Multipurpose Intensive Care Unit in a District General Hospital

The advantages of a four-bedded purpose-built general intensive care unit in a district general hospital are described. In addition to 1,447 inpatients treated between January 1968 and December 1971 the unit was used to conduct outpatient investigations. This has filled an important gap in conventional arrangements, and is practical and economical. The unit has proved to have advantages, not only for seriously ill patients but also has benefited the hospital in other ways. It has been of material assistance in recruiting and training nursing and medical staff and has been welcomed and supported by patients and their relatives. It has also attracted practical support from voluntary organizations whose generosity has enabled much additional equipment to be purchased.     

Inventing a new diagnostic test for vaginal infection.

Bacterial vaginosis, which is underdiagnosed in clinical practice, has a characteristic fishy smell because of production of diamines. This smell is the basis of a visual rapid diagnostic test that is technically simple to perform. The test has been patented in Europe and America, and a licence agreement has been negotiated. This paper describes the process from idea to invention to patenting and licensing. The combined costs of research and patenting were met by a multinational company in return for rights to exploit the patent invention. The process has taken nine years and has needed clinical, scientific, legal, and commercial input to get the test to the marketplace.     

Methods of Therapy in Alcoholism

Although the philosophy of the community mental health center has been applied to alcoholism since the early part of this decade, it has been pursued much more intensively in recent years, and there has been a decentralization in the management of alcoholics in a series of stages from the jail or work-house to the state hospital and to the clinic and the community. The medical practitioner now has opportunity to treat the alcoholic in private practice.Advances have been made in two directions. Advances in medical management have included reinforcement of the importance of hydration and electrolyte balance, particularly magnesium. Psychopharmacology has contributed three drugs particularly important in the management of acute alcoholism and its complications. These drugs are chlordiazepoxide, chlorpromazine, and thioridazine. Another drug, Antabuse, when properly used, has proven extremely valuable as a deterrent.Equally important have been administrative advances. The importance of the environment and its manipulation has been recognized, and a series of institutional and non-institutional resources, such as clinics, half-way houses, foster homes, and Alcoholics Anonymous has made it less likely that a patient will be turned away without help.     

Protein A chromatography for antibody purification

Staphylococcal protein A (SPA) is one of the first discovered immunoglobulin binding molecules and has been extensively studied during the past decades. Due to its affinity to immunoglobulins, SPA has found widespread use as a tool in the detection and purification of antibodies and the molecule has been further developed to one of the most employed affinity purification systems. Interestingly, a minimized SPA derivative has been constructed and a domain originating from SPA has been improved to withstand the harsh environment employed in industrial purifications. This review will focus on the development of different affinity molecules and matrices for usage in antibody purification.     

Establishment of normal ranges of laser Doppler blood flow in autologous tissue transplants.

Over a 3-year period, 136 patients were monitored following free autologous tissue transplantation using a laser Doppler flowmeter linked to a computerized data-acquisition system. This monitoring system has indicated perfusion compromise in free flaps more rapidly than clinical observation alone. Most important, this has resulted in an increase in salvage rate from 50.0 to 82.4 percent. In addition, our overall success rate has increased from 92.6 to 97.8 percent since introducing this monitor clinically. Computerization also has facilitated the collection of data, which has enabled us to establish expected values for postoperative blood flow in several types of donor tissues used for microvascular reconstruction. Finally, this computerized monitoring system has relieved personnel from basing decisions on subjective data.     

A survey of the year 2003 literature on applications of isothermal titration calorimetry

Over the last decade isothermal titration calorimetry (ITC) has developed from a specialist method which was largely restricted in its use to dedicated experts, to a major, commercially available tool in the arsenal directed at understanding molecular interactions. The number of those proficient in this field has multiplied dramatically, as has the range of experiments to which this method has been applied. This has led to an overwhelming amount of new data and novel applications to be assessed. With the increasing number of publications in this field comes a need to highlight works of interest and impact. In this overview of the literature we have attempted to draw attention to papers and issues for which both the experienced calorimetrist and the interested dilettante hopefully will share our enthusiasm.     

Methicillin-resistant Staphylococcus aureus: a pervasive pathogen highlights the need for new antimicrobial development

Staphylococcus aureus (S. aureus) has entered the spotlight as a globally pervasive drug-resistant pathogen. While historically associated exclusively with hospital-acquired infections in immunocompromised hosts, the methicillin-resistant form of S. aureus has been spreading throughout communities since the 1990s. Indeed, it has now become a common household term: MRSA. S. aureus has developed numerous mechanisms of virulence and strategies to evade the human immune system, including a host of surface proteins, secreted enzymes, and toxins. In hospital intensive care units, the proportion of MRSA-related S. aureus infections has increased strikingly from just 2 percent in 1974 to 64 percent in 2004. Its presence in the community has been rising similarly, posing a significant public health burden. The growing incidence of MRSA unfortunately has been met with dwindling efforts to develop new, more effective antibiotics. The continued emergence of resistant strains of bacteria such as MRSA demands an urgent revival of the search for new antibiotics.     

