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PubMed2005

Donnan effects in the steady-state diffusion of metal ions through charged thin films.

The steady-state diffusion of metals ions through thin films with fixed charged groups was investigated using diffusive gradients in thin films (DGT) measurements. Copolymers of acrylamide and sodium acrylate cross-linked with N,N'-methylenebisacrylamide were used as diffusive gels. The rate of diffusion of cadmium ions through the gels was measured by determining the mass of cadmium bound to a backing chelex resin after a known deployment time. Variation of the ionic strength as well as the fixed charge density and the thickness of the gel layer allowed evaluation of the impact of the Donnan partitioning and the diffusion layer in solution on the observed steady-state flux of ions through the layer. The results underscore that, as the Donnan partitioning increases, the impact of the diffusion layer in solution becomes more significant. At modest Donnan potentials, Donnan partitioning controls the net flux of metal ions, whereas at conditions of increasing Donnan potential, i.e., at decreasing ionic strength, the flux is increasingly limited by diffusion in solution. An analytical expression is developed to describe the influence of Donnan partitioning on the observed steady-state flux of metal ions.

Journal Article↗

PubMed1998

The influence of intestinal mucus components on the diffusion of drugs.

PURPOSE: Mucus, a potential diffusional barrier to drug absorption, is a complex mixture of mucin and other components. The objective of this study was to investigate the composition of native pig intestinal mucus (PIM) and the influence of identified mucus components on drug diffusion. METHODS: The mucus components were separated by CsCl-density gradient centrifugation and further analyzed. The self-diffusion coefficients of mannitol, metoprolol, propranolol, hydrocortisone, and testosterone, ranging in lipophilicity from logK = -3.1 to logK = 3.3, were determined, using a small scale tracer technique. The diffusion of drugs in PIM, in solutions or dispersions of individual mucus components, and in an artificial mucus model (MLPD) reconstituted from the major mucus components mucin, lipids, protein, and DNA was compared. RESULTS: The dry weight of pig intestinal mucus contained (%, w/w); mucin (5%), lipids (37%), proteins (39%), DNA (6%), and unidentified materials. The most commonly occurring lipids were free fatty acids, cholesterol, and phospholipids while the most common protein was serum albumin. In PIM, but not in the purified pig gastric mucin (PPGM) solution, the diffusion of the lipophilic drugs metoprolol, propranolol, hydrocortisone, and testosterone was reduced compared to that of the hydrophilic drug mannitol. The diffusion of the lipophilic drugs was also significantly reduced in a dispersion of identified mucus lipids compared to that of mannitol. The diffusion in MLPD was similar to that in PIM for mannitol, propranolol, hydrocortisone, and testosterone, but somewhat lower for metoprolol. CONCLUSIONS: Lipids, rather than mucin glycoproteins, are a major component which contributes to reduced diffusion of drugs in native intestinal mucus. The results suggest that reconstituted artificial mucus models are interesting alternatives to native mucus models.

Animals↗

PubMed2001

Delayed diffuse lamellar keratitis after laser in situ keratomileusis.

Two cases are reported of delayed diffuse lamellar keratitis after uneventful laser in situ keratomileusis. The first patient presented with an epithelial defect 6 weeks after laser in situ keratomileusis. Three days later the defect was healed but diffuse lamellar keratitis was noted. This was treated with topical dexamethasone and ketorolac with complete resolution of the diffuse lamellar keratitis over 3 weeks. The second patient presented with an epithelial defect and gross diffuse lamellar keratitis 10 weeks after laser in situ keratomileusis. Treatment was with topical dexamethasone and ciprofloxacin with gradual resolution of the diffuse lamellar keratitis. Common to both patients was a background of rosacea, implanted debris with no initial reaction, and epithelial defects leading to diffuse lamellar keratitis. It is suggested that these two cases represent epithelial defect associated corneal infiltration, which resembles classical diffuse lamellar keratitis with the spread of inflammatory cells through a path of least resistance.

Administration, Topical↗

PubMed2002

Temporal characterisation of pro- and anti-apoptotic mechanisms following diffuse traumatic brain injury in rats.

