Novel data interpretation method for DIII-D divertor retarding field energy analyzer with 3-D particle-in-cell simulations.

A novel data interpretation process that utilizes comprehensive particle-in-cell (PIC) simulations is developed for the new retarding field energy analyzer (RFEA) currently being constructed at DIII-D for the lower divertor using the Divertor Material Evaluation System. This probe is expected to survive a heat load of up to 100 MW/m2 for up to 5 s and reliably measure the main ion temperature (Ti) on the divertor target ranging from 10 to 200 eV. These extreme conditions posed significant engineering limitations on the probe geometry, thus extensive validation work has been performed. The conventional fitting method for the RFEA I-V characteristics is based on a simplified 1-D model without considering the ion space charge inside the probe cavity and may not be sufficient for probes designed for the DIII-D divertor environment. In this article, a more realistic description of the particle propagation process within the RFEA cavity is achieved by including both 3-D geometric effects and ion space charge in the PIC simulations, and the capability to reconstruct the ion energy distribution functions is demonstrated with reasonable consistency.

Resistance exercise and lipoproteins in postmenopausal women.

The specific aims of this study were to quantify the effects of 12 weeks of resistance training, as well as a single session of resistance exercise on lipids and lipoproteins in obese, postmenopausal women. 21 obese, postmenopausal women, not on hormone replacement therapy (age=65.9 ± 0.5 yr; BMI=32.7 ± 0.8 kg/m(2)), were randomly assigned to control (n=12) and exercise (n=9) groups matched for age and BMI. For 12 weeks, 3 days/week, the exercise group performed 10 whole body resistance exercises (3 sets at 8-RM). Fasting (10 h) blood samples were collected immediately prior to and 24 h after the first and last exercise and control session. Serum was assayed for concentrations of total cholesterol, triglycerides, LDL-C, HDL-C, HDL 2-C, HDL 3-C, non-HDL-C and TC:HDL and LDL:HDL ratios. The exercise group exhibited a significant (P<0.01) improvement in muscular strength, but no change in BMI, body mass or body composition post-training. Total cholesterol, LDL-C and non-HDL-C were significantly (P<0.05) lower in the exercise compared to the control group following the 12 weeks of resistance training. Whole body resistance training provides obese, postmenopausal women a non-pharmacological approach for the reduction of lipid and lipoprotein-cholesterol concentrations.

Nicotinic antagonists enhance process outgrowth by rat retinal ganglion cells in culture.

Functional nicotinic cholinergic receptors are found on mammalian retinal ganglion cell neurons in culture. The neurotransmitter acetylcholine (ACh) can be detected in the medium of many of these retinal cultures, after release presumably from the choline acetyltransferase-positive amacrine cells. The postsynaptic effect of endogenous or applied ACh on the ganglion cells can be blocked with specific nicotinic antagonists. Here it is shown that within 24 hours of producing such a pharmacologic blockade, the retinal ganglion cells begin to sprout or regenerate neuronal processes. Thus, the growth-enhancing effect of nicotinic antagonists may be due to the removal of inhibition to growth by tonic levels of ACh present in the culture medium. Since there is a spontaneous leak of ACh in the intact retina, the effects of nicotinic cholinergic drugs on process outgrowth in culture may reflect a normal control mechanism for growth or regeneration of retinal ganglion cell processes that is exerted by ACh in vivo.

Measuring Brain Tissue Integrity during 4 Years Using Diffusion Tensor Imaging.

