Biomedical subjects

James Sayre

Publications and source records attributed to James Sayre.

At least 19 recordsLinked to original sources

PubMed2006

PET-measured heterogeneity in longitudinal myocardial blood flow in response to sympathetic and pharmacologic stress as a non-invasive probe of epicardial vasomotor dysfunction.

PURPOSE: We investigated whether a myocardial perfusion gradient during pharmacologically induced hyperemia also occurred during sympathetic stimulation with cold pressor testing (CPT), which commonly induces a paradoxical coronary vasoconstriction in individuals with coronary risk factors. METHODS: Myocardial blood flow (MBF) was measured in absolute units (ml/g/min) with 13N-ammonia and PET at rest, during CPT, and during pharmacologic vasodilation in 59 participants with coronary risk factors ("at risk") and in 43 healthy individuals (controls). MBF was assessed globally as mean MBF, and in the mid and mid-distal myocardium of the left ventricle (LV). A decrease in MBF from mid to mid-distal LV myocardium was defined as MBF difference indicative of a perfusion gradient. RESULTS: The change in mean MBF to CPT (DeltaMBF) in the at-risk group was significantly reduced compared with controls (0.05+/-0.19 vs 0.31+/-0.20 ml/g/min, p<0.0001), whereas mean MBF during pharmacologic vasodilation in the at-risk group tended to be lower than in controls (1.72+/-0.71 vs 2.00+/-0.64 ml/g/min, p=NS). Absolute MBFs during CPT and pharmacologic vasodilation were significantly lower in the mid-distal than in the mid LV myocardium, resulting in a significant MBF difference in the at-risk group (0.15+/-0.06 and 0.27+/-0.12 ml/g/min, p<0.0001) that was not observed in controls (0.007+/-0.05 and 0.014+/-0.10 ml/g/min, p=NS). In the at-risk group there was a significant correlation between the difference of mid to mid-distal MBF during CPT and that during pharmacologic vasodilation (r=0.43, p<0.004), suggesting functional alterations of epicardial vessels as the predominant cause for the observed MBF difference. CONCLUSION: The relative decrease in MBF from the mid to the mid-distal left-ventricular myocardium suggests an intracoronary pressure decline during CPT and pharmacologic vasodilation, which is likely to reflect an impairment of flow-mediated epicardial vasomotor function.

Adult↗

PubMed2006

Relationship between increasing body weight, insulin resistance, inflammation, adipocytokine leptin, and coronary circulatory function.

OBJECTIVES: We sought to evaluate effects of obesity, insulin resistance, and inflammation on coronary circulatory function and its relationship to leptin plasma levels. BACKGROUND: It is not known whether obesity, commonly paralleled by insulin resistance, inflammation, and leptin, is independently associated with coronary circulatory dysfunction. METHODS: Myocardial blood flow (MBF) responses to cold pressor test (CPT) and pharmacologic vasodilation was measured with positron emission tomography and 13N-ammonia. Study participants were divided into three groups based on their body mass index (BMI, kg/m2): control, 20 < or = BMI <25 (n = 19); overweight, 25 < or = BMI <30 (n = 21); and obese, BMI >30 (n = 32). RESULTS: Body mass index was significantly correlated to the Homeostasis Model Assessment Index of insulin resistance and C-reactive protein levels (r = 0.60 and r = 0.47, p < 0.0001). Compared with control subjects, endothelium-related change in MBF (DeltaMBF) to CPT progressively declined in overweight and obese groups (0.32 +/- 0.09 vs. 0.21 +/- 0.19 and 0.07 +/- 0.16 ml/g/min; p < 0.03 and p < 0.0001). The dipyridamole-induced total vasodilator capacity was significantly lower in obese than in control subjects (1.77 +/- 0.51 vs. 2.04 +/- 0.37 ml/g/min, p < 0.02). On multivariate analysis, BMI (p < 0.012) and age (p < 0.035) were significant independent predictors of DeltaMBF. Finally, only in the obese group leptin plasma levels significantly correlated with DeltaMBF (r = 0.37, p < 0.036). CONCLUSIONS: Increased body weight is independently associated with abnormal coronary circulatory function that progresses from an impairment in endothelium-related coronary vasomotion in overweight individuals to an impairment of the total vasodilator capacity in obese individuals. The findings that elevated leptin plasma levels in patients that are obese might exert beneficial effects on the coronary endothelium to counterbalance the adverse effects of increases in body weight on coronary circulatory function should be tested.

