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PubMed1998

Cardiovascular risk factors associated with clinically isolated and diffuse atherosclerosis in Spanish patients with coronary artery disease.

BACKGROUND: Patients with coronary artery disease (CAD) associated with peripheral (PAD) or cerebrovascular disease (CVD), a condition called diffuse atherosclerosis, have a higher risk of death than patients with isolated CAD. The prevalence of diffuse atherosclerosis and the atherogenic risk factors associated with this condition in our geographic area have not been described previously. METHODS: A cohort of 2597 patients (62 +/- 10.8 years, 665 women) consecutively admitted at Bellvitge Hospital because of acute coronary syndromes were studied. CAD patients were divided in two groups with diffuse and located atherosclerosis according to whether they had or they had not an associated PAD or CVD. Baseline history, physical data and lipid profile were recorded in each patient according to a standardized questionnaire. RESULTS: A total of 370 patients (14.2%) had diffuse atherosclerosis. Among them, there were more men and women older than 55 years than among those with isolated CAD. Patients with diffuse atherosclerosis were more frequently hypertensive, diabetic and former smokers than those with isolated CAD (60.5% vs. 49.4%, P < 0.01; 37.4% vs. 24.5%, P < 0.01; and 47% vs. 35.7%, P < 0.01, respectively). There were no significant differences in the mean values of total cholesterol (TC), low-density cholesterol (LDL-C), high-density cholesterol (HDL-C) and triglycerides between both groups of patients, but patients with diffuse atherosclerosis had a lower HDL-C/TC ratio, with borderline statistical significance (0.18 +/- 0.06 vs. 0.19 +/- 0.06, P = 0.06). Using multiple logistic regression analysis, the variables associated with diffuse atherosclerosis in men were age greater than 55 years (OR 1.97, CI 1.33-2.93), hypertension (OR 1.50, CI 1.14-2.20), diabetes (OR 1.78, CI 1.20-2.70), smoking (former smokers) (OR 2.09, CI 1.36-3.24) and HDL-C/TC < 0.20 (OR 1.60, CI 1.18-2.17); and in women hypertension (OR 3.43, CI 1.48-7.94) and diabetes (OR 2.58, CI 1.55-4.80). CONCLUSIONS: Clinically overt diffuse atherosclerosis is a relatively common disease. Older patients and those with hypertension, diabetes or low HDL-C/TC ratio are more likely to have diffuse atherosclerosis than those without these conditions.

Aged↗

PubMed2005

Transient interfacial tension and dilatational rheology of diffuse polymer-polymer interfaces.

We demonstrate the influence of molecular weight and molecular weight asymmetry across an interface on the transient behavior of the interfacial tension. The interfacial tension was measured as a function of time for a range of polymer combinations with a broad range of interfacial properties using a pendant/sessile drop apparatus. The results show that neglecting mutual solubility, assumed to be a reasonable approximation in many cases, very often does not sustain. Instead, a diffuse interface layer develops in time with a corresponding transient interfacial tension. Depending on the specific combination of polymers, the transient interfacial tension is found to increase or decrease with time. The results are interpreted in terms of a recently proposed model [Shi et al., Macromolecules 37, 1591 (2004)], giving relative characteristic diffusion time scales in terms of molecular weight, molecular weight distribution, and viscosities. However, the time scales obtained from this theoretical approach do not give a conclusive trend. Using oscillatory dilatational interfacial experiments the viscoelastic behavior of these diffusive interfaces is demonstrated. The time evolution of the interfacial tension and the dilatational elasticity show the same trend as predicted by the theory of diffuse interfaces, supporting the idea that the polymer combinations under consideration indeed form diffuse interfaces. The dilatational elasticity and the dilatational viscosity show a frequency dependency that is described qualitatively by a simple Fickian diffusion model and quantitatively by a Maxwell model. The characteristic diffusion times provided by the latter show that the systems with thick interfaces (tens of microseconds and more) can be considered as slower diffusive systems compared to the systems with thinner interfaces (a few micrometers in thickness and less) can be considered as fast diffusive systems.

