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PubMed2006

AIDS and non-AIDS diffuse large B-cell lymphomas express different antigen profiles.

Based on gene expression profiling, diffuse large B-cell lymphomas arising in immunocompetent patients can be divided into germinal center and activated B-cell types. Since little is known about acquired immunodeficiency syndrome associated diffuse large B-cell lymphomas, we tested whether the protein expression of germinal center and activated B-cell markers differed between acquired immunodeficiency syndrome (AIDS) vs non-AIDS diffuse large B-cell lymphomas. We immunohistochemically stained tissue microarrays of 39 de novo diffuse large B-cell lymphomas: 12 AIDS associated and 27 non-AIDS, with germinal center (BCL6, CD10, CyclinH) and activated B-cell markers (MUM1, CD138, PAK1, CD44, BCL2). We scored each case for percent positive cells (0-19%=0; 20-49%=1; 50-100%=2). The activated B-cell and germinal center summation scores of each case were used as (x, y) coordinate data points to construct two-dimensional contour-frequency plots. The contour plot of non-AIDS diffuse large B-cell lymphomas showed two distinct clusters: a cluster with a high germinal center phenotype (cluster 1) and a cluster with a high activated B-cell phenotype (cluster 3). In contrast, the AIDS-related diffuse large B-cell lymphomas formed a single aggregate (cluster 2) (P=0.02, Fisher exact test). When the contour plots of the AIDS-related and the non-AIDS cases were superimposed, cluster 2 of the AIDS cases expressed an intermediate germinal center/activated B-cell phenotype compared to clusters 1 and 3 of the non-AIDS diffuse large B-cell lymphomas. Our results confirm that non-AIDS diffuse large B-cell lymphomas segregate into two groups with either germinal center or activated B-cell phenotype. We report the new finding that the AIDS status of the patient predicts the immunophenotype of the diffuse large B-cell lymphomas.

Adult↗

PubMed2006

High throughput tissue microarray analysis of FHIT expression in diffuse large cell B-cell lymphoma from Saudi Arabia.

Recent studies have suggested a potential prognostic role of alterations of the fragile histidine triad (FHIT) gene in diffuse large B-cell lymphoma. To evaluate possible mechanisms of FHIT inactivation and to further clarify its potential prognostic relevance, we analyzed a set of 114 diffuse large B-cell lymphoma with clinical follow-up information. Tissue microarrays were analyzed by immunohistochemistry for protein expression, and corresponding DNA samples were analyzed for FHIT promotor hypermethlyation. Reduced or absent FHIT expression was found in 75 of 114 diffuse large B-cell lymphoma (66%), but was unrelated to clinical tumor stage or patient prognosis. FHIT promotor hypermethylation was observed in 29 of 93 (23%) interpretable diffuse large B-cell lymphoma. Hypermethylation was not significantly correlated to protein expression loss, which could be explained by competing mechanisms for FHIT inactivation in a substantial fraction of non FHIT hypermethylated diffuse large B-cell lymphoma. Hypermethylation was significantly associated with poor prognosis of diffuse large B-cell lymphoma patients and predominantly seen in nongerminal center diffuse large B-cell lymphoma (27%), but less frequent (13%) in germinal center diffuse large B-cell lymphoma. In summary, these data suggest that promotor hypermethylation is responsible for reduced FHIT expression in a substantial subset of diffuse large B-cell lymphoma, which is primarily composed of nongerminal center subtype with poor patient prognosis.

Acid Anhydride Hydrolases↗

PubMed1997

[Diffusion-weighted MR tomography in focal cerebral ischemia: possibilities offered by a 1.0 Tesla clinical device].

PURPOSE: To develop and to implement a fast, highly diffusion-weighted MR-sequence on a conventional 1 T MR scanner and to examine this sequence as to its capability of characterising tissue damage due to focal cerebral ischaemia. METHODS: Within a CE-FAST-sequence diffusion gradients were inserted in all gradient directions. By phantom measurements the maximal diffusion weighting was determined for different T1 and T2 values and flip angles. The optimised sequence was used for monitoring the diffusion of focal cerebral ischaemia in 14 rats following endovascular occlusion of the middle cerebral artery. RESULTS: The ischaemic lesion could be easily visualised as a bright area in the images with high diffusion weighting. The mean relative decrease of the diffusion coefficient in the ischaemic brain parenchyma was 29%. The diffusion coefficient, decreased significantly with increasing occlusion time. CONCLUSION: Our study suggests that the installed sequence is capable of producing highly diffusion weighted images without requiring a special gradient system. The sequence is potentially useful for monitoring cerebral ischaemia on the basis of calculating the change of the diffusion coefficient.

