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[Applications of nine types of free pedal flaps in hand surgery].

From 1987, nine types of free skin flap or composite free flap from the food were applied to treat 22 cases of hand injury. These flaps included 1. composite skin flap of pedal dorsum, first toe-web, toe-pulp, and toe dorsums with long extensor tendons of the toes, 2. composite skin flap of the second metatarsophalangeal joint; 3. "wrap around" flap; 4. the first web flap; 5. plantar skin flap of great toe with only the artery and nerve; 6. "wrap around" flap with dorsalis pedis flap; 7. composite dorsalis pedis flap with the second toe; 8. the dorsalis pedis flap with superficial peroneal nerve; and 9. the first web flap with the second metatars. The operative results were satisfactory. The authors discussed indications, merits and demerits of the free flaps of the foot and key points of the operation.

Adolescent↗

[Development and application of an Internet-based educational system to share pharmaceutical case reports between pharmacists].

For pharmacists to enhance skill of pharmaceutical cares, it is necessary to learn many instructive clinical cases, which include drug-related incidences and checks of medication errors by pharmacists. However, these cases tend to be kept in each facility and there is no access to the cases for outside pharmacists. Therefore, we aimed to develop an internet-based educational system to gather such cases, append educational commentaries by university staffs, and share them between pharmacists. An exclusive site was set up on the world wide web (WWW) homepage of the Section of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Kyushu University (http://seizai.phar.kyushu-u.ac.jp) on November 2000. Browsing was limited to registered pharmacists. Any pharmacist can be freely registered. Cases were collected via WWW-forms in the site. After educational commentaries and elucidation were appended, the cases were distributed to the registered pharmacists by e-mails and WWW pages. Many applications for membership have been sent from around Japan to have more than 50 members per month, and many cases have been contributed. These cases were distributed weekly by e-mail magazines. The developed system enabled us to share many educational cases of drug-related problems all over the country. This system could contribute to pharmacists to enhance their skills of pharmaceutical cares.

Education, Pharmacy, Continuing↗

SPIDER and WEB: processing and visualization of images in 3D electron microscopy and related fields.

The SPIDER system has evolved into a comprehensive tool set for image processing, making use of modern graphics interfacing in the VMS and UNIX environment. SPIDER and WEB handle the complementary tasks of batch processing and visualization of the results. The emphasis of the SPIDER system remains in the area of single particle averaging and reconstruction, although a variety of other application areas have been added. Novel features are a suite of operations relating to the determination, modeling, and correction of the contrast transfer function and the availability of the entire documentation in hypertext format.

Animals↗

Effects of platelet activating factor on rat platelets in vivo.

Platelet activating factor (PAF) is not able to aggregate rat platelets in vitro. Due to the agonist effects of PAF on multiple cells, a possible role of PAF in the activation of rat platelets in vivo where different cells may influence each other was investigated. The pulmonary microembolization of 51Cr-labelled activated platelets was used as in vivo model. This model allowed us to monitor platelet behaviour by means of non-invasive methods. In contrast to results obtained in vitro, PAF activated rat platelets in vivo. The pulmonary microembolization of the platelets was dose-dependent and rapidly reversible. About 0.5 microgram/kg PAF caused a half-maximal rise of platelet-bound radioactivity in the thorax. Activation of the platelets by PAF was followed by extreme desensitization, so that a second injection of PAF did not provoke a significant response of the platelets. Platelet function was, however, not completely impaired because they still accumulated in the thorax after the application of ADP (50 micrograms/kg). That pulmonary entrapment had taken place was shown by a 3-fold increase in lung specific radioactivity. This was accompanied by a short-lasting thrombocytopenia. The PAF antagonist, WEB 2170 (30 micrograms/kg), significantly inhibited the microembolization of the platelets induced by PAF. Under in vitro conditions leukocytes purified from rat blood and activated by PAF were able to induce platelet aggregation. These results demonstrate that a PAF-specific activation of rat platelets is achievable in vivo which is probably mediated by other cells.

Adenosine Diphosphate↗

Risk of mortality and complications in people with depressive disorder and co-occurring diabetes mellitus: a systematic review and meta-analysis.

