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This paper reviews Art Winfree's contributions to the bidomain model of cardiac tissue. Specifically, he first predicted quatrefoil reentry, he showed that an S1 refractory gradient is not required for an S2 stimulus to induce reentry, and his work on spiral wave meandering led to studies on how the path of the tip of a spiral wave is influenced by tissue anisotropy.
At the beginning of their aggregation phase waves of cell density sweep across the surface of myxobacteria colonies. These waves are unlike any other in biology. Waves can be linear, concentric or spiral and when they collide, instead of annihilating one another they appear to pass through each other unchanged. Moreover, the wavelength determines the spacing and pattern of fruiting bodies that will rise up presaging sporulation. The explanation for these waves was suggested by the work of Art Winfree on cellular clocks, and confirmed by a mathematical model that explains all of the observed wave behavior. The story of how this model evolved illustrates the roles of chance and scientific networking in the search for the explanation of a new phenomenon.
Small cell lung cancer accounts for less than 20% of all lung cancer. The management of this distinct tumor entity differs from the more common non-small cell lung cancer. Primary prevention of smoking exposure remains the most important public health measure. Although small cell lung is an exquisitely chemosensitive disease it remains ultimately fatal for the great majority of patients. Combination chemotherapy regimens have improved response rate and survival of the last three decades. The combination of cisplatin and etoposide has been considered the standard therapy for over a decade. More intensive triplet combination chemotherapy and high-dose chemotherapy have shown improved response rates and survival. Early concomitant and accelerated radiotherapy improves survival in limited stage disease. This review summarizes the current state of the art and future perspectives in detection, staging and standard therapy of small cell lung cancer. Particular emphasis is given to the importance of concomitant and accelerated radiotherapy and consideration of dose-intensive combination chemotherapy regimens.
The development and function of vertebrate ovary are primarily controlled by the gonadotropins, follicle-stimulating hormone (FSH) and luteinizing hormone (LH), from the pituitary. However, most of the activities of FSH and LH are mediated or modulated by a variety of locally produced factors that form an intimate regulatory network within and between the follicles. As a top vertebrate model for genetic and developmental studies, the zebrafish has caught tremendous attention in the past two decades; however, its utility has quickly been extended to other areas including physiology. In the past few years, a variety of peptide growth factors have been identified and characterized in the zebrafish ovary including activin and epidermal growth factor (EGF), and lines of evidence point to the existence of an ovarian network of communication involving these factors. This article provides the state of the art of zebrafish as a model for analyzing ovarian development and its regulation.
Cough is the most common presenting complaint in adults seeking medical treatment in an ambulatory setting. Chronic cough (persisting greater than 3 weeks) can be associated with myriad diseases that may overlap multiple medical specialties. For this reason, a thorough assessment of the patient with chronic cough relies on a multidisciplinary approach and close cooperation between pulmonary medicine, gastroenterology, and otolaryngology. Despite this daunting task, success can be achieved in up to 90% of patients with chronic cough if a systematic and thorough approach is used. The purpose of this review is to summarize the state-of-the-art in the diagnosis and treatment of chronic cough for the practicing otolaryngologist.
Protein crystallisation has gained a new strategic and commercial relevance in the post-genomic era because of its pivotal role in structural genomics. Producing high-quality crystals has always been a bottleneck to structure determination and, with the advent of proteomics, this problem is becoming increasingly acute. The task of producing suitable crystals may be tackled using two approaches. The first relies on empirical techniques that are based mainly on trial and error, and what is perceived to be the 'art' of crystallisation. The second approach is aimed at gaining an understanding of the fundamental principles that govern crystallisation; this knowledge may be applied to design experimental methodology for producing high-quality crystals of medical and industrial interest.
OBJECTIVES: To describe the modalities used to administer radiation therapy and discuss the acute effects and long-term survivorship issues experienced by patients who receive radiation therapy. DATA SOURCES: Radiation oncology, surgical, and oncology nursing journals, textbooks, electronic resources. CONCLUSION: New technology and state-of-the-art equipment has resulted in improved treatment modalities, thereby expanding traditional treatment paradigms and exploring new frontiers. IMPLICATIONS FOR NURSING PRACTICE: It is critical that oncology nurses remain cognizant of advanced technology and its influence on treatment outcomes and patient toxicity. Such knowledge will better serve patients and hopefully influence evidence-based treatment interventions.