Animals↗

PubMed1964

CAT HEART MUSCLE IN VITRO. V. DIFFUSION THROUGH A SHEET OF RIGHT VENTRICLE.

The rate of transfer of labeled molecules across a sheet of quiescent cat right ventricle separating two chambers containing chemically identical solutions was followed at 23 degrees C. For the diffusion of sucrose, SO(4), and Na the experimental points fit the entire time course of the plot of the diffusion equation for a plane sheet. The tortuosity factor of the extracellular diffusion channel, lambda was 1.44 +/- 0.05 (mean +/- SEM) for sucrose and similar for SO(4) and Na. The fractional area available for extracellular diffusion, calculated from lambda and the slope of the linear asymptote approached during steady state diffusion, was 0.17-0.23 for both impermeant species (sucrose, SO(4), Na) and permeant species (water, urea, glycerol). Permeant molecules showed a characteristic prolongation of the approach to the steady state, with an unexplained "hump" in the curve for water. The observed time courses for diffusion of permeant molecules are interpreted in terms of a model proposed by Fatt et al. for diffusion through linear porous media containing dead-end pore volume. Large molecules like inulin and dialyzed dextran (diameter 150 to 180 A) diffuse through the sheet. These molecules may have a reflection coefficient sigma > 0. The fraction of muscle water occupied by the sucrose diffusion channel is significantly smaller than the 3 hr. mannitol, sucrose, and inulin spaces.

Biological Transport↗

PubMed1974

Ion diffusion selectivity in lecithin-water lamellar phases.

The diffusion coefficients of Na(+), Rb(+), and cl(-) were determined in lecithin-water lamellar phases at 18 degrees C as a function of phase hydration. Diffusion was measured within the phase with no transfer between phase and bulk aqueous medium. The relative diffusion coefficients of anion and cation depended strongly on phase hydration. At low water content, the diffusion coefficient of Cl(-) was greater than that of Na(+) or Rb(+) whereas at high water content both cations diffused faster than the anion. The change in relative diffusion coefficient occurred at 0.24 g water/g phase (24% water). The possibility that a change in conformation of the lecithin polar head occurs at a phase water content of 24% is considered. The diffusion coefficients of all three ions decreased at the water content where the relative diffusion rates inverted. Freeze fracture and polarizing microscopy studies were carried out to obtain information on phase structure. The latter study indicated that a change in long-range organization of the phase occured at 24% water. This change accounts for the decrease in the ion diffusion coefficients at this water content. The change in conformation of the choline phosphate group proposed as an explanation for the change in ion selectivity could lead to changes in long-range organization of the phase as a second order-effect.

Chlorides↗

PubMed2001

Diffusion tensor imaging in patients with epilepsy and malformations of cortical development.

Malformations of cortical development (MCD) are a common cause of epilepsy. Studies of structural MRIs and PET data in patients with MCD have found widespread changes outside the visually identified lesions. The aim of this study was to investigate diffusion changes interictally in patients with MCD and to test the hypothesis that MCD would be associated with widespread abnormalities of diffusion. We used diffusion tensor imaging (DTI) and statistical parametric mapping (SPM) to compare objectively tissue organization in 22 patients with partial seizures and MCD, with 30 control subjects. Whole-brain DTI was acquired using echo planar imaging. Rotationally invariant anisotropy and diffusivity maps were calculated and, after normalization to Talairach space, each patient was compared with the group of control subjects using SPM. Areas of reduced anisotropy were found in 17 patients and areas of increased diffusivity in 10. Two patients had areas of increased anisotropy. There were no patients with reduced diffusivity. Areas of increased diffusivity were in general more extensive than areas of reduced anisotropy. Changes in tissue beyond the MCD, that appeared normal on conventional MRI, were found in six patients for anisotropy and nine patients for diffusivity. Both measurements showed widespread changes in tissue beyond the MCD, i.e. adding information to conventional MRI. Increased or abnormally located grey matter or pathological white matter with abnormal myelination or ectopic neurones could cause reduced anisotropy. Increased diffusivity could be caused by a defect of neurogenesis or cell loss resulting in increased extracellular space. The widespread nature of abnormalities should be considered if surgical treatment is contemplated.

