Biomedical subjects

Mark Vangel

Publications and source records attributed to Mark Vangel.

11 recordsLinked to original sources

PubMed2006

Detailed semiautomated MRI based morphometry of the neonatal brain: preliminary results.

In the neonate, regional growth trajectories provide information about the coordinated development of cerebral substructures and help identify regional vulnerability by identifying times of faster growth. Segmentation of magnetic resonance images (MRI) has provided detailed information for the myelinated brain but few reports of regional neonatal brain growth exist. We report the method and preliminary results of detailed semiautomated segmentation of 12 normative neonatal brains (gestational age 31.1-42.6 weeks at time of MRI) using volumetric T1-weighted images. Accuracy was confirmed by expert review of every segmented image. In 5 brains, repeat segmentation resulted in intraclass correlation coefficients >0.9 (except for the right amygdala) and an average percent voxel overlap of 90.0%. Artifacts or image quality limited the number of regions segmented in 9/12 data sets and 1/12 was excluded from volumetric analysis due to ventriculomegaly. Brains were segmented into cerebral exterior (N = 8), cerebral lobes (N = 5), lateral ventricles (N = 8), cerebral cortex (N = 6), white matter (N = 6), corpus callosum (N = 7), deep central gray (N = 8), hippocampi (N = 8), amygdalae (N = 8), cerebellar hemispheres (N = 8), vermis (N = 8), midbrain (N = 8), pons (N = 8) and medulla (N = 8). Linear growth (P < 0.05) was identified in all regions except the cerebral white matter, medulla and ventricles. Striking differences in regional growth rates were noted. These preliminary results are consistent with the heterochronous nature of cerebral development and provide initial estimates of regional brain growth and therefore regional vulnerability in the perinatal time period.

Algorithms↗

PubMed2006

Schizophrenia patients show intact immediate error-related performance adjustments on an antisaccade task.

OBJECTIVE: Schizophrenia patients consistently show impairments on tasks requiring inhibition such as the antisaccade task. Deficits in performance monitoring including the detection of errors and subsequent adjustments to performance may contribute to such impairments. We examined whether immediate error-related performance adjustments during the antisaccade task were intact in schizophrenia. METHOD: We compared 21 schizophrenia patients and 14 healthy control subjects on the following measures: 1) error-related, trial-by-trial adjustments in reaction time (pre-error speeding, faster errors and post-error slowing); 2) the speed-accuracy trade-off (SATO) function; and 3) the frequency and type of error self-correction. RESULTS: Although antisaccade performance in schizophrenia was characterized by increased errors and latency of correct responses, measures of immediate error-related performance adjustments were intact. CONCLUSION: Schizophrenia is characterized by intact immediate error-related performance adjustments, even in the context of impaired antisaccade performance. It is possible that deficiencies in other aspects of error processing, indexed by electrophysiological and hemodynamic markers, contribute to antisaccade and other cognitive deficits in schizophrenia.

Adult↗

PubMed2006

Diffusion tensor imaging in presymptomatic and early Huntington's disease: Selective white matter pathology and its relationship to clinical measures.

Atrophy of cortical and subcortical gray matter is apparent in Huntington's disease (HD) before symptoms manifest. We hypothesized that the white matter (WM) connecting cortical and subcortical regions must also be affected early and that select clinical symptoms were related to systems degeneration. We used diffusion tensor magnetic resonance imaging (DTI) to examine the regional nature of WM abnormalities in early HD, including the preclinical period, and to determine whether regional changes correlated with clinical features. We studied individuals in early stages (HD), presymptomatic individuals known to carry the genetic mutation that causes HD (Pre-HD), and matched healthy controls. DTI indices of tissue integrity were obtained from several regions of interest, including the corpus callosum (CC), internal capsule (IC), and basal ganglia, were compared across groups by t tests, and were correlated to cognitive and clinical measures. WM alterations were found throughout the CC, in the anterior and posterior limbs of the IC, and in frontal subcortical WM in HD subjects, supporting the selective involvement of the pyramidal tracts in HD; a similar distribution of changes was seen in Pre-HD subjects, supporting presymptomatic alterations. There was a significant relationship between select DTI measures and cognitive performance. Alterations in diffusion indices were also seen in the striatum that were independent of atrophy. Our findings support that WM alterations occur very early in HD. The distribution of the changes suggests that these changes contribute to the disruption of pyramidal and extrapyramidal circuits and also support a role of compromised cortical circuitry in early cognitive and subtle motor impairment during the preclinical stages of HD.

