ECMO – the clinician’s view

Background Extra corporeal membrane oxygenation (ECMO) is a complex rescue therapy used to provide cardiac and/or respiratory support for critically ill patients who have failed maximal conventional medical management. ECMO is based on a modified cardiopulmonary bypass (CPB) circuit, and can provide cardiopulmonary support for up-to several months. It can be used in a veno venous configuration for isolated respiratory failure, (VV-ECMO), or in a veno arterial configuration (VA-ECMO) where support is necessary for cardiac +/- respiratory failure. The ECMO circuit consists of five main components: large bore cannulae (access cannulae) for drainage of the venous system, and return cannulae to either the venous ( in VV-ECMO) or arterial (in VA ECMO) system. An oxygenator, with a vast surface area of hollow filaments, allows addition of oxygen and removal of carbon dioxide; a centrifugal blood pump allows propulsion of blood through the circuit at upto 10 L/minute; a control module and a thermoregulatory unit, which allows for exact temperature control of the extra corporeal blood. Methods The first successful use of ECMO for ARDS in adults occurred in 1972, and its use has become more commonplace over the last 30 years, supported by the improvement in design and biocompatibility of the equipment, which has reduced the morbidity associated with this modality. Whilst the use of ECMO in neonatal population has been supported by numerous studies, the evidence upon which ECMO was integrated into adult practice was substantially less robust. Results Recent data, including the CESAR study (Conventional Ventilatory Support versus Extra corporeal membrane oxygenation for Severe Respiratory failure)has added a degree of evidence to the role of ECMO in such a patient population. The CESAR study analysed 180 patients, and confirmed that ECMO was associated with an improved rate of survival. More recently, ECMO has been utilized in numerous situations within the critical care area, including support in high-risk percutaneous interventions in cardiac catheter lab; the operating room, emergency department, as well in specialized inter-hospital retrieval services. The increased understanding of the risk:benefit profile of ECMO, along with a reduction in morbidity associated with its use will doubtless lead to a substantial rise in the utilisation of this modality. As with all extra-corporeal circuits, ECMO opposes the basic premises of the mammalian inflammation and coagulation cascade where blood comes into foreign circulation, both these cascades are activated. Anti-coagulation is readily dealt with through use of agents such as heparin, but the inflammatory excess, whilst less macroscopically obvious, continues un-abated. Platelet consumption and neutrophil activation occur rapidly, and the clinician is faced with balancing the need of anticoagulation for the circuit, against haemostasis in an acutely bleeding patient. Alterations in pharmacokinetics may result in inadequate levels of disease modifying therapeutics, such as antibiotics, hence paradoxically delaying recovery from conditions such as pneumonia. Key elements of nutrition and the innate immune system may similarly be affected. Summary This presentation will discuss the basic features of ECMO to the non-specialist, and review the clinical conundrum faced by the team treating these most complex cases.     

Microcomputers in clinical psychology – a personal view

The applications of microcomputers in clinical psychology are discussed. The author illustrates the paper with examples drawn from his own experience and suggests some ways in which microcomputers might be of value to doctors in other areas of medicine.     

Significance of calcium phosphate coatings for the enhancement of new bone osteogenesis – A review

A systematic analysis of results available from in vitro, in vivo and clinical trials on the effects of biocompatible calcium phosphate (CaP) coatings is presented. An overview of the most frequently used methods to prepare CaP-based coatings was conducted. Dense, homogeneous, highly adherent and biocompatible CaP or hybrid organic/inorganic CaP coatings with tailored properties can be deposited. It has been demonstrated that CaP coatings have a significant effect on the bone regeneration process. In vitro experiments using different cells (e.g. SaOS-2, human mesenchymal stem cells and osteoblast-like cells) have revealed that CaP coatings enhance cellular adhesion, proliferation and differentiation to promote bone regeneration. However, in vivo, the exact mechanism of osteogenesis in response to CaP coatings is unclear; indeed, there are conflicting reports of the effectiveness of CaP coatings, with results ranging from highly effective to no significant or even negative effects. This review therefore highlights progress in CaP coatings for orthopaedic implants and discusses the future research and use of these devices. Currently, an exciting area of research is in bioactive hybrid composite CaP-based coatings containing both inorganic (CaP coating) and organic (collagen, bone morphogenetic proteins, arginylglycylaspartic acid etc.) components with the aim of promoting tissue ingrowth and vascularization. Further investigations are necessary to reveal the relative influences of implant design, surgical procedure, and coating characteristics (thickness, structure, topography, porosity, wettability etc.) on the long-term clinical effects of hybrid CaP coatings. In addition to commercially available plasma spraying, other effective routes for the fabrication of hybrid CaP coatings for clinical use still need to be determined and current progress is discussed.     

Dimethylarginine dimethylaminohydrolase (DDAH) – A critical regulator of hypertensive left ventricular hypertrophy?

