Arterial stiffness assessment in coronary microvascular dysfunction and heart failure with preserved ejection fraction: An initial report from the WISE-CVD continuation study.

Background: Heart failure with preserved ejection fraction (HFpEF) is the most common cardiac complication in patients with coronary microvascular dysfunction (CMD), yet its underlying pathways remain unclear. Aortic pulse-wave velocity (aPWV) is an indicator of large artery stiffness and a predictor for cardiovascular disease. However, aPWV in CMD and HFpEF is not well characterized and may provide understanding of disease progression. Methods: Among participants without obstructive coronary artery disease, we evaluated 51 women with suspected CMD and 20 women and men with evidence of HFpEF. All participants underwent aPWV measurement (SphygmoCor, Atcor Medical) with higher aPWV indicating greater vascular stiffness. Cardiac magnetic resonance imaging (CMRI) assessed left ventricular (LV) ejection fraction, CMD via myocardial perfusion reserve index (MPRI), and ventricular remodeling via LV mass-volume ratio. . Statistical analysis was performed using Wilcoxon rank sum tests, Pearson correlations and linear regression analysis. Results: Compared to the suspected CMD group, the HFpEF participants were older (65 ± 12 vs 56 ± 11 yrs., p = 0.002) had higher BMI (31.0 ± 4.3 vs 27.8 ± 6.7 kg/m2, p = 0.013), higher aPWV (10.5 ± 2.0 vs 8.0 ± 1.6 m/s, p = 0.05) and lower MPRI (1.5 ± 0.3 vs1.8 ± 0.3, p = 0.02), but not remodeling. In a model adjusted for cardiovascular risk factors, the HFpEF group had a lower LVEF (estimate -4.78, p = 0.0437) than the suspected CMD group. Conclusions: HFpEF participants exhibit greater arterial stiffness and lower myocardial perfusion reserve, with lower LVEF albeit not remodeling, compared to suspected CMD participants. These findings suggest arterial stiffness may contribute to progression from CMD to HFpEF. Prospective work is needed and ongoing.

Cold Pressor Testing and Sympathetic Nervous System Contribution to Ischemia with No Obstructive Coronary Artery Disease: Results from the Women's Ischemia Syndrome Evaluation-Coronary Vascular Dysfunction Project.

Study Objective: Cold Pressor Testing (CPT) is a known stimulus of the sympathetic nervous system (SNS). To better understand sympathetic contribution to coronary blood flow regulation in women with suspected ischemia and no obstructive coronary arteries (INOCA), we compared myocardial perfusion reserve during CPT stress cardiac magnetic resonance (CMR) imaging between women with suspected INOCA and reference subjects. Design: Prospective cohort. Setting: Academic hospital. Participants: 107 women with suspected INOCA and 21-age-matched reference women. Interventions: CPT stress CMR was performed with measurement of myocardial perfusion reserve index (MPRI), adjusted for rate pressure product (MPRIRPP). Invasive coronary function testing in a subset of INOCA women (n=42) evaluated for endothelial dysfunction in response to acetylcholine, including impaired coronary diameter response ≤0% and coronary blood flow response (ΔCBF) <50%. Main Outcome Measure: MPRIRPP. Results: Compared to reference women, the INOCA group demonstrated higher resting RPP (p=0.005) and CPT MPRIRPP (1.09±0.36 vs 0.83±0.18, p=0.002). Furthermore, INOCA women with impaired ΔCBF (n=23) had higher CPT MPRIRPP (p=0.044) compared to reference women despite lower left ventricular ejection fraction (64±7 % vs 69±2 %, p=0.005) and mass-to-volume ratio (0.79±0.15 vs 0.62±0.09, p<0.0001). These differences in CPT MPRIRPP did not persist after adjusting for age, body mass index, and history of hypertension. CPT MPRIRPP among INOCA women did not differ based on defined acetylcholine responses. Conclusions: Myocardial perfusion reserve to CPT stress is greater among women with INOCA compared to reference subjects. CPT induced a higher MPRIRPP also in women with coronary endothelial dysfunction, suggesting a greater contribution of the SNS to coronary flow than endothelial dysfunction. Further investigation in a larger cohort is needed.