Adult↗

PubMed2005

Conversion of ischemic brain tissue into infarction increases with age.

BACKGROUND AND PURPOSE: Brain regions normal on diffusion-weighted imaging (DWI) but abnormal on mean transit time (MTT) maps represent tissue at risk of infarction, yet the fate of these regions is quite variable. The imperfect correlation between tissue outcome and initial imaging parameters suggests that each patient's brain may have different susceptibility to ischemic stress. We hypothesize that age is a marker for tissue susceptibility to ischemia and thus plays a role in determining tissue outcome in human stroke. METHODS: Sixty patients with acute ischemic stroke and a region of DWI/MTT mismatch that was >20% of the DWI volume were included. All patients were scanned twice, within 12 hours of symptom onset and on day 5 or later. The percentage mismatch lost (PML) was calculated as percentage of initial DWI/MTT mismatch volume that was infarcted on the follow-up MRI. The statistical analysis explored relationships among the covariates age, Trial of Org 10172 in Acute Stroke Treatment (TOAST) subtypes, time-to-MRI, and initial DWI, MTT volume, mean arterial blood pressure and blood glucose level at admission, and previous history of hypertension and diabetes mellitus. RESULTS: Univariate comparisons showed that age (P=0.003), hypertension (P=0.009), and diabetes mellitus (P=0.0002) were significantly associated with PML. Regression analyses showed age to be a significant covariate (P=0.02). The regression model predicted a change in PML of approximately 0.65% per year. The adjusted proportion of variance (R2) in PML that could be explained by age alone was 14%. CONCLUSIONS: Age-dependent increase in conversion of ischemic tissue into infarction suggests that age is a biological marker for the variability in tissue outcome in acute human stroke.

Adult↗

PubMed2005

Reduced density of cholinergic interneurons in the ventral striatum in schizophrenia: an in situ hybridization study.

BACKGROUND: The role of the striatum in the pathophysiology of schizophrenia is not understood. In a previous postmortem study, we found a reduction in the density of striatal interneurons that stain immunohistochemically for choline acetyltransferase (ChAT) in schizophrenia. METHODS: To determine whether this finding represents a specific alteration in ChAT gene expression, we used in situ hybridization to study the striatum of 11 control and 9 schizophrenic subjects with oligonucleotide probes complementary to human ChAT mRNA, preprosomatostatin (PPS) mRNA, and beta-actin mRNA. Densities of ChAT mRNA-positive neurons, ChAT mRNA expression per neuron, PPS mRNA-positive neurons, and beta-actin mRNA expression levels were measured. RESULTS: There were no significant differences between the two groups in densities of PPS mRNA-positive neurons and levels of beta-actin mRNA expression throughout the striatum, or in densities of ChAT mRNA-positive neurons in the caudate nucleus or putamen. However, in the ventral striatum, the mean density of ChAT mRNA-positive neurons was reduced to 26% of control levels in the schizophrenic group. CONCLUSIONS: There is a reduction in number or function of the cholinergic interneurons of the ventral striatum in schizophrenia.

Adult↗

PubMed2004

The neural substrate of arithmetic operations and procedure complexity.

Recent functional neuroimaging studies have begun to clarify how the human brain performs the everyday activities that require mental calculation. We used fMRI to test the hypotheses that there are specific neural networks dedicated to performing an arithmetic operation (e.g. + or -) and to performing processes that support more complex calculations. We found that the right inferior parietal lobule, left precuneus and left superior parietal gyrus are relatively specific for performing subtraction; and bilateral medial frontal/cingulate cortex are relatively specific for supporting arithmetic procedure complexity. We also found that greater difficulty level was associated with activation in a brain network including left inferior intraparietal sulcus, left inferior frontal gyrus and bilateral cingulate. Our results suggest that the network activated by the simplest calculation serves as a common basis, to which more regions are recruited for more difficult problems or different arithmetic operations.