Few studies have characterised apoptosis in a brain injury model that causes a significant degree of diffuse axonal injury. Such characterisation is essential from a clinical viewpoint since diffuse axonal injury is a major component of human head injury. The present study therefore, examines the expression of active and proactive caspase-3, and the bax, bcl-2 and bcl-x members of the bcl-2 family, to characterise the temporal profile of apoptosis in a model of traumatic brain injury in rats that produces significant diffuse axonal injury. Pentobarbital anaesthetised male Sprague-Dawley rats were injured using the 2m impact-acceleration model of diffuse traumatic brain injury. After injury, diffuse trauma resulted in an increased bax expression followed by induction of caspase-3. The increase in caspase-3 was simultaneous with an increase in anti-apoptotic bcl-2 expression. Bcl-x levels were increased after induction of caspase-3 and the increased levels of bcl-x were sustained to the end of the 5-day observation period. Increased active caspase-3 expression was associated with the appearance of TUNEL positive cells. These cells were detected in different brain regions at different times, with some regions showing no apoptotic cells until 3 days after injury. No TUNEL positive cells were detected at 7 and 14 days after injury. DNA electrophoresis confirmed that DNA fragmentation was maximal at 3 days after injury. Increased active caspase-3 levels were also significantly correlated with increased bcl-2 levels (r=0.80; P<0.001) suggesting that the apoptotic cascade after diffuse traumatic brain injury is a carefully controlled cellular homeostatic response. Pharmacological manipulation of this balance may offer a therapeutic approach for preventing cell death and improving outcome after diffuse traumatic brain injury.

Animals↗

PubMed2006

[Functional imaging of submandibular glands: diffusion-weighted echo-planar MRI before and after stimulation].

PURPOSE: To investigate the feasibility of diffusion-weighted (DWI) echo-planar imaging (EPI) to depict the submandibular glands and to measure different functional conditions. MATERIALS AND METHODS: Twenty-seven healthy volunteers were examined. Diffusion weighted sequence was performed prior to stimulation. Exactly 30 seconds after a commercially available lemon juice was given orally, the diffusion weighted sequence was repeated. All examinations were performed by using a 1.5-T superconducting system with a 30 mT/m maximum gradient capability and maximum slew rate of 125 mT/m/sec (Magnetom Symphony, Siemens, Erlangen, Germany). The lower part of the circularly polarized (CP) head coil and a standard two-element CP neck array coil were used. The flexibility of the neck array coil allowed positioning the N1 element (upper part of the coil) right next to the submandibular gland. The axial diffusion-weighted EPI (echo planar imaging) sequence was performed using a matrix of 119 x 128, a field of view of 250 x 250 mm (pixel size 2.1 x 1.95 mm), a section thickness of 5 mm with an interslice gap of 1 mm. The b factors used were 0 sec/mm(2), 500 sec/ mm(2) and 1000 sec/mm(2). Apparent diffusion coefficiant (ADC) maps were digitally transferred to MRIcro (Chris Rorden, Universitiy of Nottingham, Great Britain). After detecting the submandibular glands a region of interest (ROI) was placed manually exactly within the boarder of both submandibular glands, excluding the external carotid artery on ADC maps. These procedures were performed on all ADC slices the submandibular glands could be differentiated in before and after oral stimulation. For statistical comparison of results, a student's t-test was performed with an overall two-tailed significance level of p = 0.05. RESULTS: The visualization of the submandibular glands using the diffusion-weighted EPI sequence was possible in all of the 27 volunteers. Prior to oral stimulation an ADC of 1.31 x 10(-3) mm(2)/sec (95 % CI, 1.39 x 10(-3) mm(2)/sec, 1.44 x 10(-3) mm(2)/sec) was calculated which increased to 1.41 x 10(-3) mm(2)/sec (95 % KI, 1.39 x 10(- 3) mm(2)/sec, 1.44 x 10(-3) mm(2)/sec) 30 seconds after stimulation. This increase proved to be significant (p < 0.001). CONCLUSION: Diffusion-weighted echo-planar MR imaging allows non-invasive quantification of functional changes in the submandibular gland.

Adult↗

PubMed2005

Self-diffusion in granular gases: Green-Kubo versus Chapman-Enskog.