AIMS: People with depressive disorder have increased premature mortality and higher rates of diabetes mellitus than general population. Evidence shows that diabetes may further increase their risk of premature death from diabetes-related complications, especially cardiovascular diseases (CVDs). Earlier studies examining depression-associated outcomes in diabetes patients have shown mixed results and were hindered by important limitations, especially the use of self-reported questionnaires to ascertain depression, causing misclassification bias by identifying subclinical symptoms or diabetes distress. Associations of depression with specific diabetes complications have not been systematically evaluated. This meta-analysis aimed to investigate the risk of mortality and complications among patients with depression and co-occurring diabetes (depression-diabetes group) relative to patients with diabetes-only (diabetes-only group), on their all-cause mortality rates, and if applicable cause-specific mortality rates, and occurrence of specific diabetes complications. METHODS: We systematically reviewed and quantitatively synthesized diabetes-related outcomes in patients with depression by searching Embase, MEDLINE, PsycInfo and Web-of-Science from inception to 20 December 2024, and included studies that examined mortality and complication outcomes in depression-diabetes group relative to diabetes-only group. Results were synthesized by random-effects meta-analytic models, with stratified-analyses (subgroup analyses and meta-regression) by study-level characteristics, including age, gender, study period, geographic region, follow-up duration and nature of diabetes sample. The study was registered with PROSPERO (CRD42024595145). RESULTS: Twenty-six studies were identified from nine geographic regions. Regarding mortality risk, depression-diabetes group exhibited increased risks of all-cause mortality (RR = 1.30 [95% CI: 1.21-1.39]) and CVD-specific mortality (1.15 [1.02-1.29]) relative to diabetes-only group. Regarding complication risk, depression-diabetes group showed increased risk of complications (1.28 [1.18-1.40]) relative to diabetes-only group, especially in incident-diabetes sample signifying advanced disease stage upon presentation, with stratified-analyses showing higher risk of metabolic complications (1.63 [1.33-1.99]) and cardiovascular complications (1.20 [1.11-1.29]), and lower likelihood of retinopathy (0.84 [0.76-0.94]), albeit comparable rates of cerebrovascular complications (1.36 [0.99-1.87]), nephropathy (1.09 [0.93-1.27]) and peripheral-vascular complications (0.97 [0.79-1.18]). Both overall mortality and complication risks were present in various regions and persisted over time. Heterogeneities were noted and could not be entirely explained by stratified analyses. CONCLUSIONS: Our study demonstrated that patients with depression and co-occurring diabetes were associated with elevated overall mortality risk and complication risk (particularly metabolic and cardiovascular-complications) than non-depressed counterparts, suggesting an overall poorer glycemic control that might eventually drive their earlier death. Comprehensive and multipronged interventions are needed for individualized risk estimation of diabetes-related outcomes, with consequent early interventions to minimize the avoidable physical morbidity and premature mortality in this vulnerable population.

Humans↗

Time to learn: the outlook for renewal of patient-centred education in the digital age.

BACKGROUND: Major forces in society and within health systems are fragmenting patient care and clinical learning. The distancing of physician and trainee from the patient undermines learning about the patient-doctor relationship. The disconnection of care and learning from one successive venue to another impedes the ability of trainees to learn about illness longitudinally. METHODS: As a conceptual piece, our methods have been those of witnessing the experiences of patients, practitioners, and students over time and observing the impact of fragmented systems and changing expectations on care and learning. We have reflected on the opportunities created by digital information systems and interactive telemedicine to help renew essential relationships. RESULTS: Although there is, as yet, little in the literature on educational or health outcomes of this kind of technological enablement, we anticipate opportunities for a renewed focus on the patient in that patient's own space and time. Multimedia applications can achieve not only real-time connections, but can help construct a "virtual patient" as a platform for supervision and assessment, permitting preceptors to evaluate trainee-patient interactions, utilization of Web-based data and human resources, and on-line professionalism. CONCLUSIONS: Just as diverse elements in society are capitalizing upon digital technology to create advantageous relationships, all of the elements in the complex systems of health care and medical training can be better connected, so as to put the patient back in the centre of care and the trainee's ongoing relationship to the patient back in the centre of education.

Clinical Competence↗

Bioinformatics in drug development and assessment.

Bioinformatics is playing an increasingly important role in nearly all aspects of drug discovery, drug assessment, and drug development. This growing importance lies not only in the role that bioinformatics plays in handling large volumes of data, but also in the utility of bioinformatics tools to predict, analyze, or help interpret clinical and preclinical findings. This review focuses on describing and evaluating some of the newer or more important bioinformatics resources (i.e., databases and software) that are of growing importance to understanding or predicting drug metabolism, especially with respect to the absorption, distribution, metabolism, excretion, (ADME), and toxicity (T) of both existing drugs and potential drug leads. Detailed descriptions and critical assessments of a number of potentially useful bioinformatics/cheminformatics databases and predictive ADMET software tools are provided. Additionally, several pharmaceutically important applications of both the databases and software are highlighted. Given the rapid growth in this area and the rapid changes that are taking place, a special emphasis is placed on freely available or Web-accessible resources.

