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The informatics nurse specialist as change agent. Application of innovation-diffusion theory.

The informatics nurse specialist (INS) is often the primary change agent in facilitating the implementation of clinical information systems (CIS) in healthcare settings. The INS has a unique understanding of the nursing issues that can affect the change process, and thus is in a key position to facilitate positive implementation outcomes. Innovation-diffusion theory is particularly useful in its application to the change agent role of the INS. With this theoretical knowledge, the INS can design CIS training interventions according to the psychological phenomena of Rogers' Innovation-Decision Process. An understanding of the decision-making process and the distribution of different rates of innovation adoption within a given population enable the INS to anticipate and address influential factors that affect the implementation process. Thus, Innovation-Diffusion Theory may be used as a powerful cognitive tool for the INS in facilitating the diffusion process and nurses' adoption of the technology in practice.

Attitude of Health Personnel↗

Diffuse excess mucosal collagen in rectal biopsies facilitates differential diagnosis of solitary rectal ulcer syndrome from other inflammatory bowel diseases.

Solitary rectal ulcer syndrome (SRUS) is sufficiently uncommon that the clinician or general pathologist may lack familiarity with the disorder and may confuse it with other inflammatory bowel diseases. To evaluate the role of collagen staining in facilitating the differential diagnosis of SRUS, an initial open review was undertaken on 1672 consecutive patients whose 4780 colorectal biopsies were stained with H&E with added saffron to demonstrate collagen. Excess mucosal collagen was present in 39 (2.3%) of these patients. Twenty patients with a diffuse excess of mucosal collagen in biopsies from rectal ulcer margins or from otherwise abnormal rectal mucosa had SRUS; in the remaining 19 patients, excess mucosal collagen was focal (seven ischemic colitis, five collagenous colitis, three adenocarcinoma, and four chronic idiopathic ulcerative colitis). Diffuse excess mucosal collagen never was seen in idiopathic inflammatory bowel disease (128 Crohn's colitis and 446 ulcerative colitis). Blinded reviews then were performed on rectal biopsies from 33 patients with a variety of diagnoses (14 SRUS and 19 controls). Diffuse excess collagen by saffron staining was consistently observed in SRUS but was absent in all 19 controls. Additional blinded reviews were carried out because the collagen staining pattern in ischemic colitis, although focal, could potentially be confused with SRUS. It was possible to differentiate these two diseases blindly from one another by using additional histologic criteria (14 SRUS and 12 ischemic colitis). We conclude that the demonstration of a diffuse excess of mucosal collagen in rectal biopsies facilitates the diagnosis of SRUS and differentiates it from idiopathic ulcerative colitis and Crohn's disease, with which SRUS is often confused, and other inflammatory bowl diseases.(ABSTRACT TRUNCATED AT 250 WORDS)

Biopsy↗

Myoglobin-O2-saturation profiles in muscle sections of chicken gizzard and the facilitated O2-transport by Mb+.

It has been shown that the oxygen transport in intact muscle can be quantitatively determined using Mb as an oxygen indicator in the cryomicrophotometric method. 1) The influence of the parameters such as time, temperature, boundary PO2 and metabolism on the oxygen transport in sections of chicken gizzard could be quantitatively determined from measured MbsO2-profiles; 2) The MbsO2-profiles measured under various conditions can be reproduced using a mathematical model which considers not only the diffusion of dissolved O2 but also the facilitated diffusion as well as O2 consumption. From this mathematical results it can be concluded that the mobility of the Mb in the muscle cells is limited and that Mb in the PO2-region between 5 and 0 mmHg contributes to at most 40% to the total O2-transport in chicken gizzard.

Animals↗

Two competing influences that may explain concomitant tumor resistance.