We study the diffusion of tracers (self-diffusion) in a homogeneously cooling gas of dissipative particles, using the Green-Kubo relation and the Chapman-Enskog approach. The dissipative particle collisions are described by the coefficient of restitution epsilon which for realistic material properties depends on the impact velocity. First, we consider self-diffusion using a constant coefficient of restitution, epsilon=const, as frequently used to simplify the analysis. Second, self-diffusion is studied for a simplified (stepwise) dependence of epsilon on the impact velocity. Finally, diffusion is considered for gases of realistic viscoelastic particles. We find that for epsilon=const both methods lead to the same result for the self-diffusion coefficient. For the case of impact-velocity dependent coefficients of restitution, the Green-Kubo method is, however, either restrictive or too complicated for practical application, therefore we compute the diffusion coefficient using the Chapman-Enskog method. We conclude that in application to granular gases, the Chapman-Enskog approach is preferable for deriving kinetic coefficients.

Journal Article↗

PubMed2006

Solute size effects on the solvation structure and diffusion of ions in liquid methanol under normal and cold conditions.

We have performed a series of molecular dynamics simulations of alkali metal (Li+, Na+, K+, Rb+, and Cs+) and halide (F-, Cl-, Br-, and I-) ions in liquid methanol at two different temperatures to investigate the effects of ion size on the hydration structure and diffusion of ions in methanol under normal and cold conditions. Simulations are also carried out for some of the larger cations such as I+, (CH3)4N+, and (C2H5)4N+ and also neutral alkali metal atoms in methanol at both temperatures. With the increase of ion size, the diffusion coefficients of both positive and negative ions are found to show anomalous behavior. For cations, it is found that the maximum of the diffusion coefficient versus ion size curve occurs at the rather large cation of (CH3)4N+ unlike in water where the maximum occurs at the relatively smaller ion of Rb+. For halide ions, the anomalous behavior, i.e., the increase of diffusion with ion size, continues up to iodide ion and no maximum is observed. These results are in good agreement with experimental observations. The diffusion coefficients of neutral atoms are found to be greater in methanol than that in water and they decrease monotonically with solute size, whereas the diffusion coefficients of the corresponding ions are found to be smaller in methanol. Accordingly, an ion experiences a smaller Stokes friction and a higher dielectric friction in methanol than in water. These contrasting effects are believed to be responsible for the shift of the maximum of ion diffusion toward a larger ion size when compared with similar anomalous size dependence in liquid water.

Journal Article↗

PubMed2006

Self-diffusion in submonolayer colloidal fluids near a wall.

Theoretical expressions are developed to describe self-diffusion in submonolayer colloidal fluids that require only equilibrium structural information as input. Submonolayer colloidal fluids are defined for the purpose of this work to occur when gravity confines colloids near a planar wall surface so that they behave thermodynamically as two dimensional fluids. Expressions for self-diffusion are generalized to consider different colloid and surface interaction potentials and interfacial concentrations from infinite dilution to near fluid-solid coexistence. The accuracy of these expressions is demonstrated by comparing self-diffusion coefficients predicted from Monte Carlo simulated equilibrium particle configurations with standard measures of self-diffusion evaluated from Stokesian Dynamics simulated particle trajectories. It is shown that diffusivities predicted for simulated equilibrium fluid structures via multibody hydrodynamic resistance tensors and particle distribution functions display excellent agreement with values computed from mean squared displacements and autocorrelation functions of simulated tracer particles. Results are obtained for short and long time self-diffusion both parallel and normal to underlying planar wall surfaces in fluids composed of particles having either repulsive electrostatic or attractive van der Waals interactions. The demonstrated accuracy of these expressions for self-diffusion should allow their direct application to experiments involving submonolayer colloidal fluids having a range of interaction potentials and interfacial concentrations.

Journal Article↗

PubMed1978

Fluorescence energy transfer in the rapid-diffusion limit.

