Micrometer-scale structure in shark vertebral centra.

The vertebral centra of sharks consist of cartilage, and many species' centra contain a bioapatite related to that in bone. Centra microarchitectures at the 0.5-50 µm scale do not appear to have been described previously. This study examines centrum microarchitecture in lamniform and carcharhiniform sharks with synchrotron microComputed Tomography (microCT), scanning electron microscopy and spectroscopy and light microscopy. The analysis centers on the blue shark (carcharhiniform) and shortfin mako (lamniform), species studied with all three modalities. Synchrotron microCT results from seven other species complete the report. The main centrum structures, the corpus calcareum and intermedialia, consist of fine, closely-spaced, mineralized trabeculae whose mean thicknesses and spacings range from 4.5 to 11.2 µm and 4.5 to 15.6 µm, respectively. A significant (p = 0.00001) positive linear relationship between and exists for multiple positions within one mako centrum. Carcharhiniform species' and exhibit an inverse linear relationship (p = 0.005) while in lamniforms these variables tend toward a positive relationship which does not reach statistical significance (p = 0.099). In all species, the trabeculae form an uninterrupted, interconnected network, and the unmineralized volumes are similarly interconnected. Small differences in mineralization level are observed in trabeculae. Centrum growth band pairs are found to consist of locally higher /lower mineral volume fraction. Within the intermedialia, radial canals and radial microrods were characterized, and compacted trabeculae are prominent in the mako intermedialia. The centra's mineralized central zones were non-trabecular and are also described. STATEMENT OF SIGNIFICANCE: This study's novel result is the demonstration that the mineralized cartilage of sharks' vertebral bodies (centra) consists of a fine 3D array of interconnected plates (trabeculae) and an interpenetrating network of unmineralized tissue. This microstructure is radically different from that in tesserae or in teeth, the other main mineralized shark tissues. Using volumetric synchrotron microComputed Tomography, numerical values of mean trabecular thickness and spacing and their relationship were measured for nine species. Scanning electron microscopy added a higher resolution view of the microstructures, and histology provided complementary information on cartilage and cells. The present results suggest centra microstructure helps accommodate the very large in vivo strains and may prevent damage accumulation during millions of cycles of swimming-induced loading.

Antlers - Evolution, development, structure, composition, and biomechanics of an outstanding type of bone.

Antlers are bony appendages of deer that undergo periodic regeneration from the top of permanent outgrowths (the pedicles) of the frontal bones. Of the "less familiar" bone types whose study was advocated by John Currey to gain a better understanding of structure-function relationships of mineralized tissues and organs, antlers were of special interest to him. The present review summarizes our current knowledge about the evolution, development, structure, mineralization, and biomechanics of antlers and how their formation is affected by environmental factors like nutrition. Furthermore, the potential role of antlers as a model in bone biology and several fields of biomedicine as well as their use as a monitoring tool in environmental studies are discussed.

[Choosing wisely recommendations in intensive care medicine]. / Klug-entscheiden-Empfehlungen in der internistischen Intensivmedizin.

Intensive care medicine is an important and integral part of internal medicine. Modern intensive care medicine permits survival of many patients with severe and life-threatening internal diseases in acute situations. Decisive for therapeutic success is often not the application of complicated and expensive medical technologies, but rather the rapid diagnosis and identification of core issues, with immediate and competent initiation of standard treatment regimens. An adequately staffed, well-organized interprofessional team is of central importance. With the application of standard therapies, it has been increasingly demonstrated that "less is more", and that personalized treatment concepts are better than aggressive strategies with higher therapeutic goals. In accordance with the Choosing wisely recommendations of the American societies for intensive care medicine, the extended board of the Deutsche Gesellschaft für Internistische Intensivmedizin und Notfallmedizin (DGIIN) has formulated five positive and five negative recommendations reflecting these principles. The current paper is an updated version of the manuscript originally published in the Deutsches Ärzteblatt. When applying these recommendations, it is important to consider that intensive care patients are very complex; therefore, the applicability of these principles must be assessed on an individual basis and, where necessary, modified appropriately.

[Dialysis patients in intensive care units]. / Der Dialysepatient auf der Intensivstation.