BACKGROUND AND PURPOSE: DTI is an MR imaging measure of brain tissue integrity. Little is known regarding the long-term longitudinal evolution of lesional and nonlesional tissue DTI parameters in multiple sclerosis and the present study examines DTI evolution over 4 years. MATERIALS AND METHODS: Twenty-one patients with multiple sclerosis were imaged for up to 48 months after starting natalizumab therapy. Gadolinium-enhancing lesions at baseline, chronic T2 lesions, and normal-appearing white matter were followed longitudinally. T2 lesions were subclassified as black holes and non-black holes. Within each ROI, the average values of DTI metrics were derived by using Analysis of Functional Neuro Images software. The longitudinal trend in DTI metrics was estimated by using a mixed-model regression analysis. RESULTS: A significant increase was observed for axial diffusivity (P < .001) in gadolinium-enhancing lesions and chronic T2 lesions during 4 years. No significant change in radial diffusivity either in normal-appearing white matter or lesional tissue was observed. The evolution of axial diffusivity was different in gadolinium-enhancing lesions (P < .001) and chronic T2 lesions (P = .02) compared with normal-appearing white matter. CONCLUSIONS: An increase in axial diffusion in both gadolinium-enhancing lesions and T2 lesions may relate to the complex evolution of chronically demyelinated brain tissue. Pathologic changes in normal-appearing white matter are likely more subtle than in lesional tissue and may explain the stability of these measures with DTI.

Mutations in polycombeotic, a Drosophila polycomb-group gene, cause a wide range of maternal and zygotic phenotypes.

The polycomb-group genes, a set of genes characterized by mutations that cause similar phenotypes and dosage-dependent interactions, are required for the normal expression of segment-specific homeotic loci. Here we report that polycombeotic (formerly 1(3)1902), originally identified by a lethal mutation that causes a small-disc phenotype, is also a member of this group of essential genes. Adults homozygous for temperature-sensitive pco alleles that were exposed to the restrictive temperature during larval life display the second and third leg to first leg transformation characteristic of polycomb-group mutants. Adult females homozygous for temperature-sensitive alleles exposed to the restrictive temperature during oogenesis produce embryos that show anterior segments with structures normally unique to the eighth abdominal segment, another transformation characteristic of polycomb-group mutants. Mutations in the polycombeotic gene also cause defects not reported for mutations in other polycomb-group genes. Females homozygous for the most extreme temperature-sensitive allele are sterile, and larvae homozygous for null alleles have small imaginal discs and reduced frequencies of mitotic figures in the brain. Dominant mutations originally identified as enhancers or suppressors of zeste are gain-of-function alleles of polycombeotic. The type and variety of defects displayed by different mutations in this gene indicate that the product might be involved in chromosome structure and/or function.

Quantitative comparison of functional contrast from BOLD-weighted spin-echo and gradient-echo echoplanar imaging at 1.5 Tesla and H2 15O PET in the whole brain.

Spin-echo and gradient-echo echoplanar functional magnetic resonance imaging (fMRI) studies at 1.5 Tesla (T) were used to obtain blood oxygenation level-dependent (BOLD) contrast images of the whole brain in seven strongly right-handed women during execution of a complex motor task. Five subjects underwent subsequent H215O positron emission tomography (PET) studies while performing the same task. Group-averaged results for changes in the MRI relaxation rates R2* and R2 at 1.5T in response to neuronal activation in nine cortical, subcortical, and cerebellar motor regions are reported. Results for each method are grouped according to tissue type-cerebral cortex (precentral gyrus and supplementary motor area), subcortical regions (thalamus and putamen), and cerebellar cortex (superior lobule). The observed changes in R2* from activation-induced oxygenation changes were more variable across brain regions with different tissue characteristics than observed changes in R2. The ratio of deltaR2* to deltaR2 was 3.3 +/- 0.9 for cerebral cortex and 2.0 +/- 0.6 for subcortical tissue. deltaR2*, deltaR2, and relative blood flow changes were deltaR2* = -0.201 +/- 0.040 (s-1), deltaR2 = -0.064 +/- 0.011 s(-1), and deltaf/f = 16.7 +/- 0.8% in the cerebral cortex; deltaR2* = -0.100 +/- 0.026 s(-1), deltaR2 = -0.049 +/- 0.009 s(-1), and deltaf/f = 9.4 +/- 0.7% in the subcortical regions; and deltaR2* = -0.215 +/- 0.093 s(-1), deltaR2 = -0.069 +/- 0.012 s(-1), and deltaf/f = 16.2 +/- 1.2% in the cerebellar cortex.

Postexercise rehydration: effect of Na(+) and volume on restoration of fluid spaces and cardiovascular function.

