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PubMed2005

Case based learning--a review of the literature: is there scope for this educational paradigm in prehospital education?

This paper discusses the findings of a literature review of case based learning (CBL) from a multidisciplinary health science education perspective and attempts to draw comparisons with the available literature relating to prehospital education and CBL.CBL is an exciting educational prospect in which to develop research capacity, strategies, and opportunities. This paper provides an examination of the literature exploring the major consistencies and inconsistencies, and reveals areas of potential future research for prehospital education institutions.

Consumer Behavior↗

PubMed1987

Psychosocial issues in childhood cancer. An ecological framework for research.

A number of psychosocial issues are evolving as childhood cancer becomes a chronic rather than a fatal condition. These include issues associated with extended hospitalization and social isolation, as well as long-term adjustment to survival that may involve recurrence of disease. Primary emphasis in current research and intervention is placed on how children and their families adapt to long-term survival. This article reviews the scope and limitations of previous research in this area, which focuses on the individual with little reference to the family, school, or social networks or to the interactions occurring among these arenas. An ecological model is suggested as the most useful perspective for enhancing our understanding of the impact of childhood cancer on the child, family, and community. Much of what is already known about how cancer and its treatment affect children and families is consistent with the propositions of an ecological model. The transactional, reciprocal, and interdependent nature of coping behaviors within a family system is perhaps the most obvious indicant of the need for multiple perspectives for understanding how families respond to the pressures of a chronic, but possibly life-threatening, illness. An ecological approach is timely, therefore, in that there is a need for psychological research and intervention directed beyond the immediate context of treatment to extended levels of social interaction and social systems.

Adaptation, Psychological↗

PubMed2004

Bacterial responses to neutrophil phagocytosis.

PURPOSE OF REVIEW: This review focuses on adaptive bacterial interactions with neutrophils, emphasizing information communicated within the past year about bacterial factors that respond to contact with or phagocytosis by PMN. RECENT FINDINGS: Since the discovery of type III and IV secretion, progress in the analysis of bacterial interactions with host phagocytes has been extensive but largely focused on the macrophage. The remarkable growth of information about bacterial subversion of macrophage metabolism has been summarized in several excellent reviews. The scope of progress on neutrophil-bacteria interactions is more limited and dominated by recent studies of the granulocyte pathogen, Anaplasma phagocytophilum, the agent of granulocytic ehrlichiosis. SUMMARY: For many pathogens, contact with or ingestion by phagocytes elicits a vigorous but varied microbial response. The response repertoire includes activation of type III and type IV secretion systems that inject effector molecules into the host cell. Effectors modify host cell signaling and metabolic pathways to favor survival of the microbe. Whereas microbial secretory structures are few in kind and relatively conserved, effector molecules are numerous and variable. Effectors may promote phagocytosis by nonphagocytic cells or suppress phagocytosis by macrophages and neutrophils. They may suppress assembly or misdirect localization of the phagocyte NADPH oxidase that is responsible for generating toxic oxidants, and they may suppress phagosome-lysosome fusion. Phagocytosed bacteria may also up-regulate the expression of defensive proteins that attenuate the effects of phagocyte-derived antimicrobial toxins. These pathogenic stratagems probably have their origins in the competition among single-celled organisms, eukaryotes versus prokaryotes, that arose early in evolution.

Anaplasma phagocytophilum↗

PubMed2003

CDP 571: anti-TNF monoclonal antibody, BAY 103356, BAY W 3356, Humicade.