The number of dialysis patients needing intensive medical care is steadily increasing, mostly due to cardiovascular diseases. Of the patients 50% are admitted due to myocardial infarction, malignant arrhythmia or acute cardiac failure and many also due to hyperkalemia and acute volume overload against the background of anuria or oligouria associated with arterial hypertension and hypervolemic hypertensive pulmonary edema. The treatment of an acute cardiac syndrome is comparable to the treatment of patients with healthy kidneys and despite the significantly higher cardiovascular mortality of these patients the acute prognosis is not significantly different to non-dialysis patients. In association with hypervolemic hypertensive pulmonary edema and all forms of hyperkalemia, dialysis treatment is always necessary. In the case of complications due to infections, in particular septicemia, dialysis patients seem to profit from the general therapy guidelines for septic patients, such as early goal-directed therapy. Underdosing of antibiotics for dialysis patients with sepsis represents a substantial problem in the clinical practice and can additionally endanger these patients.

Labeling studies on cortical bone formation in the antlers of red deer (Cervus elaphus).

The formation and mineralization process of antlers, which constitute the fastest growing bones in vertebrates, is still not fully understood. We used oxytetracycline injections to label different stages of bone formation in antlers of 14 red deer between days 28 and 156 of antler growth. Results show that initially a trabecular scaffold of woven bone is formed which largely replaces a pre-existing scaffold of mineralized cartilage. Lamellar bone is then deposited and from about day 70 onwards, primary osteons fill in the longitudinal tubes lined by the scaffold in a proximal to distal sequence. Mineral apposition rate (MAR) in early stages of primary osteon formation is very high (average 2.15 µm/d). Lower MARs were recorded for later stages of primary osteon formation (1.56 µm/d) and for the smaller secondary osteons (0.89 µm/d). Results suggest a peak in mineral demand around day 100 when the extent of mineralizing surfaces is maximal. A few secondary osteons were formed in a process of antler modeling rather than remodeling, as it occurred simultaneously with formation of primary osteons. The degree of cortical porosity reflects a reduction in MAR during later stages of osteonal growth, whereas cortical thickness is determined earlier. Injections given when the antlers were largely or completely clean from velvet produced no labels in antler bone, strongly suggesting that antlers are dead after velvet shedding. The rapidity of antler mineralization and the short lifespan of antlers make them an extraordinary model to assess the effects of chemicals impairing or promoting bone mineralization.

Development of the permanent mandibular cheek teeth in fallow deer (Dama dama).

The study describes crown and root formation of the permanent mandibular cheek teeth of fallow deer from a gestational age of 22-23 weeks up to a post-natal age of 33 months. Tooth development was recorded using a scoring scheme based on morphological criteria ranging from crypt formation to completion of root growth. The morphological appearance of the enamel surface during three different stages (secretory-stage enamel, maturation-stage enamel and mature enamel) was described, and the approximate age at termination of the secretory stage of amelogenesis in the deciduous and permanent mandibular cheek teeth was determined. The data enable an age estimation of fallow deer up to 3 years of age and provide a basis for assessing the timing of stress episodes that affect tooth crown formation. This information is useful for the management of the species as well as in bioarchaeological and bioindication studies.

Enamel hypoplasia in molars of sheep and goats, and its relationship to the pattern of tooth crown growth.

Enamel is the most highly mineralized and durable tissue of the mammalian body. As enamel does not undergo remodeling or repair, disturbances of enamel formation leave a permanent record in the tissue that can be used for life history reconstruction. This study reports light and scanning electron microscope findings on hypoplastic enamel defects, and on the chronology of crown growth in the molars of sheep and goats. A marked reduction of enamel extension rates in cervical compared with more cuspal crown portions of sheep and goat molars was recorded, with formation of the cervical 25% of the crown taking about the same time as that of the upper 75% of the crown. This explains the more frequent occurrence of enamel hypoplasia in cervical compared with upper and middle crown portions. Regarding the identification of hypoplastic enamel defects by external inspection, our results suggest a dependence on the type of defect and the associated presence of smaller or larger amounts of coronal cementum. Defects considered to reflect a slight to moderate impairment of secretory ameloblast function can normally be correctly diagnosed as they are not occluded by thick layers of cementum. In contrast, defects denoting a severe impairment of enamel matrix secretion can typically not be correctly identified because they are occluded by large amounts of cementum, so that neither depth nor extension of the defects can be assessed on external inspection. In these cases, microscopic analysis of tooth sections is required for a correct diagnosis of the hypoplastic enamel defects.

