Adrenal gland development and defects

The network regulating human adrenal development is complex. Studies of patients with adrenal insufficiency due to gene mutations established a central role for transcription factors GLI3, SF1 and DAX1 in the initial steps of adrenal formation. Adrenal differentiation seems to depend on adrenocorticotropic hormone (ACTH) stimulation and signalling, including biosynthesis and action of POMC, PC1, TPIT, MC2R, MRAP and ALADIN, all of which cause adrenocortical hypoplasia when mutated in humans. Studies of knockout mice revealed many more factors involved in adrenal development; however, in contrast to rodents, in humans several of those factors had no adrenal phenotype when mutated (e.g. WT1, WNT4) or, alternatively, human mutations have not (yet) been identified. Tissue profiling of fetal and adult adrenals suggested 69 genes involved in adrenal development. Among them were genes coding for steroidogenic enzymes, transcription and growth factors, signalling molecules, regulators of cell cycle and angiogenesis, and extracellular matrix proteins; however, the exact role of most of them remains to be elucidated.

Regulation of fetal growth: consequences and impact of being born small

The first trimester of pregnancy is the time during which organogenesis takes place and tissue patterns and organ systems are established. In the second trimester the fetus undergoes major cellular adaptation and an increase in body size, and in the third trimester organ systems mature ready for extrauterine life. In addition, during that very last period of intrauterine life there is a significant increase in body weight. In contrast to the postnatal endocrine control of growth, where the principal hormones directly influencing growth are growth hormone (GH) and the insulin-like growth factors (IGFs) via the GH-IGF axis, fetal growth throughout gestation is constrained by maternal factors and placental function and is coordinated by growth factors. In general, growth disorders only become apparent postnatally, but they may well be related to fetal life. Thus, fetal growth always needs to be considered in the overall picture of human growth as well as in its metabolic development.

Thermoregulatory management for mild therapeutic hypothermia

In recent years the use of mild therapeutic hypothermia as a means of neuroprotection has become an important concept for treatment after cerebral ischemic hypoxic injury. Mild therapeutic hypothermia has been shown to improve outcome after out-of-hospital cardiac arrest, and many studies suggest a beneficial effect of mild therapeutic hypothermia on patient outcome after traumatic brain injury, cerebrovascular damage and neonatal asphyxia. This review article explores the numerous possibilities and methods for the induction of mild therapeutic hypothermia, reviews thermoregulatory management during maintenance and discusses associated risks and complications.

The mucosal immune system at the gastrointestinal barrier

The immune system faces a considerable challenge in its efforts to maintain tissue homeostasis in the intestinal mucosa. It is constantly confronted with a large array of antigens, and has to prevent the dissemination and proliferation of potentially harmful agents while sparing the vital structures of the intestine from immune-mediated destruction. Complex interactions between the highly adapted effector cells and mechanisms of the innate and adaptive immune system generally prevent the luminal microflora from penetrating the intestinal mucosa and from spreading systemically. Non-haematopoietic cells critically contribute to the maintenance of local tissue homeostasis in an antigen-rich environment by producing protective factors (e.g. production of mucus by goblet cells, or secretion of microbicidal defensins by Paneth cells) and also through interactions with the adaptive and innate immune system (such as the production of chemotactic factors that lead to the selective recruitment of immune cell subsets). The complexity of the regulatory mechanisms that control the local immune response to luminal antigens is also reflected in the observation that mutations in immunologically relevant genes often lead to the development of uncontrolled inflammatory reactions in the microbially colonized intestine of experimental animals.

General laboratory diagnostics of eosinophilic GI diseases

Eosinophils and gastrointestinal tract interact in an intimate and enigmatic relationship. Under inflammatory conditions, eosinophil infiltration in the gastrointestinal tract is a common feature of numerous eosinophilic gastrointestinal disorders (EGIDs). EGIDs are disorders, for which the diagnosis is relatively difficult. Nevertheless, some common laboratory techniques are currently used for their diagnosis and disease monitoring. Besides eosinophils, mast cells and T cells have also been suggested to play a role in the pathogenesis of these disorders. Here, we review the pathogenesis and common laboratory approaches applied for their diagnosis, in particular eosinophil and mast cell markers.

Diabetes and acute coronary syndromes

Diabetic patients with acute coronary syndromes (ACSs) are at a high risk for subsequent cardiovascular events but derive, at the same time, greater benefit from evidence-based therapy than non-diabetic individuals. State-of-the-art anti-thrombotic therapy includes a triple anti-platelet combination - aspirin, clopidogrel and glycoprotein (GP) IIb/IIIa receptor inhibitors - and unfractionated heparin or enoxaparin. For low- or medium-risk individuals, a treatment based on aspirin, clopidogrel and bivalirudin is a valuable alternative. Prasugrel, a new and more potent inhibitor of the platelet P2Y(12) receptor, has to be regarded as the most promising anti-thrombotic agent for diabetic patients with ACS. This agent may replace clopidogrel - and possibly GP IIb/IIIa inhibitors - in the future. In addition to aggressive anti-thrombotic therapy, diabetic patients should undergo systematic early invasive angiography if presenting with non-ST-segment elevation ACS, and immediate percutaneous coronary intervention if presenting with ST-segment elevation myocardial infarction. Indeed, the benefit derived from these strategies appears to be more pronounced in the diabetic population than in non-diabetic individuals. Despite the benefit, multiple surveys have demonstrated that, in the setting of ACS, diabetic patients receive evidence-based therapy less frequently than non-diabetic counterparts.

