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PubMed1994

Corticosteroids as adjunctive therapy for diffuse alveolar hemorrhage associated with bone marrow transplantation. University of Nebraska Medical Center Bone Marrow Transplant Group.

BACKGROUND: Diffuse alveolar hemorrhage is a frequent complication of treating malignancies with high-dose chemotherapy and bone marrow transplantation and is associated with very high mortality. This disorder's association with pulmonary inflammation, its coincidence with marrow recovery, and the usefulness of corticosteroids for treating other pulmonary hemorrhage syndromes provided the rationale for this study. METHODS: We retrospectively studied 65 episodes of diffuse alveolar hemorrhage that has occurred in 63 of 603 consecutively treated patients who had undergone high-dose chemotherapy with bone marrow transplantation. Patients were divided into three groups according to the therapy they had received for diffuse alveolar hemorrhage: supportive therapy alone (n = 12); low-dose corticosteroids (30 mg or less of methylprednisolone or its equivalent; n = 10); and high-dose corticosteroids (more than 30 mg methylprednisolone or its equivalent; n = 43). The primary outcome measures were overall survival and survival to hospital discharge, occurrence of respiratory failure requiring intubation, and development of infections subsequent to the diagnosis of diffuse alveolar hemorrhage. RESULTS: Overall survival at the end of the follow-up period was significantly higher for the high-dose corticosteroid group compared with the supportive therapy group (P = 0.005); however, treatment with low-dose steroids did not increase survival over supportive therapy alone (P = 0.198). In addition, survival to discharge was significantly increased for the high-dose group compared with the other two groups combined (33% versus 9.1%, P = 0.038). Respiratory failure after the diagnosis of diffuse alveolar hemorrhage developed in only 12 of the 22 unintubated patients in the high-dose group compared with 9 of the 10 initially unintubated patients in the other two groups (P = 0.056). Although the incidence of infections was high (40%) subsequent to diffuse alveolar hemorrhage, neither high-dose nor low-dose corticosteroid treatment significantly increased the risk of infections (P > 0.4, all comparisons). CONCLUSIONS: In this study, high-dose corticosteroid therapy for diffuse alveolar hemorrhage related to bone marrow transplantation was associated with improved total survival and survival to hospital discharge, and decreased development of respiratory failure in these patients. These results suggest the therapy is beneficial, and further prospective studies are warranted to verify the effectiveness of the treatment.

Adult↗

PubMed1988

Effects of square-wave gratings and diffuse light on metabolic activity in the rat visual system.

The 2-deoxyglucose (2-DG) technique was used to determine the effects of pattern and diffuse light stimulation on glucose metabolism with hooded rats. Rats placed in a stimulation chamber covered with horizontal and vertical square wave gratings while wearing goggles with one of three pairings of light-occluding, diffusing, or clear lenses, allowed the assessment of the effects of different but simultaneous visual conditions on two sides of the strongly crossed visual system. Eyes covered with occluding lenses were lid-sutured shut 24 h before 2-DG. In order to assess the possibly confounding effects of this lid suture a second group of rats had one eyelid sutured for 24 h, and the other covered with an occluding lens for 20 min, before 2-DG. To further assess the effects of diffuse light a third group of rats was tested in a featureless white box with one eye occluded and the other covered by a diffusing lens. Exposure to pattern stimulation significantly increased metabolic activity in the dorsal lateral geniculate nucleus (LGNd), lateral posterior nucleus (LPN), superior colliculus (SC), and in visual cortex (VC). In contrast, diffuse light only slightly elevated LGNd activity and appeared to have little or no effect in the LPN or VC. Diffuse light, however, was as effective as patterned light in increasing ventral lateral geniculate nucleus activity and strongly suppressed SC activity to a level well below that produced by darkness. Evidently diffuse light, not just patterned light, can significantly govern the operation of central nervous system visual structures.

Animals↗

PubMed1992

In vivo magnetic resonance diffusion measurement in the brain of patients with multiple sclerosis.

