The use of external counterpressure (G-suit) in the management of traumatic retroperitoneal hemorrhage.
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The suitability of ferocyanide as an indicator for the measurement of extracellular fluid volume was tested. Added ferrocyanide could be recovered completely from urine, plasma and blood. In in vitro experiments ferrocyanide did not penetrate into erythrocytes, nor did it adhere to the red cell membrane. In gel filtration and electrophoresis experiments binding of ferrocyanide to plasma proteins could not be demonstrated. In in vivo experiments on dogs, the urinary recovery of intravenously administered ferrocyanide was 98.9 +/- 2.1% (n = 14). The partition ratio of ferrocyanide between lymph water and plasma water was 0.99 +/- 0.02 (n = 20). Ferrocyanide could not be detected in cerebrospinal fluid or red cells of dogs after administration by intravenous infusion. No untoward effects of the infused ferrocyanide were observed during or after the experiments. In nephrectomized dogs ferrocyanide reached its ultimate distribution volume 2 hrs after intravenous administration of a single dose and remained constant for up to 10 hrs. The average distribution volume was 224 +/- 17 ml-kg-1 body mass (n = 6). In intact dogs continuously infused with indicator, ferrocyanide also reached its ultimate distribution volume in 2 hrs and remained constant thereafter for up to 7 hrs after the start of the infusion. The average distribution volume was 237 +/- 27 ml-kg-1 body mass (n = 14). It is concluded that ferrocyanide fulfils the requirements to be met by an indicator for the measurement of the extracellular volume, and is well suited for repeated determinations of the extracellular fluid volume in one and the same experiment.
The Japanese quail is a precocial species, and because of its relatively rapid development, sexual maturation in about 40 days after hatching, and prolific breeding capacity, it promises to become an organism well suited for avian research. One stumbling block has been the inability to induce, with any consistency, parental behavior in laboratory stocks. The study reported herein demonstrates a method for establishing a self-perpetuating population under seminaturalistic conditions. In addition, given the limitions of finite space, chick mortality appears to have been mostly density dependent, thus indicating that the increase in the size of the population is circumscribed in part by population density.
Navigation systems for image-guided therapy: A review. Navigation is visually interactive targeting based on the simultaneous display of instrument position and of the corresponding two- or three-dimensional image data sets. In this way it unifies anatomic information and therapeutic action. Medical navigation systems (MNS) can simulate realtime image guidance and thereby reduce radiation exposure as well as provide the full range of digital image processing during an intervention. Navigation is based on the tracking of medical instruments in space and the transformation of image, patient, and instrument coordinates into a common reference system. If the patient coordinate system is used as the common base, the process is called patient-based navigation (PBN). If, however, the imaging modality is present in the interventional suite and its reference system is used, modality-based navigation (MBN) results. MBN does not need pre-interventional registration and inherently provides intra-operative imaging. In neurosurgery MNS's have been well established since years. They are in use for frameless biopsies and for minimizing the access morbidity in deeply situated pathologies. Currently there is a fast expansion of navigation into other surgical disciplines, e.g., orthopaedic surgery. The clinical accuracy of an MNS is hard to determine since an independent method of measurement is mostly not available during surgery. Normally, a deviation of below one up to about 5 mm between the display of the MNS and the actual position of an anatomic structure is reported. So far there have been only very few prospective randomized clinical trials between conventional and navigated interventions.
PURPOSE: Subcellular Ca2+ signaling patterns, such as Ca2+ waves, gradients, and oscillations, are an important aspect of cell regulation, but the molecular basis for these signaling patterns is not understood. Because Ca2+ release patterns differ among isoforms of the inositol 1,4,5-trisphosphate (InsP3) receptor, the relationship between the distribution of these isoforms and subcellular Ca2+ signaling patterns in nonpigmented epithelial (NPE) cells was investigated. METHODS: The distributions of the types I, II, and III InsP3 receptors were determined in NPE cells by immunofluorescence, and subcellular Ca2+ signaling patterns in these cells were examined by confocal line scanning microscopy. RESULTS: The type I InsP3 receptor was concentrated at the basal pole of NPE cells, whereas the type III receptor was localized to the apical pole. The type II InsP3 receptor was not expressed in detectable amounts. Acetylcholine induced increases in Ca2+ that were mediated by InsP3, and these Ca2+ increases began as Ca2+ waves that were initiated at the apical pole, in the region of the type III InsP3 receptor. Acetylcholine occasionally induced sustained or repetitive Ca2+ increases that were prominent at the basal pole, in the region of the type I InsP3 receptor, but only subtle or absent apically. CONCLUSIONS: Because the type I InsP3 receptor is thought to be responsible for repetitive Ca2+ release events, and the type III InsP3 receptor instead is suited to initiate Ca2+ signals, the subcellular distribution of these two isoforms corresponds to the Ca2+ signaling patterns observed in this cell type. Differential subcellular expression of InsP3 receptor isoforms may be an important molecular mechanism by which NPE cells organize their Ca2+ signals in space and time.