Animals↗

Low-dose lidocaine suppresses experimentally induced hyperalgesia in humans.

BACKGROUND: The antinociceptive effects of systemically administered local anesthetics have been shown in various conditions, such as neuralgia, polyneuropathy, fibromyalgia, and postoperative pain. The objective of the study was to identify the peripheral mechanisms of action of low-dose local anesthetics in a model of experimental pain. METHODS: In a first experimental trial, participants (n=12) received lidocaine systemically (a bolus injection of 2 mg/kg in 10 min followed by an intravenous infusion of 2 mg x kg(-1) x h(-1) for another 50 min). In a second trial, modified intravenous regional anesthesia was administered to exclude possible central analgesic effects. In one arm, patients received an infusion of 40 ml lidocaine, 0.05%; in their other arm, 40 ml NaCl, 0.9%, served as a control. In both trials, calibrated tonic and phasic mechanical and chemical (histamine) stimuli were applied to determine differentially the impairment of tactile and nociceptive perception. RESULTS: Mechanical sensitivity to touch, phasic mechanical stimuli of noxious intensity, and heat pain thresholds remained unchanged after systemic and regional application of the anesthetic. In contrast, histamine-induced itch (intravenous regional anesthesia), axon reflex flare (systemic treatment), and development of acute mechanical hyperalgesia during tonic pressure (12 N; 2 min) of an interdigital web was significantly suppressed after both treatments. CONCLUSIONS: Increasing painfulness during sustained pinching has been attributed to excitation and simultaneous sensitization of particular Adelta- and C-nociceptors. This hyperalgesic mechanism seems to be particularly sensitive to low concentrations of lidocaine. These findings confirm clinical experience with lidocaine in pain states dominated by hyperalgesia.

Adult↗

Uptake of Bt endotoxins by nontarget herbivores and higher order arthropod predators: molecular evidence from a transgenic corn agroecosystem.

The planting of transgenic crops expressing Bacillus thuringiensis endotoxins is widespread throughout the world; the prolific increase in their application exposes nontarget organisms to toxins designed to control pests. To date, studies have focused upon the effects of Bt endotoxins on specific herbivores and detritivores, without consideration of their persistence within arthropod food webs. Here, we report the first quantitative field evaluation of levels of Bt endotoxin within nontarget herbivores and the uptake by higher order arthropods. Antibody-based assays indicated significant quantities of detectable Cry1Ab endotoxin within nontarget herbivores which feed on transgenic corn (including the corn flea beetle, Chaetocnema pulicaria, Japanese beetle, Popillia japonica and southern corn rootworm, Diabrotica undecimpunctata howardi). Furthermore, arthropod predators (Coccinellidae, Araneae, and Nabidae) collected from these agroecosystems also contained significant quantities of Cry1Ab endotoxin indicating its movement into higher trophic levels. This uptake by predators is likely to have occurred by direct feeding on plant material (in predators which are facultatively phytophagous) or the consumption of arthropod prey which contained these proteins. These data indicate that long-term exposure to insecticidal toxins occurs in the field. These levels of exposure should therefore be considered during future risk assessments of transgenic crops to nontarget herbivores and arthropod predators.

Agriculture↗

Real-Time linux dynamic clamp: a fast and flexible way to construct virtual ion channels in living cells.

We describe a system for real-time control of biological and other experiments. This device, based around the Real-Time Linux operating system, was tested specifically in the context of dynamic clamping, a demanding real-time task in which a computational system mimics the effects of nonlinear membrane conductances in living cells. The system is fast enough to represent dozens of nonlinear conductances in real time at clock rates well above 10 kHz. Conductances can be represented in deterministic form, or more accurately as discrete collections of stochastically gating ion channels. Tests were performed using a variety of complex models of nonlinear membrane mechanisms in excitable cells, including simulations of spatially extended excitable structures, and multiple interacting cells. Only in extreme cases does the computational load interfere with high-speed "hard" real-time processing (i.e., real-time processing that never falters). Freely available on the worldwide web, this experimental control system combines good performance. immense flexibility, low cost, and reasonable ease of use. It is easily adapted to any task involving real-time control, and excels in particular for applications requiring complex control algorithms that must operate at speeds over 1 kHz.

Computer Simulation↗

Generating interactive molecular documentaries using a library of graphical actions.