Ventricular shape and relative position abnormalities in preterm neonates.

Recent neuroimaging findings have highlighted the impact of premature birth on subcortical development and morphological changes in the deep grey nuclei and ventricular system. To help characterize subcortical microstructural changes in preterm neonates, we recently implemented a multivariate tensor-based method (mTBM). This method allows to precisely measure local surface deformation of brain structures in infants. Here, we investigated ventricular abnormalities and their spatial relationships with surrounding subcortical structures in preterm neonates. We performed regional group comparisons on the surface morphometry and relative position of the lateral ventricles between 19 full-term and 17 preterm born neonates at term-equivalent age. Furthermore, a relative pose analysis was used to detect individual differences in translation, rotation, and scale of a given brain structure with respect to an average. Our mTBM results revealed broad areas of alterations on the frontal horn and body of the left ventricle, and narrower areas of differences on the temporal horn of the right ventricle. A significant shift in the rotation of the left ventricle was also found in preterm neonates. Furthermore, we located significant correlations between morphology and pose parameters of the lateral ventricles and that of the putamen and thalamus. These results show that regional abnormalities on the surface and pose of the ventricles are also associated with alterations on the putamen and thalamus. The complementarity of the information provided by the surface and pose analysis may help to identify abnormal white and grey matter growth, hinting toward a pattern of neural and cellular dysmaturation.

Corrigendum to "Developmental synergy between thalamic structure and interhemispheric connectivity in the visual system of preterm infants" [NeuroImage: Clinical 8 (2015) 462-472].

[This corrects the article DOI: 10.1016/j.nicl.2015.05.014.].

Statistical analysis of relative pose of the thalamus in preterm neonates.

Preterm neonates are at higher risk of neurocognitive and neurosensory abnormalities. While numerous studies have looked at the effect of prematurity on brain anatomy, none to date have attempted to understand the relative pose of subcortical structures and to assess its potential as a biomarker of abnormal growth. Here, we perform the first relative pose analysis on a point distribution model (PDM) of the thalamus between 17 preterm and 19 term-born healthy neonates. Initially, linear registration and constrained harmonic registration were computed to remove the irrelevant global pose information and obtain correspondence in vertices. All the parameters for the relative pose were then obtained through similarity transformation. Subsequently, all the pose parameters (scale, rotation and translation) were projected into a log-Euclidean space, where univariate and multivariate statistics were performed. Our method detected relative pose differences in the preterm birth for the left thalamus. Our results suggest that relative pose in subcortical structures is a useful indicator of brain injury, particularly along the anterior surface and the posterior surface. Our study supports the concept that there are regional thalamic asymmetries in the preterm that may be related to subtle white matter injury, have prognostic significance, or be related to preterm birth itself.

The neuropeptide NLP-22 regulates a sleep-like state in Caenorhabditis elegans.

Neuropeptides have central roles in the regulation of homoeostatic behaviours such as sleep and feeding. Caenorhabditis elegans displays sleep-like quiescence of locomotion and feeding during a larval transition stage called lethargus and feeds during active larval and adult stages. Here we show that the neuropeptide NLP-22 is a regulator of Caenorhabditis elegans sleep-like quiescence observed during lethargus. nlp-22 shows cyclical mRNA expression in synchrony with lethargus; it is regulated by LIN-42, an orthologue of the core circadian protein PERIOD; and it is expressed solely in the two RIA interneurons. nlp-22 and the RIA interneurons are required for normal lethargus quiescence, and forced expression of nlp-22 during active stages causes anachronistic locomotion and feeding quiescence. Optogenetic stimulation of the RIA interneurons has a movement-promoting effect, demonstrating functional complexity in a single-neuron type. Our work defines a quiescence-regulating role for NLP-22 and expands our knowledge of the neural circuitry controlling Caenorhabditis elegans behavioural quiescence.

Abnormal cerebral microstructure in premature neonates with congenital heart disease.

