist, 6-cyano-7-nitroquinoxaline-2,3-dione decreased the percentage of substance P-like immunoreactive (SP-IR) tectal cells in the untreated lobe while disrupting topographic map formation in the treated one. Treatment with the NMDA receptor antagonist d-(-)-2-amino-5-phosphonovaleric acid (d-AP-5) disrupted the topographic map but had no affect on SP-IR cells. These results indicate that maintenance of the topographic map is dependent on direct input from the glutamatergic retinal ganglion cells, whereas substance P (SP) expression is being regulated by a pathway that relays activity from one tectal lobe to the other. Such a pathway is provided by the cholinergic nucleus isthmi, which is reciprocally connected to the ipsilateral tectum and sends a projection to the contralateral one. Mecamylamine and atropine, antagonists of nicotinic and muscarinic receptors, respectively, were used together to block all cholinergic activity or alone to block receptor subclass activity. All three treatments decreased SP expression and disrupted the topographic map in the treated tectal lobe. We conclude that both SP expression and topographic map maintenance in the adult optic tectum are activity-dependent processes. Although our results are consistent with the maintenance of the topographic map through an NMDA receptor-based mechanism, they suggest that SP expression is regulated by a cholinergic interaction that depends on retinal ganglion cell input only for its activation.

2-Amino-5-phosphonovalerate↗