Maintenance of ionic gradients within the various fluids compartments of the inner ear requires transport active cellular systems at different locations. LAMMA analysis is ideally suited for detection of ions in microquantity on cellular levels overcoming many technical difficulties. The present paper summarizes the results of microprobe analysis obtained with laser induced mass spectrometry (LAMMA) supplemented by X-ray microprobe analysis of epithelial cell layers adjacent to the endolymphatic space in the cochlear duct, in the vestibular organ and in the endolymphatic sac. The possible role of inner ear as well as ocular melanin in the mechanisms of active ion transport is discussed.
Goal-directed self-motion through space is anything but a trivial task. What we take for granted in everyday life requires the complex interplay of different sensory and motor systems. On the sensory side most importantly a target of interest has to be localized relative to one's own position in space. On the motor side the most critical step in neural processing is to define and perform a movement towards the target as well as the avoidance of obstacles. Furthermore, the multisensory (visual, tactile and auditory) motion signals as induced by one's own movement have to be identified and differentiated from the real motion of visual, tactile or auditory objects in the outside world. In a number of experimental studies performed in recent years we and others have functionally characterized a subregion within monkey posterior parietal cortex (PPC) that appears to be well suited to contribute to such multisensory encoding of spatial and motion information. In this review I will summarize the most important experimental findings on the functional properties of this very region in monkey PPC, i.e. the ventral intraparietal area.
Planning is an important component of cognition that contributes, for example, to efficient movement through space. In the current study we presented novel two-dimensional alley mazes to four chimpanzees and three capuchin monkeys to identify the nature and efficiency of planning in relation to varying task parameters. All the subjects solved more mazes without error than expected by chance, providing compelling evidence that both species planned their choices in some manner. The probability of making a correct choice on mazes designed to be more demanding and presented later in the testing series was higher than on earlier, simpler mazes (chimpanzees), or unchanged (capuchin monkeys), suggesting microdevelopment of strategic choice. Structural properties of the mazes affected both species' choices. Capuchin monkeys were less likely than chimpanzees to take a correct path that initially led away from the goal but that eventually led to the goal. Chimpanzees were more likely to make an error by passing a correct path than by turning onto a wrong path. Chimpanzees and one capuchin made more errors on choices farther in sequence from the goal. Each species corrected errors before running into the end of an alley in approximately 40% of cases. Together, these findings suggest nascent planning abilities in each species, and the prospect for significant development of strategic planning capabilities on tasks presenting multiple simultaneous or sequential spatial relations. The computerized maze paradigm appears well suited to investigate movement planning and spatial perception in human and nonhuman primates alike.
The met repressor from Escherichia coli has been crystallized in space group P21, with unit cell dimensions a = 35.6 A, b = 62.6 A, c = 44.5 A, beta = 102.4 degrees and one aporepressor dimer per asymmetric unit. Preliminary X-ray diffraction photographs show measurable intensities to beyond 1.5 A resolution, and the crystal form is ideally suited to high-resolution crystallographic analysis (1 A = 0.1 nm).
