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Metabolic assessment.

Although no techniques are currently available that meet the needs of nutrition-support professionals, the future is promising. This article reviews various methods and techniques used to assess the metabolic and nutritional status of surgical patients. Technologic advances in bioengineering, molecular biology, and physiology are providing exciting new tools that may eventually replace or supplement traditional static indices of metabolic assessment. At the very least, an increased understanding of the cellular abnormalities associated with various diseases will likely change our view of illness and our approaches to nutritional and metabolic intervention.

Anthropometry↗

Growth factors in clinical practice.

Growth factors enhance protein synthesis and thus reduce the catabolic response to injury. As a result of bioengineering and new manufacturing techniques several anabolic agents have become available for clinical use and have been evaluated in surgical patients with catabolic illness. Data support the anabolic effects of growth home in such patients, but its expense and possible deleterious effects during the acute phase of illness limit its use to selected patient groups. Insulin-like growth factor-1 has also been studied, but specific indications for its use have not been identified in catabolic patients. Testosterone and derivatives of this hormone exert anabolic effects, but few randomized trials include catabolic surgical patients, and higher doses of some derivative compounds are associated with hepatic dysfunction. Nonetheless, as we move into the future, studies will determine the specific doses for administration of these and other anabolic factors in specific patient groups. Anabolic therapy will shorten the length of therapy and improve the outcome in the future.

Anabolic Agents↗

Characterization of the 16S-23S internal transcribed spacer among 34 higher plants: suitability for interspecific plastid transformation.

Biomanufacturing by chloroplast transgene expression has the potential to produce significant amounts of biopharmaceuticals, endow plants with novel commercial or humanitarian capabilities, enhance phytoremediation methods and harden plants against adverse environments. Plastid bioengineering exploits the phenomenon of homologous recombination to specifically integrate heterologous sequences into the plastid genome. Previous research suggests the plastid genome 16S-23S internal transcribed spacer provides an advantageous integration site for transgene expression. To characterize the suitability of the 16S-23S region for interspecific recombination, we developed primers against conserved plastid sequences and amplified approximately 2.6 kb from 25 plant species. We analyzed the amplicons with nine species from Genbank for homeology, phylogenetic relationships, potential to form chimeric rDNA elements disruptive to translational/replication systems, and the potential number of recombination events for various minimal essential processing segments (MEPS) lengths. Multiple sequence alignment of the 34 species revealed considerable conservation, with identities exceeding 95% among the angiosperms. Substitutions were statistically clustered, generally in noncoding sites, although proposed functional elements such as the OriA region and 3' terminus of the 16S rRNA exhibited unexpected variation. The nonrandom distribution of substitutions undermines the established, statistical method of estimating the number of recombination initiation sites. This finding is further substantiated by comparing statistical estimates of the number of MEPS sites to a direct count at three different MEPS lengths. We frame this in silico analysis in terms of the potential of the 16S-23S region as a target for interspecific transformation, and describe a 'primer-to-plastid' system to rapidly generate species-specific flanking regions for transformation vectors.

Base Sequence↗

Tissue engineering of the bladder.

When gastrointestinal tissue is used for bladder augmentation or replacement, multiple complications may ensue, such as infection, metabolic disturbances, urolithiasis, perforation, increased mucous production, and malignancy. Therefore, alternative methods are being sought for cystoplasty. There has been a resurgence of interest in the use of acellular collagen-based matrices as scaffolds for bladder regeneration. Experimental work involving several collagen matrices, such as allogenic bladder and intestinal tissues, is currently being conducted in several academic centers. Recently, functional bladder tissue has been engineered using selective cell transplantation. The approach that has been followed for bioengineering of bladder tissue involves the use of autologous cells, thus avoiding rejection, whereby a biopsy of tissue is obtained from the host, after which the cells are dissociated and expanded in vitro, reattached to a matrix, and implanted into the same host.

Biocompatible Materials↗

History of German pediatric cardiology.

