bluuebunny/crossref_metadata_2025 huggingface dataset:
Human and animal bites and venomous stings
Authors: MacFarlane C , van Loggerenberg CJ
Published: January 2007

Human and animal bites and venomous stings demand careful handling. Immediate resuscitation may be necessary. Severe tissue damage from larger animals frequently requires urgent haemorrhage control, followed by debridement. Subsequent reconstruction is commonly necessary. Smaller bites, and particularly human bites, may easily be underestimated, and can have significant infective sequellae, with particular attention being paid to the potential finger joint injury. Surgical exploration is frequently indicated, debridement, irrigation and antimicrobial therapy being required. Viral transmission, as well as bacterial infection, can result from bites.

With regard to envenomation, often a great deal of time and effort is directed at identifying the offending animal and focusing on a specific toxin. It is important to ensure effective general resuscitation first. Thereafter, specific antivenom and antianaphylaxis measures may be taken.

A description of the three common envenomation symptom complexes -cyto-complex, neuro-complex and haemo-complex - is presented, along with some causative sources. Principles of resuscitation, wound care and general treatment measures are indicated, and then appropriate specific treatments are recommended.

Bites and envenomations vary in different parts of the world and it is important that emergency departments develop appropriate protocols relevant to their locations. Common poisonous animal sources should be identified and symptom complexes anticipated. Specific antivenom therapy, appropriate to the area, should be available. However, the general principles of resuscitation and wound care have pride of place.
Mediastinal trauma
Authors: Salim Ali , Demetriades Demetrios
Published: January 2007

The evaluation of mediastinal trauma has undergone some important changes in the last few years. Electrocardiography (ECG) combined with troponin measurements have become the standard of evaluation of suspected blunt cardiac trauma. Spiral computerized tomography (CT) scan has largely replaced angiography for suspected blunt aortic rupture. There is good evidence that with a suspicious mechanism of injury the thoracic aorta should be evaluated irrespective of chest X-ray findings.

In penetrating trauma the introduction of trauma ultrasound in the emergency room has revolutionized the early diagnosis of cardiac tamponade. Most mediastinal gunshot wounds in haemodynamically stable patients can safely be managed non-operatively. Evaluation of the direction of the bullet tract by means of spiral CT scan has replaced angiography and oesophageal studies in about 75% of patients with mediastinal gunshot wounds who are haemodynamically stable.
The role of steroids following major trauma
Authors: Lockey David J , Manara Alexander R
Published: January 2007

This article reviews the indications and evidence for the administration of steroids to patients who have suffered significant trauma. Uncontroversial indications are rare. In spinal cord injury steroids are often given but the practical benefits are questionable. The case for treatment in head injury is unproven. Consideration should be given to treating all those patients who develop acute respiratory distress syndrome (ARDS), although treatment should be deferred to the later (fibroproliferative) stages. The role of steroids in sepsis is complicated and, although steroid administration can have dramatic effects on vasopressor requirements, convincing evidence for mortality reduction is not available.
Cardiac trauma
Authors: Asensio Juan A , Roldán Gustavo , Petrone Patrizio , Forno Walter , Rowe Vincent , Salim Ali
Published: January 2007

The first description of a cardiac injury is found in The Iliad. Cardiac injuries are one of the most challenging injuries, requiring immediate surgical intervention, excellent surgical skills and critical care. The clinical presentation of penetrating cardiac injuries has a broad range, from haemodynamic stability to cardio-pulmonary arrest. Two-dimensional echocardiography is now the procedure of choice over subxiphoid pericardial window to evaluate for the presence of these injuries. Emergency department thoracotomy is indicated for management of penetrating cardiac injuries with immediate cardiography, aortic cross-clamping and open cardiac massage. The left anterolateral thoracotomy is the incision of choice for patients that arrive in extremis. The repair of the wounds should be performed according to the anatomy of the injured area. Mortality remains high, although better patient selection according to physiologic scoring leads to increase in survival.
The systemic inflammatory response syndrome
Authors: Meeran Hanif , Messent Mark
Published: January 2007

The systemic inflammatory response syndrome (SIRS) describes the clinical presentation of patients with systemic activation of the inflammatory response from any underlying cause. SIRS is a common problem in acute medical and surgical practice and an important cause of morbidity and mortality. As a consequence of SIRS, patients may develop multiple organ dysfunction syndrome and acute respiratory distress syndrome (ARDS). Over the recent years our understanding of the inflammatory response in SIRS has increased, but as yet specific immunomodulatory therapies have not proved useful. The mainstay of treatment for patients with SIRS and ARDS remains a general supportive care. It is in this area that more encouraging advances are being made, particularly in the management of invasive ventilation and nutrition. In this review we summarize the definitions, epidemiology and pathophysiology of SIRS, ARDS and related conditions. We then give a description of the clinical consequences and treatment of SIRS and ARDS with an emphasis on current aspects of supportive care.
Recent advances in trauma management
Authors: Stoneham John , Riley Bernard , Brooks Adam , Matthews Stuart
Published: January 2007