Journal Article↗

PubMed1992

Fibrinolytic activity in bronchoalveolar lavage of baboons with diffuse alveolar damage: trends in two forms of lung injury.

BACKGROUND AND METHODS: Alveolar fibrin deposition is prominent in diffuse alveolar damage, the morphologic hallmark of the adult respiratory distress syndrome. To determine if a persistent abnormality of fibrin clearance occurs in the alveolar compartment during evolving diffuse alveolar damage, we characterized abnormalities of fibrin turnover in serial bronchoalveolar lavage specimens from two baboon models: a) diffuse alveolar damage induced by 80% oxygen and bronchoscopic seeding of Pseudomonas aeruginosa; and b) a more fulminant form of diffuse alveolar damage induced by bronchoscopic seeding of Pseudomonas and the infusion of oleic acid. RESULTS: Lavage procoagulant activity, due mainly to tissue factor associated with Factor VII, was increased and exceeded regulation by extrinsic pathway inhibitor in both models. Fibrinolytic activity was transiently diminished in baboons with evolving diffuse alveolar damage induced by oleic acid/Pseudomonas, but was preserved after 80% oxygen/Pseudomonas. Concentrations of plasminogen activator inhibitor-2 did not increase in lavage specimens obtained during evolving diffuse alveolar damage. Concentrations of alpha 2 antiplasmin and plasminogen activator inhibitor-1 tended to be higher in the lavage of oleic acid/Pseudomonas baboons with low fibrinolytic activity. Immunohistochemical analyses showed that tissue factor was distributed along the alveolar surface of controls and baboons with diffuse alveolar damage. Alveolar fibrin deposition was increased, by morphometric analyses, in both models. CONCLUSIONS: These data indicate that while increased procoagulant activity is characteristic of evolving diffuse alveolar damage and favors alveolar fibrin deposition, fibrinolytic activity may be transiently diminished or remain intact during evolving diffuse alveolar damage in baboons.

Animals↗

PubMed1989

Symplastic Transport of Carboxyfluorescein in Staminal Hairs of Setcreasea purpurea Is Diffusive and Includes Loss to the Vacuole.

The kinetics of symplastic transport in staminal hairs of Setcreasea purpurea was studied. The tip cell of a staminal hair was microinjected with carboxyfluorescein (CF) and the symplastic transport of this CF was videotaped and the digital data analyzed to produce kinetic curves. Using a finite difference equation for diffusion between cells and for loss of dye into the vacuole, kinetic curves were calculated and fitted to the observed data. These curves were matched with data from actual microinjection experiments by adjusting K (the coefficient of intercellular junction diffusion) and L (the coefficient of intracellular loss) until a minimum in the least squares difference between the curves was obtained. (a) Symplastic transport of CF was governed by diffusion through intercellular pores (plasmodesmata) and intracellular loss. Diffusion within the cell cytoplasm was never limiting. (b) Each cell and its plasmodesmata must be considered as its own diffusion system. Therefore, a diffusion coefficient cannot be calculated for an entire chain of cells. (c) The movement through plasmodesmata in either direction was the same since the data are fit by a diffusion equation. (d) Diffusion through the intercellular pores was estimated to be slower than diffusion through similar pores filled with water.

Journal Article↗

PubMed2004

Comparison of results of fluconazole disk diffusion testing for Candida species with results from a central reference laboratory in the ARTEMIS global antifungal surveillance program.