The use of Computational Fluid Dynamics (CFD) and in particular Large Eddy Simulation (LES) codes to model fires provides an efficient tool for the prediction of large-scale effects that include plume characteristics, combustion product dispersion, and heat effects to adjacent objects. This paper illustrates the strengths of the Fire Dynamics Simulator (FDS), an LES code developed by the National Institute of Standards and Technology (NIST), through several small and large-scale validation runs and process safety applications. The paper presents two fire experiments--a small room fire and a large (15 m diameter) pool fire. The model results are compared to experimental data and demonstrate good agreement between the models and data. The validation work is then extended to demonstrate applicability to process safety concerns by detailing a model of a tank farm fire and a model of the ignition of a gaseous fuel in a confined space. In this simulation, a room was filled with propane, given time to disperse, and was then ignited. The model yields accurate results of the dispersion of the gas throughout the space. This information can be used to determine flammability and explosive limits in a space and can be used in subsequent models to determine the pressure and temperature waves that would result from an explosion. The model dispersion results were compared to an experiment performed by Factory Mutual. Using the above examples, this paper will demonstrate that FDS is ideally suited to build realistic models of process geometries in which large scale explosion and fire failure risks can be evaluated with several distinct advantages over more traditional CFD codes. Namely transient solutions to fire and explosion growth can be produced with less sophisticated hardware (lower cost) than needed for traditional CFD codes (PC type computer verses UNIX workstation) and can be solved for longer time histories (on the order of hundreds of seconds of computed time) with minimal computer resources and length of model run. Additionally results that are produced can be analyzed, viewed, and tabulated during and following a model run within a PC environment. There are some tradeoffs, however, as rapid computations in PC's may require a sacrifice in the grid resolution or in the sub-grid modeling, depending on the size of the geometry modeled.
Cystic fibrosis (CF) is an autosomal recessive disease that reflects mutations in the CFTR gene. Multiple mutations in this gene have been detected that lead to a protein (CFTR) that is abnormally metabolized, dysfunction, or both. The full spectrum of the activities of the gene product have not been defined, but it is clear that CFTR can act as a cAMP-regulated Cl- channel. This type of defect is consistent with the physiologic characterization of CF epithelia, which has revealed abnormalities in salt and water transport. In the lung, abnormalities in epithelial salt and water metabolism lead to abnormal mucociliary clearance. This defect in clerance represents a major failure of lung defense and leads ultimately to infection of the lung with Staphylococcus aureus, Pseudomonas aeruginosa, and other bacterial organisms. The chronic inflammatory response to this persistent intraluminal bacterial infection leads to protease-induced destruction of airway walls and finally, lung failure. More than 95% of CF patients die of lung disease. The clinical therapy of CF lung disease is limited to agents designed to promote clearance of secretions from the lung and antibiotics to treat the chronic bacterial infection. Recent laboratory demonstrations that introduction of the normal CFTR cDNA into CF cells corrects the ion transport defects of these cells has led to the hypothesis that gene therapy in the lung can be an effective, novel mode of therapy for this lung disease. The classic gene transfer vectors, e.g., retroviruses, appear to be not well suited for therapy of lung disease because of the low proliferation rate of airway epithelia in vivo. Recently, adenoviruses, which have a natural tropism for airway epithelia, have been genetically modified (E1-deleted) in an attempt to reduce potential toxicity of this virus and provide space for the CFTR cDNA. A series of in vitro studies have shown that this vector is highly efficient for transferring CFTR into airway epithelial cells in culture and correcting the CF defect. Further, studies in whole animals appear to indicate that this mode of gene transfer is associated with a low degree of toxicity. The present study is a dose-effect study designed to test for the safety and efficacy of E1-deleted recombinant adenovirus containing the CFTR cDNA under a CMV-beta-actin promoter in CF nasal epithelia.(ABSTRACT TRUNCATED AT 400 WORDS)
It has recently been shown that strategies aimed at preventing ventilator-induced lung injury, such as ventilating with low tidal volumes, can reduce mortality in patients with acute respiratory distress syndrome (ARDS). High-frequency oscillatory ventilation (HFOV) seems ideally suited as a lung-protective strategy for these patients. HFOV provides both active inspiration and expiration at frequencies generally between 3 and 10 Hz in adults. The amount of gas that enters and exits the lung with each oscillation is frequently below the anatomic dead space. Despite this, gas exchange occurs and potential adverse effects of conventional ventilation, such as overdistension and the repetitive opening and closing of collapsed lung units, are arguably mitigated. Although many investigators have studied the merits of HFOV in neonates and in pediatric populations, evidence for its use in adults with ARDS is limited. A recent multicenter, randomized, controlled trial has shown that HFOV, when used early in ARDS, is at least equivalent to conventional ventilation and may have beneficial effects on mortality. The present article reviews the principles and practical aspects of HFOV, and the current evidence for its application in adults with ARDS.