CDP 571 [anti-TNF monoclonal antibody, BAY 103356, BAY W 3356, Humicade] is a recombinant humanised antibody directed against tumour necrosis factor (TNF). CDP 571 has an advantage over the mouse/human chimera anti-TNF-alpha antibody, nerelimomab, in that it is suitable for multiple dosing as it is not so immunogenic. Celltech constructed CDP 571 by grafting the section of mouse antibody that recognises TNF onto a human IgG4 antibody. In the third quarter of 1999, Celltech merged with Chiroscience to form Celltech Chiroscience. In January 2000, Medeva was merged into Celltech Chiroscience, which was renamed as Celltech Group. The research division of Celltech Group is now called Celltech R&D (formerly Celltech Chiroscience Discovery) and the manufacturing and marketing division is called Celltech Pharmaceuticals (formerly Celltech Medeva Pharma). Celltech has completed two phase III trials, involving around 670 patients with moderate-to-severe Crohn's disease; however, both these trials failed to meet their primary endpoints. Biogen and Celltech group will review the scope of their collaboration following additional analysis of the phase III data and discussions with regulatory authorities. The Celltech Group intends to devote significant resources towards enhancing the capability of Celltech Pharmaceuticals to market CDP 571 and other new drugs (such as CDP 860 and CDP 870) as specialised hospital products. Phase II trials were underway in the United Kingdom for use of the drug in the treatment of type 2 diabetes mellitus. However, these trials have also been discontinued. Celltech Group is no longer developing CDP 571 for septic shock, based on negative results with the related compound nerelimomab. The compound was in phase III trials for septic shock in France, Belgium, the United Kingdom, Germany and the US. Celltech also plans to investigate the use of CDP 571 in psoriasis via a collaboration with Biogen (USA). In January 2002, AFX (Agence France-Presse and the Financial Times Group) reported that analysts at Morgan Stanley have forecast Humicade trade mark to reach sales of 250 million US dollars in 2008--at that time, the market value for anti-TNF products to treat rheumatoid arthritis and Crohn's disease will exceed 4 billion US dollars, according to Morgan Stanley.

Anti-Inflammatory Agents↗

PubMed2006

Disclosing errors and adverse events in the intensive care unit.

OBJECTIVE: To review the issue of disclosing errors in care and adverse events that have caused harm to patients in critical care. DESIGN: Review the scope of the problem, the definitions of errors and adverse events, and the benefits and problems of disclosing errors and adverse events and provide an approach by which to have these difficult discussions. SETTING: Medical center. PATIENTS: Critically ill patients and their families. INTERVENTIONS: Applying a systematic framework for disclosing errors and adverse events to affected patients and their families. MEASUREMENTS AND MAIN RESULTS: Several national organizations mandate that physicians discuss errors in care and adverse events that have caused harm with affected patients, but failure to do so is a common problem in critical care as surveys of intensivists indicate that, although most believe that errors should be disclosed, few routinely do so. The likelihood of an adverse event is increased in intensive care units because of the nature of critical care. Not all errors or adverse events require disclosure. There are ethical, financial, legal, systems, and personal benefits to disclosing errors, and disclosure discussions should address common patient concerns. CONCLUSIONS: Failure to disclose errors and adverse events in critical care is an important and common problem. There are numerous reasons why errors and adverse events should be disclosed, and use of a standard framework for doing so will facilitate the process.

Disclosure↗

PubMed2005

Imaging cancer using single photon techniques.

Though positron emission tomography (PET) has attained a rightful place in the vanguard of nuclear oncology imaging there is still much that can be done using single photon tracers. Whether or not it is the use of general agents such as (201)Tl or receptor targeting using somatostatin analogues many cancers and the processes involved with them are still best seen with g-emitting radionuclides and gamma cameras. This article reviews the scope of using these tracers in oncology and emphasises that in nuclear oncology we are as much concerned with the questions as what the cancer is doing and how can be exploit differences between the cancer and normal tissue to aid diagnosis. The advent of new radionuclide therapy techniques will mean that preassessment with diagnostic agents will increase the need to have high quality single photon imaging. New receptor systems such as those using gastrin and bombesin are being developed. We can also use (99m)Tc based agents to identify hypoxia in cancer, angiogenesis and apoptosis. For those who are interested in the biology of cancer and interested in exploiting this for treatment will find that there is still much that can be done without a PET scanner and normally at a lower cost. About this issue, it is important to consider the recent development of dual-modality integrated imaging systems (SPET/CT) that allows to co-register the acquired images by means of the hardware in the same session. These new devices have a particular added value in tumour imaging since they provide the exact localisation of lesions and exclude some non correct interpretations of the physiologic uptakes for SPET findings. In addition there are many evidences that the fused images can give additional information in the diagnostic work up of patients by improving the accuracy of single photon scintigraphy. These new technologies lead to a continuous optimisation in the quality of imaging and contribute more and more to integrate the nuclear medicine modalities in the clinical management of cancer diseases.

