Despite optimistic reports about the results of amputation for advanced vascular disease, the patient’s assessment of advantages and disadvantages is seldom acknowledged. A detailed social study of 67 amputees has revealed considerable disparity between the patient’s views and those of the medical staff. About a third of the patients are forced to retire from active work by the amputation; about three-quarters report a serious decline in their social activities; only about half are really independent with prostheses in the long (...) term; a quarter report severe and intractable symptoms related to their amputation stumps; only about a quarter feel that the amputation was definitely beneficial; and only about one in five feel that the medical staff have provided adequate support during their hospital stay. Amputees face physical and financial disability, isolation, and discomfort. Every effort must be made to explain the implications of amputation honestly and realistically and to ensure continuing patient assessment and support. (shrink)

Angiogenesis is central to both the growth and metastasis of solid tumours. Anti‐angiogenic strategies result in blood vessel regression accompanied by tumour cell apoptosis. Radiotherapy and many chemotherapeutic agents kill tumours by inducing apoptotic cell death. We propose that, in addition to its role as an angiogenic factor, vascular endothelial growth factor (VEGF) can act as a survival factor for tumour cells protecting them from apoptosis. Thus anti‐angiogenics, in particular those directed against VEGF, have multiple anti‐tumour effects. We suggest (...) that anti‐VEGF strategies prevent vessel growth and block a tumour cell survival factor, VEGF, rendering tumour cells more sensitive to chemotherapy and radiotherapy. In addition, as chemotherapy and radiotherapy have been shown to increase VEGF expression, anti‐VEGF strategies may overcome therapy‐ induced tumour cell resistance. BioEssays 24:280–283, 2002. © 2002 Wiley Periodicals, Inc.; DOI 10.1002/bies.10043. (shrink)

Mononuclear phagocytes (MPs), which consist of dendritic cells, monocytes, and macrophages, are distributed throughout the body and actively eliminate invading microorganisms and abnormal cells. Depending on the local microenvironment, MPs manifest considerably various lifespans and phenotypes to maintain tissue homeostasis. Vascular‐associated mononuclear phagocytes (VaMPs) are the special subsets of MPs that are localized either within the lumen side or on the apical surface of vessels, acting as the critical sentinels to recognize and defend against disseminated tumor cells. In this (...) review, we introduce three major types of VaMPs, patrolling monocytes, Kupffer cells, and perivascular macrophages, and discuss their emerging roles in immunosurveillance during incipient metastasis. We also explore the roles of lineage‐determining transcription factors and cell surface receptors that endow VaMPs with potent anti‐tumor activity. Finally, we highlight the molecular and cellular mechanisms that drive the phenotypic plasticity of VaMPs and summarize combinatory strategies for targeting VaMPs in overt metastasis. (shrink)

Neural activity varies continually from moment to moment. Such temporal variability (TV) has been highlighted as a functionally specific brain property playing a fundamental role in cognition. We sought to investigate the mechanisms involved in TV changes between two basic behavioral states, namely having the eyes open (EO) or eyes closed (EC) in vivo in humans. To these ends we acquired BOLD fMRI, ASL, and [18F]-fluoro-deoxyglucose PET in a group of healthy participants (n = 15), along with BOLD fMRI and (...) [18F]-flumazenil PET in a separate group (n = 19). Focusing on an EO- vs EC-sensitive region in the occipital cortex (identified in an independent sample), we show that TV is constrained in the EO condition compared to EC. This reduction is correlated with an increase in energy consumption and with regional GABAA receptor density. This suggests that the modulation of TV by behavioral state involves an increase in overall neural activity that is related to an increased effect from GABAergic inhibition in addition to any excitatory changes. These findings contribute to our understanding of the mechanisms underlying activity variability in the human brain and its control. (shrink)

Vascular Endothelial Growth Factor (VEGF) is the most potent and ubiquitous vascular growth factor known to date. Yet, prior to its description as a secreted mitogen for endothelial cells, it was identified as a vascular permeability factor. These seemingly disparate avenues of discovery highlight VEGF's ability to control many distinct aspects of endothelial cell behaviour, including proliferation, migration, specialisation and survival. The versatility of VEGF as a patterning molecule is likely linked to its association with various signalling (...) receptor complexes, but also its expression in several isoforms with a differential affinity for heparan sulfate proteoglycans in the extracellular matrix. In contrast to the absolute requirement for all known VEGF receptors, the presence of only a single VEGF isoform is sufficient for vascular development. However, the isoforms serve as exquisite tools for the fine patterning of growing vessel networks during embryogenesis and in postnatal life. BioEssays 25:1052–1060, 2003. © 2003 Wiley Periodicals, Inc. (shrink)