Paper-based publishing of scientific articles limits the types of presentations that can be used. The emergence of electronic publishing has created opportunities to increase the range of formats available for conveying scientific content. We introduce the Graphical Explanation Markup Language, GEML, implemented as an XML format for defining molecular documentaries which exploit the interactive capabilities of electronic publishing. GEML builds upon existing molecular structure definitions such as the Protein Data Bank (PDB) standard file format. GEML provides a library of gestures (or actions) commonly used for structural explanations, and is extensible. XML allows us to separate explicit statements about how to highlight a molecular structure from the implementation of these instructions. We also present GEIS (Generator of Explanatory Interactive Systems), a program that takes as input a GEML documentary definition file and produces all the files necessary for an interactive, web-based molecular documentary. To demonstrate GEML and GEIS, we constructed a documentary capturing the difficult 3D notions expressed in two selected published reports about human topoisomerase I. We have created a prototype Java application, GEMLBuilder, as an editor of GEML files.

Computer Graphics↗

RE-AIM: evidence-based standards and a Web resource to improve translation of research into practice.

BACKGROUND: Health services data indicate that under present conditions evidence-based medical and preventive practices are not consistently implemented in clinical practice and affect the quality of care provided to patients. Operating with similar conditions and resources, it is unlikely that evidence-based behavioral medicine (EBBM) practices will be more successfully implemented. PURPOSE: In this article we propose ways to help improve the implementation of EBBM practice. METHODS: This article describes the RE-AIM (Reach, Efficacy/Effectiveness, Adoption, Implementation, and Maintenance) framework that is available on a free-use Web site (http://www.re-aim.org), which offers practical research translation tools, resources, and support for program planners, community leaders, and researchers. The material located at www.re-aim.org can be used to help anticipate and overcome likely barriers to dissemination and to estimate eventual public health impact. RESULTS: Data on Web site utilization and lessons learned thus far in its implementation are presented. CONCLUSIONS: Scientists and public health leaders should devote greater attention to reporting practice-oriented issues such as generalizability, breadth of application, and pragmatic and setting or contextual issues in addition to the current focus on internal validity issues. We hope that this and similar efforts will assist EBBM interventions to have broader applications, be consistently implemented, and be sustained.

Behavioral Medicine↗

Developing a European Internet and kiosk-based health information system.

A consortium of partner organisations (universities, health care organisations and information technology companies) from Northern Ireland, Germany, Portugal and Italy have collaborated to develop a multi-lingual, multi-media Internet and kiosk-based health information system in cardiology and skin cancer. The project, CATCH II (Citizens Advisory System based on Telematics for Communication and Health), has been funded by the European Commission under the Fourth Framework Research and Development TELEMATICS Applications Program (TAP), Health Care Sector. In this paper we provide an overview of the system and the methodological approach adopted. Key characteristics with respect to the technical architecture and flexible customisation of different web and kiosk-based versions will be presented. In particular, the development of dedicated software for the procurement, structuring and management of the information knowledge-base is illustrated. Some of the most interesting findings from a cross-national study of health information needs on the internet are presented along with information on the validation of the system by the general public, content providers and health care authorities.

European Union↗

Systems of evidence-based healthcare and personalised health information: some international and national trends.

In Europe, North America and elsewhere, growing interest has focussed on evidence-based healthcare systems, incorporating the deployment of practice guidelines, as a field of application for health telematics. The clinical benefit and technical feasibility of common European approaches to this task has recently been demonstrated. In Europe it is likely that, building on recent progress in electronic health record architecture (EHRA) standards, a sufficient state of maturity can be reached to justify initiation within CEN TC251 of a prestandards process on guideline content formats during the current 5th Framework of EC RT&D activity. There is now a similar impetus to agree standards for this field in North America. Thanks to fruitful EC-USA contacts during the 4th Framework programme, there is now a chance, given well-planned coordination, to establish a global consensus optimally suited to serve the world-wide delivery and application of evidence-based medicine. This review notes three factors which may accelerate progress to convergence: (1) revolutionary changes in the knowledge basis of professional/patient/public healthcare partnerships, involving the key role of the Web as a health knowledge resource for citizens, and a rapidly growing market for personalised health information and advice; (2) the emergence at national levels of digital warehouses of clinical guidelines and EBM knowledge resources, agencies which are capable of brokering common mark-up and interchange media definitions between knowledge providers, industry and healthcare organizations; (3) the closing gap in knowledge management technology, with the advent of XML and RDF, between approaches and services based respectively on text mark-up and knowledge-base paradigms. A current project in the UK National Health Service (the National electronic Library of Health) is cited as an example of a national initiative designed to harness these trends.