A Regional health care network: eHealth.Braunschweig. Domain fields and architectural challenges.

BACKGROUND: Health care network eHealth.Braunschweig has been started in the South-East region of Lower Saxony in Germany in 2009. It composes major health care players, participants from research institutions and important local industry partners. OBJECTIVES: The objective of this paper is firstly to describe the relevant regional characteristics and distinctions of the eHealth.Braunschweig health care network and to inform about the goals and structure of eHealth.Braunschweig; secondly to picture and discuss the main concepts and domain fields which are addressed in the health care network; and finally to discuss the architectural challenges of eHealth.Braunschweig regarding the addressed domain fields and defined requirements. METHODS: Based on respective literature and former conducted projects we discuss the project structure and goals of eHealth.Braunschweig, depict major domain fields and requirements gained in workshops with participants and discuss the architectural challenges as well as the architectural approach of eHealth.Braunschweig network. RESULTS: The regional healthcare network eHealth.Braunschweig has been established in April 2009. Since then the network has grown constantly and a sufficient progress in network activities has been achieved. The main domain fields have been specified in different workshops with network participants and an architectural realization approach for the transinstitutional information system architecture in the healthcare network has been developed. However, the effects on quality of information processing and quality of patient care have not been proved yet. Systematic evaluation studies have to be done in future in order to investigate the impact of information and communication technology on the quality of information processing and the quality of patient care. CONCLUSIONS: In general, the aspects described in this paper are expected to contribute to a systematic approach for the establishment of regional health care networks with lasting and sustainable effects on patient-centered health care in a regional context.

[Renal replacement therapy in acute renal failure]. / Nierenersatztherapie beim akuten Nierenversagen.

Acute kidney injury (AKI) is characterized by a sudden breakdown of the incretoric and excretoric functions of the kidneys. In intensive care it is always part of a multiple organ failure (MOF). It has a high incidence in intensive care (5 - 20 %), increasing up to 50 % in patients with septic shock. Its prognosis is variable (mortality 20 - 80 %) due to the fact, that up to the establishing of RIFLE and AKIN no consistent classification existed. Early start of extracorporeal treatment may lead to a reduced mortality in critically ill with AKI and MOF as the negative influence of AKI on other vital function disturbances may be reduced. Independent of the treatment form, all critically ill need a dosage of dialysis enabling negative effects of the hypercatabolic situation for these patients. An increase of the dosage over these demands did not lead to a better survival in the inhomogeneous group of all patients with AKI and MOF. In continuous forms of treatment an exchange amount of 20 ml/kg/h should be reached, as in intermittent hemodialysis a Kt/V lower 4 - 4.5/week should be avoided. According to the survival of the patients there is no evidence that either continuous forms of treatment or intermittent dialysis is superior over the other, comparing always these heterogeneous groups of medical and surgical AKI patients. There seems to be a small group of patients (mortality > 80 %) never included in any prospective randomized trial which can only be treated continuously.

Parenteral nutrition in patients with renal failure - Guidelines on Parenteral Nutrition, Chapter 17.