The skin is the main target tissue for exogenous noxes, protecting us from harmful environmental hazards, UV-irradiation and endogenous water loss. It is composed of three layers, whereas the outermost epidermis is a squamous epithelium that mainly consists of keratinocytes. These cells execute a terminal differentiation, which finally results in the assembly of the stratum corneum. This layer, consisting of cornified keratinocytes, is an effective barrier against a vast number of substances. Apart of this, keratinocytes play crucial roles in the immune surveillance and the initiation, modulation and regulation of inflammation in the epidermis. Regarding cutaneous inflammatory reactions, skin irritation is one of the most common adverse effect in humans. For reasons of human safety assessment new chemicals are still evaluated for irritant potentials by application to animals followed by visible changes such as erythema and oedema. Testing for skin irritation in animals potentially cause them pain and discomfort. Furthermore, the results are not always predictive for those found in humans. In order to replace animal testing and to improve the prediction of irritants, the cosmetic and toiletry industry, in Europe represented by Colipa, develops and uses several alternative in vitro test systems. In this respect, the use of in vitro reconstructed organotypic skin equivalents are mostly favored, because of their increasingly close resemblance to human skin. Due to ethical and scientific questions and on account of the 7th amendment of the European Council Directive 76/768/EEC, the authors see the requirement to drive the development of alternative tests for irritants. Therefore, this article centres on cosmetic ingredients and provides the readership an overview of the state of art of cellular mechanisms of skin irritation and summarizes the results of the commonly used skin equivalents to evaluate irritation in vitro.
Molecular-, gene-, cellular-, and tissue-based therapies have become increasingly acceptable modes of clinical therapy. Regulatory requirements and oversight have increased, and the need for facilities suited for production of such therapies has become more apparent. The Minnesota Molecular and Cellular Therapeutics Facility is a state-of-the-art laboratory at the University of Minnesota, Saint Paul, Minn, that was designed to support production of biologic products for use in clinical trials. A talented staff experienced in the medical, scientific, technical, and regulatory aspects of the development, production, and administration of such products complements the special design and construction of the facility. Hematopoietic stem cells (HSCs) are manipulated for transplant, and current clinical trials involving novel therapies include the use of allogeneic natural killer (NK) cells and tumor vaccines for the treatment of various malignancies and suicide gene-transduced T cells for the prevention of graft-vs-host disease (GVHD) after bone marrow transplantation. Other therapies, including marrow-derived multipotent adult progenitor cells (MAPCs), umbilical cord blood (UCB) stem cells, regulatory T cells, skeletal myoblasts, and monoclonal antibodies, will be used to treat a spectrum of disease and are in various phases of development. Here we provide an overview of the Minnesota Molecular and Cellular Therapeutics (MMCT) Facility, detailing our approach to the manufacture of novel therapeutics and highlighting current and future activities.
Study of left ventricular (LV) regional and global function represents a main point of the cardiologic evaluation. This article presents an overview of the state of the art in quantitative analysis of ventricular wall motion and describes the different techniques available in clinical settings; we also present the personal experience of the authors in comparing conventional 2-dimensional (2D) echocardiography with other recently developed, more sophisticated techniques. Conventional 2D echocardiography mainly depends on the operator's ability. Moreover, the physiologic regional pattern of myocardial wall motion in different segments of left ventricle is still not completely known as well as the heart's rotational and translational movements. Qualitative and quantitative transesophageal echocardiography allows a better and more accurate evaluation of regional wall motion, and improves the on-line border detection feasibility even in patients with poor transthoracic echocardiographic window. The automated system for on-line endocardial border detection, color kinesis, and the power Doppler are, at the moment, promising techniques. Using magnetic resonance imaging as a "gold standard" for the study of global and regional left ventricular function, the investigators describe personal experiences with tissue Doppler imaging and a new computerized system for tissue Doppler images postprocessing analysis.
Axillary staging for breast cancer is vitally important for determining appropriate adjuvant hormone and chemotherapy. In the absence of distant metastases, axillary lymph node status remains the most accurate predictor of clinical outcome. Sentinel lymph node biopsy is a minimally invasive approach with enhanced accuracy and less morbidity than conventional axillary dissection. The stage is now set for the sentinel lymphadenectomy staging to move from state-of-the-art care to the standard care in coming years.