Left ventricular hypertrophy (LVH) is an early manifestation of cardiovascular target organ damage in patients with arterial hypertension. It is not only a target organ response to increased after-load, but is also the most potent cardiovascular risk factor. LVH is multifactorial sign which has several causative factors in addition to blood pressure. Asymmetrical dimethylarginine (ADMA) is an endogenous inhibitor of NO synthase. ADMA plasma levels have been shown to be elevated in diseases related to endothelial dysfunction such as hypertension, hyperlipidemia, diabetes mellitus. Because cardiac remodeling is associated with endothelial NO pathway, some recent studies investigated whether the plasma ADMA was related to LVH and found that there is a link between ADMA and left ventricular mass and geometry. ADMA was two times higher in patients with concentric LVH than in those normal controls. In many experimental systems, accumulation of ADMA is accompanied by reduced dimethylarginine dimethylaminohydrolase (DDAH) activity. Plasma ADMA is cleared in small part by urinary excretion, but the bulk of ADMA is degraded by DDAH. Therefore, we proposed that change in DDAH activity could disturb the metabolism of ADMA and result in hypertensive LVH through the ADMA/NO pathway.     

Clinical modeling—A critical analysis

BackgroundModeling clinical processes (and their informational representation) is a prerequisite for optimally enabling and supporting high quality and safe care through information and communication technology and meaningful use of gathered information.ObjectivesThe paper investigates existing approaches to clinical modeling, thereby systematically analyzing the underlying principles, the consistency with and the integration opportunity to other existing or emerging projects, as well as the correctness of representing the reality of health and health services.MethodsThe analysis is performed using an architectural framework for modeling real-world systems. In addition, fundamental work on the representation of facts, relations, and processes in the clinical domain by ontologies is applied, thereby including the integration of advanced methodologies such as translational and system medicine.ResultsThe paper demonstrates fundamental weaknesses and different maturity as well as evolutionary potential in the approaches considered. It offers a development process starting with the business domain and its ontologies, continuing with the Reference Model-Open Distributed Processing (RM-ODP) related conceptual models in the ICT ontology space, the information and the computational view, and concluding with the implementation details represented as engineering and technology view, respectively.ConclusionThe existing approaches reflect at different levels the clinical domain, put the main focus on different phases of the development process instead of first establishing the real business process representation and therefore enable quite differently and partially limitedly the domain experts’ involvement.     

The long view: Salmonella – the last forty years

As a part of the 40th anniversary celebrations of Avian Pathology we review the last four decades of Salmonella research which has led to major progress in our understanding of the bacteriology and infection biology of the organism through the huge advances in molecular biology and immunology that have accompanied technical advances in biology generally. In many countries combinations of improvements in management, sometimes under legislative pressure and supported by a number of basic biological interventions, have resulted in reductions in incidence in the Salmonella serovars that are commonly associated with food-poisoning to unprecedented low levels in parent flocks, broilers and layers. Utilisation of the information generated during the past few decades should improve the efficacy of surveillance and biological interventions both for the intestinal carriage that is associated most frequently with human infection and also for systemic diseases, including fowl typhoid and pullorum disease. These two diseases continue to be major economic problems in many countries where the possibilities for improvements in hygiene may be limited but which, nevertheless, are increasingly a significant part of the global economy in poultry meat.     

Renal sympathetic denervation for resistant hypertension – An alternate view

Catheter-based renal denervation (RDN) is an effective treatment for resistant hypertension. But negative results with this procedure are also not uncommon. It is believed that the effectiveness of RDN is due to decreased sympathetic activity. It is suggested that the beneficial action of RDN could also at least, in part, due to restoration of balance between sympathetic and parasympathetic nervous systems. Thus, occasional negative results seen with RDN to decrease blood pressure may be attributed to failure of restoration of this balance to near normal or normal. This hypothesis explains the involvement of free radicals, immune system and nitric oxide pathways in the pathogenesis of essential hypertension since both sympathetic and parasympathetic branches of autonomic nervous system have modulatory influence on these systems. Hence, it is suggested that efforts made to augment parasympathetic tone in addition to RDN may form a more effective strategy to reduce blood pressure in resistant hypertension than RDN alone.     

Renal sympathetic denervation for resistant hypertension – An alternate view

Catheter-based renal denervation (RDN) is an effective treatment for resistant hypertension. But negative results with this procedure are also not uncommon. It is believed that the effectiveness of RDN is due to decreased sympathetic activity. It is suggested that the beneficial action of RDN could also at least, in part, due to restoration of balance between sympathetic and parasympathetic nervous systems. Thus, occasional negative results seen with RDN to decrease blood pressure may be attributed to failure of restoration of this balance to near normal or normal. This hypothesis explains the involvement of free radicals, immune system and nitric oxide pathways in the pathogenesis of essential hypertension since both sympathetic and parasympathetic branches of autonomic nervous system have modulatory influence on these systems. Hence, it is suggested that efforts made to augment parasympathetic tone in addition to RDN may form a more effective strategy to reduce blood pressure in resistant hypertension than RDN alone.     