Adult↗

PubMed2006

Hepatic encephalopathy: a neurochemical, neuroanatomical, and neuropsychological study.

Hepatic encephalopathy (HE) is normally diagnosed by neuropsychological (NP) tests, which are not very specific and do not reveal the underlying pathology. Magnetic resonance imaging (MRI) and spectroscopy (MRS) of the brain offer alternative and possibly more specific markers for HE. These methods were applied in conjunction with NP testing in order to determine their usefulness in the identification of HE and to understand the pathogenesis of HE more clearly. MR imaging and spectroscopy examinations, in addition to a battery of 15 NP tests, were administered to investigate 31 patients awaiting liver transplantation and 23 healthy controls. MR image intensities from the globus pallidus region were calculated and normalized to those of the thalamus. Absolute concentrations and ratios with respect to creatine (Cr) of several metabolites were computed from MR spectra. The MR data were correlated with the results of NP tests. The patients showed impairment in NP tests of attention and visuospatial and verbal fluency. In T1-weighted MRI, the relative intensity of the globus pallidus with respect to that of the thalamus region was significantly elevated in patients and correlated(negatively) with three NP tests (Hooper, FAS, and Trails B). The absolute concentrations of myo-inositol (mI) and choline (Ch) were significantly reduced in three brain regions. In addition, the absolute concentrations of glutamine (Gln) and combined glutamate and glutamine (Glx) were increased in all three locations, with Gln increase being significant in all areas while that of Glx only in the occipital white matter. In summary, this study partially confirms a hypothesized mechanism of HE pathogenesis, an increased synthesis of glutamine by brain glutamate in astrocytes due to excessive blood ammonia, followed by a compensatory loss of myo-inositol to maintain astrocyte volume homeostasis. It also indicates that the hyperintensity observed in globus pallidus could be used as complementary to the NP test scores in evaluating the mental health of HE patients.

Adult↗

PubMed2006

Quantitative metrics for evaluating parallel acquisition techniques in diffusion tensor imaging at 3 Tesla.

OBJECTIVES: Single-shot echo-planar based diffusion tensor imaging is prone to geometric and intensity distortions. Parallel imaging is a means of reducing these distortions while preserving spatial resolution. A quantitative comparison at 3 T of parallel imaging for diffusion tensor images (DTI) using k-space (generalized auto-calibrating partially parallel acquisitions; GRAPPA) and image domain (sensitivity encoding; SENSE) reconstructions at different acceleration factors, R, is reported here. MATERIALS AND METHODS: Images were evaluated using 8 human subjects with repeated scans for 2 subjects to estimate reproducibility. Mutual information (MI) was used to assess the global changes in geometric distortions. The effects of parallel imaging techniques on random noise and reconstruction artifacts were evaluated by placing 26 regions of interest and computing the standard deviation of apparent diffusion coefficient and fractional anisotropy along with the error of fitting the data to the diffusion model (residual error). RESULTS: The larger positive values in mutual information index with increasing R values confirmed the anticipated decrease in distortions. Further, the MI index of GRAPPA sequences for a given R factor was larger than the corresponding mSENSE images. The residual error was lowest in the images acquired without parallel imaging and among the parallel reconstruction methods, the R = 2 acquisitions had the least error. The standard deviation, accuracy, and reproducibility of the apparent diffusion coefficient and fractional anisotropy in homogenous tissue regions showed that GRAPPA acquired with R = 2 had the least amount of systematic and random noise and of these, significant differences with mSENSE, R = 2 were found only for the fractional anisotropy index. CONCLUSION: Evaluation of the current implementation of parallel reconstruction algorithms identified GRAPPA acquired with R = 2 as optimal for diffusion tensor imaging.

Adult↗

PubMed2006

Stereotactic radiosurgery of the rete mirabile in swine: a longitudinal study of histopathological changes.