Partial EN (enteral nutrition) should always be aimed for in patients with renal failure that require nutritional support. Nevertheless PN (parenteral nutrition) may be necessary in renal failure in patient groups with acute or chronic renal failure (ARF or CRF) and additional acute diseases but without extracorporeal renal replacement therapy, or in patients with ARF or CRF with additional acute diseases on extracorporeal renal replacement therapy, haemodialysis therapy (HD), peritoneal dialysis (PD) or continuous renal replacement therapy (CRRT), or in patients on HD therapy with intradialytic PN. Patients with renal failure who show marked metabolic derangements and changes in nutritional requirements require the use of specifically adapted nutrient solutions. The substrate requirements of acutely ill, non-hypercatabolic patients with CRF correspond to those of patients with ARF who are not receiving any renal replacement patients therapy (utilisation of the administered nutrients has to be monitored carefully). In ARF patients and acutely ill CRF patients on renal replacement therapy, substrate requirements depend on disease severity, type and extent/frequency of extracorporeal renal replacement therapy, nutritional status, underlying disease and complications occurring during the course of the disease. Patients under HD have a higher risk of developing malnutrition. Intradialytic PN (IDPN) should be used if causes of malnutrition cannot be eliminated and other interventions fail. IDPN should only be carried out when modifiable causes of malnutrition are excluded and enhanced oral (like i.e. additional energy drinks) or enteral supply is unsuccessful or cannot be carried out.

Insights from the inside: histological analysis of abnormal enamel microstructure associated with hypoplastic enamel defects in human teeth.

We studied the abnormalities in enamel microstructure associated with enamel hypoplasia in human teeth from the early medieval (5th-7th century AD) cemetery of Barbing, Germany, using light and scanning electron microscopy. The main aim of the study was to test the hypothesis that by analyzing the microstructure of fully formed enamel it is possible to reconstruct the reaction pattern of secretory ameloblasts to stress events leading to enamel hypoplasia. From the histological findings, a sequence of increasing impairment of secretory ameloblast function involving three thresholds was deduced. Surpassing of each of these thresholds is assumed to result in characteristic changes in enamel microstructure attributable to specific functional/morphological alterations of secretory ameloblasts. Based on our results we propose a model identifying the principal factors influencing the reaction of secretory ameloblasts to stress. The present study demonstrates that by including microscopic analysis in the study of enamel hypoplasia, it is possible to obtain a more complete picture of the formation of these developmental defects than is possible by inspection of crown surface features alone, and to draw more substantiated conclusions about the possible nature of developmental defects of enamel.

Deposition of cellular cementum onto hypoplastic enamel of fluorotic teeth in wild boars (Sus scrofa L.).

The nature of deposits present in hypoplastic defects of fluorotic enamel of wild boar teeth was studied by light microscopy and scanning electron microscopy. The fluorotic enamel showed different developmental abnormalities, denoting a severe disturbance of ameloblast function during the secretory stage of amelogenesis. These abnormalities included the occurrence of grossly accentuated incremental lines with associated zones of aprismatic enamel and the presence of different forms of hypoplastic defects. Two types of deposits were present on the hypoplastic enamel: cellular cementum and posteruptively acquired, presumably partially mineralized dental plaque. Coronal cementum is not normally formed in pig teeth. Presence of this tissue in fluorotic teeth of wild boars is seen as indicative of a premature disintegration of the enamel epithelium prior to the completion of amelogenesis. This was supposed to have resulted in a contact of mesenchymal cells of the dental follicle with the surface of the immature enamel and, in consequence, in a differentiation of these cells into cementoblasts. To our knowledge, this is the first study reporting the formation of coronal cementum as part of the spectrum of pathological changes in fluorotic teeth in a species whose tooth crowns are normally free of cementum.

Fluoride-induced alterations of enamel structure: an experimental study in the miniature pig.

We studied the structural changes in the enamel of mandibular third molars of miniature pigs administered a daily oral dose of 2 mg NaF (approximately 0.9 mg of fluoride) per kg body weight (added to the feed) for 1 year. The treatment period covered most of the secretory stage and the entire post-secretory stage of amelogenesis of the M(3). The enamel of the molars from the fluoride-fed pigs appeared opaque and chalky, and the erupted portions were stained brown. The underlying histopathological change was a pronounced subsurface hypomineralization of the enamel beneath a thin surface rim of higher mineral content. This enamel hypomineralization was attributed to a fluoride-induced impairment of the process of enamel maturation. The most conspicuous finding in the fluorotic enamel was the presence of numerous pit-type hypoplastic defects, denoting a marked fluoride-induced disturbance also of the secretory stage of amelogenesis. Microradiography and scanning electron microscopy revealed an enhanced incremental pattern in the outer enamel of the fluorotic molars. Typically, the bottom of larger hypoplastic defects was underlain by a broad, grossly accentuated incremental line. Occurrence of larger hypoplasias was further associated with the presence of aprismatic enamel, the formation of which was attributed to a loss of the prism-forming (distal) portion of the Tomes' processes of secretory ameloblasts. The findings in the miniature pigs closely parallel earlier observations on fluorotic enamel of free-ranging deer and wild boar from fluoride-polluted areas.