Due to the isolation of German medicine in World War II accompanied by the destruction of many hospitals, German pediatricians did not show any serious interest in the treatment of children with congenital heart diseases, nor did they take notice of the progress achieved by Helen Taussig, Alfred Blalock and other cardiologists and surgeons in the western world. This problem was even worse in East Germany. Only a few German internists and forward-looking surgeons were able and ready to take care of this group of principally operable children in places like Bonn/Düsseldorf, Marburg/Munich, Berlin, and Hamburg. However, in the early 1950s some directors of pediatrics at university hospitals--largely motivated by the cardiac surgeons--allowed or even encouraged younger colleagues to concentrate on pediatric cardiology and to begin application of heart catheterization and angiocardiography. In 1960 a group of colleagues interested in pediatric cardiology met for the first time in Frankfurt and became the nucleus of the future "working group" (1969) and finally the "German Society of Pediatric Cardiology" (1974). By 1972 pediatric cardiology had been approved as an independent (sub)specialty. Colleagues and friends from surrounding countries (Austria, Great Britain, Sweden, Switzerland, and the Netherlands) and also from the US and some eastern countries were either members or regular guests during or between the meetings. Pediatric cardiology is now represented in Germany by specialized practitioners, trainees and assistants who work in both community and university hospitals, and in specialized departments. Due to the foresightedness of the Chief of Pediatrics, Prof. G. Joppich, the first Chair of Pediatric Cardiology was founded in Göttingen in 1960 under the direction of A. Beuren. Another model of interdisciplinary cooperation between pediatric cardiologists, bioengineers, mathematicians and computer scientists was established in Kiel in 1966. In other places pediatric and adult cardiologists were brought together in "Heart Centers" with cardiovascular surgeons. The first of these Heart Centers was founded in 1974 in Munich under the directorship of K. Bühlmeyer and comparable centers were later established in Bad Oeynhausen (1985) and Berlin (1986). Following reunification in 1990, pediatric cardiologists from the east and west came together. Thus, within the last three to four decades German pediatric cardiology gradually caught up with international standards and in some fields of cardiovascular research even assumed a leading role. The care of the growing numbers of surviving patients with congenital heart disease has become a new challenge that has to be met by experienced cardiologists. To maintain the level of competence, future activities should however, not only concentrate on the optimal care of patients with congenital heart disease but also be responsible for cardiovascular research.

Cardiology↗

Optical coherence tomography in contact dermatitis and psoriasis.

Optical coherence tomography (OCT) is a new noninvasive imaging technique. In this study, it was used for the investigation of contact dermatitis and psoriasis. In these common inflammatory skin diseases the value of OCT for quantification and monitoring of the changes in comparison with other bioengineering methods was evaluated. Repeated measurements were performed in healthy volunteers after experimental induction of irritant contact dermatitis and in patients with psoriasis. In the OCT images, the thickness of the epidermis and the signal attenuation coefficient in the upper dermis were evaluated. The changes were compared with measurements of transepidermal water loss, hydration, skin colour and surface roughness, and with high-frequency ultrasound measurements. In irritant dermatitis and psoriasis, thickening of the epidermis was detected and could be monitored over time. The light scattering in the upper dermis was lower than in healthy skin. This was interpreted to be due to the inflammation and oedema, leading to a less-dense arrangement of the collagen fibres. The changes in the OCT images did not significantly correlate with the changes shown by the other methods. OCT is an interesting tool for investigation of inflammatory skin diseases. It is a simple method for determination of epidermal thickness and therefore provides, in addition to other methods, information on the severity of the disease and on treatment effects.

Case-Control Studies↗

Effects of CO2-enriched water on barrier recovery.

The objective of the present study was to evaluate the impact of CO2-enriched water on barrier recovery of detergent-damaged skin compared to tap water employing bioengineering methods and thin-layer chromatography (TLC) analysis of stratum corneum (SC) lipids. Irritation of the skin was elicited on the forearms of 20 volunteers using 1% sodium lauryl sulphate (SLS). The degree of skin irritation was followed over 10 days in terms of skin colour reflectance (L*a*b*), transepidermal water loss (TEWL), and skin capacitance expressed as median values. For TLC analysis, SC lipids were extracted prior to and during the observation period. Clinical examination showed the efficacy of CO2-enriched water on barrier recovery. Compared to unenriched tap water, CO2-enriched water produced a significant (P < 0.01) increase in total SC lipids and in particular in the ceramide fraction. Furthermore, TEWL was significantly (P < 0.01) lower in skin treated with CO2-enriched water than in skin treated with unenriched water. These findings may indicate that rinsing with CO2-enriched water enhances (1) clinical regeneration of detergent-damaged skin, (2) epidermal lipid synthesis, and (3) barrier repair after detergent-induced perturbation.