The accuracy of antifungal susceptibility tests is important for accurate resistance surveillance and for the clinical management of patients with serious infections. Our main objective was to compare the results of fluconazole disk diffusion testing of Candida spp. performed by ARTEMIS participating centers with disk diffusion and MIC results obtained by the central reference laboratory. A total of 2,949 isolates of Candida spp. were tested by NCCLS disk diffusion and reference broth microdilution methods in the central reference laboratory. These results were compared to the results of disk diffusion testing performed in the 54 participating centers. All tests were performed and interpreted following NCCLS recommendations. Overall categorical agreement between participant disk diffusion test results and reference laboratory MIC results was 87.4%, with 0.2% very major errors (VME) and 3.3% major errors (ME). The categorical agreement between the disk diffusion test results obtained in the reference laboratory with the MIC test results was similar: 92.8%. Likewise, good agreement was observed between participant disk diffusion test results and reference laboratory disk diffusion test results: 90.4%, 0.4% VME, and 3.4% ME. The disk diffusion test was especially reliable in detecting those isolates of Candida spp. that were characterized as resistant by reference MIC testing. External quality assurance data obtained by surveillance programs such as the ARTEMIS Global Antifungal Surveillance Program ensure the generation of useful surveillance data and result in the continued improvement of antifungal susceptibility testing practices.

Antifungal Agents↗

PubMed1998

Microstructural development of human newborn cerebral white matter assessed in vivo by diffusion tensor magnetic resonance imaging.

Alterations of the architecture of cerebral white matter in the developing human brain can affect cortical development and result in functional disabilities. A line scan diffusion-weighted magnetic resonance imaging (MRI) sequence with diffusion tensor analysis was applied to measure the apparent diffusion coefficient, to calculate relative anisotropy, and to delineate three-dimensional fiber architecture in cerebral white matter in preterm (n = 17) and full-term infants (n = 7). To assess effects of prematurity on cerebral white matter development, early gestation preterm infants (n = 10) were studied a second time at term. In the central white matter the mean apparent diffusion coefficient at 28 wk was high, 1.8 microm2/ms, and decreased toward term to 1.2 microm2/ms. In the posterior limb of the internal capsule, the mean apparent diffusion coefficients at both times were similar (1.2 versus 1.1 microm2/ms). Relative anisotropy was higher the closer birth was to term with greater absolute values in the internal capsule than in the central white matter. Preterm infants at term showed higher mean diffusion coefficients in the central white matter (1.4 +/- 0.24 versus 1.15 +/- 0.09 microm2/ms, p = 0.016) and lower relative anisotropy in both areas compared with full-term infants (white matter, 10.9 +/- 0.6 versus 22.9 +/- 3.0%, p = 0.001; internal capsule, 24.0 +/- 4.44 versus 33.1 +/- 0.6% p = 0.006). Nonmyelinated fibers in the corpus callosum were visible by diffusion tensor MRI as early as 28 wk; full-term and preterm infants at term showed marked differences in white matter fiber organization. The data indicate that quantitative assessment of water diffusion by diffusion tensor MRI provides insight into microstructural development in cerebral white matter in living infants.

Anisotropy↗

PubMed2001

Investigation of MS normal-appearing brain using diffusion tensor MRI with clinical correlations.

OBJECTIVE: To quantitatively investigate water diffusion changes in normal-appearing white matter (NAWM) and gray matter in patients with MS, and to evaluate whether these changes are correlated with clinical disability and disease duration. BACKGROUND: Diffusion tensor imaging provides quantitative information about the magnitude and directionality (anisotropy) of water diffusion in vivo and detects pathologic changes in MS brain tissue. METHODS: Diffusion tensor imaging was performed in 39 patients with MS and in 21 age-matched control subjects. Quantitative indices, including fractional anisotropy, volume ratio, and mean diffusivity, were obtained in 30 regions of interest located in normal-appearing basal ganglia, cerebellar gray matter, and supratentorial and infratentorial NAWM. RESULTS: Patients with MS showed significantly reduced anisotropy and a trend toward increased diffusivity in the infratentorial and supratentorial NAWM, and significantly increased anisotropy in the basal ganglia. In all patients with MS, both fractional anisotropy and mean diffusivity in the cerebral peduncles were inversely correlated with the Expanded Disability Status Scale and pyramidal functional scores. In patients with relapsing-remitting MS, there was a strong correlation between Expanded Disability Status Scale score and fractional anisotropy in both supratentorial and infratentorial NAWM. In primary and secondary progressive MS, disease duration correlated strongly with mean diffusivity in infratentorial NAWM and fractional anisotropy in the cerebral peduncles, respectively. CONCLUSION: The most striking finding of decreased fractional anisotropy in supratentorial and infratentorial NAWM and increased fractional anisotropy in basal ganglia may result from axonal degeneration due to fiber transection in remote focal lesions. Diffusion tensor imaging indices, in particular fractional anisotropy, appear sensitive to structural damage in NAWM that is associated with disability and progression in MS.