Adult↗

PubMed2004

Trastuzumab in the treatment of advanced non-small-cell lung cancer: is there a role? Focus on Eastern Cooperative Oncology Group study 2598.

PURPOSE: Multiple non-small-cell lung cancer (NSCLC) cell lines and 20% to 50% of pathologic specimens express HER-2/neu, the target of trastuzumab, and HER-2/neu expression has proven to be an independent, unfavorable prognostic factor in resected patients with NSCLC. Trastuzumab, in vitro, has demonstrated growth-inhibiting synergy with platinating agents, and additivity with paclitaxel. The Eastern Cooperative Oncology Group therefore launched a phase II study evaluating combination carboplatin, paclitaxel, and trastuzumab in patients with advanced NSCLC. MATERIALS AND METHODS: Eligibility stipulated the following: measurable tumor, HER-2/neu positivity (1+ to 3+ by Herceptest [Dako Corp, Carpinteria, CA], confirmed by central review), Eastern Cooperative Oncology Group PS 0 to 1, adequate marrow, hepatic and renal function, and left ventricular ejection fraction >or= 45%. Patients received paclitaxel 225 mg/m(2)/3 hours, and carboplatin (area under the curve, 6) every 3 weeks, and trastuzumab 4 mg/kg intravenously on day 1, then 2 mg/kg weekly for or= 3 neutropenia and thrombocytopenia was 57% (34%) and 16% (2%), respectively. Asymptomatic grade <or= 2 reduction in left ventricular ejection fraction occurred in 7%. Other nonhematologic toxicities, including nausea, fatigue, arthralgias, and peripheral sensory neuropathy, were mild to moderate and matched those expected with carboplatin and paclitaxel alone. Eighteen patients (35%) received maintenance trastuzumab. Median progression-free survival was 3.3 months; median survival was 10.1 months, and 1-year survival rate was 42%. CONCLUSION: Combination paclitaxel, carboplatin, and trastuzumab is feasible. Toxicity appears no worse than cytotoxic therapy alone. Overall survival is similar to historical data using carboplatin and paclitaxel alone. However, patients with 3+ HER-2/neu expression did well in contrast to historical data suggesting potential benefit for trastuzumab in this rare subset of NSCLC. Critical assessment of trastuzumab's role in advanced NSCLC will require phase III trials.

Adult↗

PubMed2004

A multiagent strategy to decrease regimen-related toxicity in children undergoing allogeneic hematopoietic stem cell transplantation.

Regimen-related toxicity (RRT) is a frequent cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation (HSCT). In this pilot study, we examined the feasibility and potential efficacy of administering a fixed combination of agents as a novel approach to reducing RRT in children undergoing HSCT. Thirty-seven patients were treated with ursodeoxycholic acid, folinic acid, vitamin E, and parenteral nutrition titrated to measured energy expenditure in the peritransplantation period. Outcomes were compared with those in historical controls (n = 131). Compliance with oral ursodeoxycholic acid and vitamin E of at least 90% was achieved in a mean of 86% (95% confidence interval, 75%-97%) of patients. In the study group, we observed (1) reduced prevalence and severity of mucositis (P = .008 and.004, respectively); (2) less severe hepatic toxicity (P = .007); and (3) shorter time to engraftment (P = .02) compared with the control group. These benefits appeared most pronounced among high-risk patients. The administration of this regimen, including oral medications, is feasible during the peritransplantation period, and it is well tolerated. The decreased RRT observed in comparison to historical controls suggests that combination approaches deserve exploration as a means of reducing the morbidity of HSCT.

Adolescent↗

PubMed2004

Activation of the fusiform gyrus when individuals with autism spectrum disorder view faces.