Adult↗

Age-related changes in skin topography and microcirculation.

Skin topography and microvasculature undergo characteristic changes with age. Although several non-invasive bioengineering methods are currently available to measure them quantitatively, few publications have referred to their relationship with age in different anatomical sites. This study was carried out to observe the age-related changes of the skin topography and skin microcirculation. The microrelief was assessed with special processing software from scanning by interference fringe profilometry of silicone replicas performed on two sites (volar forearm and back of hand) on 50 female volunteers (aged 20-74 years who consisted of ten probands in each decade). The superficial vascular network of both sites was assessed by videocapillaroscopy, and the subpapillary vascular plexus was studied with laser Doppler flowmetry. Skin color, which is affected by blood flow, was observed by colorimeter. The skin roughness and the mean height between peak and valley increased with age. There were statistically significant differences between the evaluated sites. This study also shows that the capillary loops in the dermal papillae decrease but the subpapillary plexus increase with age. The interference fringe profilometry associated with videocapillaroscopy may be useful and accurate to measure the efficacy of medical or cosmetic products to delay skin aging.

Adult↗

Smoothelin-positive cells in human and porcine semilunar valves.

Our aim was to further characterize the interstitial cell phenotypes of normal porcine and human semilunar valves, information necessary for the design of bioengineered valves and for the understanding of valve disease processes such as aortic valve sclerosis. Existence of fibroblasts, myofibroblasts, and smooth muscle-like cells within semilunar heart valves has been established. However, the nature of the smooth muscle cell population has been controversial. We used immunochemical and western blotting methods to determine the status of smoothelin and smooth muscle alpha-actin in the valve. Our examination of valve interstitial cells confirmed the presence of terminally differentiated, contractile smooth muscle cells in situ. They were arranged in small bundles of 5-35 cells within the ventricularis or as individual cells scattered throughout the valvular layers in vivo, and were present in cells explanted from the valves in vitro. Colocalization of these proteins in semilunar heart valves was achieved with double-labeling experiments. Protein extraction, followed by coimmunoprecipitation, electrophoresis, and western blotting confirmed the immunochemical analysis and suggested that smooth muscle alpha-actin and smoothelin interact, as has been previously postulated. The presence of contractile smooth muscle within the valve may be an important factor in understanding valve pathology and in the design of tissue engineering efforts.

Animals↗

Recent developments in the monitoring, modeling and control of biological production systems.

Current trends in the development of methods for monitoring, modeling and controlling biological production systems are reviewed from a bioengineering perspective. The ability to measure intracellular conditions in bioprocesses using genomics and other bioinformatics tools is addressed. Devices provided via micromachining techniques and new real-time optical technology are other novel methods that may facilitate biosystem engineering. Mathematical modeling of data obtained from bioinformatics or real-time monitoring methods are necessary in order to handle the dense flows of data that are generated. Furthermore, control methods must be able to cope with these data flows in efficient ways that can be implemented in plant-wide computer communication systems.

Animals↗

Disruptive visions: biosurgery.

There are a number of new therapeutic options generated by the biotechnology, bioengineering, and bioimaging revolutions in terms of organ-specific designer drugs, genetically engineered cells, cell-specific proteins and drugs, directed energy instruments, therapeutic microdevices, etc. Many of these new therapies need to be placed exactly on, within, or adjacent to an organ, and many others are delivered by endoluminal or endovascular approaches. The common requirements are (1) the accurate delivery of the modality and (2) the functional importance of targeting the biologic basis rather than the anatomic structure--hence the term biosurgery. As more of these therapies achieve clinical applicability and FDA approval, there will be the need for the precision of delivery to be at the micro- and nanoscale, which is well beyond human physical limitations. The surgeon of the future must be able to identify those therapeutic modalities that would benefit from such exact placement or implantation and acquire the skills, training, and equipment to use surgical expertise to deliver these new modalities. A review of some of the emerging opportunities is presented. Ignoring these challenges will relinquish these new procedures to other nonsurgical interventionalists, perhaps to the detriment of patient safety.

Biotechnology↗

Elastic stabilization alone or combined with rigid fusion in spinal surgery: a biomechanical study and clinical experience based on 82 cases.