Energy transfer is enhanced by translational diffusion of the donor and acceptor [Steinberg, I. Z. & Katchalski, E. (1968) J. Chem. Phys. 48, 2404-2410]. The effect of diffusion on energy transfer depends on Dtau(0)/s(2), in which D is the sum of the diffusion coefficients of the donor and acceptor, tau(0) is the lifetime of the donor in the absence of transfer, and s is the mean distance between donors and acceptors. In most previous studies, Dtau(0)/s(2) << 1, corresponding to the static limit. We report here steady-state and kinetic fluorescence experiments showing that Dtau(0)/s(2) >> 1, the rapid-diffusion limit, can be attained by using Tb(3+) chelated to dipicolinate as a long-lived energy donor (tau(0) = 2.2 msec). The concentration of rhodamine B, the energy acceptor, resulting in 50% transfer was 0.67 muM, which is three orders of magnitude less than the concentration giving 50% transfer in the static limit. The dependence of the transfer efficiency on diffusion coefficients varying from 5 x 10(-11) to 1.5 x 10(-4) cm(2)/sec, spanning the range from the static limit to the rapid-diffusion limit, is in excellent agreement with theory. It is evident that energy donors with millisecond or longer excited state lifetimes can be used to probe translational motions in membranes and other assemblies. Energy transfer in the rapid diffusion limit is sensitive to the distance of closest approach (a) of the donor and acceptor. For a Tb.(DPA)(3) chelate trapped inside the aqueous space of a membrane vesicle containing eosin phosphatidylethanolamine, a = 10 A. The transverse location of chromophores in model membranes and biological membranes can be determined by this technique.

Journal Article↗

PubMed1998

Intranuclear diffusion and hybridization state of oligonucleotides measured by fluorescence correlation spectroscopy in living cells.

Fluorescein-labeled oligodeoxynucleotides (oligos) were introduced into cultured rat myoblasts, and their molecular movements inside the nucleus were studied by fluorescence correlation spectroscopy (FCS) and fluorescence recovery after photobleaching (FRAP). FCS revealed that a large fraction of both intranuclear oligo(dT) (43%) and oligo(dA) (77%) moves rapidly with a diffusion coefficient of 4 x 10(-7) cm2/s. Interestingly, this rate of intranuclear oligo movement is similar to their diffusion rates measured in aqueous solution. In addition, we detected a large fraction (45%) of the intranuclear oligo(dT), but not oligo(dA), diffusing at slower rates (</=1 x 10(-7) cm2/s). The amount of this slower-moving oligo(dT) was greatly reduced if the oligo(dT) was prehybridized in solution with (unlabeled) oligo(dA) prior to introduction to cells, presumably because the oligo(dT) was then unavailable for subsequent hybridization to endogenous poly(A) RNA. The FCS-measured diffusion rate for much of the slower oligo(dT) population approximated the diffusion rate in aqueous solution of oligo(dT) hybridized to a large polyadenylated RNA (1.0 x 10(-7) cm2/s). Moreover, this intranuclear movement rate falls within the range of calculated diffusion rates for an average-sized heterogeneous nuclear ribonucleoprotein particle in aqueous solution. A subfraction of oligo(dT) (15%) moved over 10-fold more slowly, suggesting it was bound to very large macromolecular complexes. Average diffusion coefficients obtained from FRAP experiments were in agreement with the FCS data. These results demonstrate that oligos can move about within the nucleus at rates comparable to those in aqueous solution and further suggest that this is true for large ribonucleoprotein complexes as well.

Animals↗

PubMed1989

Increased brain water content in pseudotumour cerebri measured by magnetic resonance imaging of brain water self diffusion.

Brain water self diffusion was investigated by magnetic resonance scanning in 7 patients fulfilling conventional diagnostic criteria for pseudotumour cerebri. Quantitative diffusion measurements were obtained using single spin echo pulse sequences with pulsed magnetic field gradients of different magnitude. In all patients the diffusion images showed an increased diffusion in various brain regions when compared with the diffusion coefficients for corresponding regions in healthy subjects. In 3 pseudotumour patients the increased self diffusion was localized to the periventricular regions, while 4 patients had increased diffusion in the whole brain. The findings indicate the presence of increased brain water content both intra- and extracellularly suggesting that patients with pseudotumour have two defects of pathogenetical significance: intracellular water accumulation and increased resistance to cerebrospinal fluid (CSF) outflow leading to an interstitial oedema.