OBJECTIVE: Stereotactic radiosurgery is an established, effective treatment for brain arteriovenous malformations. The mechanisms of vessel occlusion in arteriovenous malformations has not been extensively evaluated. To better understand these mechanisms, we report histopathological changes in the swine rete mirabile after stereotactic radiosurgery. METHODS: Thirty-five swine were used, 15 as nonradiated controls and 20 as radiated. Two in the control group and five in the radiated group were sacrificed before the study endpoint. Tissue was obtained from 13 nonradiated (4 at 3 mo, 5 at 6 mo, 4 at 9 mo) and 15 radiated swine (2 at 3 mo, 3 at 6 mo, 10 at 9 mo) for histological, immunohistochemical, and morphometric analysis. RESULTS: Radiated vessels showed increasing intimal hyperplasia over the follow-up period. Histometrical analysis confirmed this with evidence of progressive luminal narrowing over the follow-up period. Immunohistochemical analysis showed intimal cells to be proliferating smooth muscle cells with surrounding extracellular collagen Type IV. Adventitial fibrosis composed of collagen Type IV was also seen with smooth muscle cells interspersed within the collagen matrix. The nonradiated animals showed no intimal hyperplasia or change in the appearance or size of the vessels over the same follow-up period. Adventitial fibrosis was minimal in the nonradiated animals. CONCLUSION: The vessels show an intimal response to radiation with progressive occlusion caused by migrating, proliferating smooth muscle cells, a likely source of the extracellular collagen in the intima. Cytokine mediated pathways likely produce these morphological changes. Future studies will be directed toward elucidating these underlying molecular mechanisms.

Animals↗

PubMed2006

Curcuminoids enhance amyloid-beta uptake by macrophages of Alzheimer's disease patients.

Treatment of Alzheimer's disease (AD) is difficult due to ignorance of its pathogenesis. AD patients have defects in phagocytosis of amyloid-beta (1-42) (Abeta) in vitro by the innate immune cells, monocyte/macrophages and in clearance of Abeta plaques [5]. The natural product curcuminoids enhanced brain clearance of Abeta in animal models. We, therefore, treated macrophages of six AD patients and 3 controls by curcuminoids in vitro and measured Abeta uptake using fluorescence and confocal microscopy. At baseline, the intensity of Abeta uptake by AD macrophages was significantly lower in comparison to control macrophages and involved surface binding but no intracellular uptake. After treatment of macrophages with curcuminoids, Abeta uptake by macrophages of three of the six AD patients was significantly (P<0.001 to 0.081) increased. Confocal microscopy of AD macrophages responsive to curcuminoids showed surface binding in untreated macrophages but co-localization with phalloidin in an intracellular compartment after treatment. Immunomodulation of the innate immune system by curcuminoids might be a safe approach to immune clearance of amyloidosis in AD brain.

Aged↗

PubMed2005

Positron emission tomography-measured abnormal responses of myocardial blood flow to sympathetic stimulation are associated with the risk of developing cardiovascular events.

OBJECTIVES: We sought to assess prospectively whether patients with normal coronary angiograms but with impaired myocardial blood flow (MBF) increases to cold pressor testing (CPT) are at increased risk for cardiovascular events. BACKGROUND: Invasive angiographic assessments of coronary vasomotor function have demonstrated an impairment of endothelium-related coronary flow increases to independently predict future cardiovascular events. It is unknown whether noninvasive positron emission tomography (PET)-measured MBF alterations to sympathetic stimulation with CPT are associated with the risk of developing cardiovascular events. METHODS: A total of 72 patients (44 men, 28 women, age 58 +/- 8 years) referred for diagnostic cardiac catheterization were studied. Myocardial blood flow was measured in absolute units with (13)N-ammonia using PET, at baseline and during CPT in each patient. Cardiovascular events (cardiovascular death, acute coronary syndrome, myocardial infarction, percutaneous transluminal coronary angioplasty, coronary artery bypass grafting, ischemic stroke, or peripheral revascularization) were assessed as clinical outcome parameters over a mean follow-up period of 66 +/- 8 months. Patients were assigned to three groups: group 1, patients with >/=40% increase in MBF (%DeltaMBF), n = 22; group 2, patients with >0 and <40% increases in MBF, n = 32; and group 3, patients with decreases in MBF (</=0%), n = 18. RESULTS: During follow-up, one of the group 1 patients developed a cerebral stroke. In group 2, 15 cardiovascular events occurred in 9 patients and in group 3, 7 patients experienced 9 cardiovascular events (p </= 0.0001, univariate by log-rank test). Impaired MBF increases in group 2 and group 3 were associated with a significantly higher incidence of cardiovascular events by Kaplan-Meier analysis (p = 0.033, log-rank test). After adjusting for known coronary risk factors, MBF responses to CPT revealed a nonsignificant trend to be independently associated with a higher incidence for cardiovascular events (p = 0.065, multivariate by Cox regression model). CONCLUSIONS: Noninvasive PET-measured impaired MBF increases to sympathetic stimulation are associated with the risk of developing cardiovascular events.