Adult↗

PubMedDate not supplied

Pretreatment prediction of brain tumors' response to radiation therapy using high b-value diffusion-weighted MRI.

Diffusion-weighted magnetic resonance imaging (DWMRI) is sensitive to tissues' biophysical characteristics, including apparent diffusion coefficients (ADCs) and volume fractions of water in different populations. In this work, we evaluate the clinical efficacy of DWMRI and high diffusion-weighted magnetic resonance imaging (HDWMRI), acquired up to b = 4000 sec/mm(2) to amplify sensitivity to water diffusion properties, in pretreatment prediction of brain tumors' response to radiotherapy. Twelve patients with 20 brain lesions were studied. Six ring-enhancing lesions were excluded due to their distinct diffusion characteristics. Conventional and DWMRI were acquired on a 0.5-T MRI. Response to therapy was determined from relative changes in tumor volumes calculated from contrast-enhanced T1-weighted MRI, acquired before and a mean of 46 days after beginning therapy. ADCs and a diffusion index, R(D), reflecting tissue viability based on water diffusion were calculated from DWMRIs. Pretreatment values of ADC and R(D) were found to correlate significantly with later tumor response/nonresponse (r = 0.76, P <.002 and r = 0.77, P <.001). This correlation implies that tumors with low pretreatment diffusion values, indicating high viability, will respond better to radiotherapy than tumors with high diffusion values, indicating necrosis. These results demonstrate the feasibility of using DWMRI for pretreatment prediction of response to therapy in patients with brain tumors undergoing radiotherapy.

Brain↗

PubMed2000

Neonatal hypoxic-ischemic encephalopathy: detection with diffusion-weighted MR imaging.

BACKGROUND AND PURPOSE: Although diffusion-weighted imaging has been shown to be highly sensitive in detecting acute cerebral infarction in adults, its use in detecting neonatal hypoxic-ischemic encephalopathy (HIE) has not been fully assessed. We examined the ability of this technique to detect cerebral changes of acute neonatal HIE in different brain locations. METHODS: Fifteen MR examinations were performed in 14 neonates with HIE (median age, 6.5 days; range, 2-11 days). Imaging comprised conventional T1-weighted, proton density-weighted, and T2-weighted sequences and echo-planar diffusion-weighted sequences. The location, extent, and image timing of ischemic damage on conventional and diffusion-weighted sequences and apparent diffusion coefficient (ADC) maps were compared. RESULTS: Although conventional sequences showed cerebral changes consistent with ischemia on all examinations, diffusion-weighted imaging showed signal hyperintensity associated with decreased ADC values in only seven subjects (47%). All subjects with isolated cortical infarction on conventional sequences had corresponding hyperintensity on diffusion-weighted images and decreased ADC values, as compared with 14% of subjects with deep gray matter/perirolandic cortical damage. The timing of imaging did not significantly alter diffusion-weighted imaging findings. CONCLUSION: Diffusion-weighted imaging, performed with the technical parameters in this study, may have a lower correlation with clinical evidence of HIE than does conventional MR imaging. The sensitivity of diffusion-weighted imaging in detecting neonatal HIE appears to be affected by the pattern of ischemic damage, with a lower sensitivity if the deep gray matter is affected as compared with isolated cerebral cortex involvement.

Aging↗

PubMed2001

Restricted diffusion within ring enhancement is not pathognomonic for brain abscess.

