Thomas S. Kuhn (18 July 1922-17 June 1996).
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Historiography↗
Biomedical subjects
S Fuller
Publications and source records attributed to S Fuller.
Meeting clinician information needs by integrating access to the medical record and knowledge resources via the Web.
MINDscape is a web based integrated interface to diverse sources of clinical information including both patient specific information (electronic medical record) as well as medical knowledge (the "digital library") to provide "just in time" information at the point of care. It was developed at the University of Washington to meet clinical information needs both as identified locally and by a review of the literature. Beta testing by over 600 clinicians is in progress and medical centers wide access scheduled for Fall 1997. We describe the information needs we sought to meet and the ongoing evaluation approach we are taking to ensure the information needs of a diverse group of clinicians are met. The iterative evolution of the interface from prototype, to alpha to large scale beta testing is reported. Integration of information occurs at three levels: integration of information by patient, integration of information by provider, and integration of patient specific information with medical reference material and decision support tools.
Computer Communication Networks↗
Combination but not single-agent methotrexate chemotherapy for gestational trophoblastic tumors increases the incidence of second tumors.
PURPOSE: No increase in second tumor incidence was found in a previous analysis of women treated with chemotherapy for gestational trophoblastic tumors (GTT). More patient years at risk enabled a further analysis of the risk of second tumors to be performed in the 1,377 women treated in this until up to 1990. PATIENTS AND METHODS: Health questionnaires were returned on 93.3% of patients who successfully completed chemotherapy and were living in the United Kingdom. The remainder were flagged for death or developing further cancers by the Office of Population Census and Surveys and by the Thames Cancer Registry. Incidence density analysis was performed based on 15,279 person-years of observation available. Standardized incidence ratio (SIR) was used to estimate the relative risk (RR) of second tumors associated with the treatment. To calculate the expected number, the actual incidence rates observed by the Thames Cancer Registry during the same calendar period of observation were used. RESULTS: An overall 50% excess of risk (RR = 1.5; 95% confidence interval [CI], 1.1 to 2.1; P < .011) was observed: there were 37 second tumors, when 24.5 were expected. For specific second tumors, the risk was significantly increased for myeloid leukemia (RR = 16.6; 95% CI, 5.4 to 38.9), colon (RR = 4.6; 95% CI, 1.5 to 10.7), and breast cancer when the survival exceeded 25 years (RR = 5.8; 95% CI, 1.2 to 16.9). The risk was not significantly increased among the 554 women receiving single-agent therapy (RR = 1.3; 95% CI, 0.6 to 2.1). Leukemias only developed in patients receiving etoposide plus other cytotoxic drugs. CONCLUSION: This study suggests that there is a slight increased risk of second tumors after sequential or combination chemotherapy for GTT. This has become apparent since the introduction of etoposide and longer follow-up.
Adolescent↗
Clinical trials: testing of adult chemical heating pad.
Chemical packs are recent innovations in the delivery of dry heat. Because these delivery systems do not have any mechanism for verifying temperature during application, research to determine their safety seems warranted. The purpose of this study was to measure the skin temperature of adults during a 30-minute application of the MediHeat adult heating pad (MH-AHP). Seventy-seven subjects received a 30-minute application of the MH-AHP to their backs while lying in both supine and prone positions. The mean skin temperature in both positions was 101 degrees F. There were significant differences, however, in minimum and maximum skin temperature between positions. Subjects in the prone position had significantly higher maximum skin temperature and significantly lower minimum skin temperature than subjects in the supine position. It is possible that the prone position allows for more air flow over the MH-AHP and that more heat was generated causing the higher maximum temperature. This explanation does not account for the lower minimum temperature. There were no significant differences in perception of heat between the positions at either 5 minutes or 30 minutes. Findings suggest that caution is necessary when applying heating devices that depend on air circulation for heat generation.
Adult↗
Isolation of small, primitive human hematopoietic stem cells: distribution of cell surface cytokine receptors and growth in SCID-Hu mice.