BACKGROUND AND PURPOSE: Abnormal cerebral microstructure has been documented in term neonates with congenital heart disease, portending risk for injury and poor neurodevelopmental outcome. Our hypothesis was that preterm neonates with congenital heart disease would demonstrate diffuse cerebral microstructural abnormalities when compared with critically ill neonates without congenital heart disease. A secondary aim was to identify any association between microstructural abnormalities, white matter injury (eg, punctate white matter lesions), and other clinical variables, including heart lesions. MATERIALS AND METHODS: With the use of tract-based spatial statistics, an unbiased, voxelwise method for analyzing diffusion tensor imaging data, we compared 21 preterm neonates with congenital heart disease with 2 cohorts of neonates without congenital heart disease: 28 term and 27 preterm neonates, identified from the same neonatal intensive care unit. RESULTS: Compared with term neonates without congenital heart disease, preterm neonates with congenital heart disease had microstructural abnormalities in widespread regions of the central white matter. However, 42% of the preterm neonates with congenital heart disease had punctate white matter lesions. When neonates with punctate white matter lesions were excluded, microstructural abnormalities remained only in the splenium. Preterm neonates with congenital heart disease had similar microstructure to preterm neonates without congenital heart disease. CONCLUSIONS: Diffuse microstructural abnormalities were observed in preterm neonates with congenital heart disease, strongly associated with punctate white matter lesions. Independently, regional vulnerability of the splenium, a structure associated with visual spatial function, was observed in all preterm neonates with congenital heart disease.

Aging blunts hyperventilation-induced hypocapnia and reduction in cerebral blood flow velocity during maximal exercise.

Cerebral blood flow (CBF) increases from rest to ∼60% of peak oxygen uptake (VO(2peak)) and thereafter decreases towards baseline due to hyperventilation-induced hypocapnia and subsequent cerebral vasoconstriction. It is unknown what happens to CBF in older adults (OA), who experience a decline in CBF at rest coupled with a blunted ventilatory response during VO(2peak). In 14 OA (71 ± 10 year) and 21 young controls (YA; 23 ± 4 years), we hypothesized that OA would experience less hyperventilation-induced cerebral vasoconstriction and therefore an attenuated reduction in CBF at VO(2peak). Incremental exercise was performed on a cycle ergometer, whilst bilateral middle cerebral artery blood flow velocity (MCA V (mean); transcranial Doppler ultrasound), heart rate (HR; ECG) and end-tidal PCO(2) (P(ET)CO(2)) were monitored continuously. Blood pressure (BP) was monitored intermittently. From rest to 50% of VO(2peak), despite greater elevations in BP in OA, the change in MCA V(mean) was greater in YA compared to OA (28% vs. 15%, respectively; P < 0.0005). In the YA, at intensities >70% of VO(2peak), the hyperventilation-induced declines in both P(ET)CO(2) (14 mmHg (YA) vs. 4 mmHg (OA); P < 0.05) and MCA V(mean) (-21% (YA) vs. -7% (OA); P < 0.0005) were greater in YA compared to OA. Our findings show (1), from rest-to-mild intensity exercise (50% VO(2peak)), elevations in CBF are reduced in OA and (2) age-related declines in hyperventilation during maximal exercise result in less hypocapnic-induced cerebral vasoconstriction.

Abnormal microstructure of the atrophic thalamus in preterm survivors with periventricular leukomalacia.