Adult↗

PubMed2003

Radon transport through concrete and determination of its diffusion coefficient.

The diffusion transport of radon was simulated for different types of concrete, by varying the parameters of concrete. The time t(s), needed to achieve a steady state, was determined for different diffusion constants. The graphical dependence of t(s) relative to the diffusion constant, called the diffusion curve has been calculated. By comparing the experimentally obtained values for t(s) and the diffusion curve, the diffusion constants were determined for the most frequently used type of concrete in our country. The diffusion coefficient determined for this type of concrete is in the range of data for various types of concrete found in the literature. The method described and applied here could be used to determine the diffusion coefficient for each type of concrete. Knowledge of the diffusion coefficient could enable estimation of the radon flux density into the building.

Air Pollution, Indoor↗

PubMed2001

Magnetic resonance imaging measurement of relaxation and water diffusion in the human lumbar intervertebral disc under compression in vitro.

STUDY DESIGN: Twelve lumbar intervertebral disc specimens were imaged with magnetic resonance imaging to estimate relaxation constants, T1 and T2, and tissue water diffusion, before and after applying compression. OBJECTIVES: The objectives of the study were to measure T1, T2, and water diffusion for differences with loading state, region of the disc (anulus fibrosus or nucleus pulposus), and grade of degeneration. SUMMARY OF BACKGROUND DATA: Magnetic resonance imaging can be used qualitatively to estimate water content and degeneration of the intervertebral disc. Beyond structural information of images, the relaxation times T1 and T2 may contain information on the changes occurring with degeneration. A modified spin-echo sequence can be used to estimate tissue water diffusion in cartilage and disc specimens with the ability to measure anisotropy. METHODS: Specimens were imaged in a 1.5-Tesla clinical scanner. T1, T2, and water diffusion were estimated from midsagittal images. Magnetic resonance imaging parameters were calculated before and after axial loading. The measured T1, T2, and D (diffusion coefficient) were compared before and after compression, and for the diffusion data, also by direction to consider anisotropy. RESULTS: For the T1 data, a significant difference was found by region, nucleus > anulus, and loading state, loaded > unloaded. For the T2 values, there was a significant difference by region, nucleus > anulus, and Thompson grade. For diffusion, significant differences were found by region, nucleus > anulus, Thompson grade, direction of diffusion, and state of compression, loaded > unloaded. CONCLUSIONS: This study demonstrated that magnetic resonance imaging can be used to measure significant changes in T1, T2, or diffusion in intervertebral disc specimens by region, loading condition, or Thompson grade.

Adolescent↗

PubMed2005

Solving the advection-diffusion equations in biological contexts using the cellular Potts model.

The cellular Potts model (CPM) is a robust, cell-level methodology for simulation of biological tissues and morphogenesis. Both tissue physiology and morphogenesis depend on diffusion of chemical morphogens in the extra-cellular fluid or matrix (ECM). Standard diffusion solvers applied to the cellular potts model use finite difference methods on the underlying CPM lattice. However, these methods produce a diffusing field tied to the underlying lattice, which is inaccurate in many biological situations in which cell or ECM movement causes advection rapid compared to diffusion. Finite difference schemes suffer numerical instabilities solving the resulting advection-diffusion equations. To circumvent these problems we simulate advection diffusion within the framework of the CPM using off-lattice finite-difference methods. We define a set of generalized fluid particles which detach advection and diffusion from the lattice. Diffusion occurs between neighboring fluid particles by local averaging rules which approximate the Laplacian. Directed spin flips in the CPM handle the advective movement of the fluid particles. A constraint on relative velocities in the fluid explicitly accounts for fluid viscosity. We use the CPM to solve various diffusion examples including multiple instantaneous sources, continuous sources, moving sources, and different boundary geometries and conditions to validate our approximation against analytical and established numerical solutions. We also verify the CPM results for Poiseuille flow and Taylor-Aris dispersion.

Algorithms↗

PubMed1979

Intra-axonal diffusion of [3H]acetylcholine and [3H]gamma-aminobutyric acid in a neurone of Aplysia.