The authors report their experience with the treatment of lumbar instability by a kind of spine stabilization. The elastic stabilization, which follows a new philosophy, is obtained by an interspinous device, and should be used alone in degenerative disc disease, recurrent disc herniation and in very low grade instability, or in association with rigid fusion for the prevention of pathology of the border area. In collaboration with bioengineers, we carried out an experimental study on a lumbar spine model in order to calculate stresses and deformations of lumbar disc during simulation of motion, in physiological conditions and when elastic stabilization is combined with rigid fusion. Results suggest that elastic stabilization reduces stresses on the adjacent disc up to 28 degrees of flexion. Based on this preliminary result, we began to use elastic stabilization alone or combined with fusion in 1994. To date, we have performed 82 surgical procedures, 57 using stabilization alone and 25 combined with fusion, in patients affected by degenerative disc disease, disc herniation, recurrence of disc herniation or other pathologies. Clinical results are satisfactory, especially in the group of patients affected by recurrent disc herniation, in whom the elastic device was used alone.

Adult↗

A biological approach to treating disc degeneration: not for today, but maybe for tomorrow.

The intervertebral disc unites the vertebrae in the spine, providing the flexibility required for bending and twisting and resisting the compression inflicted by gravity when in an upright posture. The discs have a complex structure, with the outer annulus fibrosus having lamellae of organized collagen fibrils and the inner nucleus pulposus having a more random collagen organization and an abundance of aggregating proteoglycans. This composite nature endows the disc with both the tension-resisting properties of a ligament and the compression-resisting properties of articular cartilage. Unfortunately, disc structure and function does not remain optimal throughout life, but undergoes progressive degeneration, commencing in the young adult, and is particularly evident in the nucleus pulposus. With time, disc degeneration may result in clinical symptoms, such as low back pain, and require medical intervention. Such treatment may involve removal of the offending disc by surgery rather than its repair, which would be the preferred course of action. In the near future, current bioengineering techniques may offer the possibility of repairing the damaged disc, if an engineered tissue with the appropriate functional properties can be generated to augment the ailing disc. In this report, we summarized our recent results, in which disc cells were implanted into a scaffold of collagen and hyaluronan, or entrapped into a chitosan gel, and growth factors were used to modulate matrix synthesis in an attempt to produce a tissue with a similar molecular composition to native nucleus pulposus tissue.

Cell Transplantation↗

Skin function and skin disorders in Parkinson's disease.

Cutaneous symptoms (seborrhoea and hyperhidrosis) in Parkinson's disease were investigated. In 70 treated patients with Parkinson's disease and 22 control subjects, non-invasive bioengineering methods (sebumetry, corneometry, pH) were carried out on the forehead, sternum and forearm. In addition, concomitant dermatoses and medication were recorded. 18.6% of the patients had seborrhoea on the forehead (>220 microg/cm2), 51.4% showed normal sebum values (100-220 microg/cm2) and 30% a sebostasis (<100 microg/cm2). Males has significantly higher sebum values than females. No relationship between the seborrhoea and the therapy for Morbus Parkinson was found. Patients with hyperhidrosis (n = 36) had significantly lower pH values (p < 0.05) on the forehead than those without hyperhidrosis. 22 patients (31.9%) reported a cold/hot flush and a further 13 (18.8%) had clinical rosacea. Seborrhoea is rare in treated Parkinsonian patients but hyperhidrosis is frequently found. Furthermore, a particular lack of vasostability (flush) appears to be an autonomic dysregulation in the skin related to Morbus Parkinson, which has not been studied to any extent to date.

Aged↗

Developments toward large-scale bacterial bioprocesses in the presence of bulk amounts of organic solvents.

Many pseudomonads and other bacteria can grow on aliphatic and aromatic hydrocarbons that occur in the environment. We are examining the potential of such organisms as biocatalysts for the oxidation of a variety of substituted aliphatic and aromatic compounds. To attain a high production rate of oxidation products via such biotransformations, we have focused on two-liquid phase culture systems. In these systems, cells are grown in liquid media consisting of an aqueous phase containing water-soluble growth substrates and droplets of a water-immicible organic solvent containing bioconversion substrates and products. For industrial applications of such two-liquid phase processes, several questions remain. What are the maximum rates at which apolar compounds can be transferred from the apolar phase to cells growing in the aqueous phase, i.e., what are the maximum space-time yields attainable in two-liquid phase fermentations under practical conditions? What does an efficient downstream processing of two-liquid phase medium involve? What safety regimes should be considered in working with flammable organic solvents? Can elevated pressure be used to increase oxygen transfer? Based on answers to these questions, we have recently developed a high-pressure, explosion-proof bioreactor system with Bioengineering AG (Wald, Switzerland), which will be installed in our pilot plant and used to explore two-liquid phase bioconversions at a pilot scale.