BACKGROUND AND PURPOSE: The neuroanatomic substrate of cognitive deficits in long-term survivors of prematurity with PVL is poorly understood. The thalamus is critically involved in cognition via extensive interconnections with the cerebral cortex. We hypothesized that the thalamus is atrophic (reduced in volume) in childhood survivors of prematurity with neuroimaging evidence of PVL and that the atrophy is associated with selective microstructural abnormalities within its subdivisions. MATERIALS AND METHODS: We performed quantitative volumetric and DTI measurements of the thalamus in 17 children with neuroimaging evidence of PVL (mean postconceptional age, 5.6 ± 4.0 years) who were born prematurely and compared these with 74 term control children (5.7 ± 3.4 years). RESULTS: The major findings were the following: 1) a significant reduction in the overall volume of the thalamus in patients with PVL compared with controls (P < .0001), which also correlated with the severity of PVL (P = .001); 2) significantly decreased FA (P = .003) and increased λ(⊥) (P = .02) in the thalamus overall and increased axial, radial, and mean diffusivities in the pulvinar (P < .03), suggesting injury to afferent and efferent myelinated axons; and 3) a positive correlation of pulvinar abnormalities with those of the parieto-occipital white matter in periventricular leukomalacia, suggesting that the pulvinar abnormalities reflect secondary effects of damaged interconnections between the pulvinar and parieto-occipital cortices in the cognitive visual network. CONCLUSIONS: There are volumetric and microstructural abnormalities of the thalamus in preterm children with PVL, very likely reflecting neuronal loss and myelinated axonal injury. The selective microstructural damage in the pulvinar very likely contributes to abnormal cognitive visual processing known to occur in such survivors.

Apparent diffusion and fractional anisotropy of diffuse intrinsic brain stem gliomas.

BACKGROUND AND PURPOSE: DIBSGs have the worst prognosis among pediatric brain tumors with no improvement of outcome for several decades. In this study, we determined whether diffusion imaging could improve patient stratification and our understanding of the impact of therapies. MATERIALS AND METHODS: Nine baseline and 24 follow-up DTI studies performed in 9 patients on a 1.5T clinical MR imaging scanner were reviewed. ADC and FA were measured for the whole lesion and at 5 anatomic levels: the rostral medulla, caudal pons, midpons, rostral pons, and caudal midbrain. Reference data were obtained from 8 controls with normal brain stem, 6 patients with medulloblastoma, and 7 patients with pilocytic astrocytoma. RESULTS: ADC was higher in untreated DIBSG than in normal brain stem and medulloblastoma (1.14 ± 0.18 [×10⁻³ mm²/s] versus 0.75 ± 0.06 and 0.56 ± 0.05, both P < .001). FA was lower in DIBSG than in normal brain stem (0.24 ± 0.04 versus 0.43 ± 0.02, P < .001) but was higher than that in pilocytic astrocytoma (0.17 ± 0.05, P < .05). Lower baseline ADC and higher FA correlated with a worse clinical course. Correlations were more significant at the caudal midbrain than in other regions. ADC decreased and FA increased after RT. Changes of FA after RT at the caudal midbrain correlated with event-free survival. CONCLUSIONS: Baseline ADC and FA of DIBSG revealed hypocellular tumors with extensive edema. Diffusion changes after therapy implied reduced edema but did not support a significant response to therapy. The significance of diffusion properties varied with anatomic locations, the caudal midbrain being particularly important.

Citrate in pediatric CNS tumors?

BACKGROUND AND PURPOSE: In a subset of in vivo MR spectra acquired from pediatric brain tumors, we have observed an unassigned peak. The goal of this study was to determine the molecule of origin, and the prevalence and concentration of this chemical in various pediatric brain tumors. MATERIALS AND METHODS: Single-voxel point-resolved spectroscopy (PRESS) spectra from 85 patients with brain tumors and 469 control subjects were analyzed. Citrate seemed to be a likely candidate, and model spectra of citrate were added to the basis set of metabolites for automated processing with use of LCModel software. Absolute "apparent" concentrations of citrate and the Cramer-Rao lower bounds (CRLB), indicators for the reliability of detection, were determined. RESULTS: "Apparent" citrate was detected in 26 of 85 patients with CRLB of less than 25%. Diffuse intrinsic brain stem glioma (DIBSG) had the highest mean concentration (4.0 +/- 1.1 mmol/kg in all subjects), and 8 of 12 patients had CRLB less than 25%. A significant reduction of citrate (P < .01) was observed in 6 DIBSGs that had follow-up MR spectroscopy studies after radiation therapy. "Apparent" citrate with CRLB less than 25% was detected in 5 of 22 medulloblastomas (mean citrate, 2.9 +/- 2.2 mmol/kg), in 5 of 14 ependymomas (2.6 +/- 1.8 mmol/kg), 5 of 14 astrocytomas (1.9 +/- 1.2 mmol/kg), and 3 of 23 pilocytic astrocytomas (1.4 +/- 1.1 mmol/kg). In control subjects older than 6 months, CRLB less than 25% was not observed, whereas CRLB less than 25% was observed in 39 of 194 subjects younger than 6 months,. CONCLUSION: MR signal consistent with citrate was observed in pediatric brain tumors and in the developing brain of infants younger than 6 months.