Clinical Trials as Topic↗

PubMed2005

Selecting an anticoagulant for recurrent venous thromboembolism in cancer.

PURPOSE: The thrombogenicity of newer anticancer agents and the challenges associated with managing cancer patients on warfarin have led to the evaluation of the low-molecular-weight heparins (LMWHs) for primary and secondary prophylaxis in this high-risk patient population. SUMMARY: The first published trial of LMWH in cancer compared three months of warfarin therapy with enoxaparin in cancer patients with proximal deep venous thrombosis (DVT), pulmonary embolism (PE), or both. All patients received four days of enoxaparin 1.5 mg/kg and were then randomized to continue receiving enoxaparin or begin warfarin therapy. Due to inadequate patient enrollment, no statistically significant differences were detected between the two treatment groups. In a similar patient population, the Comparison of Low-Molecular-Weight Heparin versus Oral Anticoagulant Therapy for the Prevention of Recurrent Venous Thromboembolism in Patients with Cancer (CLOT) trial evaluated the use of long-term dalteparin for the prevention of recurrent venous thromboembolism (VTE) in patients with cancer. Cancer patients with proximal DVT, PE, or both were randomized to initial treatment with dalteparin followed by either six months of oral anticoagulant therapy or dalteparin monotherapy. The primary outcome was symptomatic, recurrent VTE, and secondary outcomes were bleeding events and survival time. The cumulative risk of recurrent VTE at six months was reduced from 17% in the oral anticoagulant group to 9% in the dalteparin group, a risk reduction of 52% (p=0.002). No significant differences in bleeding events or overall mortality occurred between the groups. Recent recommendations from the American College of Chest Physicians on the treatment of cancer-associated thrombosis are based in part on data from the CLOT trial and support the use of dalteparin and tinzaparin in the long-term treatment of patients with DVT and cancer. Finally, results of recent trials support the concept that antithrombotic therapy with dalteparin or nadroparin may have an antineoplastic effect, resulting in improved survival time. However, these results require further validation. CONCLUSION: Despite the absence of oncology-specific guidelines for cancer-associated thrombosis, pharmacists now have a number of new tools available for selecting an anticoagulant, including results from several clinical trials with LMWHs and recent reports from national meetings.

Anticoagulants↗

PubMed1976

Mixed vascular deformities of the lower limbs, with particular reference to lymphography and surgical treatment.

A series of patients with congenital blood and lymph anomalies of the lower limb investigated and treated at St Thomas's Hospital, London, are reviewed. They fell into three classes: (1) those in which the venous element predominated (Klippel and other syndromes), (2) those with arteriovenous shunts and (3) those with angiomas of blood or lymph vessels scattered through the limb (diffuse mixed angiomas). Most of the patients were investigated by angiography (of blood or lymph systems) as well as by plethysmography, dermal temperature measurements and other techniques in the thermal laboratory. Phlebography showed most abnormalities in the Klippel group and was useful in delineating them before operation. The importance of confirming the existence of an adequate deep venous circulation prior to ablation of abnormal superficial vessels is emphasized. Arteriography showed most abnormalities in the group with suspected arteriovenous shunts. The most commonly performed operations in this group were for control of overgrowth of the limb or for ulceration. Lymphography showed many of the Klippel group to suffer from insufficiency of the main pathways, either aplasia or hypoplasia. In addition many had vesicles, fistulas and lymph cysts. Patients in the arteriovenous shunt group had large hyperplastic lymph pathways, which were possibly either congenital or a hypertrophic response. One hundred and thirty-eight operations were performed in 46 patients for a variety of lesions and disabilities. These are reviewed. The scope and benefit of surgery in these children are greater than has been accepted in the past. Three patients required amputation of a limb. There were 5 deaths in the series, 4 of these being in the scattered angioma group and in patients in whom the deformities extended beyond the limb into the trunk.