1. [3H]acetylcholine (ACh) or [3H]gamma-aminobutyric acid (GABA) was injected into the cell body of a cholinergic neurone of Aplysia kurodai. 2. [3H]ACh moved down the axon at a maximum speed of 2.5 mm/sec at 20 degrees C. 3. 20 mM-colchicine suppressed this movement, but some passive movement of radioactivity was noted along the axon. 4. Profiles of the passive movement coincided with theoretically obtained diffusion profiles. 5. The diffusion coefficient of ACh in the axoplasm was estimated. It was 3 x 10(-6) cm2/sec at 5 degrees C, 4 X 10(-6) cm2/sec at 15 degrees C and 6.5 x 10(-6) cm2/sec at 30 degrees C. The Q10 was 1.35, the activation energy was about 5 kcal/degrees C. These diffusion coefficients were lower than that of free diffusion of ACh (8 x 10(-6) cm2/sec at 18 degrees C, Fatt, 1954), and assumed to be reasonable, if one considers frictional resistivity of axoplasm in the diffusion of ACh molecules. 6. [3H]GABA diffused similarly to ACh, and the diffusion coefficients agreed with the estimated value when the molecular size differences were taken into account. 7. Both ACh and GABA seemed to diffuse in soluble form or as single molecules in the axoplasm. 8. Intra-axonal diffusion is very effective for short distances.

Acetylcholine↗

PubMed1981

The effect of the red cell membrane and a diffusion boundary layer on the rate of oxygen uptake by human erythrocytes.

1. This paper deals with the contributions of the red cell membrane and an external diffusion boundary layer (;unstirred layer') to the resistance to O(2) entry into the red cell. Bovine serum albumin (BSA) was added to the extracellular fluid to enhance the effect of the diffusion boundary layer by diminishing both the solubility and the diffusivity of O(2). The rate of O(2) uptake by human red cells at various extracellular BSA concentrations was determined with a stopped-flow rapid-reaction apparatus.2. The initial rate of O(2) uptake by the red cells was directly proportional to the diffusion coefficient of O(2) in the extracellular fluid.3. If the diffusion boundary layer and the plasma membrane are considered as resistors in series, we estimate that 82-100% of the total resistance to O(2) entering the cell is due to the diffusion boundary layer. Our best estimate is that 95% of the resistance resides in the diffusion boundary layer.4. Our best estimate of the O(2) permeability of the red cell membrane is 3.15 x 10(-6) m-mole/(cm(2) sec mmHg). With this permeability the membrane would account for only 5% of the total resistance to O(2) entering the cell. Partly because the membrane O(2) diffusion resistance is a small fraction of the total resistance our estimate of the membrane resistance has a large standard deviation. Taking our estimate of the membrane resistance plus and minus its standard deviation we find that the membrane may account for 0-18% of the total resistance to O(2) entering the cell.5. The effective thickness of the diffusion boundary layer immediately after mixing is about 1.93 mum according to our analysis.

Diffusion↗

PubMed1981

Ion diffusion modified by tortuosity and volume fraction in the extracellular microenvironment of the rat cerebellum.

1. The validity of the macroscopic laws of ion diffusion was critically examined within the microenvironment of the extracellular space in the rat cerebellum using ion-selective micropipettes and ionophoretic point sources. 2. The concepts of volume averaging, volume fraction (alpha) and tortuosity (lambda) were defined and shown to be theoretically appropriate for quantifying diffusion in a complex medium such as the brain. 3. Diffusion studies were made with the cations tetramethylammonium and tetraethylammonium and the anions alpha-naphthalene sulphonate and hexafluoro-arsenate, all of which remained essentially extracellular during the measurements. Diffusion parameters were measured for a period of 50s and over distances of the order of 0.1 mm. 4. Measurements of the diffusion coefficients of the ions in agar gel gave values that were very close to those derivable from the literature, thus confirming the validity of the method. 5. Measurements in the cerebellum did not reveal any systematic influences of ionophoretic current strength, electrode separation, anisotropy, inhomogeneity, charge discrimination or uptake, within the limits tested. 6. The pooled data from measurements with all the ions gave alpha = 0.21 +/- 0.02 (mean +/- S.E. of mean) and lambda = 1.55 +/- 0.05 (mean +/- S.E. of mean). 7. These results show that the extracellular space occupies about 20% of the rat cerebellum and that the diffusion coefficient for small monovalent extracellular ions is reduced by a factor of 2.4 (i.e. lambda 2) without regard to charge sign. The over-all effect of this is to increase the apparent strength of any ionic source in the cerebellum by a factor of lambda 2/alpha, about 12-fold in the present case, and to modify the time course of diffusion. 8. These conclusions confirm that the laws of macroscopic diffusion are closely obeyed in the cerebellum for small ions in the extracellular space, provided that volume fraction and tortuosity are explicitly taken into account. It is likely that these conclusions are generally applicable to other brain regions and other diffusing substances.