Ammonia↗

PubMed2005

Two-dimensional MR spectroscopic characterization of breast cancer in vivo.

The major goal of this work was to characterize invasive ductal carcinoma and healthy fatty breast tissues noninvasively using the classification and regression tree analysis (CART) of 2D MR spectral data. 2D L-COSY spectra were acquired in 14 invasive breast carcinoma and 21 healthy fatty breasts using a GE 1.5 Tesla MRI/MRS scanner equipped with a 2-channel phased-array breast MR coil. The 2D spectra were recorded in approximately 10 minutes using a minimum voxel size of 1 ml without any water suppression technique. For healthy breasts, spectra were acquired from at least one fatty region. 2D L-COSY spectra were recorded in a total of 43 voxels. Five diagonal and six cross peak volumes were integrated and at least eighteen ratios were selected as potential features for the statistical method, namely CART. The 2D L-COSY data showed a significant increase for the majority of these ratios in invasive breast carcinomas compared to healthy fatty tissues. Better accuracy of identifying carcinomas and fatty tissues is reported using CART analysis of different combinations of ratios calculated from the relative levels of water, choline, and saturated and unsaturated lipids. This is a first report on the statistical classification of 2D L-COSY in human breast carcinomas in vivo.

Adult↗

PubMed2005

Aneurysms of the posterior circulation: detection and treatment planning using volume-rendered three-dimensional helical computerized tomography angiography.

OBJECT: The aim of this study was to determine whether computerized tomography (CT) angiography could be used to identify and characterize aneurysms of the posterior circulation and guide optimal treatment selection, and how data obtained using this method compared with intraoperative findings. METHODS: Patients suspected of harboring brain aneurysms underwent CT angiography and digital subtraction (DS) angiography; the results were prospectively interpreted by blinded independent evaluators. All patients with posterior circulation aneurysms were consecutively enrolled in the study. After treatment, neurosurgeons and endovascular therapists evaluated the ability of CT and DS angiography to demonstrate features of the lesions important for triage between treatment options (Wilcoxon signed-rank test) and to allow for coil or clip preselection and complete treatment planning (McNemar test of proportions), while using intraoperative findings as the basis of truth. In 242 patients overall, CT angiography detected 38 aneurysms and two aneurysmal blisters in 32 patients. The sensitivity of CT angiography in revealing posterior circulation aneurysms was 100% compared with DS angiography, with no false-positive results. Furthermore, CT angiography was sufficient as the sole study at triage for 65% of the posterior circulation aneurysms (26 of 40 lesions; p < 0.001), including 62% of the complex lesions (p < 0.001), and permitted coil or clip preselection in 74% of treated cases (20 of 27 cases; p < 0.002). Results of CT angiography revealed information about mural calcification and intraluminal thrombus not available on DS angiography, which affected patient care. CONCLUSIONS: In this study population, CT angiography was comparable to DS angiography in the detection and characterization of aneurysms of the posterior circulation. Computerized tomography angiography was used successfully to triage patients between endovascular and neurosurgical treatment options in a significant proportion of cases and permitted treatment planning in more than 70% of treated cases.

Adult↗

PubMed2005

Ineffective phagocytosis of amyloid-beta by macrophages of Alzheimer's disease patients.