Isolated, rod-shaped adult rat cardiomyocytes (ARC) were kept in long-term cell cultures and the changes of the cardiomyocyte structure were investigated by confocal microscopy. The cells round up and make contact with the substrate by very flat, foot-like structures. After prolonged culture the amorphous cells regenerate a cardiomyocyte-like cytoarchitecture and myofibrils reemerge. In the perinuclear region myofibrils form continuously while in other cells discontinuous myofibrillogenesis was observed, where short sarcomeric segments occur all over the cytoplasmic space. During the regeneration of myofibrils certain proteins like a smooth muscle actin sort to non sarcomeric region, while myomesin or heart C-protein localize on myofibrils with high specificity. This culture system combined with method of epitope-tagging of contractile proteins are ideally suited to monitor the intracellular localization sites of exogenously introduced constructs to different cytoskeletal, since ARC exhibit at the same time stress fiber-like filaments (SFLF) and nascent myofibrils. The molecular properties of the different members of the myosin light chain isoprotein family were investigated by transfection experiments using epitope-tagged myosin light chain (MLC) cDNA. The sorting of the different types of MLC was shown to be isoprotein specific and with chimeric constructs it was shown that the isoprotein-specific incorporation into myofibrils was dependent on the presence of the middle domain of MLC-1f/3f. These MLC isoproteins can be arranged into a sequence of increasing affinity to myofibrils. A hierarchical order of myofibrillar assembly is postulated based on the association affinity. Similar experiments with constructs containing alpha-cardiac, alpha-smooth muscle and gamma-cytoplasmic actins have shown that expression of epitope-tagged actins in ARC result in different epitope staining patterns. While the alpha-cardiac actin showed a marked preference for sarcomeres, the alpha-smooth muscle isoproteins had an intermediate specificity and could either be preferentially incorporated into stress fiber-like filaments (SFLF) and in some cells to a lesser extent into myofibrils as well. Most striking results were obtained with gamma-cytoplasmic actin carrying a 5 or 11-mer epitope. This actin gave rise to large cells, induced the formation of filopodia filled with the transfected actin and depletion of the transfected actin from the perinuclear myofibrillar region.
Proceeding from the observation that organic anions bound to albumin have hepatic extraction fractions that are unexpectedly high, we have studied a distributed model that accounts for this phenomenon by invoking sites on the cell surface that catalyze the dissociation of albumin-anion complexes. The present report extends this model to include nonequilibrium binding and rate-limiting diffusion of bound anion to the cell surface. Simulation analysis of the extended model provides an unambiguous basis for interpreting the apparent intrinsic clearance of free anion. The model is fully consistent with the transport data that we obtained with rose bengal [Am. J. Physiol. 248 (Gastrointest. Liver Physiol. 11): G702-G708, 1985] but is suited to estimating only selected components of the unknown parameter vector. Uncertainties inherent in an alternate approach are discussed and illustrated.
A series of 442 women receiving subarachnoid block for various obstetrical procedures is described. These included caesarean section, instrumental delivery, manual removal of placenta, insertion of cervical suture and miscellaneous procedures. General anaesthesia was required in ten patients because subarachnoid block proved to be unsatisfactory. There were no serious complications. The overall headache rate, ascertained by daily direct questioning during hospital admission, was 26.2%. Clinical features of dural puncture headache (DPH) were present in 8.6% and equivocally so in a further 3.4%. A significantly higher incidence of DPH was recorded among patients receiving a cervical suture. Among the thirty-eight patients who developed DPH, a 25 or 26 SWG spinal needle had invariably been used and in most instances the procedure was described as being uneventful. There were no consistent technical features among the patients who developed DPH, although operator experience may have been a factor. DPH was graded as 'severe' in ten patients (2.3%) and an epidural blood patch was rapidly curative in each of these cases. One patient required a repeat patch. Subarachnoid block proved to be a satisfactory technique for the procedures outlined in the survey. It proved to be particularly valuable when anaesthesia was required urgently in the delivery suite and may even be regarded as the anaesthetic of choice in these circumstances.