Animals↗

PubMedDate not supplied

Site-specific molecular diffusion in articular cartilage measured using fluorescence recovery after photobleaching.

Diffusive transport of solutes is critical to the normal function of articular cartilage. The diffusion of macromolecules through cartilage may be affected by the local composition and structure, which vary with depth from the tissue surface. We hypothesized that the diffusion coefficient of uncharged molecules also varies with depth and molecular size. We used fluorescence recovery after photobleaching (FRAP) to measure site-specific diffusion coefficients of fluorescent dextran molecules (3, 40, 70, and 500 kDa) in porcine articular cartilage. The diffusion coefficients measured using FRAP exhibited an inverse size dependence and were in general agreement with those measured using other techniques. The diffusion coefficients for all molecules varied significantly with depth in a manner that depended upon the size of the diffusing molecule. The diffusion coefficients for the 3 and 500 kDa dextrans were 1.6 and 2.4 times greater, respectively, in the surface zone as compared to the middle and deep zones, whereas the diffusion coefficients of the 40 and 70 kDa dextrans were 0.3 and 0.2 times lower in the surface zone as compared to the middle and deep zones. These differences may reflect variations in the structure and composition of collagen, proteoglycans, and other macromolecules among the zones.

Animals↗

PubMed2001

b matrix errors in echo planar diffusion tensor imaging.

Diffusion-weighted magnetic resonance imaging (DW-MRI) is a recognized tool for early detection of infarction of the human brain. DW-MRI uses the signal loss associated with the random thermal motion of water molecules in the presence of magnetic field gradients to derive parameters that reflect the translational mobility of the water molecules in tissues. If diffusion-weighted images with different values of b matrix are acquired during one individual investigation, it is possible to calculate apparent diffusion coefficient maps that are the elements of the diffusion tensor. The diffusion tensor elements represent the apparent diffusion coefficient of protons of water molecules in each pixel in the corresponding sample. The relation between signal intensity in the diffusion-weighted images, diffusion tensor, and b matrix is derived from the Bloch equations. Our goal is to establish the magnitude of the error made in the calculation of the elements of the diffusion tensor when the imaging gradients are ignored.

Brain Infarction↗

PubMed1996

Theoretical aspects of antibiotic diffusion into microbial biofilms.

Antibiotic penetration into microbial biofilm was investigated theoretically by the solution of mathematical equations describing various combinations of the processes of diffusion, sorption, and reaction. Unsteady material balances on the antibiotic and on a reactive or sorptive biomass constituent, along with associated boundary and initial conditions, constitute the mathematical formulations. Five cases were examined: diffusion of a noninteracting solute; diffusion of a reversibly sorbing, nonreacting solute; diffusion of an irreversibly sorbing, nonreacting solute; diffusion of a stoichiometrically reacting solute; and diffusion of a catalytically reacting solute. A noninteracting solute was predicted to penetrate biofilms of up to 1 mm in thickness relatively quickly, within a matter of seconds or minutes. In the case of a solute that does not sorb or react in the biofilm, therefore, the diffusion barrier is not nearly large enough to account for the reduced susceptibility of biofilms to antibiotics. Reversible and irreversible sorption retards antibiotic penetration. On the basis of data available in the literature at this point, the extent of retardation of antibiotic diffusion due to sorption does not appear to be sufficient to account for reduced biofilm susceptibility. A catalytic (e.g., enzymatic) reaction, provided it is sufficiently rapid, can lead to severe antibiotic penetration failure. For example, calculation of beta-lactam penetration indicated that the reaction-diffusion mechanism may be a viable explanation for failure of certain of these agents to control biofilm infections. The theory presented in this study provides a framework for the design and analysis of experiments to test these mechanisms of reduced biofilm susceptibility to antibiotics.

Absorption↗

PubMed2003

Evaluation of liver diffusion isotropy and characterization of focal hepatic lesions with two single-shot echo-planar MR imaging sequences: prospective study in 66 patients.