The defective clearance of amyloid-beta (Abeta) in the brain of Alzheimer's disease (AD) patients is unexplained. The immunohistochemical studies of the frontal lobe and hippocampus show perivascular and intraplaque infiltration by blood-borne macrophages containing intracellular Abeta but only inefficient clearance of beta deposits. Neurons and neuronal nuclei, respectively, express interleukin-1beta and the chemokine RANTES, which could induce the inflammatory cell infiltration. To clarify the pathophysiology ofbeta clearance, we examined Abeta phagocytosis by monocytes and macrophages isolated from the blood of age-matched patients and controls. Control monocytes display excellent differentiation into macrophages and intracellular phagocytosis of Abeta followed by beta degradation or export. AD monocytes show poor differentiation and only surface uptake of Abeta and suffer apoptosis. HLA DR and cyclooxygenase-2 are abnormally expressed on neutrophils and monocytes of AD patients. AD patients have higher levels of intracellular cytokines compared to controls. Thus Abeta clearance is not restricted to brain microglia and involves systemic innate immune responses. In AD, however, macrophage phagocytosis is defective, which may elicit compensatory response by the adaptive immune system.

Aged↗

PubMed2005

Intracranial vascular stenosis and occlusive disease: evaluation with CT angiography, MR angiography, and digital subtraction angiography.

BACKGROUND AND PURPOSE: Although digital subtraction angiography (DSA) provides excellent visualization of the intracranial vasculature, it has several limitations. Our purpose was to evaluate the ability of helical CT angiography (CTA) to help detect and quantify intracranial stenosis and occlusion compared with DSA and MR angiography (MRA). METHODS: Twenty-eight patients underwent CTA, DSA, and 3D time-of-flight (TOF) MRA for suspected cerebrovascular lesions. All three studies were performed within a 30-day period. Two readers blinded to prior estimated or calculated stenoses, patient history and clinical information examined 672 vessel segments. Lesions were categorized as normal (0-9%), mild (10-29%), moderate (30-69%), severe (70-99%), or occluded (no flow detected). DSA was the reference standard. Unblinded consensus readings were obtained for all discrepancies. RESULTS: A total of 115 diseased vessel segments were identified. After consensus interpretation, CTA revealed higher sensitivity than that of MRA for intracranial stenosis (98% versus 70%, P < .001) and occlusion (100% versus 87%, P = .02). CTA had a higher positive predictive value than that of MRA for both stenosis (93% versus 65%, P < .001) and occlusion (100% versus 59%, P < .001). CTA had a high interoperator reliability. In 6 of 28 patients (21%), all 6 with low-flow states in the posterior circulation, CTA was superior to DSA in detection of vessel patency. CONCLUSION: CTA has a higher sensitivity and positive predictive value than MRA and is recommended over TOF MRA for detection of intracranial stenosis and occlusion. CTA has a high interoperator reliability. CTA is superior to DSA in the evaluation of posterior circulation steno-occlusive disease when slow flow is present. CTA results had a significant effect on patient clinical management.

Adult↗

PubMed2004

Comparison of dynamic gadolinium-enhanced and ferumoxides-enhanced MRI of the liver on high- and low-field scanners.