Wet or dry mechanochemical synthesis of calcium phosphates? Influence of the water content on DCPD-CaO reaction kinetics

Mechanosynthesis of calcium phosphates can be performed under wet or dry conditions. In most papers and patents, grinding under wet conditions was selected. So far, only a few papers were devoted to dry mechanosynthesis of calcium phosphates. To understand why wet mechanosynthesis was preferred, the influence of water addition on the kinetics of the mechanochemical reaction of dicalcium phosphate dihydrate with calcium oxide was investigated. The DCPD disappearance rate constant k and the final reaction time t(f) were determined in each case and correlated with the water content present in the slurry. Results showed that the addition water (i) slowed down the reaction rate and (ii) increased the powder contamination by mill material (hard porcelain) due to ball and vial erosion; and that (iii) wet milling did not generate the expected products, in contrast to dry grinding, because porcelain induced hydroxyapatite decomposition with the formation of beta-tricalcium phosphate and silicon-stabilized tricalcium phosphate. Consequently, dry mechanosynthesis appears preferable to wet milling in the preparation of calcium phosphates of biological interest.     

Using Sepia melanin as a PD model to describe the binding characteristics of neuromelanin – A critical review

Parkinson's disease is characterised pathologically by a relatively selective death of dopaminergic neurons in the substantia nigra of the brain. The vulnerability of these neurons appears to be linked to the pigment neuromelanin. However, as yet there is limited understanding behind the mechanisms of this disease process. Complications arise due to the difficulty in obtaining appreciable quantities of neuromelanin. Furthermore, an appropriate model for studying neuromelanin has not been identified. To date there has been many studies looking at the binding and chemical characteristics of neuromelanin. However, a range of different synthetic and organic melanins have been used as models and leading to many varied conclusions being drawn. Therefore, the aim of this review is to present Sepia melanin as the most appropriate study model for the binding characteristics of neuromelanin. Considerations included chemical structure, surface characteristics and structural features of both synthetic and organic melanins.     

Is there a chemical interaction between calcium phosphates and hydroxypropylmethylcellulose (HPMC) in organic/inorganic composites?

Solid composites of calcium phosphates and hydroxypropylmethylcellulose (HPMC) were prepared at temperatures of 121 degrees C. Three biologically relevant calcium phosphates were studied: CaHPO(4). 2H(2)O (DCPD), calcium deficient apatite (CDA), and biphasic calcium phosphate (BCP). Properties of the solid composites obtained were studied with FTIR, X-ray diffraction, and SEM techniques. Special attention was devoted to seeking a possible chemical interaction between calcium phosphates and HPMC. No interaction was found. Thus, HPMC was proven to have no influence on chemical properties of calcium phosphates.     

Bacterial collagenases – A review

Abstract

Bacterial collagenases are metalloproteinases involved in the degradation of the extracellular matrices of animal cells, due to their ability to digest native collagen. These enzymes are important virulence factors in a variety of pathogenic bacteria. Nonetheless, there is a lack of scientific consensus for a proper and well-defined classification of these enzymes and a vast controversy regarding the correct identification of collagenases. Clostridial collagenases were the first ones to be identified and characterized and are the reference enzymes for comparison of newly discovered collagenolytic enzymes. In this review we present the most recent data regarding bacterial collagenases and overview the functional and structural diversity of bacterial collagenases. An overall picture of the molecular diversity and distribution of these proteins in nature will also be given. Particular aspects of the different proteolytic activities will be contextualized within relevant areas of application, mainly biotechnological processes and therapeutic uses. At last, we will present a new classification guide for bacterial collagenases that will allow the correct and straightforward classification of these enzymes.     

Actinobacterial enzyme inhibitors – A review

Abstract

Actinobacteria have potential as important new sources of enzyme inhibitors. Enzyme inhibitors have great demand in medicine, agriculture and biotechnology. In medicine, enzyme inhibitors can be used as therapeutic agents for bacterial, fungal, viral and parasitic diseases as well as treating cancer, neurodegenerative, immunological and cardiovascular diseases. Enzyme inhibitors are also valuable for the control of carbohydrate-dependent diseases such as diabetes, obesity and hyperlipidemia and melanogenesis in skin. They can be also involved in crop protection against plant pathogens, herbivorous pests and abiotic stresses such as drought. In this review, we discuss about several actinobacterial enzyme inhibitors with various industrial uses and biotechnological applications.     

Sclerosing polycystic adenoma – A review

This review summarizes the current state of knowledge on sclerosing polycystic adenoma, including epidemiological/clinical, histopathological/cytopathological, ultrastructural, immunohistochemical and etiopathogenetic/molecular genetic aspects. Differential diagnostic issues are briefly discussed.