This Institute has developed a USARIEM Heat Strain Prediction Model for predicting physiological responses and soldier performance in the heat, which has been programmed for use by hand-held calculators and personal computers, and incorporated into the development of a heat strain decision aid. This model is demonstrated to predict accurately (generally within +/- 1 SD/SEM) rectal temperature (Tre) responses for soldiers wearing various military clothing ensembles during U.S. or non-U.S. military scenarios in the heat at home or abroad. The value of this model is shown presently for three NASA scenarios involving the Launch and Entry Suit (LES). The LES (ventilated or unventilated) is modeled during pre-launch/launch, re-entry/landing, and emergency egress after re-entry/landing scenarios, predominately to evaluate heat acclimation and hydration state effects. During the pre-launch/launch scenario, predicted final Tre closely agrees with observed values suggesting minimal heat strain (Tre approximately 38.0 degrees C). In contrast, dehydrated (3%) unacclimated individuals show moderate levels of heat strain (Tre approximately 38.5 degrees C) for this same scenario. During the re-entry/landing and emergency egress scenarios, dehydrated unacclimated individuals are predicted to exhibit excessive heat strain (Tre > 39.0 degrees C). Thermal tolerance time is predicted to be only 6 min during emergency egress if individuals are dehydrated and unacclimated to heat while wearing the LES. If heat transfer values for space operations clothing are known, NASA can use this prediction model to help avoid undue heat strain involving astronauts for most scenarios during spaceflight.
The mean-field optimization methodology has been used to recast in a single formalism the problem of phase optimization using an arbitrary energy function in the presence of an experimentally determined phase probability distribution function. It results naturally in the generalization of the notions of figure of merit and centroid phase where the weight of the energy refinement is controlled by an effective temperature in a self-consistent manner. In the limit of high temperature, the formalism reduces of course to the Blow & Crick [Acta Cryst. (1959), 12, 794-802] classical treatment. If a model is available, Sim's [Acta Cryst. (1960), 13, 511-512] weighting scheme for a combined map appears as the first step of a refinement to be conducted until self-consistency is achieved. Assuming that MIR phases exist and that they agree reasonably well with the phases of the model, a first-order expansion gives an estimate of the changes of weights and phases to be performed for the Fourier synthesis. This provides for a new way of doing phase combination that might prove useful in challenging cases of model refinement, e.g. in large macromolecular complexes. Thermodynamic considerations have been used to discuss the best determination of weights in phase refinement; they also suggest that a variational expression of maximum likelihood is best suited as a target for refinement because it is the free energy of the system. The formalism readily allows use of solvent flattening, density averaging and the atomicity criterion to refine phases, and automatically assigns a figure of merit to each reflection. Numerical tests of the method are presented in an attempt to resolve the phase-ambiguity problem of protein crystallography in the centrosymmetric P¿1¿ space group using an energy derived from the Sayre equation.
We examined the quality of Catalyst's conformational model generation algorithm via a large scale study based on the crystal structures of a sample of 510 pharmaceutically relevant protein-ligand complexes extracted from the Protein Data Bank (PDB). Our results show that the tested algorithms implemented within Catalyst are able to produce high quality conformers, which in most of the cases are well suited for in silico drug research. Catalyst-specific settings were analyzed, such as the method used for the conformational model generation (FAST vs BEST) and the maximum number of generated conformers. By setting these options for higher fitting quality, the average RMS values describing the similarity of experimental and simulated conformers were improved from an RMS of 1.06 with max. 50 FAST generated conformers to an RMS of 0.93 with max. 255 BEST generated conformers, which represents an improvement by 12%. Each method provides best fitting conformers with an RMS value<1.50 in more than 80% of all cases. We analyzed the computing time/quality ratio of various conformational model generation settings and examined ligands in high energy conformations. Furthermore, properties of the same ligands in various proteins were investigated, and the fitting qualities of experimental conformations from the PDB and the Cambridge Structural Database (CSD) were compared. One of the most important conclusions of former studies, the fact that bioactive conformers often have energy high above that of global minima, was confirmed.