Reconstructive allografts using Vascularized Composite Allotransplantation are providing individuals living with upper limb loss and facial disfigurement with new opportunities for a sensate, esthetically acceptable, and functional alternative to current treatment strategies. Important research attention is being paid to how best to assess and screen candidates for VCA, measure optimal patient outcomes, and support patient adherence to lifelong behaviors and medical regimens. Far less attention, however, has been dedicated to the team science required for these complex VCA teams to form, (...) prepare, and provide the highest quality clinical and psychosocial care to those receiving VCA. VCA teams are unique in that they require specialized team members whose scope of practice may not otherwise overlap. The team also needs to constantly negotiate balancing patient safety with multiple risks throughout the transplant process. This study aimed to elucidate the team science needed for this highly innovative and complex area of medicine. Using in-depth qualitative interviews with 14 VCA team members and observations at team meetings, we found that careful consideration of team composition, team structure, and organizational commitment influences team performance and patient outcomes, but that to be efficient and truly effective, teams need to commit to developing processes that foster collaboration. These processes are action-oriented, strategic and interpersonal. Dedication and commitment to team science allows teams to manage conflict under stress and exercise ways to leverage strengths to provide optimal performance or patient psychosocial and clinical outcomes. This study can provide insight into quality improvement efforts for VCA teams and guidance for other transplant programs that wish to consider expansion into VCA. (shrink)

Background: The vascular depression hypothesis emphasizes the significance of vascular lesions in late-life depression. At present, no meta-analytic model has investigated whether a difference in hyperintensity burden compared to controls between late-life and late-onset depression is evident. By including a substantial number of studies, focusing on a meaningful outcome measure, and considering several moderating and control variables, the present meta-analysis investigates the severity of hyperintensity burden in major depressive disorder (MDD) and bipolar disorder (BD). A major focus of (...) the present meta-analysis refers to the role of age at illness onset. It is analyzed whether late-onset rather than late-life depression characterizes vascular depression. Method: In total, 68 studies were included in the meta-analysis and a multilevel random effects model was calculated using Hedges’ g as the effect size measure. Results: The severity of hyperintensity burden was significantly greater in the patient group compared to the control group. This effect was evident regarding the whole patient group (g = 0.229) as well as both depression subgroups, with a significantly greater effect in BD (g = 0.374) compared to MDD (g = 0.189). Hyperintensity burden was more pronounced in late-onset depression than in early-onset depression or late-life depression. A considerable heterogeneity between the included studies was observed, which is reflected by the large variability in effects sizes. Conclusion: In conclusion, the present meta-analysis underscores the association of hyperintensities with MDD and BD. Especially late-onset depression is associated with an increased hyperintensity burden, which is in line with the vascular depression hypothesis. The results suggest that it might be more feasible to confine the concept of vascular depression specifically to late-onset depression as opposed to late-life depression. Further research is needed to understand the causal mechanisms that might underlie the relation between hyperintensity burden and depression. (shrink)

The genetically and experimentally accessible organs of Drosophila, such as the heart or blood‐forming tissues, have become a fertile ground for systematic projects of gene discovery and for functional studies of gene networks and signaling pathways. One argument justifying this approach is the often‐tacit assumption that clear‐cut homologies can be established between the Drosophila organs and their vertebrate counterparts. Here we investigate this assumption by surveying pertinent aspects of vascular structure and development in different invertebrate phyla, in the hope (...) that this information will help to reveal the ancestral condition of the vascular system. Evolutionary scenarios that derive the structure of the cardiovascular system of extant animal taxa from the ancestral condition will be used to qualify hypotheses regarding homologies that are based on molecular similarities. BioEssays 28: 1203–1210, 2006. © 2006 Wiley Periodicals, Inc. (shrink)

The cardiovascular system has the life‐providing task of delivering oxygen and any flaw in this system can be life‐threatening. This has encouraged extensive studies to elucidate the mechanisms behind cardiovascular development/homeostasis. The zebrafish has emerged as a formidable tool to speed up this quest, as illustrated in a recent issue of Nature Genetics.1 Baculovirus IAP repeat c2 (BIRC2), also termed cellular inhibitor of apoptosis (cIAP)‐1, was found to specifically prevent endothelial cells (ECs, lining the inside of vessels) from going into (...) suicide mode (‘apoptosis’) and so preserve vessel integrity. Here, we summarize the factors determining vascular integrity and elaborate on the suitability of the zebrafish to study this phenomenon. BioEssays 30:418–422, 2008. © 2008 Wiley Periodicals, Inc. (shrink)