Our purpose was to study the interaction between Na(+) content and fluid volume on rehydration (RH) and restoration of fluid spaces and cardiovascular (CV) function. Ten men completed four trials in which they exercised in a 35 degrees C environment until dehydrated by 2. 9% body mass, were rehydrated for 180 min, and exercised for an additional 20 min. Four RH regimens were tested: low volume (100% fluid replacement)-low (25 mM) Na(+) (LL), low volume-high (50 mM) Na(+) (LH), high volume (150% fluid replacement)-low Na(+) (HL), and high volume-high Na(+) (HH). Blood and urine samples were collected and body mass was measured before and after exercise and every hour during RH. Before and after the dehydration exercise and during the 20 min of exercise after RH, cardiac output was measured. Fluid compartment (intracellular and extracellular) restoration and percent change in plasma volume were calculated using the Cl(-) and hematocrit/Hb methods, respectively. RH was greater (P < 0.05) in HL and HH (102.0 +/- 15.2 and 103.7 +/- 14.7%, respectively) than in LL and LH (70.7 +/- 10.5 and 75.9 +/- 6.3%, respectively). Intracellular RH was greater in HL (1.12 +/- 0.4 liters) than in all other conditions (0.83 +/- 0.3, 0.69 +/- 0.2, and 0.73 +/- 0.3 liter for LL, LH, and HH, respectively), whereas extracellular RH (including plasma volume) was greater in HL and HH (1.35 +/- 0.8 and 1.63 +/- 0.4 liters, respectively) than in LL and LH (0.83 +/- 0.3 and 1.05 +/- 0.4 liters, respectively). CV function (based on stroke volume, heart rate, and cardiac output) was restored equally in all conditions. These data indicate that greater RH can be achieved through larger volumes of fluid and is not affected by Na(+) content within the range tested. Higher Na(+) content favors extracellular fluid filling, whereas intracellular fluid benefits from higher volumes of fluid with lower Na(+). Alterations in Na(+) and/or volume within the range tested do not affect the degree of restoration of CV function.

Induction of micronuclei in mouse bone marrow cells: an evaluation of nucleoside analogues used in the treatment of AIDS.

Various nucleoside analogues are being used or are being considered for use as therapeutic drugs to inhibit replication of the HTLV-III/LAV virus in infected human cells. Here, the ability of seven nucleoside analogues, a combination of two analogues, and two other therapeutic compounds to induce genotoxic and cytotoxic damage in vivo was evaluated in the mouse bone marrow micronucleus test. Using a 3-consecutive-day oral treatment protocol, almost all of the test chemicals induced a significant increase in the frequency of micronucleated polychromatic erythrocytes (MN-PCE) in male B6C3F1 mice, ranked in decreasing potency as 6-thioguanine greater than Cytarabine HCl greater than 3'-azido-3'-deoxythymidine (AZT)/2',3'-dideoxycytidine combination = AZT greater than Ribavirin = 2',3'-didehydro-3'-deoxythymidine greater than 2',3'-dideoxyadenosine = 2',3'-dideoxycytidine. The frequency of MN-PCE was not increased significantly by treatment with 2',3-dideoxyinosine (DDI) or pentamidine isethionate (PI). The differential ability of AZT and DDI to induce MN in mouse bone marrow was verified from peripheral blood smears prepared from subchronic (90 day) oral studies. The lack of genotoxic activity by DDI was route-specific since, when tested by intraperitoneal injection, a small but significant increase in MN-PCE was observed. A number of these chemicals induced a significant depression in erythropoiesis. However, there was not a significant correlation between the increase in MN-PCE and the depression in the percentage of PCE. This lack of a correlation suggests that factors other than DNA damage may contribute to the inhibition in the rate of erythropoiesis. The presence of increased levels of micronuclei in bone marrow PCE following treatment with various nucleoside analogues suggests that intrinsic genotoxic activity in mammalian cells should be one factor considered during drug selection for AIDS therapy.

M(r) 6,400 aurin tricarboxylic acid directly activates platelets.