Measurement of water self-diffusion in the brain in 25 patients with multiple sclerosis was performed by magnetic resonance imaging. Quantitative diffusion measurements were obtained using single spin-echo pulse sequences with pulsed magnetic field gradients of different magnitude. Twenty-two of these patients also underwent measurement of the transverse relaxation time (T2). Only one plaque was evaluated in each patient. Based on prior knowledge, 12 plaques were classified as being 3 mo or less in age, and 7 plaques were classified as being more than 3 mo old. In all 25 plaques, water self-diffusion was found to be higher than in apparently normal white matter. Furthermore, water self-diffusion was found to be higher in acute plaques compared with chronic plaques. Finally, a slight tendency toward a relationship between the diffusion capability and T2 was found. We believe that an increased diffusion capability signifies an increase of the extracellular water space, which probably is related to the degree of demyelination. Thus, measurement of water self-diffusion in multiple sclerosis plaques may contribute to the study of pathogenesis of demyelination.

Adult↗

PubMed2004

Effect of pH and concentration on the diffusion of radiostrontium in compacted bentonite--a capillary experimental study.

The effects of pH and Sr2+ solution concentration on diffusion and sorption of Sr2+ in compacted bentonite (rhob = 1000+/-30 kg/m3) were studied using an "in-diffusion" method at an ionic strength of 0.1M NaClO4. The results (distribution coefficients, Kd, apparent and effective diffusion coefficients, Da and De) derived from the capillary method are in good agreement with the literature data obtained for similar bentonite dry densities and fit Fick's second law very well. The results suggest that the diffusion of Sr2+ in compacted bentonite decreases slightly with increasing pH values and also increases slightly with increasing Sr2+ solution concentration. The distribution coefficients are weakly dependent on the solution concentrations and show a slight increase with increasing pH values. The average effective diffusion coefficient of Sr2+ in compacted bentonite is (1.2+/-0.2) x 10(-9) m2/s, surface diffusion effects are found for the diffusion of Sr2+ in compacted bentonite.

Journal Article↗

PubMed2004

A barrier to lateral diffusion in the cleavage furrow of dividing mammalian cells.

Barriers to diffusion of proteins and lipids play an important role in generating functionally specialized regions of the plasma membrane. Such barriers have been reported at the base of axons, at the bud neck in Saccharomyces cerevisiae, as well as at the tight junctions of epithelia. How diffusion barriers are formed and how they effect behavior of both inner and outer leaflets of the bilayer are not fully understood. Here, we provide evidence for a cortical barrier to diffusion within the cleavage furrow of mammalian cells. Photobleaching-based assays were used to measure diffusion of three membrane proteins with differing topologies and putative lipid raft association, as well as the lipid analog dialkylindocarbocyanine (DiI C18, ), across the cleavage furrow. There was a block in diffusion of proteins with a cytosolic domain, but not of proteins anchored in the outer leaflet of the PM or of DiI. Diffusion of lipid raft proteins in the inner and outer leaflets of the membrane was not directly coupled. The distribution of Septin proteins, as opposed to cortical actin, was consistent with a functional role in limiting diffusion.

Biological Transport↗

PubMed2005

Sorption kinetics of strontium in porous hydrous ferric oxide aggregates I. The Donnan diffusion model.

Sorption of ions by hydrous ferric oxide (HFO) often shows a fast initial sorption reaction followed by a much slower sorption process. The second step is diffusion-controlled and can continue for days or months before equilibrium is reached. In this paper, we demonstrate that the diffusion rate may be explained by electrostatic interactions. The internal and external surfaces of HFO are generally positively charged and therefore repel cations. This can result in extremely low cation concentrations in pores, and therefore a significant reduction in pore diffusion rate. The theory is demonstrated here for sorption of Sr(2+) in HFO aggregates. The ion concentrations in the pore space are calculated using a Donnan model and diffusion is calculated from the Donnan concentration and potential gradients. This diffusion model is compared with nonelectrostatic pore diffusion, which does not take electrostatic interactions into account. The Donnan model predicts very low concentrations of Sr(2+) in the pores and diffusion rates that are up to 8000 times lower than predicted with a nonelectrostatic model.

Journal Article↗

PubMed2006

Effect of impermeable boundaries on diffusion-attenuated MR signal.