Transarterial coil embolization of the venous component of aggressive type 4 dural arteriovenous fistulas.

We report 2 patients with aggressive intracranial dural arteriovenous fistulae that were repaired via percutaneous, transarterial coil embolization of the venous outlets.

Quantitative short echo time 1H-MR spectroscopy of untreated pediatric brain tumors: preoperative diagnosis and characterization.

PURPOSE: Our aims were to evaluate the metabolic profiles of pediatric brain tumors with short echo time (TE) MR spectroscopy and absolute quantitation of metabolite concentrations (in mmol/kg of tissue) and to describe metabolic features that distinguish individual tumor types and that may help to improve preoperative diagnosis of specific tumors. METHODS: MR imaging examinations of 60 patients with untreated brain tumors (14 medulloblastomas, 5 anaplastic astrocytomas, 3 low-grade astrocytomas, 17 pilocytic astrocytomas, 4 anaplastic ependymomas, 5 ependymomas, 3 choroid plexus papillomas, 3 choroid plexus carcinomas, and 6 pineal germinomas) were reviewed. Single-voxel proton MR spectroscopy with a TE of 35 ms was performed and absolute metabolite concentrations were determined by using fully automated quantitation. RESULTS: Taurine (Tau) was significantly elevated in medulloblastomas (P < .00001) compared with all other tumors pooled (All Other). Tau was also observed consistently, at lower concentration, in pineal germinomas. Creatine (Cr) was significantly reduced in pilocytic astrocytomas, distinguishing them from All Other (P < .000001). The MR spectra of choroid plexus papillomas exhibited low Cr (P < .01) concentrations; however, myoinositol was elevated (P < .01) and total choline (tCho) (P < .0001) was reduced relative to All Other. Choroid plexus carcinomas had low Cr (P < .01 versus All Other) and the lowest Cr/tCho ratio (P < .0001 versus All Other) among all tumors studied. Guanidinoacetate was reduced in low-grade astrocytomas and anaplastic astrocytomas (P < .00001) versus All Other, whereas ependymoma and anaplastic ependymomas exhibited particularly low N-acetylaspartate (P < .00001 versus All Other). CONCLUSION: Quantitative proton MR spectroscopy reveals features of pediatric brain tumors that are likely to improve preoperative diagnoses.

Neuropsychological outcome of subjects participating in the PKU adult collaborative study: a preliminary review.

Adult subjects with classical phenylketonuria (PKU) who were diagnosed and treated neonatally participated in this long-term follow-up study. Twenty-four subjects received neuropsychological (NP) assessment and a subset received magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) to identify: (1) pattern of cognitive dysfunction; (2) effect of high blood phenylalanine (Phe) level at time of cognitive testing; and (3) treatment variables that may be associated with cognitive difficulties in adulthood. All subjects had average IQ except one subject in the borderline range. Diet was initiated by the 15th day of life. All subjects except one were on diet until age 6 years (mean years of treatment = 15). Blood Phe levels at cognitive testing ranged from 157 to 1713 micromol/L (mean = 1038); 11 subjects had levels < 1000 micromol/L and 13 subjects had levels >1000 micromol/L. Results suggest that adults with early-treated PKU demonstrate specific cognitive deficits, a number of which are associated with the frontal and temporal area of the brain. Deficits were noted in several domains including executive functioning, attention, verbal memory, expressive naming and verbal fluency. Self-report measures of depression and anxiety were generally in the normal/mild range. The group with a Phe level > 1000 micromol/L scored lower than the group with Phe level < 1000 micromol/L on measures of focused attention, verbal fluency, reaction time, verbal recognition memory, visual memory and naming. Tests of cognitive functioning were often correlated with measures of treatment during childhood rather than with Phe level at the time of cognitive testing. Subjects with abnormal MRI scored significantly lower on two cognitive tests (Trails A and CVLT Recognition Memory). We found no significant correlation between current brain Phe level obtained through MRS (n = 10) and neuropsychological functioning. Future longitudinal investigation with a larger sample size will assist in clarifying the aetiology of neuropsychological deficits and association with treatment history.