Twenty-three thousand doctors in the UK have undertaken The Advanced Trauma Life Support Course for doctors over the past 12 years. The course was never designed to provide anything more than a framework within which inexperienced doctors could safely manage multiple injured patients until expert help arrived. Its critics will say that the course is didactic and its treatment protocols are not always up to date. Since its inception in 1976 in Nebraska it has undergone constant revision and the seventh edition of the course will appear in 2002. With each revision, evidence for new methods of management for the trauma victims are reviewed; some of these are discussed in this paper.
Rehabilitation after traumatic brain injury
Authors: Gentleman Douglas
Published: January 2007

Clinical and political responses to the worldwide epidemic of traumatic brain injury (TBI) need to recognize that the quality of outcome depends on both phases of treatment: acute care and rehabilitation. The growing scientific evidence for neural repair and regeneration has supported growing interest about what rehabilitation can offer to restore function and independence to disabled individuals. Clinicians who treat acutely head-injured patients should develop some understanding of the reality and potential of rehabilitation, to put their own work into perspective. This article reviews the common problems that follow TBI, unpacks the rehabilitation box to see what can be done about them, and considers the scientific evidence for the efficacy of the rehabilitation process.
Paediatric capillary refill times
Authors: Bumke Kirsten , Maconochie Ian
Published: January 2007

Capillary refill time (CRT) has become universally used in paediatrics; it however has a number of limitations to its use as a marker of peripheral perfusion. These limitations include the effects of ambient temperature, environmental lighting conditions as well as different values being recorded at different sites of assessment; these have all been shown to have a bearing on its value. In older patients its range varies from 2 seconds to 4 seconds. All these variations have led to the removal of CRT from the trauma score. This paper reviews the influences on paediatric CRT. CRT does have a role as one of the physiological assessments of peripheral perfusion in combination with other markers such as heart rate, respiratory rate and level of consciousness.
When to give blood
Authors: Nicol Gavin , Hunt Elizabeth , Manji Mav
Published: January 2007

With increased public awareness of the risks of blood transfusion and the decreased availability of blood products, the decision to transfuse a patient should be considered carefully. Most patients require a blood transfusion when haemoglobin levels fall below 8 g=dl or when there is greater than 30% loss of blood volume. However, the main indication for transfusing a patient is to increase their oxygen-carrying capacity and through invasive monitoring provide evidence of inadequate tissue oxygenation. Blood transfusions should be based on the patient’s risks of developing complications of inadequate oxygenation rather than on a single haemoglobin ‘trigger’.
Management of flail chest
Authors: Ranasinghe Aaron M , Hyde Jonathan AJ , Graham Timothy R
Published: January 2007

Thoracic injuries are directly responsible for 25% of trauma deaths in the United Kingdom, and a significant contributory factor to another 25%. The majority of these injuries are due to blunt thoracic trauma and flail chest can be a significant component in these injuries. Flail chest is a condition that is managed by a range of specialties, including cardiothoracic and orthopaedic surgeons, as well as anaesthetists and intensivists. Simple cases can be easily managed by analgesia and supplemental oxygen therapy. However, the literature available supports a number of practices including elective ventilation and possibly surgical fixation for more complex cases. This article sets out to review the literature on the pathophysiology, investigation, and management of this potentially life-threatening condition with particular regard to the additional management of underlying pulmonary contusion.
Aeromedical evacuation of the trauma patient
Authors: Lockey David , Weller Robin
Published: January 2007

Aeromedical evacuation of the trauma patient in the UK is uncommon but controversial. This article compares services in the UK with other, more developed services, particularly those in France and Germany. The important subject of despatch and control and the controversy over different crew configurations are considered. The available, often contradictory evidence for altered patient outcome is reviewed. As with many advances in the quality of medical care it appears that isolating the effect of aeromedical evacuation on the crude indicator of mortality is difficult. World-wide, aeromedical systems are here to stay, and it is up to individual governments and agencies to decide on the level of financial support and priority that they will receive.
The effect of scene time on survival
Authors: Driscoll P , Kent A
Published: January 2007

A review of the literature was carried out to determine the importance of pre-hospital scene times and how it can be affected. In the UK, and certain centres in North America, mortality and morbidity in critically injured patients appears to be related to scene times. The majority of these patients only require basic life support at the scene. Consequently the possible benefits of more advanced procedure need to be compared with the transportation period, the time needed to mobilize a medical team and skill proficiency. Cardiovascular resuscitation procedures in particular require reappraisal. Though haemostasis is essential, there is little evidence to support the use of fluid resuscitation in nontrapped urban patients with a significant haemorrhage problem. In contrast patients who are not bleeding do appear to benefit from advanced life support procedures even though this increases scene time. There is therefore a need for pre-hospital paramedic workers to triage patients so that appropriate resuscitation can be carried out.
Current concepts in the management of patients with so-called ‘minor’ or ‘mild’ head injury
Authors: Swann IJ , Teasdale GM
Published: January 2007

‘Mild’ head injury is increasingly recognized as a potential source of physical and psychological disability, but there is a lack of consistency about the definition and management of these patients. We discuss and define the terms ‘mild’ and ‘minor’, the assessment of post-traumatic amnesia, and the relevance of other signs and symptoms.