A second tumor inoculum is often inhibited in its growth by the presence in the recipient animal of an earlier implanted, growing tumor. The tumor resulting from the first inoculum may, paradoxically, continue to grow despite the simultaneous inhibition of the growth of the second inoculum, a phenomenon usually called "concomitant immunity." Evidence now suggests that the phenomenon can be observed in the absence of any recognizable type of immune reaction and might often be named more appropriately "concomitant tumor resistance." Consideration of a variety of probably related observations suggests that concomitant tumor resistance can best be explained by the competitive interaction of two opposing influences: a local diffusible, tumor-facilitating environment, produced by both tumor and normal tissues, that is counteracted by circulating inhibitors that are also produced by both tumor and by normal tissues. In an implanted small tumor, because of geometric considerations and diffusion, the action of the local facilitating environment is weak; in a larger tumor the local facilitating environment has a relatively greater influence and thus the larger tumor can continue to grow despite levels of circulating tumor inhibitors capable of inhibiting the smaller growth.

Animals↗

Experimental fluorescence tomography of tissues with noncontact measurements.

Noncontact optical measurements from diffuse media could facilitate the use of large detector arrays at multiple angles that are well suited for diffuse optical tomography applications. Such imaging strategy could eliminate the need for individual fibers in contact with tissue, restricted geometries, and matching fluids. Thus, it could significantly improve experimental procedures and enhance our ability to visualize functional and molecular processes in vivo. In this paper, we describe the experimental implementation of this novel concept and demonstrate capacity to perform small animal imaging.

Algorithms↗

Gaining insight into the nanoscale properties of sol-gel-derived silicate thin films by single-molecule spectroscopy.

The application of single-molecule spectroscopic methods in studies of individual nanoscale environments within sol-gel-derived silicate thin films is reviewed. Representative examples of the experiments performed and results obtained in several studies from the authors' laboratories are given. Included are investigations of the static and dynamic polarity properties of organically modified silicate (ORMOSIL) films. The results of these studies point to nonrandom variations in the film properties, providing strong evidence for the formation of phase-separated organic- and inorganic-rich domains. Studies of single-molecule diffusion through the same films yield important evidence for the formation of liquidlike silicate oligomers that facilitate probe molecule diffusion. Finally, single-molecule studies of the local pH within individual film environments are discussed. Valuable information on the contributions of local materials' acidity variations to overall sample heterogeneity is obtained. The results of immersion studies indicate that certain molecular environments are inaccessible to external solutions over periods as long as a few hours. The article concludes with a discussion of possible future challenges in this research that may be addressed by new and existing single-molecule methods.

Journal Article↗

Myoglobin: Just an Oxygen Store or Also an Oxygen Transporter?

Besides acting as an oxygen store during times of reduced blood oxygen supply, myoglobin can also facilitate intracellular oxygen transport by diffusion of oxymyoglobin along a PO(2) gradient. We reassess the importance of myoglobin-facilitated oxygen diffusion by applying new findings on the intracellular diffusivity of myoglobin in a model calculation.

Journal Article↗

Is the sheet-flow design a 'frozen core' (a Bauplan) of the gas exchangers? Comparative functional morphology of the respiratory microvascular systems: illustration of the geometry and rationalization of the fractal properties.

The sheet-flow design is ubiquitous in the respiratory microvascular systems of the modern gas exchangers. The blood percolates through a maze of narrow microvascular channels spreading out into a thin film, a "sheet". The design has been convergently conceived through remarkably different evolutionary strategies. Endothelial cells, e.g. connect parallel epithelial cells in the fish gills and reptilian lungs; epithelial cells divide the gill filaments in the crustacean gills, the amphibian lungs, and vascular channels on the lung of pneumonate gastropods; connective tissue elements weave between the blood capillaries of the mammalian lungs; and in birds, the blood capillaries attach directly and in some areas connect by short extensions of the epithelial cells. In the gills, skin, and most lungs, the blood in the capillary meshwork geometrically lies parallel to the respiratory surface. In the avian lung, where the blood capillaries anastomose intensely and interdigitate closely with the air capillaries, the blood occasions a 'volume' rather than a 'sheet.' The sheet-flow design and the intrinsic fractal properties of the respiratory microvascular systems have produced a highly tractable low-pressure low-resistance region that facilitates optimal perfusion. In complex animals, the sheet-flow design is a prescriptive evolutionary construction for efficient gas exchange by diffusion. The design facilitates the internal and external respiratory media to be exposed to each other over an extensive surface area across a thin tissue barrier. This comprehensive design is a classic paradigm of evolutionary convergence motivated by common enterprise to develop corresponding functionally efficient structures. With appropriate corrections for any relevant intertaxa differences, use of similar morphofunctional models in determining the diffusing capacities of various gas exchangers is warranted.