Time course of bioluminescent signal in orthotopic and heterotopic brain tumors in nude mice.

In vivo bioluminescence imaging is becoming increasingly popular. Quantification of bioluminescence signals requires knowledge of the variability and reproducibility of this technique. The objective of this study was to analyze the time course of luminescent signal emitted from firefly luciferase-expressing tumors in two locations, following luciferin injection and at different times after tumor cell implantation. Knowledge of the kinetics of the bioluminescent signals is required for the reliable quantification and comparison of signal during longitudinal studies. The kinetics of bioluminescence was evaluated in orthotopic and heterotopic brain tumors in mice using a human brain tumor cell line constitutively expressing luciferase. Tumor cells were implanted in the brains and flanks of the animals, and whole-body images revealing tumor location were obtained. Tumor burden was monitored over time by the quantitation of photon emission. The magnitude of bioluminescence measured in vivo varied with time after the injection of luciferin, as well as with dose, which necessitated that the comparison of the quantitative results take into consideration the time after injection. Heterotopic and orthotopic tumors exhibited significantly different time courses; however, time after implantation as characterized by kinetic studies performed on days 4 and 14 after cell implantation revealed no significant differences in orthotopic tumors. Future quantitative longitudinal studies must take into account the differences in the kinetics of different models.

Column selectivity in reversed-phase liquid chromatography I. A general quantitative relationship.

Retention factors k have been measured for 67 neutral, acidic and basic solutes of highly diverse molecular structure (size, shape, polarity, hydrogen bonding, pKa, etc.) on 10 different C18 columns (other conditions constant). These data have been combined with k values from a previous study (86 solutes, five different C8 and C18 columns) to develop a six-term equation for the correlation of retention as a function of solute and column. Values of k can be correlated with an accuracy of +/- 1-2% (1 standard deviation). This suggests that all significant contributions to column selectivity have been identified (and can be measured) for individual alkyl-silica columns which do not have an embedded polar group. That is, columns of the latter kind can be quantitatively characterized in terms of selectivity for use in the separation of any sample.

Column selectivity in reversed-phase liquid chromatography II. Effect of a change in conditions.

The isocratic retention of 67 widely-different solutes in reversed-phase liquid chromatography (RP-LC) has been investigated as a function of temperature and mobile phase composition (% B) for three different C18 columns. Similar studies were also carried out in a gradient mode, where temperature, gradient time and solvent type were varied. These results show that changes in retention with these conditions are similar for each of these three columns. This suggests that relative column selectivity as defined by experiments for one set of experimental conditions will be approximately applicable for other conditions, with the exception of changes in mobile phase pH-which can affect values of the column parameter C (a measure of silanol ionization). Column selectivity as a function of pH was explored for several columns.

Geochemical reactions resulting from in situ oxidation of PCE-DNAPL by KMnO4 in a sandy aquifer.