Adolescent↗

PubMedDate not supplied

The impact of legal provisions on barroom behavior: toward an alcohol-problems prevention policy.

State and local legal provisions have a major impact on a community's drinking patterns in licensed drinking establishments. State Alcoholic Beverage Control (ABC) laws regulate how many (if any) bars are permissible in a given locale; set standards for management practice; set limitations on location and design; establish who may have ownership interests; and establish price guidelines, either directly through price maintenance statutes or indirectly through excise tax policy. State law may also hold bar owners liable for injuries caused by their drunk or underaged patrons to members of the general public ("dram shop" laws and case decisions). This paper reviews the scope and character of these legal provisions, discusses their potential role in preventing alcohol-related problems, and analyzes the inadequacy of most existing bar studies for developing public health policy measures. It concludes with a discussion of a prevention strategy ("server intervention") and an agenda for future research studies.

Alcohol Drinking↗

PubMed2004

Electrokinetics of heterogeneous interfaces.

The influence of surface heterogeneity of various types on electrokinetic parameters is reviewed. The scope of the paper covers classical electrokinetic phenomena characterized by linear dependence of electrokinetic parameters vs. related driving forces. Neither non-linear effects nor the effects of non-equilibrium electric double layer are considered. A historical description of hydrodynamic aspect of electrokinetic phenomena exploiting the slip plane idea is briefly outlined. Attempts to estimate the slip plane location by comparing the diffuse layer and zeta potential values for some model systems are presented. The surface heterogeneity was divided into three categories. Heterogeneity of the first type was related to geometrical morphology of an interfacial region characterized by a considerable surface development producing a three-dimensional interfacial region. The effects of solid roughness, hairy surface, dense polymer layers and gel-like layers are discussed here. The very high surface conductivity detected for such interfaces seems to be a good indicator of the presence of structured layers of this type. Heterogeneous interfaces of the second class cover systems exhibiting non-uniform distribution of surface charge. The non-uniform surface charge distribution can be either of a molecular (discrete charges) or of a microscale (two-dimensional micropatches or three-dimensional structures formed by polyelectrolyte multilayers). The last class of systems examined includes interfaces composed of charged substrate covered by charged bulky objects (particles). In comparison to the homogeneous surfaces, adsorbed charged particles modify both hydrodynamic flow and the electrostatic field significantly altering the electrokinetic parameters. The new description of electrokinetics of composed interfaces presented here takes into account both hydrodynamic and electric field modification and is free of the previously assumed slip plane shift caused by adsorbed objects. This theoretical approach verified by experiments performed on well defined model systems can be successfully applied to the interpretation of experimental data obtained for surfaces covered by objects difficult to detect.

Journal Article↗

PubMed1975

Isolated heart perfusion techniques for rapid screening of myocardial preservation methods. Anoxia versus ischemia.

Isolated nonworking and working heart preparations are described and recent modifications that increase their reliability and scope are reviewed. Isolated perfused tissues are superior to other models for screening myocardial preservation techniques. The metabolic and functional differences between anoxia and ischemia are stressed, myocardial glycolysis is reviewed, and from basic studies potentially fruitful avenues for investigation of myocardial preservation techniques are outlined. Better application of available knowledge of myocardial metabolism could further reduce the risks of cardiac operation.

Animals↗

PubMed2002

Reactive immunization: a unique approach to catalytic antibodies.