Adult↗

PubMed2006

Behavior of the GABIE, 3M 3500, PerkinElmer Tenax TA, and RADIELLO 145 diffusive samplers exposed over a long time to a low concentration of VOCs.

Diffusive sampling is particularly suited to determine time-weighted average volatile organic compound (VOC) concentration in occupational hygiene and environmental air monitoring. The purpose of this study was to measure the sampling rate variation of four different samplers in a special use--the exposure to a low concentration of volatile organic compound (10 to 200 ppb) for a long period (1 to 14 days). PerkinElmer tube-type adsorbent was packed with Tenax TA and RADIELLO cartridge packed with Carbograph 4. Badge-type activated carbon diffusive samplers 3M 3500 and GABIE were exposed to the same controlled atmospheres of benzene as meta-xylene (BTX) during the same exposure times. Performance samplers were observed for variability of uptake rates according to concentration levels, exposure duration, back diffusion, and competition phenomena at the adsorption sites. Particular benzene behavior has been noted for the thermally desorbable tube-type diffusive sampler: the measured sampling rates decrease with time following an exponential profile. With badge-type active charcoal diffusive samplers, the uptake rates were found to be highly stable and unaffected by time exposure. Overall, in the region of a few tens of ppb, for long-time exposure and for the lightest compounds, 3M 3500 and GABIE diffusive samplers seem the most appropriate diffusive sampling technique in terms of performance and facility in use.

Adsorption↗

PubMed1957

Permeation and diffusion of K ions in frog muscle.

The movements of tracer K and net changes of K have been measured in frog muscle. The quantities moving can be linearly related to the square root of the time after a delay of 4 to 30 minutes depending on the external K concentration. The slope of the uptake-t((1/2)) line is increased when the external K concentration is raised. The Q(10) of the uptake is about 1.9 per unit t((1/2)). K uptake from 1 to 2 mM concentration is diminished by a factor of about 2 if strophanthin is applied. The output per unit t((1/2)) is increased by a factor of about 1.4 by strophanthin. Tetrabutylammonium substituted for 10 per cent of the Na in the medium causes a reversible slowing of K uptake and Na output. The rates of movement found in the tracer experiments can be used to calculate the net losses of K taking place in K-free or strophanthin-containing media. The results are interpreted on the basis of K movement being limited both by a resistive outer layer and by diffusion within a K-rich region. The internal diffusion constant is 10(-11) to 10(-10) cm.(2) sec.(-1) depending on the K concentration. The rate of movement of the K can be related to the electrochemical activity of the ion, the lability of the sites on which it is absorbed, and cation + anion pair diffusion within the cell. The surface resistance to K ions can be accounted for as the sum of a membrane resistance equal to that found by electrical methods and the resistance offered to the movement of K by an annulus sufficiently thick (ca. 3 micro) to accommodate the cell Na at a density equal to the mean density of cation within the cell through which K diffuses with the same diffusion constant as holds in the K-rich region. Na movement, if assumed to take place by diffusion from the annulus with diffusion constant equal to that for K ions, has a rate which agrees well with observed values. The influence of strophanthin and tetrabutylammonium on the ion movements is interpreted as being the result of these agents causing an expansion of the outer non-selective region, normally occupied mainly by Na, at the expense of the inner K-rich region.

Animals↗

PubMed1991

The interstellar C-H stretching band near 3.4 microns: constraints on the composition of organic material in the diffuse interstellar medium.