Surgical versus percutaneous revascularization of coronary artery disease in diabetic patients

Morbidity and mortality related to coronary artery disease (CAD) remain a great challenge in patients with diabetes mellitus. Revascularization of CAD is an important therapeutic intervention owing to its impact on both symptoms and prognosis. The optimal revascularization strategy continues to evolve due to the advent of new technologies and improved peri-procedural outcome with both percutaneous coronary interventions and coronary artery bypass grafting. Although clinical outcome following coronary artery bypass is worse in diabetic as opposed to non-diabetic patients, surgical revascularization tends to be associated with better outcome in stable patients with multivessel disease and reduced left ventricular function. The advent of drug-eluting stents has challenged the supremacy of coronary artery bypass grafting and has become a valuable alternative to surgery. The safety and efficacy of drug-eluting stents in the treatment of patients with diabetes and multivessel disease is currently under investigation in several ongoing randomized controlled trials. Percutaneous coronary intervention is the therapy of choice in patients with acute coronary syndromes, particularly ST-elevation myocardial infarction. The focus of this review is to present the current evidence, define the role of percutaneous and surgical revascularization in the treatment of diabetic patients with CAD, and propose a tailored approach for clinical decision-making.

Reflux monitoring: pH-metry, Bilitec and oesophageal impedance measurements

Gastro-oesophageal reflux disease (GERD) is a highly prevalent condition in Western countries leading to millions of outpatient visits per year. GERD symptoms including heartburn, regurgitation and chest pain are caused by reflux of gastric content in the oesophagus even in the absence of endoscopically visible mucosal lesions. Several procedures are used to identify gastro-oesophageal reflux, the clinically widely used are: conventional (catheter-based) pH monitoring, wireless oesophageal pH monitoring (Bravo), bilirubin monitoring (Bilitec), and combined multichannel intraluminal impedance-pH monitoring (MII-pH). Each technique has strengths and limitations of which clinicians and investigators should be aware when deciding which to choose in a particular patient. Important is the ability to quantify gastro-oesophageal reflux and evaluate the relationship between symptoms and reflux episodes. The present review summarises the technical aspects in performing and interpreting esophageal reflux monitoring procedures.

Object-Oriented Reengineering Patterns

The rapid growth of object-oriented development over the past twenty years has given rise to many object-oriented systems that are large, complex and hard to maintain. Object-Oriented Reengineering Patterns addresses the problem of understanding and reengineering such object-oriented legacy systems. This book collects and distills successful techniques in planning a reengineering project, reverse-engineering, problem detection, migration strategies and software redesign. The material in this book is presented as a set of "reengineering patterns" --- recurring solutions that experts apply while reengineering and maintaining object-oriented systems. The principles and techniques described in this book have been observed and validated in a number of industrial projects, and reflect best practice in object-oriented reengineering.

The E-learning Circle – a holistic software design tool for e-learning

The article introduces the E-learning Circle, a tool developed to assure the quality of the software design process of e-learning systems, considering pedagogical principles as well as technology. The E-learning Circle consists of a number of concentric circles which are divided into three sectors. The content of the inner circles is based on pedagogical principles, while the outer circle specifies how the pedagogical principles may be implemented with technology. The circle’s centre is dedicated to the subject taught, ensuring focus on the specific subject’s properties. The three sectors represent the student, the teacher and the learning objectives. The strengths of the E-learning Circle are the compact presentation combined with the overview it provides, as well as the usefulness of a design tool dealing with complexity, providing a common language and embedding best practice. The E-learning Circle is not a prescriptive method, but is useful in several design models and processes. The article presents two projects where the E-learning Circle was used as a design tool.

Auslegung, Konstruktion und Fertigung von strömungsmechanischen Funktionsprototypen mittels Rapid Manufacturing

Bei der Fertigung von Funktionsbauteilen für Strömungsversuche spielt das Design und die Komplexität der Bauteilgeometrie eine wesentliche Rolle. Ziel der interdisziplinären Zusammenarbeit der Lehrstühle Strömungsmaschinen, Rechnereinsatz in der Konstruktion und Fertigungstechnik mit dem Rapid Technology Center (RTC) an der Universität Duisburg-Essen ist es, das Potenzial der additiven Fertigungsverfahren bei der Herstellung von Funktionsprototypen für strömungsmechanische Anwendungen effektiv zu nutzen. An verschiedenen, auf dieser Kooperation beruhenden, Best Practise Beispielen wird gezeigt wie das Laser-Sintern in die Prozesskette zur Herstellung von Laufrädern u. Ä. in unterschiedlichen Größenordnungen integriert werden kann. In diesem Zusammenhang werden auch die Vorüberlegungen (z. B. durch Simulation), Wechselwirkungen und Folgeprozesse, die mit dieser Fertigungstechnologie verbunden sind, aufgezeigt.