What are the units of attention? In addition to standard models holding that attention can select spatial regions and visual features, recent work suggests that in some cases attention can directly select discrete objects. This paper reviews the state of the art with regard to such 'object-based' attention, and explores how objects of attention relate to locations, reference frames, perceptual groups, surfaces, parts, and features. Also discussed are the dynamic aspects of objecthood, including the question of how attended objects are individuated in time, and the possibility of attending to simple dynamic motions and events. The final sections of this review generalize these issues beyond vision science, to other modalities and fields such as auditory objects of attention and the infant's 'object concept'.
Thin-layer chromatography-mass spectrometry (TLC-MS) is a readily implemented technique that, in its simplest form, puts few demands on either chromatography or spectrometry. Nevertheless, compared to the situation with high performance liquid chromatography, it is much less highly developed. Currently, the bulk of the practical applications of TLC-MS are directed towards the use of fast atom, or ion bombardment. Recent developments, however, include the use of matrix assisted laser desorption ionisation (MALDI), surface assisted laser desorption (SALDI) and the development of a TLC-electrospray interface. Here, the state of the art of TLC-MS is described and future trends identified.
This special issue of the Journal of Immunological Methods brings together articles from some of the leaders in labelling antigen-specific T and NKT cells, describing recent technical advances and their impact on the study of immunology. Although tetramers, or tetrameric MHC class I/peptide complexes, are the best known reagents in the field, various forms of oligomeric complexes are now being successfully used to detect antigen-specific T cells, including cytotoxic T lymphocytes, MHC class II-restricted CD4+ T cells, and glycolipid-specific T cells restricted by CD1 isoforms. The articles presented here detail the breadth of the oligomeric structures being used to probe T, NK and NKT cell function, and cover both the technical and practical aspects of their use, as well as the new biology revealed. In addition to providing a summary of the current state of the art, these contributions also provide clear pointers to strategies likely to succeed in the future. In this introductory chapter, we summarise the work presented in the other articles of this issue, and provide an overarching view of this rapidly evolving field. We also provide a summary of the MHC class I molecules successfully refolded to date, and provide references to other relevant sources of technical information.
The current state of the art makes breast reconstruction possible in any patient who has undergone mastectomy, whether simple, modified radical, or radical. Indications for reconstruction are a strong desire on the part of the patient and a reasonable life expectancy. Methods of reconstruction include the simple placement of a breast prosthesis alone (submuscularly when possible) or in combination with advancement of upper abdominal skin or rotation flaps. Expander implants are useful in patients with limited skin and musculature. For the patient with serious muscle and skin deficits, more complex reconstructive procedures with use of transverse rectus abdominis or latissimus dorsi myocutaneous flaps may be performed, with or without an implant. Several methods of reconstruction of the nipple and areola are also possible. Treatment of the opposite breast is often necessary if symmetry is to be achieved. When appropriate, augmentation, mastopexy, reduction, or subcutaneous mastectomy may be performed. There is no single preferred method of reconstruction. The approach should be tailored for each patient.
A practical guide to working with parents on the discipline of their children is provided. Focus is specific to provide a practical tool of useful how-to information for the primary care provider who works with children and their families. This article focuses on basic principles and techniques that can be established within the office setting, so as to model for families, as well as to teach to families for use at home. This article also focuses on common applications to illustrate the use of these techniques. Finally, the art of consultation and referral is reviewed for situations that are assessed to be above and beyond the call of the primary practitioner.
This paper discusses the two dimensions of public health medicine competence--science and art--and explores the reasons for the importance of public health medicine artistry within an organisational context. The skills of artistry are identified as political and people management and it is noted that although the science dimension is vital, without the skills that comprise artistry, public health physicians are inadequately prepared to tackle the work of improving the health of the population. It is recommended that these skills should become an integral component of public health medicine training.
No "major" painter is known to be color deficient. Are there truly no color deficient artists, or have they not been recognized? The historical literature cites criteria for recognizing color deficiency in artists, but they are hard to apply without knowing the intentions of an artist. The work and commentary of a color-deficient artist who works currently in Paris are presented as an example. He uses a limited palette of colors, based on advice from colleagues as much as his own perceptions, and he uses colors in ways that do not always fit with expectations for color deficiency. Biographies of earlier painters suggest that there were a few whose color sense was poor, but these painters used assistants to help. The color sense of others, such as the English landscape painter John Constable (1776-1837), has been questioned because of a preponderance of suspicious color, such as murky green. However, there are good reasons to doubt that Constable was color deficient. It is instructive to know how proven color deficiency has influenced an artist's style. When medical information is unavailable, the best advice for the diagnostically-inclined observer is just to enjoy the art.