Animals↗

The diffusion process of patient education in Dutch community pharmacy: an exploration.

Patient education activities in pharmacies are receiving much attention. These activities are relatively new and implementation requires individual and organisational change in pharmacies. The aim of this study is to identify barriers and facilitators to the implementation of patient education in community pharmacies and to classify these barriers and facilitators into the diffusion stages of Rogers' 'Innovations in Organisations' model [Rogers, EM. Diffusion of innovations. 4th ed. New York: The Free Press, 1995]. Six focus group interviews, three with pharmacists and three with pharmacy technicians (total n = 38) were carried out. The initiation phase has been dealt with by community pharmacies, whereas the implementation phase has not. The barriers and facilitators in the redefining/restructuring stage were mainly related to the organisation of patient education. In the clarifying and routinizing stages, barriers were related to repetition and knowledge transfer. The facilitators in these stages relate to performing and talking about patient education. Interventions for implementation of patient education should aim at these barriers and facilitating factors.

Community Pharmacy Services↗

Electrically facilitated molecular transport. Analysis of the relative contributions of diffusion, migration, and electroosmosis to solute transport in an ion-exchange membrane.

Electrically facilitated molecular transport in an ion-exchange membrane (Nafion, 1100 equiv wt) has been studied using a scanning electrochemical microscope. The transport rates of ferrocenylmethyltrimethylammonium (a cation), acetaminophen (a neutral molecule), and ascorbate (an anion) through approximately 120-micron-thick membranes were measured as a function of the iontophoretic current passed across the membrane (-1.0 to +1.0 A/cm2). Transport rates were analyzed by employing the Nernst-Planck equation, modified to account for electric field-driven convective transport. Excellent agreement between experimental and theoretical values of the molecular flux was obtained using a single fitting parameter for each molecule (electroosmotic drag coefficient). The electroosmotic velocity of the neutral molecule, acetaminophen, was shown to be a factor of approximately 500 larger than that of the cation ferrocenylmethyltrimethylammonium, a consequence of the electrostatic interaction of the cation with the negatively charged pore walls of the ion-exchange membrane. Electroosmotic transport of ascorbate occurred at a negligible rate due to repulsion of the anion by the cation-selective membrane. These results suggest that electroosmotic velocities of solute molecules are determined by specific chemical interactions of the permeant and membrane and may be very different from the average solution velocity. The efficiency of electroosmotic transport was also shown to be a function of the membrane thickness, in addition to membrane/solute interactions.

Acetaminophen↗

Long-chain fatty acid uptake is upregulated in omental adipocytes from patients undergoing bariatric surgery for obesity.