Prior imaging studies have failed to show activation of the fusiform gyrus in response to emotionally neutral faces in individuals with autism spectrum disorder (ASD) [Critchley et al., Brain 124 (2001) 2059; Schultz et al., Arch. Gen. Psychiatry 57 (2000) 331]. However, individuals with ASD do not typically exhibit the striking behavioral deficits that might be expected to result from fusiform gyrus damage, such as those seen in prosopagnosia, and their deficits appear to extend well beyond face identification to include a wide range of impairments in social perceptual processing. In this study, our goal was to further assess the question of whether individuals with ASD have abnormal fusiform gyrus activation to faces. We used high-field (3 T) functional magnetic resonance imaging to study face perception in 11 adult individuals with autism spectrum disorder (ASD) and 10 normal controls. We used face stimuli, object stimuli, and sensory control stimuli (Fourier scrambled versions of the face and object stimuli) containing a fixation point in the center to ensure that participants were looking at and attending to the images as they were presented. We found that individuals with ASD activated the fusiform face area and other brain areas normally involved in face processing when they viewed faces as compared to non-face stimuli. These data indicate that the face-processing deficits encountered in ASD are not due to a simple dysfunction of the fusiform area, but to more complex anomalies in the distributed network of brain areas involved in social perception and cognition.

Adult↗

PubMed2003

Changes in resting energy expenditure among children undergoing allogeneic stem cell transplantation.

BACKGROUND: Because of the effects of chemotherapy and radiotherapy, patients undergoing stem cell transplantation (SCT) are commonly provided nutritional support with parenteral nutrition. The energy and nutrient needs of these patients have not been well studied. OBJECTIVE: The objective was to measure resting energy expenditure (REE), dietary intake, and biochemical and anthropometric changes in children before and after allogeneic SCT. DESIGN: This was a prospective cohort study of 37 children aged 9.1 +/- 6.4 y ( +/- SD) undergoing SCT who were enrolled in an open-label trial of a unique supportive care intervention that included the routine use of oral leucovorin, vitamin E, and ursodeoxycholic acid. Parenteral nutrition was provided to match 100% of measured or estimated REE. REE was measured weekly via indirect calorimetry. RESULTS: Baseline REE was 95% of the predicted age- and sex-matched norms and was significantly correlated with midarm muscle area (r = 0.82, P < 0.001). REE fell to a nadir of approximately 80% of the predicted levels by week 3 after SCT, with a gradual increase in weeks 4 and 5. Arm anthropometric measurements showed no change in triceps skinfold thickness but significant declines in midarm muscle area after SCT. Serum vitamin E remained in the normal range. CONCLUSIONS: Children undergoing SCT show significant declines in REE after transplantation. These changes may be due to alterations in lean body mass. Standard nutritional regimens may lead to overfeeding.

Adolescent↗

PubMed2003

Certification of standard reference material 970, ascorbic acid in serum, and analysis of associated interlaboratory bias in the measurement process.

BACKGROUND: The accurate and reproducible measurement of ascorbic acid is essential in delineating the role of ascorbic acid as a diagnostic tool for human disease and for the comparison of data acquired by different laboratories. A stabilized pair of standards of ascorbic acid in human serum, which is compatible with most analytical methods, have been prepared. METHODS: The certification was based on the gravimetric addition of ascorbic acid to metaphosphoric acid-stabilized, ascorbic acid-depleted serum and NIST liquid chromatography-electrochemical measurements. The NIST results were analyzed statistically for homogeneity, and the expanded uncertainty of each SRM was calculated using all of the NIST data. An interlaboratory comparison exercise was also performed. RESULTS: These materials, Standard Reference Material (SRM) 970 Ascorbic Acid in Serum, Level I and Level II, are homogeneous and are certified to contain (10.07 +/- 0.21) and (30.57 +/- 0.28) mmol ascorbic acid/L of solution (expanded uncertainty), respectively. In the interlaboratory comparison (n = 17), the relative SDs for the two materials were 22% and 19%. CONCLUSIONS: Two lots of serum, each containing different amounts of ascorbic acid stabilized in metaphosphoric acid, have been prepared and characterized. Many laboratories provide inaccurate results.

Ascorbic Acid↗