Human CD34+ cells were subfractionated into three size classes using counterflow centrifugal elutriation followed by immunoadsorption to polystyrene cell separation devices. The three CD34+ cell fractions (Fr), Fr 25/29, Fr 33/37, and Fr RO, had mean sizes of 8.5, 9.3 and 13.5 microns, respectively. The majority of cells in the large Fr RO CD34+ cell population expressed the committed stage antigens CD33, CD19, CD38, or HLA-DR and contained the majority of granulocyte-macrophage colony-forming units (CFU-GM), burst-forming units-erythroid (BFU-E), and CFU-mixed lineage (GEMM). In contrast, the small Fr 25/29 CD34+ cells were devoid of committed cell surface antigens and lacked colony-forming activity. When seeded to allogeneic stroma, Fr RO CD34+ cells produced few CFU-GM at week 5, whereas cells from the Fr 25/29 CD34+ cell population showed a 30- to 55-fold expansion of myeloid progenitors at this same time point. Furthermore, CD34+ cells from each size fraction supported ontogeny of T cells in human thymus/liver grafts in severe combined immunodeficient (SCID) mice. Upon cell cycle analyses, greater than 97% of the Fr 25/29 CD34+ cells were in G0/G1 phase, whereas greater proportions of the two larger CD34+ cell fractions were in active cell cycle. Binding of the cytokines interleukin (IL)-1 alpha, IL-3, IL-6, stem cell factor (SCF), macrophage inhibitory protein (MIP)-1 alpha, granulocyte colony-stimulating factor (G-CSF), and granulocyte-macrophage (GM)-CSF to these CD34+ cell populations was also analyzed by flow cytometry. As compared with the larger CD34+ cell fractions, cells in the small Fr 25/29 CD34+ cell population possessed the highest numbers of receptors for SCF, MIP1 alpha, and IL-1 alpha. Collectively, these results indicate that the Fr 25/29 CD34+ cell is a very primitive, quiescent progenitor cell population possessing a high number of receptors for SCF and MIP1 alpha and capable of yielding both myeloid and lymphoid lineages when placed in appropriate in vitro or in vivo culture conditions.
Animals↗
Informatics and medical libraries: changing needs and changing roles.
Medical librarians play a crucial role in the evolution of institutional information policy. As information professionals, they share many similarities with their medical informatics counterparts. Both groups emphasize information delivery to the point of decision making; both groups serve as curators of institutional knowledge bases. If the term "publication" encompasses the delivery of clinical information relevant to individuals or populations, both librarians and medical informaticians have an immediate interest in the nature of biomedical publishing, particularly in areas of intellectual ownership, confidentiality, distribution, and access. Both groups also have been early leaders in applying information technology to solve pressing knowledge-management problems, and both groups have a strong commitment to educating colleagues in the effective use of information. Although the challenges faced by librarians and medical informaticians are sometimes different, the evolution of information technology and new forms of biomedical communication suggest that there is now a greater convergence between the two disciplines.
Artificial Intelligence↗
The organization of the digital library.
As digital information proliferates and the difficulties of managing it threaten to overwhelm traditional publication and information delivery processes, new visions of a digital library are forming. Exactly what a digital library is and how it is to be organized have not yet been determined, and bibliographic organization of digital information has not been sufficiently addressed. Bibliography is the systematic description or classification of writings or publications considered as material objects. In today's digital world, such material objects may no longer be relevant, but the need for systematic description remains. The important issue is not whether digital bibliography is needed but, instead, whether or not existing bibliographic techniques are appropriate for this new media. A second issue is the location of the responsibility for a new digital bibliography. Does it rest with medical informaticians, often the producers of this new digital information, or with librarians, traditionally the classifiers of information? Developments in both medical informatics and medical librarianship indicate a need for greater collaboration between these specialties in order to achieve their common purpose--the creation, classification, and dissemination of scholarly information.
Bibliography of Medicine↗
Educating physicians to use the digital library.
Skill in creating, finding, managing, and using biomedical information is a vital component of modern medical practice. Medical schools recognize the revolutionary implications of computing technology and use a number of different strategies to integrate "informatics education" into their curricula. In many institutions, leadership for this effort rests with the health sciences library and/or the department of medical informatics. Examples are presented of how nine medical schools have implemented informatics education; no single informatics-education strategy prevails, and these schools' strategies do not exhaust the possibilities. Informatics education programs will require better planning and integration in the future because of the need to keep pace with curriculum reform, the changing context of medical practice, and the speed of technological innovation.
Education, Medical↗
Managing information in the academic medical center: building an integrated information environment.
The strategic importance of integrated information systems and resources for academic medical centers should not be underestimated. Ten years ago, the National Library of Medicine in collaboration with the Association of Academic Medical Centers initiated the Integrated Advanced Information Management System (IAIMS) program to assist academic medical centers in defining a process for addressing deficiencies in their information environments. The authors give a brief history of the IAIMS program, and they describe both the characteristics of an integrated information environment and the technical and organizational structures necessary to create such an environment. Strategies some institutions have used to implement integrated information systems are also outlined. Finally, the authors discuss the role of librarians in integrated information system design.