The development of antibody catalysts and indeed natural antibody responses has in the past been based on non-covalent binding to antigens. In contrast to this, reactive immunization utilizes reactive immunogens that covalently react with antibodies during the course of their induction through a designed chemical transformation. The inducing chemical transformation is designed to become part of the catalytic mechanism when the antibody is subsequently challenged with substrate molecules. Reactive immunization has proven to be an efficient approach to generating highly proficient catalytic antibodies with unusually broad substrate scope. This review describes catalytic antibodies generated by reactive immunization, their features and applications, as well as in vitro selection of catalytic antibodies based on reactive compounds.

Antibodies, Catalytic↗

PubMed2006

Structural study of metastable amyloidogenic protein oligomers by photo-induced cross-linking of unmodified proteins.

Oligomers of amyloidogenic proteins are believed to be key effectors of cytotoxicity and cause a variety of amyloid-related diseases. Dissociation or inhibition of formation of the toxic oligomers is thus an attractive strategy for the prevention and treatment of these diseases. In order to develop reagents capable of inhibiting protein oligomerization, the structures and mechanisms of oligomer formation must be understood. However, structural studies of oligomers are difficult because of the metastable nature of the oligomers and their existence in mixtures with monomers and other assemblies. A useful method for characterization of oligomer size distributions in vitro is photo-induced cross-linking of unmodified proteins (PICUP) (Fancy and Kodadek, 1999). By providing "snapshots" of dynamic oligomer mixtures, PICUP enables quantitative analysis of the relations between primary and quaternary structures, offering insights into the molecular organization of the oligomers. This chapter discusses the photochemical mechanism; reviews the scope, usefulness, and limitations of PICUP for characterizing metastable protein assemblies; and provides detailed experimental instructions for performing PICUP experiments.

2,2'-Dipyridyl↗

PubMed2005

Clinical trials in dental primary care: what research methods have been used to produce reliable evidence?

OBJECTIVE: To identify controlled clinical trials done exclusively in dental primary care and to classify the research according to design. Details of any procedures used to recruit general dental practitioners and any special organisational arrangements were also collected. DESIGN: A scoping literature review. SETTING: Dental primary care defined as general dental practice, community and school dental settings. PARTICIPANTS: Published randomised controlled trials using randomised or quasi randomised approaches and controlled clinical trials were considered for inclusion in the review. Reports were excluded if they did not describe either a randomised controlled trial or a controlled trial. Studies were excluded if the setting was not primary dental care or the intervention was for non-dental conditions. Conference abstracts without a full report and trials published in a language other than English were also excluded. MAIN OUTCOMES: Experimental and quasi-experimental designs, clinical areas and different kinds of strategies used to recruit dentists, any organisational arrangements made to support research in dental primary care. RESULTS: The search of the Cochrane Oral Health Group Controlled Trials Register found 174 articles. Forty-three randomised controlled trials met the inclusion criteria. Trials to evaluate the effects of interventions for types of anaesthesia, periodontal diseases, smoking cessation techniques, dental materials, organisational aspects of dental care, patient anxiety, post extraction healing rates, antibiotics were identified. All were done in general dental practice. Trials in school and community settings were also included. CONCLUSIONS: Practice-based research needs to be encouraged to provide dental primary care with relevant evidence upon which effective treatment can be based. This review shows there are few trials done in dental primary care to inform clinical practice, most of which have been reported since 1997. The range of trial designs shows that this method of evaluation can be used to evaluate dental primary care interventions and this is promising for those with an interest in improving dental patient outcomes. More research on how to recruit dentists into clinical trial research must be done.

Community Dentistry↗

PubMed1977

[Special indications for using the whole body scanner (author's transl)].

In addition to the role of the body scanner in the diagnosis of diseases of the body cavity and parenchymal organs, the authors review the scope and indications for using whole body computer tomography in special situations. Examples are given of its use in the diagnosis of tumours in the vicinity of the skull base, in the orbits, the facial skeleton, soft tissue tumours, bone diseases and CT-controlled biopsies.