OBJECTIVE: To determine the impact of obesity on adipocyte cell size and long-chain fatty acid (LCFA) uptake kinetics in human subjects undergoing laparoscopic abdominal surgery. SUBJECTS: A total of 10 obese patients (BMI 49.8+/-11.9 (s.d.) kg/m(2)) undergoing laparoscopic bariatric surgery, and 10 nonobese subjects (BMI 24.2+/-2.3 kg/m(2)) undergoing other clinically indicated laparoscopic abdominal surgical procedures. MEASUREMENTS: Cell size distribution and [(3)H]oleic acid uptake kinetics were studied in adipocytes isolated from omental fat biopsies obtained during surgery. Adipocyte surface area (SA) was calculated from the measured cell diameters. Plasma leptin and insulin concentrations were measured by RIA in fasting blood samples obtained on the morning of surgery. RESULTS: The mean SA of obese adipocytes (41 508+/-5381 mu(2)/cell) was increased 2.4-fold compared to that of nonobese adipocytes (16 928+/-6529 mu(2)/cell; P<0.01). LCFA uptake in each group was the sum of saturable and nonsaturable components. Both the V(max) of the saturable component (21.3+/-6.3 vs 5.1+/-1.9 pmol/s/50,000 cells) and the rate constant k of the nonsaturable component (0.015+/-0.002 vs 0.0066+/-0.0023 ml/s/50 000 cells) were increased (P<0.001) in obese adipocytes compared with nonobese controls. When expressed relative to cell size, V(max)/mu(2) SA was greater in obese than nonobese adipocytes (P<0.05), whereas k/mu(2) SA did not differ between the groups. CONCLUSION: The data support the concepts that (1) adipocyte LCFA uptake consists of distinct facilitated (saturable) and diffusive processes; (2) increased saturable LCFA uptake in obese adipocytes is not simply a consequence of increased cell size, but rather reflects upregulation of a facilitated transport process; and (3) the permeability of adipocyte plasma membranes to LCFA is not appreciably altered by obesity, and increased nonsaturable uptake in obese adipocytes principally reflects an increase in cell SA. Regulation of saturable LCFA uptake by adipocytes may be an important control point for body adiposity.

Adipocytes↗

Inorganic arsenic methylation by rat tissue slices.

Rat liver, kidney and lung slices methylate trivalent inorganic arsenic (AsIII) to monomethylarsonic acid (MMA) and dimethylarsinic acid (DMA); the liver has the greatest methylating capacity. AsIII enters the liver cells by a diffusion process followed by extensive binding to intracellular components which favors its extensive accumulation inside the cells. Reduced glutathione regulates AsIII metabolism through several mechanisms: facilitation of AsIII diffusion into the cells, stimulation of the first methylation reaction and increase of DMA excretion by the cells. An excess of AsIII inhibits DMA production by liver cells but this inhibition is reversible; mercuric ions inhibit both MMA and DMA production probably by decreasing inorganic arsenic (Asi) uptake and the second methylation reaction. DMA can be produced from MMA by rat liver slices and this methylation step is stimulated by GSH. In contrast to AsIII, AsV is not extensively taken up by the hepatocyte and is thus poorly methylated.

Animals↗

Lipid metabolism in hepatic steatosis.

Hepatic steatosis is a consequence of both obesity and ethanol use. Nonalcoholic steatosis (NASH) resemble alcoholic steatosis and steatohepatitis. Both exhibit increased hepatocellular triglycerides(TG), reflecting an increase in long chain fatty acids (LCFA). LCFA enter cells by both facilitated transport and passive diffusion. A driving force for both is the plasma unbound LCFA concentration ([LCFAu]). In both obese rodents and obese patients, adipocyte LCFA uptake via both facilitated transport and diffusion is increased. However, the LCFA uptake Vmax in hepatocytes is not increased in obese animals. Nevertheless, total LCFA uptake in obese rodents is increased ~3-fold, reflecting increased plasma LCFA concentrations. With advancing obesity, resistance to the antilipolytic effects of insulin results in increased lipolysis within the omental fat depot, a consequent further rise in portal venous LCFA, and an even greater rise in portal [LCFAu]. This causes a further increase in hepatocellular LCFA uptake, increased intracellular generation of reactive oxygen species (ROS), and transition from simple steatosis to NASH. By contrast, in rodent hepatocytes and in human hepatoma cell lines, ethanol up-regulates the LCFA uptake Vmax. Consequently, although plasma LCFA are unaltered, hepatocellular LCFA uptake in ethanol-fed rats is also increased~3-fold, leading to increased ROS generation and evolution of alcoholic hepatitis. Thus, while increased hepatic LCFA uptake contributes to the pathogenesis of both NASH and alcoholic hepatitis,the underlying mechanisms differ. Recognizing these mechanistic differences is important in developing strategies for both prevention and treatment of these conditions.