Osteoporosis (OP) is a bone disease which affects a number of post‐menopausal females and puts many at risk for fractures. A large number of patients are taking bisphosphonates (BPs) to treat their OP and a rare complication is the development of atypical femoral fractures (AFF). No real explanations for the mechanisms underlying the basis for development of where AFF develop while on BPs has emerged. The present hypothesis will discuss the possibility that part of the risk for an AFF is (...) a secondary effect of BPs on a subset of vascular cells in a genetically at‐risk population, leading to localized deregulation of the endothelial cell (EC)‐bone cell‐matrix units in nutrient channels/canals of the femur and increased risk for AFF. This concept of targeting ECs is consistent with location of AFF in the femur, the bilateral risk for occurrence of AFF, and the requirement for long term exposure to the drugs. (shrink)

As the field of vascularized composite allotransplantation (VCA) continues to evolve and technological approaches improve, VCA programs must focus on promoting greater consistency in psychosocial assessment across programs to support the equitable selection of patients. Based on a summary of published reports of VCA, we address the ethical considerations raised by the present heterogeneity of approaches to psychosocial assessment, including weighing risks and benefits, informed consent and the role of decisional capacity, and potential or perceived bias in the assessment process. (...) We propose transparency of process across the field and encourage VCA programs to work collaboratively to share approaches to psychosocial assessment both pre- and posttransplant to promote health equity. (shrink)

The development of photodynamic therapy and anti-vascular endothelial growth factor agents have revolutionized the treatment of retinal diseases, transforming the retina subspecialty by ushering in an age of pharmacological treatments for a wide range of diseases, including age-related macular degeneration.

BackgroundPeople with upper extremity amputations report receiving insufficient information about treatment options. Furthermore, patients commonly report not knowing what questions to ask providers. A question prompt sheet, or list of questions, can support patient-centered care by empowering patients to ask questions important to them, promoting patient-provider communication, and increasing patient knowledge. This study assessed information needs among people with UE amputations about UE vascularized composite allotransplantation and developed a UE VCA-QPS.MethodsThis multi-site, cross-sectional, mixed-methods study involved in-depth and semi-structured interviews with (...) people with UE amputations to assess information needs and develop a UE VCA-QPS. Qualitative data were analyzed by thematic analysis; quantitative data were analyzed by descriptive statistics. The initial UE VCA-QPS included 130 items across 18 topics.ResultsEighty-nine people with UE amputations participated. Most were male, had a mean age of 46 years, and had a unilateral and below-elbow amputation. Participants desired information about UE VCA eligibility, evaluation process, surgery, risks, rehabilitation, and functional outcomes. After refinement, the final UE VCA-QPS included 35 items, across 9 topics. All items were written at a ≤ 6th grade reading level. Most semi-structured interview participants reported being ‘completely’ or ‘very’ likely to use a UE VCA-QPS.ConclusionPeople with UE amputations have extensive information needs about UE VCA. The UE VCA-QPS aims to address patients’ information needs and foster patient-centered care. Future research should assess whether the UE VCA-QPS facilitates patient-provider discussion and informed decision-making for UE VCA. (shrink)

(1941). A survey of the growth of knowledge about certain parts of the foetal cardio-vascular apparatus, and about the foetal circulation, in Man and some other mammals. Part I: Galen to Harvey. Annals of Science: Vol. 5, No. 1, pp. 57-89.

A cost analysis of the utilization of new expensive vascular grafts is performed, applying the methodology of decision analysis to the theoretical case of a sixty year old male patient undergoing femoropopliteal grafting for limb threatening ischemia. The problem is presented graphically as a decision tree, uncertainties are quantified in terms of probabilities and end outcomes are evaluated in monetary terms. This informations is then utilized to calculate cost values associated with alternative actions.Based on initial cumulative patency figures of (...) the new more expensive grafts and the known performance of the older grafts, the initial high expense for the new grafts is justified economically, if the saphenous vein is not available. This analysis, apart from giving an answer to a specific clinical problem, can be viewed as a general model for cost analysis of surgical procedures. (shrink)