ATA is a novel anticoagulant polymeric anionic aromatic compound that inhibits von Willebrand factor binding to platelet glycoprotein Ib and thereby prevents ristocetin- and shear stress-induced platelet aggregation. To investigate its mechanism of action, ATA fractions of homogeneous M(r) have been prepared by size exclusion chromatography. ATA fractions of M(r) > or = 2,500 are most effective at inhibiting vWF-mediated platelet aggregation, and ATA of M(r) = 2,500 also inhibits thrombin-induced platelet activation. Paradoxical results were observed in studies of ATA with M(r) = 6,400. This fraction of ATA stimulates aggregation of washed platelets or platelet-rich-plasma. The dose/response of aggregation shows a bell-shaped curve with maximal aggregation at approximately 2 micrograms/ml. Platelet aggregation is associated with phosphoinositide turnover and protein kinase C- and calcium-dependent protein phosphorylation. Platelet signalling responses to ATA are inhibited by platelet pretreatment with PGI2 or dibutyryl-cyclic AMP, but are unaffected by inhibiting platelet cyclooxygenase with aspirin. These results suggest that M(r) 6,400 ATA directly activates platelet phospholipase C to initiate platelet aggregation. This effect, unique to M(r) 6,400 ATA, could potentially mitigate ATA's beneficial anti-thrombotic effect on vWF-mediated platelet responses, and should be considered when analyzing results of experiments that utilize unfractionated ATA.

Diffusion-weighted imaging of white matter abnormalities in patients with phenylketonuria.

Phenylketonuria (PKU) is an autosomal recessive disorder caused by a deficiency of the enzyme phenylalanine hydroxylase (EC 1.14.16.1). Affected patients develop elevated plasma and tissue levels of phenylalanine and its related ketoacids. Untreated patients usually exhibit severe mental retardation and poor motor function, with characteristic T2 white matter signal abnormalities on conventional MR images. In the present study, we performed diffusion-weighted imaging in three PKU patients. All three patients demonstrated significantly restricted diffusion in all white matter areas examined.

Comparison of T2 lesion volume and magnetization transfer ratio histogram analysis and of atrophy and measures of lesion burden in patients with multiple sclerosis.

PURPOSE: The purpose of this study was twofold: first, to compare two different measures of lesion burden in patients with multiple sclerosis (MS), the magnetization transfer ratio (MTR) histogram and T2 lesion volume; and, second, to investigate the relationship between lesion burden and atrophy in patients with MS. METHODS: Thirty patients with MS were examined with MR imaging, including fast spin-echo T2- and proton density-weighted sequences as well as magnetization transfer sequences. The lesion burden in each subject was quantitated by MTR histographic analysis and by a computer-based method for calculating the total volume of lesions on T2-weighted images. Additionally, the CSF volume, the brain parenchymal volume, and the percentage of brain parenchymal volume were determined in all patients by using this method and were compared with measurements in eight control subjects. RESULTS: Significant loss of parenchymal volume was seen in patients with MS as determined by increased CSF volume and decreased percentage of brain parenchymal volume relative to that in age-matched control subjects. An inverse correlation was observed between the peak height of the MTR histogram and T2 lesion volume. T2 lesion volume corresponded positively with CSF volume and inversely with percentage of brain parenchymal volume. The peak height of the MTR histogram corresponded positively with percentage of brain parenchymal volume and inversely with CSF volume. CONCLUSION: MS patients sustain a significant loss of parenchymal volume (atrophy), which corresponds strongly with increasing lesion burden. T2 lesion volume and peak height of the MTR histogram show good correlation, and the peak height of the MTR histogram shows a superior correlation with measures of brain atrophy as compared with measurements of T2 lesion volume, suggesting that the MTR histogram may be a better indicator of global disease burden than is T2 lesion volume.

Serial analysis of magnetization-transfer histograms and Expanded Disability Status Scale scores in patients with relapsing-remitting multiple sclerosis.