Cytokine and anti-cytokine therapy for the treatment of asthma and allergic disease

Until recently, the only controller treatment for chronic asthma has been corticosteroids. However, identification of specific effector molecules in asthma has led to targeting of specific pathways by using cytokines and cytokine inhibitors. Administration of a monoclonal blocking antibody against IgE has been shown to be highly efficacious in severe allergic asthma, but blockade of eosinophils using anti-IL-5 monoclonal antibodies has no clinical benefit. In more severe asthma, blockade of TNF-alpha using the decoy etanercept has revealed efficacy in a small open study suggesting that Th-1 in addition to Th-2 pathways are important as the disease adopts a more severe phenotype. It is likely that asthma is not a single disease but a group of disorders which differ in the relative contribution of specific pathophysiological pathways.     

Long-term changes in zooplankton abundance and water transparency in Lake Geneva

The water quality of Lake Geneva has declined steadily since the 1960s, due to a continuous increase of external phosphorus loading. Average P level in the lake increased steadily to a peak in 1979, and even 1981 in the case of P content in the trophogenic layer. Since then, reduced external inputs related to the delayed effects of phosphorus removal from waste waters initiated many years previously has led to a decrease in P level, and resulted in present stabilization and even improvement in water quality. Long-term changes in zooplankton abundance correspond quite closely to eutrophication level changes. After increasing since the 1960s, maximum zooplankton biomass was recorded for the first time in 1971; a second main peak appeared in 1981 together with the highest eutrophication level. Over the last seven years, zooplankton abundance has decreased continuously, while water transparency has decreased and phytoplankton production has remained at a high level.     

Protein phosphorylation in pancreatic islets: evidence for separate Ca2+ and cAMP-enhanced phosphorylation of two 57,000 Mr proteins

There is a phosphopeptide that has an Mr of 53,000 to 60,000 in insulin-secreting tissues and there is general agreement that this peptide can be phosphorylated in a calcium-dependent manner. The present report shows that there are at least two phosphoproteins with Mr's near 57,000 in rat pancreatic islet cytosol. One peptide has an Mr of 57,000, a pl of 7.5 - 8 and is phosphorylated in a Ca2+-enhanced manner, and the other has an Mr of 54,000, a pl of 5 - 5.5 and is phosphorylated in a cAMP-enhanced manner, as judged by two-dimensional polyacrylamide gel electrophoresis. Sepharose 4B chromatography indicated that the former polypeptide resides in a native protein complex that has an Mr of about 500,000 and the latter in a complex that has an Mr of about 180,000. Tritiated azido cyclic AMP binds to an islet polypeptide that has an Mr of 54,000. The results suggest that Ca2+ and cAMP could regulate stimulus-secretion coupling in pancreatic islets via protein phosphorylation.     

A Point-Wise Model of Adhesion Suitable for Real-Time Applications of Bio-Inspired Climbing Robots

Bio-inspired climbing robots relying on adhesion systems are believed to become essential tools for several industrial applications in the near future. In recent years, research has mainly focused on modeling micro-scale adhesion phenomena; a macro-scale adhesion model has however to be developed for the design of macro-scale systems. In this paper a macro-model of adhesion suitable for real-time applications is presented; it relies on a continuous representation of adhesion. An extension of the von Mises criterion is proposed as failure adhesion criterion in order to estimate the occurrence of detachment at any point of the contacting surface. An experimental set up has been designed in order to define the parameters of the model. A semi-automatic process has been developed to ensure repeatability and accuracy of the results. Polydimethylsiloxane (PDMS), which has revealed promising adhesive features for robotic use, has been used during the experimental phase. The macro-model of adhesion has been implemented in a multi-body dynamics environment based on Open Dynamics Engine (ODE) to simulate a spider-inspired robot. Simulations based on this model are suitable to represent the behaviour of climbing robots and also to optimize their design.     

Ivermectin 20 years on: maturation of a wonder drug

Ivermectin has been on the veterinary market for almost a quarter of a century and has been approved for human use for 18 years. Its use has revolutionized the treatment of nematode and arthropod parasites in animals and has provided hope for the control or even eradication of filariases in humans. Although much remains to be learned about how the drug works and how resistance to it will develop, it has earned the title of "wonder drug".     