Previous guidelines and recent evidence that a ‘mild’ injury may be followed by an intracranial complication are reviewed as a basis for recommendations for investigation and management in accident and emergency departments, for in-patient observation and for discharge planning.
Antibiotics and trauma
Authors: Mellor SG
Published: January 2007

The key to successful trauma management is appropriate, timely and adequate surgery. However, infective complications do occur and it would therefore seem prudent to use antibiotics. They should be started within an hour or so of the injury, in adequate doses and with a view to the bacteria likely to be contaminating the wound. They should be stopped as soon as possible after surgery. If evidence of infection appears after surgery, all efforts must be made to identify the source and deal with it. Narrow spectrum antibiotics should be used where possible. Only in this way can the problems of bacterial resistance to antibiotics be obviated.
Elder abuse
Authors: Dyer Christopher , Rowe Jed
Published: January 2007

Accident and emergency departments are often the first point of contact for an abused older person. Elder abuse is common and can take many forms, including physical, psychological, financial and sexual abuse, or neglect. The stereotypical victim of abuse as a frail roleless female is probably not accurate, as there appears to be little correlation between the degree of physical and mental disability of the victim and subsequent physical abuse. Elder abuse is most often domestic violence that has graduated into old age.

Identifying physical abuse is not always easy - the key feature is the incongruity between the signs of injury and the account of the process that led to it. While accident and emergency departments have well-established mechanisms to deal with suspected cases of child abuse, very few have procedures for handling elder abuse. Raising the awareness of healthcare workers in this area is seen as a vital goal in tackling this problem.
The influence of osteoporosis in trauma
Authors: Anderson FH , Cooper C
Published: January 2007

Osteoporosis is a descriptive term for a loss of bone mass and structure which predisposes to fracture in response to minimal trauma. These fractures cause pain, disability and significant mortality, with enormous resource costs to health and other services. Proximal femoral (hip) fractures account for most of the mortality and cost, and an estimated six million osteoporosis-related hip fractures occur world-wide each year, a number likely to increase dramatically due to changes in population demographics. The diagnosis of osteoporosis should be considered in all patients over the age of 50 years who sustain a fracture, unless there is obvious major trauma. Not only will this inform immediate management but it also allows measures aimed at prevention of further fractures to be implemented. Early surgery is often effective in limiting morbidity from osteoporotic fractures and in older people is best planned in collaboration with other health care professionals.
Focus on trauma systems/centres: an Australasian perspective
Authors: Civil Ian D
Published: January 2007

Over the past 15 years trauma systems in Australasia have developed through a series of reports at state and national level. The emphasis has been on integrated systems of care rather than on free-standing trauma centres. Although excellent models have been described there remains considerable work to be done before an effective and seamless system can be said to exist. Particular strengths to date relate to prehospital care and trauma training, while weaknesses relate to trauma data collection and overall trauma leadership roles.
The treatment of open and contaminated fractures
Authors: Barry M , Hughes SPF
Published: January 2007

The treatment of any open fracture should follow a logical sequence extending from injury to final rehabilitation. In the past, open fractures were usually sustained in armed conflicts and treated by military surgeons. Currently, the majority of open fractures are sustained as the result of motor vehicle accidents, but the management principles developed in the past are the same. The initial treatment should start in the resuscitation room using trauma resuscitation protocols. Once the patient is stable and any immediately life-threatening injuries treated, the wound should be debrided as early as possible and the skeleton stabilized. The wound is re-inspected 48 h later, and at that stage plans for definitive soft tissue cover can be made. Once soft tissue cover has been obtained, rehabilitation of the whole patient can start. Delayed union or bone loss should be aggressively treated to limit functional deficit and subsequent morbidity.
Fractures of the tibial plateau
Authors: Blakemore Martin E
Published: January 2007

The diagnosis, evaluation and management of the patient who sustains a fracture of the tibial plateau are complex. There are a small number of strategies and a large number of tactics that can be used. The underlying principle of assessment, lower limb alignment and early joint movement, is likely to produce the best results that can be achieved. The more severe the violence of the injury, the greater the likelihood of infection and/or delays in skin healing. Several less invasive techniques are now being more widely applied, and time will tell whether these will be effective in the hands of a wider range of trauma and orthopaedic surgeons.
Intraosseous infusions in the adult
Authors: Greaves I , Evans GA , Boyle AA
Published: January 2007

Intraosseous infusions are used in children when intravenous access is difficult or impossible. The intraosseous route is also applicable to adults, but is not widely used. In this article, the anatomy and physiology of bone marrow is described and techniques and sites of intraosseous needle placement are discussed. Fluid and drug administration by the intraosseous route is also discussed. Intraosseous anaeasthesia and diagnostic testing is possible through intraossoeous needles. Potential complications and contraindications are considered.
Clinical evaluation of the child: injury to the chest and abdomen
Authors: Ramenofsky Max L , Cash Susan
Published: January 2007