BACKGROUND AND PURPOSE: Recent experience suggests that diffusion-weighted MR imaging may be decisive in the differential diagnosis of ring-enhancing cerebral lesions. Whether restricted diffusion within a ring-enhancing cerebral mass lesion is pathognomonic for abscess was studied. METHODS: Seventeen patients with ring-enhancing cerebral lesions (three abscesses, six glioblastomas, eight metastases) on conventional contrast-enhanced T1-weighted images were examined with echo-planar diffusion-weighted MR imaging. Apparent diffusion coefficient (ADC) maps and the ADCs were calculated for all lesions. Lesions with signs of intralesional hemorrhage on unenhanced T1-weighted images were excluded. RESULTS: The central portion of all six glioblastomas and seven of eight metastases showed unrestricted diffusion, whereas two of three abscesses showed restricted diffusion (low ADC values) in their cavity. However, restricted diffusion also was found in one metastasis, and one abscess within a postoperative cavity showed unrestricted diffusion within a larger nondependent portion. CONCLUSION: In patients with ring-enhancing cerebral mass lesions, restricted diffusion might be characteristic but is not pathognomonic for abscess, as low ADC values also may be found in brain metastases.

Brain Abscess↗

PubMed2003

[Diffusion-weighted imaging of acute vertebral compression: Differential diagnosis of benign versus malignant pathologic fractures].

PURPOSE: Our purpose was to assess the value of diffusion-weighted steady-state free precession (SSFP) sequence for differentiating between benign and pathologic compression fractures. MATERIALS AND METHODS: Forty-nine patients with 63 acute vertebral compression fractures caused by osteoporosis (n = 23), trauma (n = 7), malignancy (n = 30), infection (n = 3) were examined with a diffusion-weighted SSFP sequence (diffusion gradient strength; 23 mT/m, diffusion pulse length 5 ms), T1-weighted turbo spin-echo sequence, and short-inversion-time (TI 150 ms) T2-weighted turbo inversion recovery sequence. The signal intensity characteristics were analyzed qualitatively and quantitatively for all sequences. Statistical analysis was performed with the Student's t test. RESULTS: In diffusion-weighted MR imaging, benign osteoporotic and traumatic fractures were hypo- to isointense to adjacent normal vertebral bodies. Pathologic and infectious compression fractures were hyperintense to normal vertebral bodies. Pathologic vertebral fractures had positive bone marrow contrast ratios at diffusion-weighted imaging, whereas non infectious benign vertebral fractures had negative values (p < 0.001). The difference in bone marrow contrast ratios for benign and pathologic compression fractures at T1-weighted TSE and T2-weighted turbo IR was not significant (p > 0.01). CONCLUSION: Diffusion-weighted SSFP sequence provides unique information that significantly impacts the accuracy of radiologic diagnosis. Diffusion-weighted SSFP sequence may allow the differentiation of acute benign osteoporotic fractures from malignant compression fractures. Acute benign osteoporotic or traumatic fractures show hypointense or isointense signal on diffusion-weighted sequences that reflects persistent free water proton mobility. Malignant compression fractures show hyperintensity compared with normal surrounding bone marrow probably due to altered water proton mobility within the neoplasm.

Adult↗

PubMed2006

MR imaging, MR spectroscopy, and diffusion tensor imaging of sequential studies in neonates with encephalopathy.