Gene expression signatures in primary immunodeficiencies: the experience from human disease and mouse models

Extensive research on molecular genetics in recent decades has provided a wealth of information regarding the underlying mechanisms of primary immunodeficiency diseases. The microarray technology has made its entry into the molecular biology research area and hereby enabled signature expression profiling of whole species genomes. Perhaps no other methodological approach has transformed molecular biology more in recent years than the use of microarrays. Microarray technology has led the way from studies of the individual biological functions of a few related genes, proteins or, at best, pathways towards more global investigations of cellular activity. The development of this technology immediately yielded new and interesting information, and has produced more data than can be currently dealt with. It has also helped to realize that even a 'horizontally exhaustive' molecular analysis is insufficient. Applications of this tool in primary immunodeficiency studies have generated new information, which has led to a better understanding of the underlying basic biology of the diseases. Also, the technology has been used as an exploratory tool to disease genes in immunodeficiency diseases of unknown cause as in the case of the CD3Delta-chain and the MAPBPIP deficiency. For X-linked agammaglobulinemia, the technique has provided better understanding of the genes influenced by Btk. There is considerable hope that the microarray technology will lead to a better understanding of disease processes and the molecular phenotypes obtained from microarray experiments may represent a new tool for diagnosis of the disease.     

Toponomics and neurotoponomics: a new way to medical systems biology

The fluorescence robot imaging technology multi-epitope-ligand-cartography/toponome imaging system has revolutionized the field of proteomics/functional genomics, because it enables the investigator to locate and decipher functional protein networks, the toponome, consisting of hundreds of different proteins in a single cell or tissue section. The technology has been proven to solve key problems in biology and therapy research. It has uncovered a new cellular transdifferentiation mechanism of vascular cells giving rise to myogenic cells in situ and in vivo; a finding that has led to efficient cell therapy models of muscle disorders, and discovered a new target protein in sporadic amyotrophic lateral sclerosis by hierarchical protein network analysis, a finding that has been confirmed by a mouse knockout model. A lead target protein in tumor cells that controls cell polarization as a mechanism that is fundamental for migration and metastasis formation has also been uncovered, and new functional territories in the CNS defined by high-dimensional synaptic protein clusters have been unveiled. The technology can be effectively interlocked with genomics and proteomics to optimize time-to-market and the overall attrition rate of new drugs. This review outlines major proofs of principle with an emphasis on neurotoponomics.     

Productivity improvement in xanthan gum fermentation using multiple substrate optimization

A novel and more comprehensive formulation of the optimal control problem that reflects the operational requirements of a typical industrial fermentation has been proposed in this work. This formulation has been applied to a fed-batch bioreactor with three control variables, i.e., feed rates of carbon source, nitrogen source, and an oxygen source, to result in a 148.7% increase in product formation. Xanthan gum production using Xanthomonas campestris has been used as the model system for this optimization study, and the liquid-phase oxygen supply strategy has been used to supply oxygen to the fermentation. The formulated optimization problem has several constraints associated with it due to the nature of the system. A robust stochastic technique, differential evolution, has been used to solve this challenging optimization problem. The infinite dimensional optimization problem has been approximated to a finite dimensional one by control vector parametrization. The state constraints that are path constraints have been addressed by using penalty functions and by integrating them over the total duration to ensure a feasible solution. End point constraints on final working volume of the reactor and on the final residual concentrations of carbon and nitrogen sources have been included in the problem formulation. Further, the toxicity of the oxygen source, H(2)O(2), has been addressed by imposing a constraint on its maximum usable concentration. In addition, the initial volume of the bioreactor contents and feed concentrations have been handled as decision variables, which has enabled a well-grounded choice for their values from the optimization procedure; adhoc values are normally used in the industry. All results obtained by simulation have been validated experimentally with good agreements between experimental and simulated values.     

CAMPATH: from concept to clinic

Lymphocyte depletion has a long history in the area of therapeutic immunosuppression. CAMPATH-1H (alemtuzumab) was generated in an attempt to replace anti-lymphocyte globulins in the transplant arena. Its efficacy in killing lymphocytes has established it as a licensed drug for the management of chronic lymphocyte leukaemia. Short-term therapy with alemtuzumab has demonstrated long-term benefit in a number of autoimmune conditions. This drug has the potential to facilitate recruitment of tolerance processes so enabling drug minimization in transplantation, autoimmune and hypersensitivity diseases.     

The Canadian Paediatric Society: its early years.

The Canadian Paediatric Society has continued since its origin to be a consultative organization and has been recognized as the official voice for children in matters relating to health. It has appointed a number of special committees to study and recommend policy and action to the profession, government and other health bodies as new developments in child health have become important in Canada. The dedicated involvement of so many fellows of the society makes it apparent that in its nearly 60 years of existence it has lived up to the objectives of its founders.     

Fugu: a compact vertebrate reference genome

At 400 Mb, the Japanese pufferfish, Fugu rubripes, has the smallest vertebrate genome but has a similar gene repertoire to other vertebrates. Its genes are densely packed with short intergenic and intronic sequences devoid of repetitive elements. It likely has a mutational bias towards DNA elimination and is probably close to a 'minimal' vertebrate genome. As such it is a useful reference genome for gene discovery and gene validation in other vertebrates. Its usefulness in the discovery of conserved regulatory elements has already been demonstrated. The Fugu genome sequence is a good complement to genetic studies in other vertebrates.