In the paediatric age group (under 18 years) injury continues to be the dominant cause of mortality, being more common than all other causes combined. Disability resulting from injury represents a major expenditure in financial and emotional terms. The child’s anatomy and physiology are such that directly applying the principles of adult trauma care to the child can result in a less than optimal outcome and can add to long-term and/or permanent disability. Chest and abdominal injuries are the second and third most common causes of death, respectively, in childhood and when combined represent the second leading cause of death in this age group due to injury. There are six life-threatening injuries seen in paediatric injuries: airway obstruction, tension pneumothorax, massive haemothorax, open pneumothorax, flail chest and cardiac tamponade. There are six other potentially life-threatening injuries: simple pneumothorax, pulmonary contusion, tracheobronchial disruption, blunt cardiac injury, aortic disruption and haemothorax. These entities are discussed in terms of identification and treatment.

Abdominal injuries are generally well recognized by trauma surgeons. The difference in the paediatric age group involves the diagnosis of intra-abdominal injuries. The principle of diagnosis is that the injured organ should be specifically identified, not just left at the impression that something is bleeding, perforated or otherwise disrupted. The main diagnostic modality is the spiral or helical computerized tomography scan. This is an appropriate diagnostic method in all but the most severely injured and haemodynamically abnormal children. Care in initial assessment and management and in specific diagnosis has great potential to decrease the mortality in a country’s youngest citizens.
Management of complex violent trauma to the upper urinary tract
Authors: Safir Michael H , McAninch Jack W
Published: January 2007

Since abdominal and retroperitoneal trauma may endanger both the kidney and ureter, urologists are frequently called upon to evaluate an injured patient in the emergency department or in the operating room. In this setting, the suspicion of urological injury begins a clinical cascade of decision making and diagnostic testing. The recognized injury, if appropriately managed, usually heals without incident. The unrecognized injury may jeopardize the recovery of the trauma patient, such as the patient who has sustained an occult ureteral laceration and continues to have an ‘unexplained’ ileus or fever. Although urinary injury is not usually the sole compelling event in severe trauma, thoughtful consideration and treatment of renal and ureteral injuries, collectively referred to as upper urinary tract injuries, will help the surgeon to avoid troublesome management complications.

As urological surgeons, we owe a debt to early pioneers in surgical traumatology who provided the groundwork for acute care management and the management of solid and hollow organ injuries. Upon this framework, the management of urological trauma has blossomed through experience and introspection. Advances in imaging modalities, improvements and renovations of surgical technique, and critical review of outcomes data have influenced the management of genito-urinary trauma and will certainly alter the way we treat trauma patients in the next millennium. This paper illustrates some important concepts in acute genito-urinary trauma and helps towards an improved understanding of acute urological care.
Archaeology dreaming
Authors: Shepherd Nick
Published: January 2007

This article is concerned with the materiality of memory and identity in the post-colony, as mediated by the corporeal remains of the colonial underclasses themselves. Prestwich Street is in a rapidly gentrifying part of Cape Town, close to the Waterfront, the city’s glitzy international zone. The accidental discovery of an early colonial burial site in Prestwich Street in the course of construction activities in May 2003, and its subsequent exhumation, became the occasion of a fiercely contested public campaign. This pitted pro-exhumation heritage managers, archaeologists and property developers against an alliance of community activists, spiritual leaders and First Nations representatives. The materiality of the site and its remains became a key point of focus for the working out of a range of forces and interests in post-apartheid society, including the buried legacies of slavery and colonialism in the city, the memory of apartheid forced removals, and post-apartheid struggles over restitution and representation. I argue that, even as the heightened political contexts of the events around Prestwich Street significantly determine the shape and nature of an emergent post-apartheid public sphere (on the one hand), on the other hand, its clashing epistemological and ontological concerns challenge us to rethink and reformulate core disciplinary practices and guiding ideas. Are the remains of the Prestwich Street dead artefacts? Or are they ancestors? And under what conditions might they be both of these things?
An Empirical Investigation of the Relationships between Modes and Degree of Expatriate Adjustment and Multiple Measures of Performance
Authors: Shay Jeffrey P. , Baack Sally
Published: January 2007

A model extending international research by defining relationships among Nicholson’s modes of adjustment, Black’s degree of expatriate adjustment, and expatriate task and contextual performance was developed and tested using a sample of 153 expatriate managers and 364 host country subordinates from nine multinational hotel companies. Structural equations modeling results provided overall support for the proposed model and all but one of the paths in the model. Implications for future research and practice are discussed.
A Cross Cultural Study of Communication Strategies for Building Business Relationships
Authors: Zhu Yunxia , Nel Pieter , Bhat Ravi
Published: January 2007