PURPOSE: To compare the performance of dynamic gadolinium-enhanced and ferumoxides-enhanced MRI in the detection and characterization of hepatic lesions, on 1.5-T and 0.2-T magnets MATERIALS AND METHODS: In 41 patients (23 men, 18 women), 52 hepatic MR examinations were performed and retrospectively analyzed; 39 and 13 examinations were performed on 1.5-T and 0.2-T magnets, respectively. A total of 33 of 41 patients had known malignancies, and 31 of 33 patients had biopsy of at least one lesion. First, a combination of unenhanced T2-weighted sequences and gradient-echo T1-weighted sequences were performed. Then, dynamic gadolinium-enhanced (0.1 mmol/kg) T1 GRE sequences were obtained, followed by intravenous drip infusion of ferumoxides (10 micromol/kg). The T2-weighted sequences were then repeated. The unenhanced and gadolinium-enhanced images (the Gd set) were reviewed separately from the unenhanced and ferumoxides-enhanced images (the ferumoxides set) by two abdominal imagers. The reviewers were blinded to clinical history and reviewed the individual studies in each set randomly. Each detected lesion was scored on a five-point scale for characterization scores: nonsolid (1 or 2), indeterminate (3), or solid (4 or 5). A consensus review was then performed correlating all available pathology, imaging, clinical findings, and follow-up to act as a gold standard. Receiver-operating-characteristic (ROC) curves were generated and both area-under-the-curve (Az values) and sensitivity values were calculated. Significance of Az and sensitivity differences was assessed using standard Z-test and chi-square. RESULTS: Of 270 lesions detected by consensus, 211 were on 1.5-T and 59 were on 0.2-T scanners. The accuracy (Az values) of lesion detection overall, of both readers, was greater for the ferumoxides set than for the Gd set (reader 1: 0.95 vs. 0.89 (P < 0.05); reader 2: 0.91 vs. 0.78 (P < 0.05)). Az values for both readers were greater on the ferumoxides set for both the 1.5-T scans and the 0.2-T scans. Out of 270 lesions detected, 231 were characterized by consensus review as solid (185) or nonsolid (46). There was a significant improvement in lesion characterization for both readers on the GD set compared with the ferumoxides set on both high and low field scanners (Az reader 1: 0.99 vs. 0.96 (P < 0.05); Az reader 2: 0.99 vs. 0.95 (P < 0.05)), respectively. CONCLUSION: At both 1.5-T and 0.2-T, ferumoxides-enhanced sequences were better for lesion detection, while gadolinium-enhanced sequences were better for lesion characterization, respectively.

Adult↗

PubMed2004

Effect of an imaging-based streamlined electronic healthcare process on quality and costs.

RATIONALE AND OBJECTIVES: A streamlined process of care supported by technology and imaging may be effective in managing the overall healthcare process and costs. This study examined the effect of an imaging-based electronic process of care on costs and rates of hospitalization, emergency room (ER) visits, specialist diagnostic referrals, and patient satisfaction. MATERIALS AND METHODS: A healthcare process was implemented for an employer group, highlighting improved patient access to primary care plus routine use of imaging and teleconsultation with diagnostic specialists. An electronic infrastructure supported patient access to physicians and communication among healthcare providers. The employer group, a self-insured company, manages a healthcare plan for its employees and their dependents: 4,072 employees were enrolled in the test group, and 7,639 in the control group. Outcome measures for expenses and frequency of hospitalizations, ER visits, traditional specialist referrals, primary care visits, and imaging utilization rates were measured using claims data over 1 year. Homogeneity tests of proportions were performed with a chi-square statistic, mean differences were tested by two-sample t-tests. Patient satisfaction with access to healthcare was gauged using results from an independent firm. RESULTS: Overall per member/per month costs post-implementation were lower in the enrolled population (126 dollars vs 160 dollars), even though occurrence of chronic/expensive diseases was higher in the enrolled group (18.8% vs 12.2%). Lower per member/per month costs were seen for inpatient (33.29 dollars vs 35.59 dollars); specialist referrals (21.36 dollars vs 26.84 dollars); and ER visits (3.68 dollars vs 5.22 dollars). Moreover, the utilization rate for hospital admissions, ER visits, and traditional specialist referrals were significantly lower in the enrolled group, although primary care and imaging utilization were higher. Comparison to similar employer groups showed that the company's costs were lower than national averages (119.24 dollars vs 146.32 dollars), indicating that the observed result was not attributable to normalization effects. Patient satisfaction with access to healthcare ranked in the top 21st percentile. CONCLUSION: A streamlined healthcare process supported by technology resulted in higher patient satisfaction and cost savings despite improved access to primary care and higher utilization of imaging.

Electronics, Medical↗

PubMed2004

Inflammation in amyotrophic lateral sclerosis spinal cord and brain is mediated by activated macrophages, mast cells and T cells.