Bacteria↗

Computational analysis of the three-dimensional hemodynamics of the blood sac in the twin-pulse life-support system.

Blood flow in the twin-pulse life-support system (T-PLS) pulsatile blood pump was simulated using a three-dimensional rigid body-fluid-solid interaction model. This model can delineate the blood flow in the T-PLS resulting from operation of a moving actuator. The numerical method used in this study was a commercial finite element package called ADINA. We used a contact and fluid-solid interaction model to compute the blood hemodynamics in the sac. Blood flow is generated by the motion of the actuator, which strongly interacts with the solid material surrounding the blood. To obtain basic bioengineering data on the optimum operation of the T-PLS, we simulated four models in which the actuator moved at different speeds and investigated both the flow pattern and the distribution of shear stress. During the contraction phase, a strong axial flow is observed around the outlet, whereas there is stagnant flow around the inlet. The maximum shear stress in each model depends on the operation mode; however, all four models have similar flow rates. The sinusoidal mode exhibited the lowest maximum shear stress and is thus considered the most efficient of the four operating modes.

Blood Flow Velocity↗

Diversity and biotechnological potential of the sponge-associated microbial consortia.

Sponges are well known to harbor diverse microbes and represent a significant source of bioactive natural compounds derived from the marine environment. Recent studies of the microbial communities of marine sponges have uncovered previously undescribed species and an array of new chemical compounds. In contrast to natural compounds, studies on enzymes with biotechnological potential from microbes associated with sponges are rare although enzymes with novel activities that have potential medical and biotechnological applications have been identified from sponges and microbes associated with sponges. Both bacteria and fungi have been isolated from a wide range of marine sponge, but the diversity and symbiotic relationship of bacteria has been studied to a greater extent than that of fungi isolated from sponges. Molecular methods (e.g., rDNA, DGGE, and FISH) have revealed a great diversity of the unculturable bacteria and archaea. Metagenomic approaches have identified interesting metabolic pathways responsible for the production of natural compounds and may provide a new avenue to explore the microbial diversity and biotechnological potential of marine sponges. In addition, other eukaryotic organisms such as diatoms and unicellular algae from marine sponges are also being described using these molecular techniques. Many natural compounds derived from sponges are suspected to be of bacterial origin, but only a few studies have provided convincing evidence for symbiotic producers in sponges. Microbes in sponges exist in different associations with sponges including the true symbiosis. Fungi derived from marine sponges represent the single most prolific source of diverse bioactive marine fungal compounds found to date. There is a developing interest in determining the true diversity of fungi present in marine sponges and the nature of the association. Molecular methods will allow scientists to more accurately identify fungal species and determine actual diversity of sponge-associated fungi. This is especially important as greater cooperation between bacteriologists, mycologists, natural product chemists, and bioengineers is needed to provide a well-coordinated effort in studying the diversity, ecology, physiology, and association between bacteria, fungi, and other organisms present in marine sponges.

Animals↗

Surface behaviour of biomaterials: the theta surface for biocompatibility.

"Biomaterials" are non-living substances selected to have predictable interactions with contacting biological phases, in applications ranging from medical/dental implants to food processing to control of biofouling in the sea. More than 30 years of empirical observations of the surface behaviours of various materials in biological settings, when correlated with the contact-angle-determined Critical Surface Tensions (CST) for these same materials, support the definition of the "theta surface". The "theta surface" is that characteristic expression of outermost atomic features least retentive of depositing proteins, and identified by the bioengineering criterion of having measured CST between 20 and 30 mN/m. Biomaterials applications requiring strong bioadhesion must avoid this range, while those requiring easy release of accumulating biomass should have "theta surface" qualities. Selection of blood-compatible materials is a main example. It is forecast that future biomaterials will be safely and effectively translated directly to clinical use, without requiring animal testing, based on laboratory data for CST, protein denaturation, and cell spreading alone.

Animals↗