Academic Medical Centers↗
Presentation and management of choriocarcinoma after nonmolar pregnancy.
OBJECTIVE: To ascertain the mode of presentation and treatment outcome for women with choriocarcinoma after a nonmolar pregnancy. DESIGN: Retrospective analysis of case records between 1985 and 1994. SETTING: A referral centre for trophoblastic disease. SUBJECTS: One hundred women with choriocarcinoma: 62 after a live birth, six after a live birth preceded by a molar pregnancy and 32 after a nonmolar abortion. RESULTS: Choriocarcinoma after nonmolar pregnancies represent 17% of the total gestational trophoblastic tumours requiring treatment. Vaginal bleeding was the commonest symptom in all groups, but symptoms from metastatic disease were important in the group presenting after a live birth. Metastatic disease was present in 31% of cases after live birth and 43% post-abortion. The median interval between the antecedent pregnancy and choriocarcinoma was five and six months, respectively. High risk multi-agent chemotherapy was required in 82% and 60% of cases, respectively. The mortality rate was significantly higher after a live birth than a nonmolar abortion (21% vs 6%). CONCLUSIONS: Treatment of choriocarcinoma after a live birth is associated with an unacceptably high mortality rate. Vaginal bleeding is an important early symptom and a pregnancy test should be performed if it persists after usual medical treatment.
Adolescent↗
Eosinophilic colitis due to rifampicin.
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Colitis↗
Influenza haemagglutinin: illuminating fusion.
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Hemagglutinins, Viral↗
Decreased protein catabolism after exercise in subjects with IDDM.
We examined whether the increased rates of protein catabolism (proteolysis and leucine oxidation) associated with moderate insulinopenia in subjects with IDDM would be accentuated by prior bicycle exercise (53% VO2max for 82 min). Insulin infusions maintained plasma glucose concentrations on one study day in "tight" control (TC: 6 mmol/l) and on a separate day in "loose" control (LC: 12 mmol/l). Elevations in serum ketone body, plasma NEFA, and whole-blood branched-chain amino acid concentrations on the loose control day during the basal period persisted throughout the post-exercise recovery period. Amino acid kinetics were estimated during a primed, constant infusion of L-[1-13C]leucine from plasma dilution of alpha-[1-13C]KIC and expired air 13CO2 enrichments. Loose control was associated with increased rates of whole-body leucine oxidation (LC 25 +/- 7 vs TC 21 +/- 8 mumol.kg-1.h-1) and protein degradation (LC 127 +/- 12 vs TC 118 +/- 18 mumol.kg-1.h-1) (both p < 0.05). During the 2-h post exercise recovery period, there were significant decreases in rates of leucine oxidation (LC 21 +/- 7, TC 16 +/- 7) and protein degradation (LC 112 +/- 13, TC 107 +/- 11), compared to the basal period (both p < 0.05, basal vs recovery). Rates of whole-body protein synthesis were unchanged by prior exercise. In conclusion, moderate insulinopenia is associated with significantly higher rates of protein degradation and leucine oxidation in the basal state. Following exercise, net protein catabolism is diminished due to reduced rates of protein degradation in the presence of maintained rates of protein synthesis.(ABSTRACT TRUNCATED AT 250 WORDS)
Adolescent↗
TGF-beta 1 post-treatment in a rabbit model of cerebral ischaemia.
Transforming growth factor-beta 1 (TGF-beta 1), suggested in some studies to suppress astrocyte and neutrophil function, has also reduced ischaemic brain injury when administered immediately prior to clot embolization in models of thromboembolic stroke. The effect of TGF-beta 1 as a post-treatment paradigm was investigated in a rabbit model of thromboembolic stroke. Following clot embolization, regional cerebral blood flow fell to < 10 cc 100 g-1 min-1 in all animals. TGF-beta 1 (10 micrograms) or vehicle (n = 5 each group) was infused via the contralateral carotid artery. TGF-beta 1 administration resulted in a rapid and selective reduction in the peripheral neutrophil count as compared to a significant (p < 0.05) increase in control values (2336 +/- 817 vs 4320 +/- 928 neutrophils mm3, mean +/- SEM). Neutrophil aggregation was increased within 30 min of TGF-beta 1 infusion when compared to control (2.07 +/- 0.70 vs 1.09 +/- 0.17 ohms, p < 0.05); neutrophil chemiluminescence, an index of the oxygen respiratory burst was not significantly affected by TGF-beta 1 administration. No difference in platelet counts or aggregation was noted. There was no significant difference between the two groups regarding brain infarct size (47.5 +/- 10.9 vs 56.5 +/- 10.4, n = 4, TGF-beta vs control, mean +/- SEM), intracranial pressure, or brain excitatory amino acid levels (aspartate and glutamate) within ischaemic regions.(ABSTRACT TRUNCATED AT 250 WORDS)
Analysis of Variance↗
Intensive care costing methodology: cost benefit analysis of mask continuous positive airway pressure for severe cardiogenic pulmonary oedema.