BACKGROUND AND PURPOSE: Magnetization transfer ratio histogram peak height (MTR-HPH) has been shown to correlate with macroscopic and microscopic brain disease in patients with multiple sclerosis (MS). We studied the changes in MTR-HPH and in Kurtzke's Expanded Disability Status Scale (EDSS) scores over time in a group of patients with relapsing-remitting MS. METHODS: Twenty adult patients with relapsing-remitting MS (four men and 16 women) were followed up for a period of 334 to 1313 days. In all, 86 MR imaging studies of the brain were obtained, and MTR-HPH was calculated for each MR examination by using a semiautomated technique. Changes in MTR-HPH were compared between patients over the study's duration. A neurologist specialized in the care of MS patients assessed the EDSS score for each patient as a measure of clinical disability. RESULTS: Serial MR data showed a subtle but significant decline in MTR-HPH with time. No significant changes in EDSS scores were noted over the same period. CONCLUSION: Patients with relapsing-remitting MS have a significant progressive decline in normalized MTR-HPH, which is independent of EDSS score. MTR-HPH measurements can be used to monitor subclinical disease in patients with relapsing-remitting MS over a short time frame of 1 to 4 years. This parameter might be applied in future therapeutic trials to assess its usefulness.

Improving clinical histories on radiology requisitions.

PURPOSE: The Health Care Financing Administration (HCFA) regards billing for radiologic examinations without an appropriate indication as unlawful, and both the referring physician and the radiologist are liable. HCFA regulations are interpreted as requiring that all requisitions for radiologic examinations include a current diagnosis and appropriate indication for the study. The purpose of this investigation was to determine the rates at which requisitions currently meet these criteria and to assess the effectiveness of a simple intervention designed to improve them. MATERIALS AND METHODS: One hundred fifty consecutive chest radiography requisitions were examined to determine the rate at which current diagnoses and appropriate indications were present. An intervention was then implemented that included a month-long effort to inform referring physicians and radiologists of HCFA regulations, followed by a 1-week period during which requested examinations were not performed unless accompanied by a clinical diagnosis and appropriate indication. Another 150 consecutive chest radiography requisitions were then assessed to determine the effect of the intervention. A 3-month follow-up sample of a third set of 150 consecutive requisitions was then obtained. RESULTS: The intervention produced a 69% decrease in the rate at which current diagnoses were missing from requisitions, and a 61% decrease in the corresponding rate for appropriate indications. Both results are significant with chi2 analysis at the P = .001 level. After 3 months with no additional intervention, rates decayed back toward baseline, with only a 35% remaining decrease for current diagnosis and an 18% decrease for appropriate indication. CONCLUSION: The intervention performed in this study significantly reduces the rate of noncompliance with HCFA regulations. However, this improvement decays over time if it is not reinforced.

Multidisciplinary gastrointestinal cancer clinic: abdominal radiologist as active participant.

RATIONALE AND OBJECTIVES: Abdominal radiologists actively participated and provided subspecialty radiologic expertise in a multidisciplinary gastrointestinal cancer clinic that served a tertiary referral center. The purpose of this study was to evaluate the feasibility and nonradiologists' opinions of this new approach to radiologic consultation. MATERIALS AND METHODS: One of four subspecialty-trained abdominal radiologists joined physicians from four other subspecialties in staffing weekly 4-hour clinic sessions. Images were reviewed, opinions on test selection and interventional options rendered, and patients met with when interventional options were considered. Radiologists were compensated a fixed sum for each session. A survey of nonradiologists' opinions about the radiologists' active participation was conducted after 15 months (61 clinic sessions). RESULTS: Abdominal radiologists' active participation was feasible and highly regarded by nonradiologist physicians. Specific benefits cited in the survey included improved interpretation, more efficient use of nonradiologist physician time, and improved rapport between radiologists and nonradiologists. Nonradiologist physicians believed that patient care was improved and that the radiologists' participation should continue. CONCLUSION: The active participation of abdominal radiologists in a multidisciplinary gastrointestinal cancer clinic is feasible and highly regarded by nonradiologists.

von Willebrand disease: recent advances in pathophysiology and treatment.