Reconstruction of a decline of ambient lead levels in the Ruhr area (Germany) by studying lead concentrations in antlers of roe deer (Capreolus capreolus).

We determined lead concentrations in antlers (n = 132) of roe bucks > or = 2 years of age, killed between 1951 and 1999 in the northern Ruhr area, Germany. The lead content of the antlers ranged between 0.6 and 19.0 mg/kg dry weight of bone, and overall markedly declined over the study period. As a consequence, mean lead levels in younger samples were always significantly (P<0.001) lower than those in older ones (for the periods: 1951-1969, 1970-1979, 1980-1989 and 1990-1999). Annual mean antler lead concentrations were positively correlated (r(s) = 0.74, P<0.001) with annual mean lead concentrations in airborne particulate matter of the Rhine-Ruhr area during the period 1974-1999. The findings of the present study underscore that roe deer antlers are well suited for a monitoring of temporal trends in environmental lead levels in a cost-effective way.

Assessing regional variation of environmental fluoride concentrations in western Germany by analysis of antler fluoride content in roe deer (Capreolus capreolus).

To assess regional variation in ambient fluoride levels, we analyzed the fluoride content of 188 antlers of roe deer (Capreolus capreolus) killed between 1990 and 1999 in 14 areas of the federal state of North Rhine-Westphalia, Germany. Individual antler fluoride concentrations ranged between 113 and 11,995 mg x F-/kg bone ash, and sample means differed significantly (p < 0.0001) among the study areas. Low average concentrations (geometric means of 262 and 277 mg x F-/kg bone ash, respectively) were found in antler samples from two control areas, located quite remote to major fluoride emission sources. The highest geometric mean fluoride content (1,677 mg x F-/kg bone ash) was recorded for an antler sample from a study area exposed to fluoride emissions from an aluminium smelter and two mineral coal-fired power stations. In eight antlers obtained from roe deer living in the direct vicinity of the aluminium smelter, fluoride values ranged between 2,067 and 11,995 mg x F-/kg bone ash, thereby demonstrating the strong impact of this emission source on its surroundings. The study showed that by analyzing antler fluoride concentrations, large-scale surveys of environmental contamination by fluoride can be performed in a standardized and cost-effective way in areas inhabited by deer. Due to its rather narrow home range, abundance, and high adaptability, the roe deer is particularly suited for such studies.

Fluoride concentrations in antler bone of roe deer (Capreolus capreolus) indicate decreasing fluoride pollution in an industrialized area of western Germany.

In order to reconstruct temporal changes in ambient fluoride levels in the industrialized Ruhr area (western Germany), we analyzed the bone fluoride content of 167 antlers of roe deer (Capreolus capreolus) killed between 1951 and 1999 in the northern part of this region. Individual values ranged between 110 and 8,178 mg F-/kg ash, and there was an overall marked decrease over the sampling period. Average bone fluoride concentrations in antlers from the periods 1980 through 1989 (geometric mean [95% confidence interval]: 1,490 [1,193-1,861] mg/kg ash) and 1990 through 1999 (753 [644-882] mg/kg ash) differed significantly (p < 0.001) and were both significantly (p < 0.001) lower than those from the periods 1951 through 1969 (3,720 [3,227-4,288] mg/kg ash) and 1970 through 1979 (2,573 [2,203-3,006] mg/kg ash). The findings are seen as indicative of a progressively reduced atmospheric fluoride deposition into the study area, caused by effective emission-control measures in Germany and neighboring countries. Because antlers are replaced annually, grow during a fixed period of some months, and are regularly collected and kept as trophies, they are well suited as monitoring units for analyzing temporal trends in environmental pollution by fluoride and other bone-seeking pollutants.