This study aims to explore communication strategies for relationship building across cultures from a linguistic as well as a culture-specific perspective. Specifically, it sees business relationships as part of social capital and compares communication strategies used to build relationships in sales firms. The research method is based on a discourse analysis of interviews with business managers, which also incorporates their success stories. In the analysis, relationship building is divided into two stages: the initiating stage and the maintaining stage. It has been found that more interpersonal strategies have been employed by Chinese and Indian business managers when initiating a business relationship. In contrast, the New Zealand and South African managers tend to use more impersonal communication strategies to promote public relations. Similar interpersonal communication strategies are employed in all the target cultures for maintaining relationships. However, a stronger orientation for long-term relationships in the Chinese and Indian cultures has been identified. Furthermore, the communication strategies are dynamic in all the countries investigated since they are becoming more and more multicultural and increasingly globalized in international business and management.
Conceptual Foundations of Cultural Management Research
Authors: Yeganeh Hamid , Su Zhan
Published: January 2007

This article is a reflection on conceptual foundations of cultural management research. By relying on extant literature, a few conceptual underpinnings are examined and criticized, and some suggestions for improvement are proposed. Discussing such issues can be useful not only for advancing future research but also for achieving a more profound understanding of previous studies and their limitations.
The ‘Processes’ of Learning
Authors: Moore Tim
Published: January 2007

Of the different uses of discourse analysis, one of the more significant is the way it can be used to introduce students to the culture and literary practices of the disciplines. This article describes how one type of analysis - Halliday’s transitivity - has been used in an academic advising context to assist students struggling to write effectively in a range of discipline areas: history, visual art and sociology. Analysis of this kind, it is argued, has the potential not only to clarify to students the immediate requirements of the academic tasks they have to complete, but also to help them understand some of the broader epistemological issues that may be at stake.
Supporting Collaborative Grammar Learning via a Virtual Learning Environment
Authors: Orsini-Jones Marina , Jones David
Published: January 2007

This article reports the results of an investigation into the issues encountered by undergraduate language students while engaging in ‘the Grammar Project’ - a collaborative assessment task for the module Academic and Professional Skills for Language Learning - and shows how encouraging students to take ownership of their learning process with the support of a Virtual Learning Environment (VLE) can increase their motivation and their understanding of the subject matter. It shows that students’ beliefs may hinder their learning experience, while maintaining that an effective social-interactive environment can help them understand subject-specific concepts, particularly if this is supported by recording their reflections both within the VLE and in a portfolio.
musical style discrimination in the early years
Authors: Marshall Nigel A. , Hargreaves David J.
Published: January 2007

Previous research has suggested that by the age of six, children display high levels of competence in identifying and reliably distinguishing between different musical styles. Until now, it has been difficult to investigate musical style sensitivity in the early years because the test procedures have relied heavily on the use of language, including the use of verbal instructions and written responses, and because they have demanded levels of concentration, attention and memory span that are beyond most preschoolers. This study reports on the development and piloting of a new procedure which overcomes these problems, and the results suggest that many preschool children do seem able to distinguish between different musical styles.
trusting children's accounts in research
Authors: Dockett Sue , Perry Bob
Published: January 2007

Much of the current rhetoric in areas of child and family research and in early childhood education emphasizes the importance of listening to children in research that has a direct impact on them. Despite this, there remain qualms in some research contexts and amongst some researchers about the reliability, validity and generalizability of children's research input. This article argues that engaging with children as research participants requires a commitment to, and the facilitation of, listening to and hearing their accounts in research. Drawing on research conducted in both New South Wales and Queensland, Australia, this article adopts the stance that children are active and effective participants in research. It examines selected protocols that stand to support such engagement. Specifi cally, it considers issues of ethics and research protocols, mechanisms of engagement, principles of co-construction of the research interaction, the analysis and dissemination of data, and negotiating the research space. This article contributes to methodological understandings of research with children.
teaching preschoolers about inheritance
Authors: Schroeder Meadow , McKeough Anne , Graham Susan A. , Stock Hayli , Palmer Jaime
Published: January 2007

This study aimed to promote advanced reasoning about biological inheritance in four-and five-year-olds. A total of 78 preschoolers (Experimental n = 40; Comparison n = 38) completed pre-and post-test versions of two biological reasoning tasks. The Experimental condition received 15 lessons on biological inheritance, whereas the Comparison condition received regular story time activities. The results showed that the Experimental group outperformed the Comparison group at posttest. Overall, the results are an encouraging indication that an increased understanding of biological inheritance can be effectively supported in preschool years.
A novel role for PECAM-1 in megakaryocytokinesis and recovery of platelet counts in thrombocytopenic mice
Authors: Dhanjal Tarvinder S. , Pendaries Caroline , Ross Ewan A. , Larson Mark K. , Protty Majd B. , Buckley Chris D. , Watson Steve P.
Published: January 2007