Animals↗

Oxygen transport and the function of myoglobin. Theoretical model and experiments in chicken gizzard smooth muscle.

We studied the steady-state oxygen transfer across thin layers of respiring chicken gizzard smooth muscle and compared three models for oxygen consumption with respect to their influence on the facilitation of oxygen diffusion by myoglobin. These models assumed zero-order, Michaelis-Menten or exponential kinetics. The transport equation was solved for these models with simultaneous oxygen facilitation assuming chemical equilibrium between oxygen and myoglobin. Experimental flux data were obtained in two situations: a) high oxygen pressure throughout the layer of tissue providing maximum oxygen consumption and oxygen permeability, and b) anoxic conditions in part of the layer and with submaximal oxygen consumption and desaturation of myoglobin. Measurements in the presence of functional myoglobin were compared with data obtained after abolishing the transport function of myoglobin by application of 1 kPa carbon monoxide. It was found that oxygen consumption interferes with the facilitation effect. The oxygen pressure at half maximum oxygen consumption in the Michaelis-Menten model was 0.3 +/- 0.1 (S.E) kPa. The facilitation of the oxygen transport by myoglobin was 50 to 100% of the maximum value to be expected on the basis of the prevailing myoglobin concentration.

Amobarbital↗

Distribution of salicylate in pigmented rabbit ocular tissues after application of a prodrug, sodium monomethyl trisilanol orthohydroxybenzoate: in vivo and ex vivo studies.

SMB (sodium monomethyl trisilanol orthohydroxybenzoate) is an organic complex of silicium and salicylate and the main component of a collyrium used in lens transparency abnormalities. Biotransformation and penetration of salicylate in the whole eyeball have been investigated in vivo after repeated instillations of those 14C-radiolabeled eyedrops. We also studied more accurately the salicylate diffusion within the lens under ex vivo conditions. In vivo experiments demonstrated that 8 to 48 hours after the last instillation, radioactivity was detectable in most tissues and remained stable except in the chorioretina. The following gradient of distribution was observed: conjunctiva > cornea > iris-ciliary body > chorioretina > lens > vitreous body > aqueous humor >> plasma and blood. The diffusion of the radiolabeled compound in lens fibres was low, but a more important retention was observed in lens capsule. Though salicylate-metabolizing activities have been demonstrated in ocular tissues, no biotransformation could be detected under our experimental conditions. The lens SA-biotransformation activity was reported to be low and we can most probably consider that, in our ex vivo pharmacokinetic study, the lens metabolite amounts were negligible compared with the salicylate levels. Under such conditions, results showed that the salicylate reached a steady-state between 6 and 12 hours of incubation, characteristic of a passive diffusion mechanism. Quantitative image analysis of lens section autoradiograms revealed a more intense labeling of the anterior part of the lens and suggests that the lens epithelium may facilitate the salicylate diffusion. Furthermore, renal excretion is important since 40% of the administered eyedrops were eliminated during the study period.

Animals↗

The role of zinc ions in reverse transport mediated by monoamine transporters.

The human dopamine transporter (hDAT) contains an endogenous high affinity Zn2+ binding site with three coordinating residues on its extracellular face (His193, His375, and Glu396). Upon binding to this site, Zn2+ causes inhibition of [3H]1-methyl-4-phenylpyridinium ([3H]MPP+) uptake. We investigated the effect of Zn2+ on outward transport by superfusing hDAT-expressing HEK-293 cells preloaded with [3H]MPP+. Although Zn2+ inhibited uptake, Zn2+ facilitated [3H]MPP+ release induced by amphetamine, MPP+, or K+-induced depolarization specifically at hDAT but not at the human serotonin and the norepinephrine transporter (hNET). Mutation of the Zn2+ coordinating residue His(193) to Lys (the corresponding residue in hNET) eliminated the effect of Zn2+ on efflux. Conversely, the reciprocal mutation (K189H) conferred Zn2+ sensitivity to hNET. The intracellular [3H]MPP+ concentration was varied to generate saturation isotherms; these showed that Zn2+ increased V(max) for efflux (rather than K(M-Efflux-intracellular)). Thus, blockage of inward transport by Zn2+ is not due to a simple inhibition of the transporter turnover rate. The observations provide evidence against the model of facilitated exchange-diffusion and support the concept that inward and outward transport represent discrete operational modes of the transporter. In addition, they indicate a physiological role of Zn2+, because Zn2+ also facilitated transport reversal of DAT in rat striatal slices.