PURPOSE: To (a) evaluate liver diffusion isotropy, (b) compare two diffusion-weighted magnetic resonance (MR) imaging sequences for the characterization of focal hepatic lesions by using two or four b values, and (c) determine an apparent diffusion coefficient (ADC) threshold value to differentiate benign from malignant lesions. MATERIALS AND METHODS: Sixty-six patients were examined with two single-shot echo-planar diffusion-weighted MR sequences. In the first sequence, liver diffusion isotropy was evaluated by using diffusion gradients in three directions with two b values. In the second sequence, a unidirectional diffusion gradient was used with four b values. ADCs were measured in 43 patients with 52 focal hepatic lesions more than 1 cm in diameter and in 23 patients with 14 normal and nine cirrhotic livers and were compared by using nonparametric tests. RESULTS: Diffusion in the liver parenchyma was isotropic. ADCs of focal hepatic lesions were significantly different between sequences (P <.01). The mean (+/- SD) ADCs in the first sequence were 0.94 x 10(-3) mm(2)/sec +/- 0.60 for metastases, 1.33 x 10(-3) mm(2)/sec +/- 0.13 for HCCs, 1.75 x 10(-3) mm(2)/sec +/- 0.46 for benign hepatocellular lesions, 2.95 x 10(-3) mm(2)/sec +/- 0.67 for hemangiomas, and 3.63 x 10(-3) mm(2)/sec +/- 0.56 for cysts. There was a significant difference between benign (2.45 x 10(-3) mm(2)/sec +/- 0.96, isotropic value) and malignant (1.08 x 10(-3) mm(2)/sec +/- 0.50) lesions (P <.01 for both sequences). CONCLUSION: Diffusion-weighted MR imaging can help differentiate benign from malignant hepatic lesions. The use of two b values in one direction could be sufficient for the design of MR sequences in the liver.

Adult↗

PubMed1993

Influence of diffusion on estimations of protein reflection coefficient by double-indicator method.

In isolated perfused organs, vascular protein reflection coefficients (sigma) can be calculated from the changes in hematocrit and perfusate protein concentration (CP) that occur during edema formation. This technique requires the assumption that transvascular protein flux by diffusion is negligible. To assess diffusion-induced errors in calculations of sigma, we derived an expression for CP that includes determinants of diffusive protein flux: protein permeability-surface area product (PS), transvascular fluid flux (J), true sigma, and transvascular protein concentration. We used this expression to obtain values of CP under various experimental conditions and then calculated values of sigma (measured sigma) for those conditions. Diffusion causes measured sigma to be lower than true sigma. The diffusion-induced error is larger and potentially substantial when J/PS is low and when true sigma is high. Diffusion-induced error is also larger when the amount of edema formation is greater. In recent isolated canine lung experiments where J/PS was approximately 2.7, diffusion-induced errors in measured sigma for albumin would have been approximately 0.06 (at true sigma = 0.5) and approximately 0.18 (at true sigma = 0.9). When J/PS was higher, the potential for diffusion-induced errors was much smaller. We conclude that diffusion causes underestimation of true sigma and that the error in measured sigma may be substantial when J/PS is < 5 and when true sigma is > 0.5.

Animals↗

PubMed2002

Impact of axial diffusion on nitric oxide exchange in the lungs.

Nitric oxide (NO) appears in the exhaled breath and is a potentially important clinical marker. The accepted model of NO gas exchange includes two compartments, representing the airway and alveolar region of the lungs, but neglects axial diffusion. We incorporated axial diffusion into a one-dimensional trumpet model of the lungs to assess the impact on NO exchange dynamics, particularly the impact on the estimation of flow-independent NO exchange parameters such as the airway diffusing capacity and the maximum flux of NO in the airways. Axial diffusion reduces exhaled NO concentrations because of diffusion of NO from the airways to the alveolar region of the lungs. The magnitude is inversely related to exhalation flow rate. To simulate experimental data from two different breathing maneuvers, NO airway diffusing capacity and maximum flux of NO in the airways needed to be increased approximately fourfold. These results depend strongly on the assumption of a significant production of NO in the small airways. We conclude that axial diffusion may decrease exhaled NO levels; however, more advanced knowledge of the longitudinal distribution of NO production and diffusion is needed to develop a complete understanding of the impact of axial diffusion.

Diffusion↗