Adult↗

PubMed2004

Genetic dissection of root formation in maize (Zea mays) reveals root-type specific developmental programmes.

BACKGROUND: Maize (Zea mays) forms a complex root system comprising embryonic and post-embryonic roots. The embryonically formed root system is made up of the primary root and a variable number of seminal roots. Later in development the post-embryonic shoot-borne root system becomes dominant and is responsible together with its lateral roots for the major portion of water and nutrient uptake. Although the anatomical structure of the different root-types is very similar they are initiated from different tissues during embryonic and post-embryonic development. Recently, a number of mutants specifically affected in maize root development have been identified. These mutants indicate that various root-type specific developmental programmes are involved in the establishment of the maize root stock. SCOPE: This review summarizes these genetic data in the context of the maize root morphology and anatomy and gives an outlook on possible perspectives of the molecular analysis of maize root formation.

Mutation↗

PubMed2005

Auxin: regulation, action, and interaction.

BACKGROUND: The phytohormone auxin is critical for plant growth and orchestrates many developmental processes. SCOPE: This review considers the complex array of mechanisms plants use to control auxin levels, the movement of auxin through the plant, the emerging view of auxin-signalling mechanisms, and several interactions between auxin and other phytohormones. Though many natural and synthetic compounds exhibit auxin-like activity in bioassays, indole-3-acetic acid (IAA) is recognized as the key auxin in most plants. IAA is synthesized both from tryptophan (Trp) using Trp-dependent pathways and from an indolic Trp precursor via Trp-independent pathways; none of these pathways is fully elucidated. Plants can also obtain IAA by beta-oxidation of indole-3-butyric acid (IBA), a second endogenous auxin, or by hydrolysing IAA conjugates, in which IAA is linked to amino acids, sugars or peptides. To permanently inactivate IAA, plants can employ conjugation and direct oxidation. Consistent with its definition as a hormone, IAA can be transported the length of the plant from the shoot to the root; this transport is necessary for normal development, and more localized transport is needed for tropic responses. Auxin signalling is mediated, at least in large part, by an SCFTIR1 E3 ubiquitin ligase complex that accelerates Aux/IAA repressor degradation in response to IAA, thereby altering gene expression. Two classes of auxin-induced genes encode negatively acting products (the Aux/IAA transcriptional repressors and GH3 family of IAA conjugating enzymes), suggesting that timely termination of the auxin signal is crucial. Auxin interaction with other hormone signals adds further challenges to understanding auxin response. CONCLUSIONS: Nearly six decades after the structural elucidation of IAA, many aspects of auxin metabolism, transport and signalling are well established; however, more than a few fundamental questions and innumerable details remain unresolved.

Arabidopsis↗

PubMed2005

Ethylene signal transduction.

BACKGROUND: The phytohormone ethylene is a key regulator of plant growth and development. Components of the pathway for ethylene signal transduction were identified by genetic approaches in Arabidopsis and have now been shown to function in agronomically important plants as well. SCOPE: This review focuses on recent advances in our knowledge on ethylene signal transduction, in particular on recently proposed components of the pathway, on the interaction between the pathway components and on the roles of transcriptional and post-transcriptional regulation in ethylene signalling. CONCLUSIONS: Data indicate that the site of ethylene perception is at the endoplasmic reticulum and point to the importance of protein complexes in mediating the initial steps in ethylene signal transduction. The expression level of pathway components is regulated by both transcriptional and post-transcriptional mechanisms, degradation of the transcription factor EIN3 being a primary means by which the sensitivity of plants to ethylene is regulated. EIN3 also represents a control point for cross-talk with other signalling pathways, as exemplified by the effects of glucose upon its expression level. Amplification of the initial ethylene signal is likely to play a significant role in signal transduction and several mechanisms exist by which this may occur based on properties of known pathway components. Signal output from the pathway is mediated in part by carefully orchestrated changes in gene expression, the breadth of these changes now becoming clear through expression analysis using microarrays.

Arabidopsis↗