Although the potential for KMnO4 to destroy chlorinated ethenes in situ was first recognized more than a decade ago, the geochemical processes that accompany the oxidation have not previously been examined. In this study, aqueous KMnO4 solutions (10-30 g/L) were injected into an unconfined sand aquifer contaminated by the dense non-aqueous-phase liquid (DNAPL) tetrachloroethylene (PCE). The effects of the injections were monitored using depth-specific, multilevel groundwater samplers, and continuous cores. Two distinct geochemical zones evolved within several days after injection. In one zone where DNAPL is present, reactions between KMnO4 and dissolved PCE resulted in the release of abundant chloride and hydrogen ions to the water. Calcite and dolomite dissolved, buffering the pH in the range of 5.8-6.5, releasing Ca, Mg, and CO2 to the pore water. In this zone, the aqueous Ca/Cl concentration ratio is close to 5:12, consistent with the following reaction for the oxidation of PCE in a carbonate-rich aquifer: 3C2Cl4 + 5CaCO3(s) + 4KMnO4 + 2H+ --> 11CO2 + 4MnO2(s) + H2O + 12Cl- + 5Ca2+ + 4K+. In addition to Mg from dolomite dissolution, increases in the concentration of Mg as well as Na may result from exchange with K at cation-exchange sites. In the second zone, where lesser amounts of PCE were present, KMnO4 persisted in the aquifer for more than 14 months, and the porewater pH increased graduallyto between 9 and 10 as a resultof reaction between KMnO4 and H2O. A small increase in SO4 concentrations in the zones invaded by KMnO4 suggests that KMnO4 injections caused oxidation of sulfide minerals. There are important benefits of carbonate mineral buffering during DNAPL remediation by in situ oxidation. In a carbonate-buffered system, Mn(VII) is reduced to Mn(IV) and is immobilized in the groundwater by precipitating as insoluble manganese oxide. Energy-dispersive X-ray spectroscopy analyses of the manganese oxide coatings on aquifer mineral grains have detected the impurities Al, Ca, Cl, Cu, Pb, P, K, Si, S, Ti, U, and Zn indicating that, similar to natural systems, precipitation of manganese oxide is accompanied by coprecipitation of other elements. In addition, the consumption of excess KMnO4 by reaction with reduced minerals such as magnetite will be minimized because the rates of these reactions increase with decreasing pH. Aquifer cores collected after the KMnO4 injections exhibit dark brown to black bands of manganese oxide reaction products in sand layers where DNAPL was originally present. Mineralogical investigations indicate that the manganese oxide coatings are uniformly distributed over the mineral grains. Observations of the coatings using transmission electron microscopy indicate that they are on the order of 1 microm thick, and consequently, the decrease in porosity through the formation of the coatings is negligible.

Primary angiitis of the central nervous system in children: 5 cases.

We describe 5 children who meet criteria for primary angiitis of the central nervous system (PACNS). All patients presented with headache and/or focal neurologic deficits and exhibited clinical and/or radiographic evidence of disease progression. Two patients had disease progression prior to combined treatment with cyclophosphamide and corticosteroids; one progressed while receiving intravenous cyclophosphamide and stabilized after a change to daily oral dosing; one progressed after discontinuing therapy after less than 12 months and improved after retreatment; and one progressed on steroid therapy alone but was lost to followup. Children who have frequent or severe headaches or focal neurologic deficits should be carefully evaluated and those meeting criteria for PACNS should be treated aggressively.

Incidence of focal white matter lesions in a population of hemophiliac children and their normal siblings. Hemophilia Growth and Development Study.

OBJECTIVE: This analysis was undertaken to evaluate the etiology and sequelae of 2- to 5-mm focal white matter hyperintensities on T2-weighted MR images of some participants enrolled in the Hemophilia Growth and Development Study (HGDS). MATERIALS AND METHODS: The HGDS is a multicenter study of the growth and development, neurological, neuropsychological, and immune functioning of a cohort of children and adolescents, 62% of whom were infected with HIV through the use of clotting factor concentrates, and their non-hemophiliac, non-HIV infected male siblings. The current investigation was conducted with all three groups of HGDS participants: HIV-positive hemophiliacs (n = 207), HIV-negative hemophiliacs (n = 126), and their siblings (n = 47). Magnetic resonance imaging was performed at each center, with a variety of 0.3 to 1.5 T instruments. Standard examinations included 5-mm-thick T1-weighted sagittal and axial images, intermediate, and T2-weighted axial images. A study of abnormalities of the coagulation system known to be associated with thrombotic events was conducted among a subgroup of participants (n = 51) from eight centers. RESULTS: Lesions were not associated with hemophilia-related factors, immune function, hematologic, or neurologic factors. There were no associations between the presence of white matter lesions and defects of coagulation in any of the assays completed. CONCLUSION: The 2- to 5-mm focal white matter hyperintensities on T2-weighted MR images of the brain were incidental findings in our study population.