BackgroundVascular surgery offers a range of treatments to relieve pain and ulcerations, and to prevent sudden death by rupture of blood vessels. The surgical procedures involve risk of injury and harm, which increases with age and frailty leading to complex decision-making processes that raise ethical questions. However, how vascular surgeons negotiate these questions is scarcely studied. The aim was therefore to explore vascular surgeons’ moral reasoning of what ought to be done for the patient.MethodsQualitative, semi-structured interviews were conducted (...) with 19 vascular surgeons working at three Swedish university hospitals. Data were analysed according to systematic text condensation.ResultsThe surgeons’ moral reasoning about what ought to be done comprised a quest to relieve suffering and avoid harm by exploring what is reasonable to do for the patient. Exploring reasonableness included to shift one´s perspective from the vessels to the whole person, to balance patient’s conflicting needs and to place responsibility for right decision on one´s shoulders. The shift from blood vessels to the whole person implied gaining holistic knowledge in pondering of what is best, struggling with one´s authority for surgery through dialogue, and building relationship for mutual security. To balance patient’s conflicting needs implied weighing the patient’s independence and a sense of being whole against ease of suffering, respecting the patient’s will against protecting life and well-being, and weighing longer life against protecting the present well-being. Finally, to place responsibility on one´s shoulders was conveyed as an urge to remind oneself of the risk of complications, withholding one’s power of proficiency, and managing time during the illness course.ConclusionsThis study contributes to uncovering how moral reasoning is embodied in the vascular surgeons’ everyday clinical discourse as a tangible part of their patient care. The results underpin the significance of moral considerations in the assemblage of medical knowledge and technical skills to further understand vascular surgeons’ clinical practice. The clinical application of these results is the need of forums with sufficient possibilities for articulating these important moral considerations in everyday care. (shrink)

Four classes of naturally rare vascular plant species are described and classified, based on parameters of spatial distribution and longevity. Properties intrinsic to these time/space parameters are explored and an importance hierarchy of causes of rarity is proposed for each class. These hierarchies serve as the basis for a predictive classification. Human causes of rarity such as habitat destruction and taxonomic difficulties are not considered in detail here but are discussed as confounding factors in the elucidation of rarity in (...) vascular plants. Several examples are provided to illustrate this classification and provide testable hypotheses concerning the origins of natural rarity in plant species. (shrink)

Radial growth has long been a subject of interest in tree biology research. Recent studies have brought a significant change in the understanding of some basic processes characteristic to the vascular cambium, a meristem that produces secondary vascular tissues (phloem and xylem) in woody plants. A new hypothesis regarding the mechanism of intrusive growth of the cambial initials, which has been ratified by studies of the arrangement of cambial cells, negates the influence of this apical cell growth on (...) the expansion of the cambial circumference. Instead, it suggests that the tip of the elongating cambial initial intrudes between the tangential (periclinal) walls, rather than the radial (anticlinal) walls, of the initial(s) and its(their) derivative(s) lying ahead of the elongating cell tip. The new concept also explains the hitherto obscure mechanism of the cell event called ‘elimination of initials’. This article evaluates these new concepts of the cambial cell dynamics and offers a new interpretation for some curious events occurring in the cambial meristem in relation to the radial growth in woody plants. (shrink)

Endothelial cells, when cultured on gelled basement membrane matrix exert forces of tension through which they deform the matrix and at the same time they aggregate into clusters. The cells eventually form a network of cord-like structures connecting cell aggregates. In this network, almost all of the matrix has been pulled underneath the cell cords and cell clusters. This phenomenon has been proposed as a possible model for the growth and development of planar vascular systems in vitro. Our hypothesis (...) is that the matrix is reorganized and the cellular networks form as a result of traction forces exerted by the cells on the matrix and the latter's elasticity. We construct and analyze a mathematical model based on this hypothesis and examine conditions necessary for the formation of the pattern. We show cell migration is not necessary for pattern formation and that isotropic, strain-stimulated traction is sufficient to form the observed patterns. (shrink)

The establishment of distinct cellular identities was pivotal during the evolution of Metazoa, enabling the emergence of an array of specialized tissues with different functions. In most animals including vertebrates, cell specialization occurs in response to a combination of intrinsic (e.g., cellular ontogeny) and extrinsic (e.g., local environment) factors that drive the acquisition of unique characteristics at the single‐cell level. The first functional organ system to form in vertebrates is the cardiovascular system, which is lined by a network of endothelial (...) cells whose organ‐specific characteristics have long been recognized. Recent genetic analyses at the single‐cell level have revealed that heterogeneity exists not only at the organ level but also between neighboring endothelial cells. Thus, how endothelial heterogeneity is established has become a key question in vascular biology. Drawing upon evidence from multiple organ systems, here we will discuss the role that lineage history may play in establishing endothelial heterogeneity. (shrink)

Complex regional pain syndromes (reflex sympathetic dystrophy, causalgia) are often characterized by pain and autonomic and motor abnormalities. Pathophysiological mechanisms are in the central and peripheral nervous system. Differences in skin temperature and may be used as diagnostic criteria. Sympathetic blocks relieve pain and other symptoms in a subgroup of patients (sympathetically maintained pain, SMP).[blumberg et al.].