The nonlinear dependence between the logarithm of the diffusion weighted signal, lnS, and the b-value, b, has often been interpreted as a manifestation of two physically distinct compartments, resulting in a biexponential form of the signal. This model fits to experimental data, however, has failed to yield realistic compartment sizes, severely jeopardizing the use of DWI to infer structural information on a cellular level. It has been hypothesized that the biexponential behavior can be attributed to the effect of confining boundaries that restrict diffusion in individual physical compartments. This interpretation is based on the analysis of diffusion in the presence of impermeable interfaces for short diffusion times such that the layer in which diffusion is affected by the boundary is thin as compared with the dimensions of the whole compartment. This model system is analyzed from the point of view of the cumulant expansion of the diffusion-weighted signal that results in a Taylor expansion of lnS in powers of b. Termination of this expansion to a polynomial form provides an excellent accuracy for small b-factors, but the series diverges for large b. The convergence of the series is studied, yielding a large range of b-values in which the absolute error of terminating the series at the second term remains smaller than 1% relative to the signal magnitude without diffusion weighting. With this accuracy, the signal in the studied model can be described as lnS approximately -A.bD+B.(bD)2, where the parameters A and B can be expressed in terms of correlation functions of molecular velocity. Fitting of these parameters to the exact signal is more stable than for the three parameters of the biexponential function. This description fails for large b, for which the cumulant expansion diverges. The signal at even larger b-values is proportional to 1/b, 1/b3/2, and 1/b2 in one-, two-, and three-dimensional systems, respectively.

Journal Article↗

PubMed2004

The pathobiology of moderate diffuse traumatic brain injury as identified using a new experimental model of injury in rats.

Experimental models of traumatic brain injury have been developed to replicate selected aspects of human head injury, such as contusion, concussion, and/or diffuse axonal injury. Although diffuse axonal injury is a major feature of clinical head injury, relatively few experimental models of diffuse traumatic brain injury (TBI) have been developed, particularly in smaller animals such as rodents. Here, we describe the pathophysiological consequences of moderate diffuse TBI in rats generated by a newly developed, highly controlled, and reproducible model. This model of TBI caused brain edema beginning 20 min after injury and peaking at 24 h post-trauma, as shown by wet weight/dry weight ratios and diffusion-weighted magnetic resonance imaging. Increased permeability of the blood-brain barrier was present up to 4 h post-injury as evaluated using Evans blue dye. Phosphorus magnetic resonance spectroscopy showed significant declines in brain-free magnesium concentration and reduced cytosolic phosphorylation potential at 4 h post-injury. Diffuse axonal damage was demonstrated using manganese-enhanced magnetic resonance imaging, and intracerebral injection of a fluorescent vital dye (Fluoro-Ruby) at 24-h and 7-day post-injury. Morphological evidence of apoptosis and caspase-3 activation were also found in the cerebral hemisphere and brainstem at 24 h after trauma. These results show that this model is capable of reproducing major biochemical and neurological changes of diffuse clinical TBI.

Animals↗

PubMed2006

Modeling dendrite density from magnetic resonance diffusion measurements.

Diffusion-weighted imaging (DWI) provides a noninvasive tool to probe tissue microstructure. We propose a simplified model of neural cytoarchitecture intended to capture the essential features important for water diffusion as measured by NMR. Two components contribute to the NMR signal in this model: (i) the dendrites and axons, which are modeled as long cylinders with two diffusion coefficients, parallel (D(L)) and perpendicular (D(T)) to the cylindrical axis, and (ii) an isotropic monoexponential diffusion component describing water diffusion within and across all other structures, i.e., in extracellular space and glia cells. The model parameters are estimated from 153 diffusion-weighted images acquired from a formalin-fixed baboon brain. A close correspondence between the data and the signal model is found, with the model parameters consistent with literature values. The model provides an estimate of dendrite density from noninvasive MR diffusion measurements, a parameter likely to be of value for understanding normal as well as abnormal brain development and function.

Computer Simulation↗

PubMed2005

Diffuse expression of laminin gamma2 chain in disseminating and infiltrating cancer cells indicates a highly malignant state in advanced tongue cancer.