BACKGROUND: Although the imaging, spectroscopic, and diffusion characteristics of brains of infants with neonatal encephalopathy have been described, the time course during which these changes evolve is not clear. The results of sequential MR imaging studies--including anatomic MR imaging, proton MR spectroscopy, and diffusion tensor imaging (DTI)--of 10 patients enrolled prospectively in a study of neonatal encephalopathy are reported to help to clarify the time course of changes in different brain regions during the first 2 weeks of life. METHODS: Ten neonates were prospectively enrolled in a study of the evolution of MR findings in neonatal encephalopathy and were studied 2 (8 patients) or 3 (2 patients) times within the first 2 weeks of life. The MR examination included spin-echo T1 and T2-weighted images, DTI, and long echo time (288 milliseconds) proton MR spectroscopy. Diffusion parameters (diffusivity [D(av)], fractional anisotropy [FA], and individual eigenvalues) were calculated for 10 1-cm2 regions of interest in each hemisphere that were placed based on anatomic landmarks. D(av) and FA were then measured manually in the same areas on a workstation. Metabolite ratios (NAA/Ch, Cr/Ch, Cr/NAA, Lac/Ch, and Lac/NAA) were calculated in 7 regions of interest. Imaging appearance, diffusion parameters, and metabolite ratios were then evaluated longitudinally (comparing with other studies on the same patient at different times) and cross-sectionally (comparing all studies performed on the same postnatal day). RESULTS: In most of the patients a characteristic evolution of DTI and MR spectroscopy parameters was seen during the first 2 weeks after birth. Although the anatomic images were normal or nearly normal on the first 2 days after birth in most patients, abnormalities were detected on DTI (both visually and by quantitative interrogation of D(av) maps) and proton MR spectroscopy (abnormal metabolite ratios). These parameters tended to worsen until about day 5 and then normalize, though in several patients abnormal metabolite ratios persisted. Of interest, as areas of abnormal diffusivity pseudonormalized within one region of the brain they would develop in other areas. Therefore, the pattern of injury looked very different when imaging was performed at different times during this evolution. CONCLUSION: Patterns of injury detected by standard anatomic imaging sequences, DTI sequences, and proton MR spectroscopy varied considerably during the first 2 weeks after injury. The appearance of new areas of reduced diffusion simultaneous with the pseudonormalization of areas that had reduced diffusion at earlier times can result in an entirely different pattern of injury on diffusivity maps acquired at different time points. Awareness of these evolving patterns is essential if studies are performed and interpreted during this critical period of time.

Brain Diseases↗

PubMed1978

[Clinicopathological study of diffuse carcinoma of stomach (author's transl)].

The biological behavior of ulcer type gastric carcinoma was studied on 114 cases of diffuse carcinoma (Borrmann's 4 type) and 262 cases of early like advanced carcinoma (including superficial spreading type). In both types of gastric carcinoma, the age distribution, location, ulcer with cancer focus and prognosis differed greatly. The early like carcinoma was speculated to have advanced maintaining the groos findings of early gastric carcinoma, and its location and associated ulcer were the same as the early ulcer type of carcinoma. The prognosis of this type of carcinoma was good, showing a figure of 70% in 3 year survival rate. On the other hand, diffuse carcinoma demonstrated diffuse extensive infiltration of tumor cells along the gastric wall, resulting in poor prognosis with a 3 year survival rate of almost 0%. Histologically, diffuse type of carcinoma showed lymphatic infiltration of tumor cells, and this is probably the main reason for the diffuse infiltration in this type of carcinoma. Diffuse carcinoma is, therefore, considered to be one special type of carcinoma having different biological behavior compared with the other ulcer type of carcinoma, and diffuse carcinoma is not the terminal stage of early like advanced carcinoma. There are three stages in diffuse carcinoma: 1. Infiltrative stage: wide spread infiltration of cancer cells through lymphatic channels (lymphangiosis carcinomatosa) 2. Edematous stage: soluble collagen appearing in gastric wall 3. Sclerosing stage: soluble collagen changing into insoluble collagen leading to marked thickening and stiffness of the gastric wall. This is the end stage of gastric diffuse carcinoma. It is difficult to explain that the marked fibrosis of gastric wall is a result to stromal reaction from tumor cell infiltration, since extensive fibrosis is found in areas without tumor cells and stiffness of the gastric wall occurs in a too short period of time. The production of abundunt soluble collagen is probably related to cancer cells.

Adenocarcinoma, Scirrhous↗

PubMed1983

Rapid lateral diffusion of extrajunctional acetylcholine receptors in the developing muscle membrane of Xenopus tadpole.