During thrombopoiesis, maturing megakaryocytes (MKs) migrate within the complex bone marrow stromal microenvironment from the proliferative osteoblastic niche to the capillary-rich vascular niche where proplatelet formation and platelet release occurs. This physiologic process involves proliferation, differentiation, migration, and maturation of MKs before platelet production occurs. In this study, we report a role for the glycoprotein PECAM-1 in thrombopoiesis. We show that following induced thrombocytopenia, recovery of the peripheral platelet count is impaired in PECAM-1–deficient mice. Whereas MK maturation, proplatelet formation, and platelet production under in vitro conditions were unaffected, we identified a migration defect in PECAM-1–deficient MKs in response to a gradient of stromal cell–derived factor 1 (SDF1), a major chemokine regulating MK migration within the bone marrow. This defect could be explained by defective PECAM-1−/− MK polarization of the SDF1 receptor CXCR4 and an increase in adhesion to immobilized bone marrow matrix proteins that can be explained by an increase in integrin activation. The defect of migration and polarization was confirmed in vivo with demonstration of altered spatial localization of MKs within the bone marrow in PECAM-1–deficient mice, following immune-induced thrombocytopenia. This study identifies a novel role for PECAM-1 in regulating MK migration and thrombopoiesis.
Prognostic impact of elevated pretransplantation serum ferritin in patients undergoing myeloablative stem cell transplantation
Authors: Armand Philippe , Kim Haesook T. , Cutler Corey S. , Ho Vincent T. , Koreth John , Alyea Edwin P. , Soiffer Robert J. , Antin Joseph H.
Published: January 2007

Iron overload could be a significant contributor to treatment-related mortality (TRM) for patients with hematologic malignancies undergoing hematopoietic stem cell transplantation (HSCT). We studied 590 patients who underwent myeloablative allogeneic HSCT at our institution, and on whom a pretransplantation serum ferritin was available. An elevated pretransplantation serum ferritin level was strongly associated with lower overall and disease-free survival. Subgroup multivariable analyses demonstrated that this association was restricted to patients with acute leukemia or myelodysplastic syndrome (MDS); in the latter group, the inferior survival was attributable to a significant increase in TRM. There was also a trend toward an increased risk of veno-occlusive disease in patients with high ferritin. Our results argue that iron overload plays an important role in transplantation outcome for patients with acute leukemia or MDS, as it does in thalassemia. They also suggest future prospective trials to examine the potential benefit of chelation therapy in this setting.
The molecular basis of IL-21–mediated proliferation
Authors: Zeng Rong , Spolski Rosanne , Casas Esther , Zhu Wei , Levy David E. , Leonard Warren J.
Published: January 2007

Interleukin-21 (IL-21) is a type I cytokine that modulates functions of T, B, natural killer (NK), and myeloid cells. The IL-21 receptor (IL-21R) is closely related to the IL-2 receptor β chain and is capable of transducing signals through its dimerization with the common cytokine receptor γ chain (γc), the protein whose expression is defective in humans with X-linked severe combined immunodeficiency. To clarify the molecular basis of IL-21 actions, we investigated the role of tyrosine residues in the IL-21R cytoplasmic domain. Simultaneous mutation of all 6 tyrosines greatly diminished IL-21–mediated proliferation, whereas retention of tyrosine 510 (Y510) allowed full proliferation. Y510 efficiently mediated IL-21–induced phosphorylation of Stat1 and Stat3, but not of Stat5, and CD8+ T cells from Stat1/Stat3 double knock-out mice exhibited decreased proliferation in response to IL-21 + IL-15. In addition, IL-21 weakly induced phosphorylation of Shc and Akt, and consistent with this, specific inhibitors of the MAPK and PI3K pathways inhibited IL-21–mediated proliferation. Collectively, these data indicate the involvement of the Jak-STAT, MAPK, and PI3K pathways in IL-21 signaling.
Fgf-dependent otic induction requires competence provided by Foxi1 and Dlx3b
Authors: Hans Stefan , Christison Joe , Liu Dong , Westerfield Monte
Published: January 2007

Background

The inner ear arises from a specialized set of cells, the otic placode, that forms at the lateral edge of the neural plate adjacent to the hindbrain. Previous studies indicated that fibroblast growth factors (Fgfs) are required for otic induction; in zebrafish, loss of both Fgf3 and Fgf8 results in total ablation of otic tissue. Furthermore, gain-of-function studies suggested that Fgf signaling is not only necessary but also sufficient for otic induction, although the amount of induced ectopic otic tissue reported after misexpression of fgf3 or fgf8 varies among different studies. We previously suggested that Foxi1 and Dlx3b may provide competence to form the ear because loss of both foxi1 and dlx3b results in ablation of all otic tissue even in the presence of a fully functional Fgf signaling pathway.