This review focuses on new developments in the pathophysiology and treatment of von Willebrand disease (vWd). New aspects of the cell biology, gene control, and structure-function correlates of von Willebrand factor (vWf) are reviewed. vWd is more prevalent than previously recognized, affecting up to 1% of the population; this is particularly evident in women's health. Blood group is an important determinant of von Willebrand factor levels; individuals of blood group O tend to have lower plasma levels of vWf than those in other blood groups. Currently available blood tests of vWf quantity and function are discussed, in addition to newer tests undergoing validation. Treatment of classical vWd with desmopressin acetate and plasma derivatives is discussed, as is the potential for intravenous immunoglobulin and corticosteroids in acquired vWd. Special situations, such as the management of vWd in pregnancy, are also discussed.

Diffusion imaging in pediatric hypoxic ischemia injury.

This article is a brief review on the physics of diffusion imaging as well as the pertinent adult literature regarding stroke and diffusion imaging. The remainder of the article focuses on the potential uses of diffusion imaging for the evaluation of hypoxic ischemia injury in pediatric populations. In particular, diffusion changes in hypoxic ischemia injury in newborns are reviewed as the diffusion abnormalities in immature brain may behave in a manner different from adults.

Approach to functional magnetic resonance imaging of language based on models of language organization.

Functional MR imaging (fMRI) has been a useful tool in the evaluation of language both in normal individuals and patient populations. The purpose of this article is to use various models of language as a framework to review fMRI studies. Specifically, fMRI language studies are subdivided into the following categories: word generation or fluency, passive listening, orthography, phonology, semantics, and syntax.

Anticoagulants and hematomas in free flap surgery.

A review of systemic anticoagulant use in 517 free flap procedures was performed to determine the associated risk of hematoma formation. Patients were divided retrospectively (not randomly) into five groups: no anticoagulation (227 flaps, 5.3 percent hematomas), low-dose heparin bolus of 2000 to 3000 units and postoperative infusion at a rate of 100 to 400 units/hr for 5 to 7 days (192 flaps, 6.7 percent hematomas), intraoperative bolus of 5000 units of heparin without postoperative anticoagulation (46 flaps, 6.5 percent hematomas), high-dose heparin infusion at a rate of 500 to 1200 units/hr (30 flaps, 20 percent hematomas), and dextran 40 infusion at a rate of 25 ml/hr (22 flaps, 9.1 percent hematomas). Intraoperative blood loss was similar for all groups. The flap loss rate was lower in the bolus (1.0 percent) and low-dose (1.0 percent) heparin groups than in the no-anticoagulation group (4.4 percent), but this difference was not statistically significant. The pedicle thrombosis rate also was lower in the bolus (2.2 percent) and low-dose (2.1 percent) heparin groups than in the no-anticoagulation group (6.2 percent). A cause-and-effect relationship between the use of anticoagulants and flap loss or prevention of thrombosis could not be established. We can conclude, however, that the use of low-dose heparin does not increase significantly the risk of hematoma or intraoperative bleeding.

Sensorimotor cortex gamma-aminobutyric acid concentration correlates with impaired performance in patients with MS.

BACKGROUND AND PURPOSE: Abnormalities in GABA concentration [GABA] have been associated with several neuropsychiatric disorders, and research has suggested that GABA may play a role in sensorimotor cortex function. We sought to determine whether identifying a change in [GABA] within the sensorimotor cortex of patients with MS has any effect on motor function and would provide information about the adaptive/compensatory mechanisms involved in the attempt to maintain motor function during disease progression. MATERIALS AND METHODS: In 19 healthy controls and 30 patients with MS, we assessed task performance with the MS Functional Composite scale and its components (T25FW test, 9HPT, and PASAT). With in vivo MR spectroscopy, we measured [GABA] in the sensorimotor cortex and determined correlations between [GABA] and task performance. We also assessed the association between [GABA] and cortical activation volume after a bilateral finger-tapping task. RESULTS: [GABA] was inversely correlated with 9HPT scores in patients with MS, indicating a worsening of performance with increased [GABA]. No significant correlation was observed between [GABA] and T25FW or PASAT scores. [GABA] was directly correlated with primary motor cortex activation volume after the finger-tapping task in patients with MS. CONCLUSIONS: These results suggest that cortical [GABA] may be a marker of function and reorganization/adaptation of cortical gray matter in MS.