We have studied the lateral diffusion of acetylcholine (ACh) receptors in the extrajunctional region of developing myotomal muscle cell membrane of Xenopus tadpoles by a technique of local inactivation. The myotomal muscle cell surfaces of Xenopus tadpoles were exposed to external solution by gently removing the skin of the tail. The density of ACh receptors was monitored by membrane depolarizations in response to iontophoretically applied pulses of ACh. A pulse of alpha-bungarotoxin was pressure ejected onto the exposed fiber surface, resulting in a rapid local inactivation of the ACh receptors. With time, the functional ACh receptors diffused into the region of inactivation, producing a recovery of ACh response. That the observed recovery of ACh sensitivity is due to diffusion of ACh receptors from the unexposed undersurface of the fiber to the inactivated region was evidenced by the following: (1) no recovery was observed following prolonged toxin application; (2) pretreatment of the muscle cells with concanavalin A, which cross-links and immobilizes ACh receptors, prevented recovery; (3) mapping of ACh response along the muscle cell axis showed that the recovery cannot be accounted for by diffusion along the longitudinal axis of the fiber; and (4) the diffusion coefficients observed after scaling the recovery rate with fiber radius fell within a small range (1.5 to 4.0 X 10(-9) cm2/sec), consistent with diffusion of ACh receptors around the fiber circumference. This finding of rapid lateral diffusion within developing tadpole myotomal muscle membrane supports the notion that the localization of ACh receptors induced by innervation could be achieved by a "diffusion-trap" mechanism where the nerve contact region serves as a trap for rapidly diffusing receptors in the membrane.

Acetylcholine↗

PubMed1996

Correlates and consequences of diffuse atherosclerosis in men with coronary heart disease. Veterans Affairs High-Density Lipoprotein Intervention Trial Study Group.

BACKGROUND: Peripheral atherosclerosis is a strong and independent predictor of mortality even in patients with known coronary heart disease. However, the prevalence, correlates, and potential adverse effects on quality of life associated with combined coronary heart disease and clinically evident cerebrovascular or lower-extremity atherosclerosis are not known. Identification of patients with "diffuse atherosclerosis" may enhance treatment of modifiable risk factors and alter therapeutic strategies. METHODS: We conducted a cross-sectional analysis of 2531 men younger than 73 years with coronary heart disease, low-density lipoprotein cholesterol levels of 3.62 mmol/L (140 mg/dL) or less, and high-density lipoprotein cholesterol level of 1.03 mmol/L (40 mg/dL) or less who were participating in Department of Veterans Affairs Cooperative Study 363 (the Veterans Affairs High-Density Lipo-protein Intervention Trial. Baseline demographic, medication, comorbidity, and atherosclerotic risk factor data were assessed by means of a standardized questionnaire. All plasma lipid levels were determined after a 12-hour fast by a central standardized lipid laboratory. Health status was determined by baseline reported symptoms, medical comorbidities, and the Psychological General Well-being Index. Clinically evident diffuse atherosclerosis was defined as a documented history of lower-extremity atherosclerosis or cerebrovascular disease. RESULTS: The mean age of all participants was 63.5 years. The mean plasma lipid values were as follows: total cholesterol, 4,52 mmol/L (174.6 mg/dL); high-density lipo-protein cholesterol, 0.81 mmol/L (31.5 mg/dL); low-density lipoprotein cholesterol, 2.88 mmol/L (111.2 mg/dL); and triglycerides, 1.81 mmol/L (160.6 mg/dL). Diffuse atherosclerosis was present in 525 (21%). Lower-extremity atherosclerosis was reported in 10%, while cerebrovascular disease was present in 13%. After controlling for other variables, the following factors were associated with the presence of diffuse atherosclerosis: increased age, being unmarried, being retired, having less than a high school education, increased alcohol use, hypertension, cigarette smoking, and diabetes. There was no association between lipid levels and the presence of diffuse atherosclerosis. After adjustment for age, race, and comorbidities, men with diffuse disease still had a reduced quality of life compared with men without diffuse atherosclerosis, as defined by having a greater number of clinical symptoms, lower psychological well-being scores, and more advanced or complicated coronary heart disease. CONCLUSIONS: Clinically evident diffuse atherosclerosis is common in men with coronary heart disease and low levels of high-density lipoprotein cholesterol. Because diffuse atherosclerosis is associated with a reduced quality of life and several modifiable risk factors, early detection and aggressive risk factor intervention appear justified.