The expression of laminin (LN)gamma2 chain in the primary lesions of 20 patients with advanced tongue cancer was analyzed. Positive expressions of LNgamma2 were noted in all of the primary tissue specimens, however, the expression patterns clearly differed according to the mode of growth and invasion of cancer cells. In tumor nests where cancer cells preserved cell-cell adhesiveness and showed polar differentiation, LNgamma2 was expressed only in the peripheral cells of the tumor nests; peripheral expression. On the other hands when cancer cells diminished their cell-cell adhesiveness and strongly infiltrated through stroma, almost all of the cancer cells diffusely expressed LNgamma2; diffuse expression. The peripheral expression of LNgamma2 were noted in 13 patients and the diffuse expressions were noted in 7 patients. The rates of positive cervical metastases according to the expression type were 7/13 for the peripheral expression and 7/7 for the diffuse expression (p = 0.02). The diseases specific 3-year survival rates for the patients with the peripheral expression and the diffuse expression were 68% and 14%, respectively (p = 0.02). The diffuse expression of LNgamma2 in the disseminating and infiltrating cancer cells might indicate a highly malignant state in advanced tongue cancer. Therefore, a more intensive treatment modality would be necessary for the patients with advanced tongue cancer showing the diffuse LNgamma2 expression.

Adult↗

PubMed1990

Lateral diffusivity of lipid analogue excimeric probes in dimyristoylphosphatidylcholine bilayers.

The lateral mobility of pyrenyl phospholipid probes in dimyristoylphosphatidylcholine (DMPC) vesicles was determined from the dependence of the pyrene monomeric and excimeric fluorescence yields on the molar probe ratio. The analysis of the experimental data makes use of the milling crowd model for two-dimensional diffusivity and the computer simulated random walks of probes in an array of lipids. The fluorescence yields for 1-palmitoyl-2-(1'-pyrenedecanoyl)phosphatidylcholine (py10PC) in DMPC bilayers are well fitted by the model both below and above the fluid-gel phase transition temperature (Tc) and permit the evaluation of the probe diffusion rate (f), which is the frequency with which probes take random steps of length L, the host membrane lipid-lipid spacing. The lateral diffusion coefficient is then obtained from the relationship D = fL2/4. In passing through the fluid-gel phase transition of DMPC (Tc = 24 degrees C), the lateral mobility of py10PC determined in this way decrease only moderately, while D measured by fluorescence photobleaching recovery (FPR) experiments is lowered by two or more orders of magnitude in gel phase. This difference in gel phase diffusivities is discussed and considered to be related either to (a) the diffusion length in FPR experiments being about a micrometer or over 100 times greater than that of excimeric probes (approximately 1 nm), or (b) to nonrandomicity in the distribution of the pyrenyl probes in gel phase DMPC. At 35 degrees C, in fluid DMPC vesicles, the diffusion rate is f = 1.8 x 10(8) s-1, corresponding to D = 29 microns2 s-1, which is about three times larger than the value obtained in FPR experiments. The activation energy for lateral diffusion in fluid DMPC was determined to be 8.0 kcal/mol.

Dimyristoylphosphatidylcholine↗

PubMed1992

Cytoplasmic hydrogen ion diffusion coefficient.

The apparent cytoplasmic proton diffusion coefficient was measured using pH electrodes and samples of cytoplasm extracted from the giant neuron of a marine invertebrate. By suddenly changing the pH at one surface of the sample and recording the relaxation of pH within the sample, an apparent diffusion coefficient of 1.4 +/- 0.5 x 10(-6) cm2/s (N = 7) was measured in the acidic or neutral range of pH (6.0-7.2). This value is approximately 5x lower than the diffusion coefficient of the mobile pH buffers (approximately 8 x 10(-6) cm2/s) and approximately 68x lower than the diffusion coefficient of the hydronium ion (93 x 10(-6) cm2/s). A mobile pH buffer (approximately 15% of the buffering power) and an immobile buffer (approximately 85% of the buffering power) could quantitatively account for the results at acidic or neutral pH. At alkaline pH (8.2-8.6), the apparent proton diffusion coefficient increased to 4.1 +/- 0.8 x 10(-6) cm2/s (N = 7). This larger diffusion coefficient at alkaline pH could be explained quantitatively by the enhanced buffering power of the mobile amino acids. Under the conditions of these experiments, it is unlikely that hydroxide movement influences the apparent hydrogen ion diffusion coefficient.