Costing data for intensive care admissions is important, not only for unit funding, but also for cost outcome analysis of new therapies. This paper presents an intensive care episode costing methodology using the example of a cost-benefit analysis of mask CPAP for severe cardiogenic pulmonary oedema (CPO). This analysis examines the intervention of admitting all patients with severe CPO to the intensive care unit for mask CPAP, compared with the previous practice of admitting only patients failing conventional non-CPAP treatment and requiring mechanical ventilation. The episode costs were determined from a prospective study which showed mask CPAP reduced the need for mechanical ventilation from 35% to 0%. The mean cost of a mask CPAP episode was $1,156, with a mean stay of 1.2 days, compared with ventilated patients, $5,055 and 4.2 days. The major contributors to cost in both groups were nursing and medical salaries, and hospital overheads. The cost of previous estimated yearly caseload of 35 ventilated patients ($176,925) was greater than the cost associated with an increased caseload of 100 mask CPAP patients ($115,600). We conclude that, despite an increase in admissions, mask CPAP for severe CPO is cost-effective.
Cost-Benefit Analysis↗
Immunization with recombinant woodchuck hepatitis virus nucleocapsid antigen or hepatitis B virus nucleocapsid antigen protects woodchucks from woodchuck hepatitis virus infection.
Woodchucks were immunized with recombinant woodchuck hepatitis virus (WHV) nucleocapsid antigen (WHcAg) or hepatitis B virus (HBV) nucleocapsid antigen (HBcAg) and challenged with 10(6) WHV ID50. Six out of six woodchucks immunized with WHcAg and four out of six immunized with HBcAg were protected from WHV infection. Woodchucks immunized with WHcAg or HBcAg developed high serum antibody titres against WHcAg or HBcAg. Antibodies against WHc and HBc displayed little cross-reactivity (< 1%). This confirms and extends previous reports of protection against homologous challenge after immunization with HBcAg/WHcAg which are both internal viral antigens. As the dominant B-cell epitope(s) on particulate WHcAg and HBcAg appear not to be conserved it also demonstrates that antibodies against HBcAg/WHcAg are not important for this protection. Woodchucks immunized with WHcAg/HBcAg reacted with a fast serum antibody response against viral envelope proteins upon challenge with WHV, indicative of functional intrastructural/intermolecular T-cell help as one potential mechanism of protection after immunization with an internal viral antigen.
Animals↗
Creating the integrated information infrastructure for the 21st century at the University of Washington Warren G. Magnuson Health Sciences Center.
Successful integrated information systems implementation requires an effective marriage of technology and information resources in response to critical institutional needs. The University of Washington technical infrastructure, developed over the past five years, includes ubiquitous, high-speed network access throughout the Health Sciences Center and hospitals, agreement on network standards and protocols, uniform interface to common databases (character-based and GUI) and network availability of a variety of databases and information resources at no charge to the individual. As a result of this heavy institutional investment in technical infrastructure, our implementation process will focus on expanding the number of available resources as well as developing and refining tools and services to enhance the utility of electronic information resources. Above all we will study and develop strategies for dealing with the myriad of information policy issues which confront and confound us all today.
Academic Medical Centers↗
From bench to bedside: research and testing of Internet resources and connections in community hospital libraries.
Access to information becomes more valuable with the continuing proliferation of medical knowledge and the increasing economic pressure being experienced by health care organizations. This is particularly so for community hospitals in rural or isolated areas, where the economic pressures are at least as great as in urban areas and where access to information is often inadequate. These conditions have implications for the quality of patient care and for economic viability. In response to this, the National Library of Medicine, the University of Washington, and seven community hospitals in five Pacific Northwest states have joined forces in a broad-scale technology diffusion project to facilitate the application of research work to clinical care. There are three components to the project: 1) a pilot connections component to extend Internet access to the community hospitals, 2) a research component to test the performance of a client/server model for network access to anatomical text and images, and 3) a clinical component to develop a registry of DNA diagnostic laboratories facilitating the provision of genetic information to clinicians. The pilot connections component is described and preliminary findings are reported.
Computer Communication Networks↗