Results

Using a transgenic line that allows us to misexpress fgf8 under the control of the zebrafish temperature-inducible hsp70 promoter, we readdressed the role of Fgf signaling and otic competence during placode induction. We find that misexpression of fgf8 fails to induce formation of ectopic otic vesicles outside of the endogenous ear field and has different consequences depending upon the developmental stage. Overexpression of fgf8 from 1-cell to midgastrula stages leads to formation of no or small otic vesicles, respectively. Overexpression of fgf8 at these stages never leads to ectopic expression of foxi1 or dlx3b, contrary to previous studies that indicated that foxi1 is activated by Fgf signaling. Consistent with our results we find that pharmacological inhibition of Fgf signaling has no effect on foxi1 or dlx3b expression, but instead, Bmp signaling activates foxi1, directly and dlx3b, indirectly. In contrast to early activation of fgf8, fgf8 overexpression at the end of gastrulation, when otic induction begins, leads to much larger otic vesicles. We further show that application of a low dose of retinoic acid that does not perturb patterning of the anterior neural plate leads to expansion of foxi1 and to a massive Fgf-dependent otic induction.

Conclusion

These results provide further support for the hypothesis that Foxi1 and Dlx3b provide competence for cells to respond to Fgf and form an otic placode.
Factor structure of the Singapore English version of the KINDL® children quality of life questionnaire
Authors: Wee Hwee-Lin , Ravens-Sieberer Ulrike , Erhart Michael , Li Shu-Chuen
Published: January 2007

Background

Quality of life (QoL) outcomes are useful in the assessment of physical, mental and social well-being and for informed healthcare decision making. However, few studies have evaluated QoL issues among Asian children due largely to the lack of culturally valid and reliable QoL questionnaires. Hence, we aimed to report the psychometric properties, in particular factor structure, of KINDL (Singapore) questionnaires among school-going children.

Methods

Students aged 8–16 years from participating schools were selected by convenience sampling. Subjects self-completed KINDL-Kid (Singapore) and KINDL-Kiddo (Singapore) questionnaires, which were cross-culturally adapted from KINDL (Germany English) for use in Singapore. We evaluated floor and ceiling effects, internal consistency and performed factor analysis.

Results

A total of 328 respondents (mean (SD) age: 9.6 (1.31) years; 67% female; 75% Chinese, 16% Malays, 9% Indians and others) completed KINDL-Kid while 1,026 respondents (mean (SD) age: 14.0 (1.00) years; 82% female; 82% Chinese, 12% Malays; 6% Indians and others) completed KINDL-Kiddo. Mean (SD) TOTAL QoL score was 65.5 (12.76) and 56.6 (11.92) for KINDL-Kid and KINDL-Kiddo, respectively. Floor and ceiling effects were important in five of six KINDL-Kid and two of six KINDL-Kiddo subscales. Reliability coefficients ranged from 0.40 to 0.71 (KINDL-Kid) and 0.44 to 0.84 (KINDL-Kiddo). Factor analysis generated eight and seven factors in KINDL-Kid and KINDL-Kiddo, respectively.

Conclusion

KINDL-Kiddo exhibited good psychometric properties and may be used to assess QoL in this multi-ethnic English-speaking Asian population. However, psychometric properties of KINDL-Kid may need to be improved either by developing new items or modifying existing items.
Hormone receptor status, tumor characteristics, and prognosis: a prospective cohort of breast cancer patients
Authors: Dunnwald Lisa K , Rossing Mary Anne , Li Christopher I
Published: January 2007

Background

Breast cancer patients with tumors that are estrogen receptor (ER)-positive and/or progesterone receptor (PR)-positive have lower risks of mortality after their diagnosis compared to women with ER- and/or PR-negative disease. However, few studies have evaluated variations in the risks of breast cancer-specific mortality across ER/PR status by either demographic or clinical characteristics.

Methods

Using data from 11 population-based cancer registries that participate in the SEER (Surveillance, Epidemiology, and End Results) program, 155,175 women at least 30 years old with a primary diagnosis of invasive breast carcinoma from 1990 to 2001 were included in the study. Associations between joint hormone receptor status and breast cancer mortality risk within categories of diagnosis age, diagnosis year, race/ethnicity, histologic tumor type, stage, grade, size, and axillary lymph node status were evaluated using the Cox proportional hazards model.

Results

Compared to ER+/PR+ cases, elevations in risk of mortality were observed across all subcategories of age at diagnosis, ranging from 1.2- to 1.5-fold differences for ER+/PR- cases, 1.5- to 2.1-fold differences for ER-/PR+ cases, and 2.1- to 2.6-fold differences for ER-/PR- cases. Greater differences were observed in analyses stratified by grade; among women with low-grade lesions, ER-/PR- patients had a 2.6-fold (95% confidence interval [CI] 1.7 to 3.9) to 3.1-fold (95% CI 2.8 to 3.4) increased risk of mortality compared to ER+/PR+ patients, but among women with high-grade lesions, they had a 2.1-fold (95% CI 1.9 to 2.2) to 2.3-fold (95% CI 1.8 to 2.8) increased risk.