Animals↗

PubMed1994

MR diffusion tensor spectroscopy and imaging.

This paper describes a new NMR imaging modality--MR diffusion tensor imaging. It consists of estimating an effective diffusion tensor, Deff, within a voxel, and then displaying useful quantities derived from it. We show how the phenomenon of anisotropic diffusion of water (or metabolites) in anisotropic tissues, measured noninvasively by these NMR methods, is exploited to determine fiber tract orientation and mean particle displacements. Once Deff is estimated from a series of NMR pulsed-gradient, spin-echo experiments, a tissue's three orthotropic axes can be determined. They coincide with the eigenvectors of Deff, while the effective diffusivities along these orthotropic directions are the eigenvalues of Deff. Diffusion ellipsoids, constructed in each voxel from Deff, depict both these orthotropic axes and the mean diffusion distances in these directions. Moreover, the three scalar invariants of Deff, which are independent of the tissue's orientation in the laboratory frame of reference, reveal useful information about molecular mobility reflective of local microstructure and anatomy. Inherently tensors (like Deff) describing transport processes in anisotropic media contain new information within a macroscopic voxel that scalars (such as the apparent diffusivity, proton density, T1, and T2) do not.

Animals↗

PubMed1998

Light diffusion in photosensitive epilepsy.

Photosensitivity is usually tested by intermittent photic stimulation. Photoparoxysmal responses in the EEG are enhanced when the eyes remain closed during stimulation. We tested the hypothesis that this is due to diffusion of light by the eyelids. In 25 photosensitive patients, conditions 'eye closure', 'eyes closed', 'eyes open' and 'eyes open with diffuser' were tested for frequencies of 2-60 Hz. Additional influences of a red filter and fixation were also examined. The photosensitivity range was maximal in the condition 'eyes open with diffuser', due to an increase of the upper limit to a median 60 Hz (range 25-60), from 35 (15-50) Hz with eyes open, 37.5 (25-60) Hz with eyes closed and 40 (23-60) Hz with eye closure (P = 0.0002). This effect was attenuated in patients on valproic acid and with the use of a red or white filter. Testing with a diffuser was more sensitive than without, except for one patient who was photosensitive only in the eye closure condition. The influence of the eyelids on photosensitivity can be explained by diffusion of light, attentuated by an intensity loss. Use of a diffuser may simplify testing for photosensitivity in the EEG laboratory. The diffusion effect may explain seizure susceptibility in front of 50 and 60 Hz television screens.

Adolescent↗

PubMed2003

Diffuse perineuronal nets and modified pyramidal cells immunoreactive for glutamate and the GABA(A) receptor alpha1 subunit form a unique entity in rat cerebral cortex.

Perineuronal nets (PNs) consisting of polyanionic chondroitin sulfate proteoglycans (CSPG) and other extracellular matrix components create an exceptional microenvironment around certain types of neurons. In rat neocortex, three types of PNs can be distinguished after staining with Wisteria floribunda agglutinin (WFA) by their different morphological structure: lattice-like PNs associated with subpopulations of nonpyramidal neurons, weakly labeled PNs showing a pyramidal morphology, and diffuse PNs that possess a thick, strongly labeled matrix sheath located mainly in layer VIb above the white matter. The type of neuron surrounded by diffuse nets has not been described so far. This study is focused on the cytochemical and morphological characteristics of neurons associated with diffusely contoured PNs in rat parietal cortex using immunocytochemical staining, intracellular injection, and retrograde tracing methods. Cells surrounded by diffuse PNs were glutamate-immunoreactive in contrast to nonpyramidal, net-associated neurons that showed immunoreactivity for GABA, the calcium-binding protein parvalbumin and the potassium channel subunit Kv3.1b. Both groups of PN-ensheathed cells were mostly immunoreactive for the GABA(A) receptor alpha1 subunit. Lucifer Yellow-injected neurons surrounded by diffuse PNs displayed the morphological properties of modified pyramidal cells with intracortical main axons. Many neurons with diffuse PNs were retrogradely labeled over a long distance after Fluoro-Gold tracer injection in the parietal cortex, but remained unlabeled after intrathalamic injection. We conclude that neurons associated with diffuse PNs are a subpopulation of glutamatergic modified pyramidal cells that could act as excitatory long-range intracortically projecting neurons.