Amphetamines↗

Transfer of urea, sodium, and chloride across the perfused human placenta.

Clearance indices (clearance of experimental material: clearance of antipyrine, CI) across the perfused human placenta were determined for urea, sodium, and chloride. The selected materials are of relatively small molecular weight and are water soluble. Clearance of urea was determined under conditions of net transfer and of exchange and no difference was detected. Sodium and chloride clearances were measured as exchange rates. The CI were: urea, 0.32 and 0.38 toward fetus and mother, respectively); sodium, 0.28; and chloride, 0.41 (measured toward the fetus). Recalculation of data as the diffusion limitation (LD) facilitated comparison with data in the literature on the monkey, rabbit, and sheep. LD for urea was comparable among the four species whereas the sheep placenta differed, sharply limiting the diffusion of sodium and chloride. The discrepancy in the sheep between urea and sodium indicates that the low transfer rate of the latter cannot be explained by the "thickness" of the syndesmochorial placenta, as is often stated. Inferences concerning nitrogen metabolism in the fetus have been derived by others from data on transplacental urea gradients and urea clearance. Available data in the human are incomplete but are consistent with amino acids providing approximately 10% of fetal energy needs, with glucose serving as the predominant substrate.

Animals↗

Molecular mechanisms of hepatic bile salt transport from sinusoidal blood into bile.

An increasingly complex picture has emerged in recent years regarding the bile salt transport polarity of hepatocytes. At the sinusoidal (or basolateral) plasma membrane two bile salt-transporting polypeptides have been cloned. The Na(+)-taurocholate-cotransporting polypeptide (Ntcp) can account for most, if not all, physiological properties of the Na(+)-dependent bile salt uptake function in mammalian hepatocytes. The cloned organic anion-transporting protein (Oatp1) can mediate Na(+)-independent transport of bile salts, sulfobromophthalein, estrogen conjugates, and a variety of other amphipathic cholephilic compounds. Hence, Oatp1 appears to correspond to the previously suggested basolateral multispecific bile sale transporter. Intracellular bile salt transport can be mediated by different pathways. Under basal bile salt flux conditions, conjugated trihydroxy bile salts bind to cytoplasmic binding proteins and reach the canalicular plasma membrane predominantly via cytoplasmic diffusion. More hydrophobic mono- and dihydroxy and high concentrations of trihydroxy bile salts associate with intracellular membrane-bound compartments, including transcytotic vesicles, endoplasmic reticulum (ER), and Golgi complex. A facilitated bile salt diffusion pathway has been demonstrated in the ER. The exact role of these and other (e.g., lysosomes, "tubulovesicular structures") organelles in overall vectorial transport of bile salts across hepatocytes is not yet known. Canalicular bile salt secretion is mediated by two ATP-dependent transport systems, one for monovalent bile salts and the second for divalent sulfated or glucuronidated bile salt conjugates. The latter is identical with the canalicular multispecific organic anion transporter, which also transports other divalent organic anions, such as glutathione S-conjugates. Potential dependent canalicular bile salt secretion has also been suggested to occur, but its exact mechanism and physiological significance remain unclear, since a potential driven bile salt uptake system has also been identified in the ER. Hypothetically, and similar to changes in cell volume, the intracellular potential could also play a role in the regulation of the number of bile salt carriers at the canalicular membrane and thereby indirectly influence the maximal canalicular bile salt transport capacity of hepatocytes.

Animals↗