Conclusion

Compared to women with ER+/PR+ tumors, women with ER+/PR-, ER-/PR+, or ER-/PR- tumors experienced higher risks of mortality, which were largely independent of the various demographic and clinical tumor characteristics assessed in this study. The higher relative mortality risks identified among ER-/PR- patients with small or low-grade tumors raise the question of whether there may be a beneficial role for adjuvant chemotherapy in this population.
Comparative genomics reveals a constant rate of origination and convergent acquisition of functional retrogenes in Drosophila
Authors: Bai Yongsheng , Casola Claudio , Feschotte Cédric , Betrán Esther
Published: January 2007

Background

Processed copies of genes (retrogenes) are duplicate genes that originated through the reverse-transcription of a host transcript and insertion in the genome. This type of gene duplication, as any other, could be a source of new genes and functions. Using whole genome sequence data for 12 Drosophila species, we dated the origin of 94 retroposition events that gave rise to candidate functional genes in D. melanogaster.

Results

Based on this analysis, we infer that functional retrogenes have emerged at a fairly constant rate of 0.5 genes per million years per lineage over the last approximately 63 million years of Drosophila evolution. The number of functional retrogenes and the rate at which they are recruited in the D. melanogaster lineage are of the same order of magnitude as those estimated in the human lineage, despite the higher deletion bias in the Drosophila genome. However, unlike primates, the rate of retroposition in Drosophila seems to be fairly constant and no burst of retroposition can be inferred from our analyses. In addition, our data also support an important role for retrogenes as a source of lineage-specific male functions, in agreement with previous hypotheses. Finally, we identified three cases of functional retrogenes in D. melanogaster that have been independently retroposed and recruited in parallel as new genes in other Drosophila lineages.

Conclusion

Together, these results indicate that retroposition is a persistent mechanism and a recurrent pathway for the emergence of new genes in Drosophila.
Massive, sustained γδ T cell migration from the bovine skin in vivo
Authors: Van Rhijn Ildiko , Rutten Victor P M G , Charleston Bryan , Smits Mieke , van Eden Willem , Koets Ad P
Published: January 2007

In all species studied so far, γδ T cells are abundantly present in epithelia. The functions of these cells are largely unknown. Using a lymph duct cannulation method, which is only possible in large animals such as cattle, we show that large numbers of γδ T cells, but not αβ T cells, are constitutively present in pseudoafferent lymph draining bovine skin. The γδ T cells, which are present in pseudoafferent lymph, use Vγ segments that are characteristic for bovine dermal γδ T cells, suggesting that these cells migrated from the skin. Further supporting the origin of these cells is the fact that fluorescent latex beads injected in the skin could be recovered in cells in the pseudoafferent lymph. The cannulation method is minimally invasive, and the lymph flow, which was sustained and remained essentially unaltered during 14 days, closely represents the in vivo situation. The γδ T cells could not be induced to produce IFN-γ, TNF-α, and IL-10, and they did not express costimulatory molecules, IL-2 receptor, and MHC Class II molecules. The level of γδ T cell egress was 6.7 × 103 γδ T cells per cm2 skin per hour, which is enough to deplete all γδ T cells from the skin within 46 h. As this massive γδ T cell migration was observed during 14 days, constant replenishment of these cells must take place. Our data suggest that γδ T cells in tissues fulfill more than exclusively local functions.
High-Dose α-Tocopherol Therapy Does Not Affect HDL Subfractions in Patients with Coronary Artery Disease on Statin Therapy
Authors: Singh Uma , Otvos James , Dasgupta Amitava , de Lemos James A , Devaraj Sridevi , Jialal Ishwarlal
Published: January 2007

Background: Subfractions of HDL, particularly large HDL (HDL2), are inversely correlated with the severity of coronary artery disease (CAD). α-Tocopherol (AT) is the main lipid-soluble antioxidant in plasma. Results of a previous small study (n = 44) suggested that either a combination of an antioxidant cocktail [800 IU/day 2R,4′R,8′R-(RRR)-AT plus 1 g vitamin C, 25 mg β-carotene, and 100 μg selenium] or individual antioxidant vitamins combined with simvastatin–niacin (S-N) therapy attenuated the protective increase in HDL2 seen with S-N alone. Few data are available on the effect of AT therapy alone on HDL subfractions, which we addressed in this study.

Methods: In a prospective placebo-controlled study, we randomized 127 patients with stable CAD to receive high-dose RRR-AT (1200 IU/day for 2 years) or placebo. HDL subfractions (small, medium, and large HDL particles) were analyzed by nuclear magnetic resonance spectroscopy.

Results: AT concentrations significantly increased in the AT arm but not with placebo. No differences were noted between AT and placebo groups in concentrations of total cholesterol, triglyceride, LDL-cholesterol, or HDL-cholesterol. AT therapy did not affect total, small, medium, or large HDL particles compared with baseline or placebo. Furthermore, serum apolipoprotein A1 concentrations did not change after 2 years AT therapy as compared with baseline.

Conclusions: High-dose AT therapy administered for a 2-year period does not negatively affect either HDL subfractions or apolipoprotein A1 in patients with CAD on statin therapy. Thus the negative interaction previously proposed between antioxidant cocktail and statin therapy cannot be attributed to AT.