Animals↗

PubMed1999

Early detection of periventricular leukomalacia by diffusion-weighted magnetic resonance imaging techniques.

Periventricular leukomalacia (PVL), the principal form of brain injury in the premature infant, is characterized by overt focal necrotic lesions in periventricular white matter and less prominent, more diffuse cerebral white matter injury. The early detection of the latter, diffuse component of PVL is not consistently possible with conventional brain imaging techniques. We demonstrate the early detection of the diffuse component of PVL by diffusion-weighted magnetic resonance imaging (DWI). In a premature infant with no definite cerebral abnormality detectable by cranial ultrasonography or conventional magnetic resonance imaging, DWI showed a striking bilateral decrease in water diffusion in cerebral white matter. The DWI abnormality (ie, decreased apparent diffusion coefficient) was similar to that observed with acute cerebral ischemic lesions in adults. At 10 weeks of age, conventional magnetic resonance imaging and ultrasonography showed striking changes consistent with PVL, including the presence of small cysts. The observations indicate the importance of DWI in the early identification of the diffuse component of PVL and also perhaps the role of ischemia in the pathogenesis of the lesion.

Female↗

PubMed1998

New acrylic resin composite with improved thermal diffusivity.

STATEMENT OF PROBLEM: Studies have shown that physical characteristics of denture base materials may affect patient acceptance of denture prostheses by altering sensory experience of food during mastication. Thermal diffusivity is one material property that has been cited as being important in determining gustatory response, with denture base acrylic resins having low thermal diffusivity compared with denture base metal alloys. PURPOSE: This study prepared and characterized experimental acrylic resin composite material with increased thermal diffusivity. MATERIAL AND METHODS: Sapphire (Al2O3) whiskers were added to conventional denture base acrylic resin during processing to achieve loadings of 9.35% and 15% by volume. Cylindrical test specimens containing an embedded thermocouple were used to determine thermal diffusivity over a physiologic temperature range (0 degree to 70 degrees C). RESULTS: Thermal diffusivities of the sapphire containing composites were found to be significantly higher than the unmodified acrylic resin. Thermal diffusivity was found to increase in proportion to the volume percentage of sapphire filler, which suggested that the high aspect ratio ceramic particles formed a pathway for heat conduction through the insulating polymer matrix. CONCLUSION: The thermal diffusivity of denture base acrylic resin was increased by the addition of thermally conducting sapphire whiskers.

Acrylic Resins↗

PubMed1999

Intermittent rhythmic delta activity (IRDA) morphology cannot distinguish between focal and diffuse brain disturbances.

IRDA (intermittent rhythmic delta activity) is an abnormal generalized EEG pattern that is not specific to any single etiology and can occur with diffuse or focal cerebral disturbances. To determine whether different electrographic features of IRDA and associated EEG findings can differentiate underlying focal from diffuse brain disturbances, we performed a blind analysis of 58 consecutive EEGs with an IRDA pattern, recorded from 1993 until 1996, in which we evaluated posterior background activity, focal slowing and IRDA characteristics (frequency, distribution, duration, symmetry and abundance). The clinical diagnosis, state of consciousness and CT brain findings were retrieved from the patients' hospital records. There were 58 patients (33 females; mean age, 58+/-21 years). Twelve (21%) had only focal brain lesions, while 46 (79%) had diffuse brain abnormalities, (15 diffuse structural, 19 metabolic abnormalities, 12 postictal). Normal consciousness and focal EEG slowing were more frequent in patients with focal abnormalities, however, this was not statistically significant. Of the patients with focal abnormality, 11 (92%) had normal posterior background activity either bilaterally (n=4) or contralateral to the focal lesion (n=7). Bilaterally normal posterior background activity was observed in about 30% in both groups. Bilaterally abnormal posterior background activity was apparent in one patient (8%) with focal brain lesion and in 31 patients (67%) with diffuse brain abnormalities (P<0.0001). There were no significant differences in IRDA electrographic features between the focal group and the group with diffuse brain disturbances. We conclude that IRDA morphology cannot distinguish between focal and diffuse brain abnormalities.

Adolescent↗