To better constrain and quantify the composition of material in the diffuse interstellar medium (ISM), absorption spectra between 3600 and 2700 cm-1 (2.8 and 3.7 microns) have been taken of objects which have widely varying amounts of visual extinction along different lines of sight. The spectra of these objects contain a broad feature centered at approximately 3300 cm-1 (approximately 3.0 microns), attributed to O-H stretching vibrations, and/or a feature near 2950 cm-1 (3.4 microns) attributed to C-H stretching vibrations. The lack of correlation between the strengths of these two bands indicates that they do not arise from the same molecular carrier. The features in the 3100-2700 cm-1 (3.2-3.7 microns) region fall into one of two classes. We attribute the first class of features to material in the diffuse ISM on the basis of the similarity between the band profiles along the very different lines of sight to Galactic center source IRS 7 and VI Cygni #12. Similar features are also reported for Galactic center source IRS 3, Ve 2-45, and AFGL 2179. Higher resolution spectra of the objects OH 01-477 and T629-5, which are known to be M stars, are dominated by a series of narrow bands in this region. These bands are largely due to OH in the stars' photospheres. While the spectra of OH 01-477 and T629-5 are likely to contain C-H absorption from diffuse ISM dust, the strength of the overlapping photospheric OH features presently prevents us from quantifying the depths of the interstellar C-H feature towards these objects. The interstellar feature for Galactic center source IRS 7 has subpeaks near 2955, 2925, and 2870 cm-1 (+/- 5 cm-1), which we attribute to C-H stretching vibrations in the -CH2- and -CH3 groups of aliphatic hydrocarbons. These band positions fall within 5 cm-1 of the values normal for saturated aliphatics. The absence of a distinct band near 2855 cm-1 suggests that the material contains small amounts of electronegative groups like -O-H or -C triple bond N. The relative strengths and profiles of the 2955 and 2925 cm-1 features towards five objects suggests an average diffuse ISM line-of-sight -CH2-/-CH3 ratio of about 2.5, indicating the presence of relatively complex organic materials. The strengths of the subpeaks at 2925 and 2955 cm-1, due to -CH2- and -CH3 groups, respectively, correlate with visual extinction, strongly suggesting that the C-H stretching band is a general feature of the material along different lines of sight in the diffuse ISM. We find average ratios of A nu/tau(2925 cm-1) = 240 +/- 40 and A nu/tau(2955 cm-1) = 310 +/- 90 for the objects we have observed. We deduce that 2.6%-35% of the cosmic carbon in the ISM is tied up in the carrier of this band with the most likely value falling near 10%. The interstellar C-H band is remarkably similar to the feature in lab residues produced by irradiating analogs of dense molecular cloud ices. This is consistent with a model in which the hydrocarbon component in the diffuse interstellar medium consists of complex hydrocarbons containing aliphatic side chains and bridges which are produced in dense molecular clouds and subsequently modified in the diffuse medium.

Astronomical Phenomena↗

PubMed1995

Diffusion in Fe(II/III) radiation dosimetry gels measured by magnetic resonance imaging.

We analyse the diffusion problem in the traditional Fe(II/III) agarose gel system employed in MRI studies of radiation dosimetry. The diffusion coefficient is measured using an inversion recovery null-point imaging method in a model gel/water phantom. The diffusion coefficient of Fe(III) in 1% agarose gel at pH 1.1 is D = 2.7 +/- 0.3 x 10(-6) cm2 s-1. The diffusion coefficient of Fe(II) is D = 3.3 +/- 0.5 x 10(-6) cm2 s-1. Measurement of the diffusion coefficients permits simulation of the MRI signal intensity from phantoms with model radiation dose distributions. We allow for diffusion of both Fe(II) and Fe(III) in our simulations as well as the effect of both relaxation agents on the local spin-lattice relaxation time T1. We also analyse the effects of the physical penumbra on the diffusion problem.

Gels↗

PubMed1996

Detection of acute pathologic changes following experimental traumatic brain injury using diffusion-weighted magnetic resonance imaging.

Standard magnetic resonance imaging (MRI) has been shown to be remarkably insensitive to acute changes following traumatic brain injury. Because diffusion-weighted MRI has recently demonstrated excellent sensitivity to acute ischemic injury and other CNS abnormalities, we evaluated the use of diffusion MRI for the detection of pathologic changes in the rat brain during the first hours following parasagittal fluid percussion brain injury. Diffusion MRI was able to demonstrate a significant diffusion decrease in the primary cortical contusion injury and a comparable decrease in the ipsilateral thalamus. Tissue damage in the thalamus region is much weaker than in the cortex, but the thalamus is a primary site of axonal and dendritic injury in this model. T2 imaging in the same subjects showed slight enhancement in the neighborhood of the injured cortex but was unable to demonstrate injury elsewhere. Diffusion imaging was superior to T2 at demonstrating injury and the prominent diffusion decrease in the thalamus suggests that diffusion MRI is preferentially sensitive to axonal or dendritic injury.