Recent studies have shown inflammatory markers in affected neural tissues of amyotrophic lateral sclerosis (ALS) patients. We examined immunocytochemically spinal cord tissues of six patients with ALS, two with corticospinal tract degeneration secondary to cerebral infarcts and three control subjects without neuropathologic abnormalities. ALS spinal cords had dense macrophage infiltration (one log greater than control spinal cords) involving the white and gray matter, with heaviest infiltration of lateral and ventral columns and, in one patient, prefrontal gyrus and the occipital lobes of the brain. Macrophages in ALS spinal cord showed strong expression of cyclooxygenase-2 (COX-2) (one log greater than control tissues) and inducible nitric oxide synthase. In the gray matter, macrophages surrounded and appeared to phagocytize neurons (NeuN-positive) that appeared to be dying. Vessels showed damage to the tight junction protein ZO-1 in relation to perivascular CD40 receptor-positive macrophages and CD40 ligand-positive T lymphocytes. ALS spinal cords, but not control cords, were sparsely infiltrated with mast cells. In control cases with corticospinal tract degeneration following hemispheric cerebral infarction, macrophage infiltration of the white matter was COX-2-negative and restricted to lateral and anterior corticospinal tracts. Our data suggest that inflammation in ALS spinal cord and cortex is based on innate immune responses by macrophages and mast cells and adaptive immune responses by T cells.

Aged↗

PubMed2004

Macrovesicular hepatic steatosis in living related liver donors: correlation between CT and histologic findings.

PURPOSE: To assess degree of macrovesicular steatosis with unenhanced computed tomography (CT) and correlate it with histologic findings in potential donors for living related liver transplantation. MATERIALS AND METHODS: Forty-two candidates underwent unenhanced CT within 4 weeks of core liver biopsy. An experienced liver pathologist, blinded to both CT and surgical findings, retrospectively reviewed biopsy specimens and determined degree of macrovesicular steatosis. A radiologist blinded to histologic grading calculated mean hepatic attenuation in each donor liver by averaging 25 region-of-interest (ROI) measurements on five sections (five ROIs per section). Mean splenic attenuation was calculated with three separate ROI measurements. Liver attenuation index (LAI) was derived and defined as the difference between mean hepatic and mean splenic attenuation. Body mass index (BMI) was determined for each patient. Linear regression analysis was used to correlate degree of macrovesicular steatosis with both LAI and BMI. RESULTS: LAI correctly predicted degree of macrovesicular steatosis in 38 (90%) of 42 cases. In four of four livers, LAI below -10 HU correlated with greater than 30% macrovesicular steatosis (unacceptable for liver transplantation). In nine of 11 livers, LAI was between -10 and 5 HU and correctly predicted 6%-30% steatosis (relative contraindication). In two of 11 cases, LAI overestimated degree of hepatic steatosis. LAI above 5 HU correctly predicted 0%-5% steatosis in 25 of 27 livers. In two of 27 cases, parenchymal hemosiderin deposition led to an increase in LAI into the normal range, despite mild histologically confirmed steatosis. Degree of histologic macrovesicular steatosis correlated well with LAI (r = 0.92) and marginally with BMI (r = 0.45). Of 27 potential donors with normal livers at CT and acceptable LAI levels, four (15%) were deemed poor donor candidates because core biopsy revealed subtle hepatic necrosis and nonspecific hepatitis. CONCLUSION: Although unenhanced CT quantifies the degree of macrovesicular steatosis relatively well, it may preclude a liver biopsy only in a small percentage of potential donors with low LAI (unacceptable degree of steatosis). Core liver biopsy is still necessary in the majority of donors with normal LAI to identify those with both fatty liver and coexistent hemosiderin deposition or radiologically occult diffuse liver diseases.

Adult↗

PubMed2004

Minimizing central bile duct injury during radiofrequency ablation: use of intraductal chilled saline perfusion--initial observations from a study in pigs.

PURPOSE: To determine whether intraductal perfusion with chilled saline reduces thermal injury to bile ducts during radiofrequency (RF) ablation. MATERIALS AND METHODS: In swine, anesthesia was induced and the common bile duct was surgically cannulated with a pediatric feeding tube. RF thermal lesions were created adjacent to bile ducts by using an expandable-hook 2-cm RF electrode and 90-W generator. In three pigs, chilled saline was perfused through the ducts at 1.5 L/h (26 mL/min), and in another pig, room-temperature saline was perfused at the same rate. In three pigs (control group), RF lesions were created without perfusion. After 48 hours, animals were sacrificed. Periductal sections from all animals were reviewed by a liver pathologist. The degree of injury to biliary epithelium and subepithelial glands was assessed on a scale of 0%-100%. Significance of differences between degrees of injury was assessed with the Mann-Whitney test. RESULTS: In the control group, there was a mean of 100% injury to biliary ductal epithelium and 99.3% to subepithelial ductal glands. In the room-temperature saline group, there was a mean of 100% biliary epithelial injury and 84.4% glandular injury. In the chilled saline group, there was a mean of 52.9% ductal epithelial injury and 12.1% subepithelial glandular injury. In comparison with the control group, there was significantly less (P <.05) thermal injury to biliary epithelium in the chilled saline group and to subepithelial glands in both the room-temperature and chilled saline perfusion groups. CONCLUSION: RF-induced bile duct injury may be decreased significantly with an intraductal infusion of chilled saline.