Adult↗

PubMed2003

Oscillating gradient measurements of water diffusion in normal and globally ischemic rat brain.

Oscillating gradients were used to probe the diffusion-time/frequency dependence of water diffusion in the gray matter of normal and globally ischemic rat brain. In terms of a conventional definition of diffusion time, the oscillating gradient measurements provided the apparent diffusion coefficient (ADC) of water with diffusion times between 9.75 ms and 375 micros, an order of magnitude shorter than previously studied in vivo. Over this range, ADCs increased as much as 24% in vivo and 50% postmortem, depending on the nature of the oscillating gradient waveform used. Novel waveforms were employed to sample narrow frequency bands of the so-called diffusion spectrum. This spectral description of ADC includes the effects of restriction and/or flow, and is independent of experimental parameters, such as diffusion time. The results in rat brain were found to be consistent with restricted diffusion and the known micro-anatomy of gray matter. Differences between normal and postmortem data were consistent with an increase in water restriction and/or a decrease in flow, and tentatively suggest that physical changes following the onset of ischemia occur on a scale of about 2 microm, similar to a typical cellular dimension in gray matter.

Animals↗

PubMed2005

Acquisition of pure-phase diffusion spectra using oscillating-gradient spin echo.

Oscillating-gradient spin echo (OGSE) diffusion experiments have long been used to measure the short-time apparent diffusion coefficient, D(app)(t), in the presence of restricted diffusion, as well as the spectrum of the slow-motion velocity autocorrelation function. In this work, we focus on two previously unexplored aspects of OGSE experiments: convection compensation and acquisition of pure-phase diffusion spectra in the presence of homonuclear scalar couplings. We demonstrate that convection compensation afforded by single-echo OGSE compares well with that in double-echo convection-compensated PGSE experiments. We also show that, in the presence of homonuclear scalar couplings, setting the OGSE echo time to 1/2J enables acquisition of pure-phase diffusion spectra and yields more reliable D estimates than mixed-phase PGSE or OGSE spectra. Pure-phase OGSE acquisition is also compatible with measurements of the apparent diffusion coefficient at an arbitrary diffusion time. These features of OGSE can be valuable in diffusion measurements of scalar-coupled small-molecule probes in cellular and other heterogeneous systems.

Algorithms↗

PubMed2003

Diffusion magnetic resonance imaging study of a rat hippocampal slice model for acute brain injury.

Diffusion magnetic resonance imaging (MRI) provides a surrogate marker of acute brain pathology, yet few studies have resolved the evolution of water diffusion changes during the first 8 hours after acute injury, a critical period for therapeutic intervention. To characterize this early period, this study used a 17.6-T wide-bore magnet to measure multicomponent water diffusion at high b-values (7 to 8,080 s/mm(2)) for rat hippocampal slices at baseline and serially for 8 hours after treatment with the calcium ionophore A23187. The mean fast diffusing water fraction (Ffast) progressively decreased for slices treated with 10-microM/L A23187 (-20.9 +/- 6.3% at 8 hours). Slices treated with 50-micromol/L A23187 had significantly reduced Ffast 80 minutes earlier than slices treated with 10-microM/L A23187 (P < 0.05), but otherwise, the two doses had equivalent effects on the diffusion properties of tissue water. Correlative histologic analysis showed dose-related selective vulnerability of hippocampal pyramidal neurons (CA1 > CA3) to pathologic swelling induced by A23187, confirming that particular intravoxel cell populations may contribute disproportionately to water diffusion changes observed by MRI after acute brain injury. These data suggest diffusion-weighted images at high b-values and the diffusion parameter Ffast may be highly sensitive correlates of cell swelling in nervous issue after acute injury.

Acute Disease↗