Artificial Intelligence↗

The UMLS Knowledge Source Server: a versatile Internet-based research tool.

The National Library of Medicine's Unified Medical Language System (UMLS) project regularly distributes a set of Knowledge Sources to the research community. In 1995 the UMLS data were made available for the first time through the Internet-based UMLS Knowledge Source Server. The server can be accessed through three different client interfaces. The World Wide Web interface allows users to browse and explore the data and to see how those data are organized in the UMLS. The command-line interface is best suited for batch processing, and the application programming interface allows developers at remote sites to embed calls in their application programs to the Knowledge Source Server.

Computer Communication Networks↗

Morphological diversity of the avian foot is related with the pattern of msx gene expression in the developing autopod.

The formation of the digits in amniota embryos is accompanied by apoptotic cell death of the interdigital mesoderm triggered through BMP signaling. Differences in the intensity of this apoptotic process account for the establishment of the different morphological types of feet observed in amniota (i.e., free-digits, webbed digits, lobulated digits). The molecular basis accounting for the differential pattern of interdigital cell death remains uncertain since the reduction of cell death in species with webbed digits is not accompanied by a parallel reduction in the pattern of expression of bmp genes in the interdigital regions. In this study we show that the duck interdigital web mesoderm exhibits an attenuated response to both BMP-induced apoptosis and TGFbeta-induced chondrogenesis in comparison with species with free digits. The attenuated response to these signals is accompanied by a reduced pattern of expression of msx-1 and msx-2 genes. Local application of FGF in the duck interdigit expands the domain of msx-2 expression but not the domain of msx-1 expression. This change in the expression of msx-2 is followed by a parallel increase in spontaneous and exogenous BMP-induced interdigital cell death, while the chondrogenic response to TGFbetas is unchanged. The regression of AER, as deduced by the pattern of extinction of fgf-8 expression, takes place in a similar fashion in the chick and duck regardless of the differences in interdigital cell death and msx gene expression. Implantation of BMP-beads in the distal limb mesoderm induces AER regression in both the chick and duck. This finding suggests an additional role for BMPs in the physiological regression of the AER. It is proposed that the formation of webbed vs free-digit feet in amniota results from a premature differentiation of the interdigital mesoderm into connective tissue caused by a reduced expression of msx genes in the developing autopod.

Animals↗

Patient experiences and attitudes about access to a patient electronic health care record and linked web messaging.

OBJECTIVE: Patient access to their electronic health care record (EHR) and Web-based communication between patients and providers can potentially improve the quality of health care, but little is known about patients' attitudes toward this combined electronic access. The objective of our study was to evaluate patients' values and perceptions regarding Web-based communication with their primary care providers in the context of access to their electronic health care record. METHODS: We conducted an online survey of 4,282 members of the Geisinger Health System who are registered users of an application (MyChart) that allows patients to communicate electronically with their providers and view selected portions of their EHR. To supplement the survey, we also conducted focus groups with 25 patients who were using the system and conducted one-on-one interviews with ten primary care clinicians. We collected and analyzed data on user satisfaction, ease of use, communication preferences, and the completeness and accuracy of the patient EHR. RESULTS: A total of 4,282 registered patient EHR users were invited to participate in the survey; 1,421 users (33%) completed the survey, 60% of them female. The age distribution of users was as follows: 18 to 30 (5%), 31 to 45 (24%), 46 to 64 (54%), 65 and older (16%). Using a continuous scale from 1 to 100, the majority of users indicated that the system was easy to use (mean scores ranged from 78 to 85) and that their medical record information was complete, accurate, and understandable (mean scores ranged from 65 to 85). Only a minority of users was concerned about the confidentiality of their information or about seeing abnormal test results after receiving only an explanatory electronic message from their provider. Patients preferred e-mail communication for some interactions (e.g., requesting prescription renewals, obtaining general medical information), whereas they preferred in-person communication for others (e.g., getting treatment instructions). Telephone or written communication was never their preferred communication channel. In contrast, physicians were more likely to prefer telephone communication and less likely to prefer e-mail communication. CONCLUSION: Patients' attitudes about the use of Web messaging and online access to their EHR were mostly positive. Patients were satisfied that their medical information was complete and accurate. A minority of patients was mildly concerned about the confidentiality and privacy of their information and about learning of abnormal test results electronically. Clinicians were less positive about using electronic communication than their patients. Patients and clinicians differed substantially regarding their preferred means of communication for different types of interactions.

Attitude to Computers↗