Animals↗

PubMed2004

Aortic calcification and the risk of osteoporosis and fractures.

We investigated the relation between computed tomography measures of aortic calcification and values for bone density and the number of fragility fractures in 2348 healthy, postmenopausal women. To determine whether increases in vascular calcification and bone loss progress in parallel, baseline values were compared with measurements obtained 9 months to 8 yr later in a subgroup of 228 women. Of the 2348 subjects studied, 70% had osteoporosis, 30% had at least one vertebral fracture, and 9% had at least one hip fracture. Aortic calcifications were inversely related to bone density and directly related to fractures. After adjusting for age and potential confounders, measures for aortic calcification predicted 26.1% of the variance in bone density (P < 0.001). Compared with women without calcification, the odds ratios for vertebral and hip fractures in those with calcification were estimated to be 4.8 (95% confidence interval, 3.6-6.5) and 2.9 (95% confidence interval, 1.8-4.8), respectively. The subgroup analysis of 228 women longitudinally studied showed that the percentage of yearly increase in aortic calcification accounted for 47% of the variance in the percentage rate of bone loss (P < 0.001). Moreover, a strong graded association was observed between the progression of vascular calcification and bone loss for each quartile. Women in the highest quartile for gains in aortic calcification had four times greater yearly bone loss (5.3 vs.1.3% yearly; P < 0.001) than women of similar age in the lowest quartile. Smaller, but highly significant differences were also found between all other quartiles. We conclude that aortic calcifications are a strong predictor for low bone density and fragility fractures.

Aged↗

PubMed2004

Minimizing diaphragmatic injury during radiofrequency ablation: efficacy of intraabdominal carbon dioxide insufflation.

OBJECTIVE: The purpose of our study was to determine whether intraperitoneal insufflation of carbon dioxide (CO(2)) reduces adjacent diaphragmatic injury. MATERIALS AND METHODS: In seven pigs under anesthesia, a 17-gauge percutaneous insufflation needle was inserted in the infraumbilical midline using a standard insufflator. Three to six liters of CO(2) was infused into the peritoneal space to achieve at least a 1-cm separation between the liver and the diaphragm and maintained by a pressure of 8-10 mm Hg. Seven control lesions in six historical controls were used. In addition, five lesions were created in one animal from this cohort who served as a control. Superficial areas of liver separated from diaphragm were fluoroscopically targeted for radiofrequency ablation, and several 2-cm-diameter radiofrequency lesions were generated. The pigs were sacrificed at 48 hr, and at laparotomy, the liver surface was inspected and sectioned to select lesions with centers within 1 cm of the surface. The thermal injury to the corresponding adjacent diaphragm was examined to determine the depth of injury. Diaphragmatic injury was graded on a scale from 0 to III (0, no injury; I, mild injury to one-third thickness; II, moderate injury to two-thirds thickness; III, severe injury to full thickness.) RESULTS: Of 72 total lesions created, 60 had centers less than 1 cm from the liver surface (i.e., superficial) at laparotomy. Of these 60 lesions, 55 caused no significant diaphragmatic injury, two caused grade I injury and three caused grade III injury. In comparison, seven of seven historic superficial control lesions and five of five superficial radiofrequency control lesions from the current cohort caused grade III injury. Superficial radiofrequency lesions created after intraperitoneal CO(2) insufflation caused significantly less (p < 0.01) diaphragmatic injury. CONCLUSION: We have shown that in pigs, intraperitoneal CO(2) insufflation helped significantly reduce severe diaphragmatic injury when superficial hepatic radiofrequency ablation was performed.

Animals↗