Animals↗

PubMed1998

Clinical forms of presentation and evolution of diffuse sclerosing variant of papillary carcinoma and insular variant of follicular carcinoma of the thyroid.

We investigated whether the diffuse sclerosing variant of papillary carcinoma (diffuse sclerosing PC) and insular carcinoma (IC), two different subforms of differentiated carcinoma of the thyroid gland, have different clinical behaviors and prognosis in order to select appropriate therapy. The characteristics of clinical presentation, and outcome after therapy were evaluated in a series of 113 patients (18 males and 95 females) with differentiated thyroid carcinoma treated with the same protocol, of which 7 had diffuse sclerosing PC and 6 had IC; within this series, patients with diffuse sclerosing PC and IC were compared with 76 cases of papillary carcinoma (PC) and 24 cases of follicular carcinoma (FC), respectively. Diffuse sclerosing PC patients were younger (23+/-9 vs. 38+/-16 years) and had a higher degree of lymphatic metastases at diagnosis (100%) than patients with PC (47%). Five of 7 patients with diffuse sclerosing PC were alive and without evidence of disease compared to 34 of 76 patients with PC at follow-up (6.4+/-5.1 and 7.9+/-7 years, respectively). No prognostic differences were found between them. IC showed a more advanced stage of disease at diagnosis and a more aggressive clinical course with a higher percent of metastases and mortality than patients with FC at follow-up (1 patient died and 5 were alive with persistent disease at 4.8+/-3.7 years for IC; 22 were alive, 13 of them with persistent disease; and 2 died at 8.4+/-5.3 years for FC). We conclude that patients with diffuse sclerosing PC do not require a different treatment than that given to PC patients, while in contrast, IC cases need a more aggressive therapeutic approach.

Adenocarcinoma, Follicular↗

PubMed1998

Comparison of a novel, inhibitor-potentiated disc-diffusion test with other methods for the detection of extended-spectrum beta-lactamases in Escherichia coli and Klebsiella pneumoniae.

A novel, inhibitor-potentiated disc-diffusion test for detecting extended-spectrum beta-lactamases (ESBLs) in bacteria was evaluated. This test uses the principle of augmentation (by > or = 10 mm) of inhibition zones produced by ceftazidime, cefotaxime, ceftriaxone or aztreonam discs on Mueller-Hinton agar supplemented with clavulanate (4 mg/L). The test was initially compared with the double-disc synergy test, Kirby-Bauer disc-diffusion test and Etest ESBL screen with a panel of 45 reference strains with known resistance profiles. This panel consisted of 27 ESBL-positive Escherichia coli strains expressing 14 Bush group 2be enzymes and 18 other E. coli and Klebsiella pneumoniae strains (14 non-ESBL beta-lactamase producers and four non-beta-lactamase producers). The Kirby-Bauer disc-diffusion test was the least sensitive method: 11-44% of the ESBL-positive control strains were misclassified as susceptible to ceftazidime, cefotaxime, ceftriaxone or aztreonam when interpreted by National Committee for Clinical Laboratory Standards (NCCLS) criteria. The sensitivities of the inhibitor-potentiated disc-diffusion test, the double-disc synergy test (when discs were 25 or 30 mm apart) and the Etest ESBL screen (with a breakpoint of > 4-fold reduction in ceftazidime MIC in the presence of clavulanate) were 100%, 96% and 89-96%, respectively. The inhibitor-potentiated disc-diffusion test was further evaluated with 81 E. coli and K. pneumoniae clinical isolates, which were identified as putative ESBL-producers by the double-disc synergy test. For these isolates, the sensitivity of both the inhibitor-potentiated disc-diffusion test and the Etest ESBL screen was 100%. In conclusion, the inhibitor-potentiated disc-diffusion test is a sensitive, convenient and inexpensive method of screening for ESBLs in E. coli and K. pneumoniae isolates, with potential for incorporation into routine clinical laboratory service.

Anti-Bacterial Agents↗